Based on the traditional Chinese medicine theory that "all pain， itching， and sores are related to the heart"， this paper proposes treating recurrent aphthous ulcers from the perspective of the heart. It suggests that excessive heart fire and tissue erosion due to flaming fire in the heart meridian constitute the core pathogenesis of this condition. Hyperactive heart fire is identified as the key pathogenic factor， while heart yin deficiency， obstruction of the heart collaterals， and malnourishment of the heart spirit are considered significant contributing factors. Clinically， the treatment follows the principle of clearing heart fire as the main strategy， supplemented by nourishing yin， activating collaterals， and calming the spirit. The self-formulated Qingxin Yuchuang Formulation （清心愈疮方） serves as the base prescription， with flexible modifications incorporating the Yuyin Formulation （育阴方）， Huoxue Formulation （活血方）， and Yu'an Formulation （郁安方） to address specific syndromes involving heart yin deficiency， collateral blockage， and emotional disturbance.

BACKGROUND:Activation of nuclear factor-κB/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling leads to endothelial dysfunction,oxidative stress,and plays a key role in the initiation of lipid metabolism disorders and arteriosclerosis.However,currenty,the effect of walnut oil and peanut oil on skeletal muscle inflammatory factors in arteriosclerotic rats remains unclear.OBJECTIVE:To discuss the effect and mechanism of walnut oil and peanut oil on atherosclerosis.METHODS:Forty 8-week-old SD male rats were randomly divided into normal control group(n=10)and high fat group(n=30)after 1 week of adaptive feeding.The atherosclerosis model was established by high-fat diet combined with vitamin D3 injection.The rats with successful modeling were randomly divided into model group(n=10),peanut oil group(n=8)and walnut oil group(n=8).The latter two groups were gavaged with peanut oil or walnut oil for 4 weeks(5 days/week,1.2 g/kg per day).After the intervention,ELISA was used to detect the related indexes of blood lipids in rats.The morphological changes of aorta were observed by hematoxylin-eosin staining.The RT-qPCR and western blot assay were used to detect nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,interleukin-18 mRNA and nuclear factor-κB,NLRP3,interleukin-1β protein expression levels in skeletal muscle.The protein expressions of nuclear factor-κB and NLRP3 were detected by immunofluorescence immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the aortic wall of rats in the model group was thickened,the damage and lipid precipitation were more serious,the blood lipid levels and arteriosclerosis index were significantly increased(P＜0.01).The mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18,and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly increased(P＜0.01).(2)Compared with model group,the vulnerable area of aortic tissue in peanut oil group and walnut oil group was significantly reduced,the levels of total cholesterol,triglyceride,low density lipoprotein cholesterol in serum,and atherosclerosis index were decreased(P＜0.01),and the mRNA expressions of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18 and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly decreased(P＜0.01 or P＜0.05).(3)Compared with peanut oil group,the serum total cholesterol,triglyceride,and low density lipoprotein cholesterol levels in walnut oil group were significantly decreased(P＜0.01 or P＜0.05),and the mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-18,and the protein levels of nuclear factor-κB,NLRP3,interleukin-1β decreased significantly in skeletal muscle(P＜0.01 or P＜0.05).It is concluded that both peanut oil and walnut oil have ameliorative effect on atherosclerotic damage,which may be related to nuclear factor-κB/NLRP3 signaling pathway,and walnut oil has better ameliorative effect than peanut oil.

This article summarized Professor Liu Qiquan's clinical experience in the treatment of acne from the perspective of"internal retention and stagnation of heat pathogen".Professor Liu believes that the core pathogenesis of acne lies in the internal retention and stagnation of heat pathogen,which manifests as external skin inflammation,with the primary focus being on the heat pathogen.With the pathogen inside the body,the progress of disease and syndrome is related to"toxin,depression,blood stasis and deficiency".At the same time,the disease is also closely related to the dysfunction of the five-zang organs.Professor Liu points out that"to resist the outside,one must first settle the inside",and treats acne from the five internal organs.Based on the idea of"internal retention and stagnation of heat pathogen",according to the symptoms of the patients,the comprehensive use of methods to guide the treatment,such as penetrating turbidity,removing pathogenic factors and detoxifying heat,promoting qi and dispersing stagnant heat,cooling collaterals to control blood and breaking stasis heat,and restraining qi,softening yin and supporting deficiency heat,has been proved to have a good clinical effect.One medical case was attached as evidence.

BACKGROUND:Exercise interventions play a key role in disease prevention and treatment,which can effectively activate the nuclear factor erythroid2-related factor 2(Nrf2)signaling pathway to prevent the occurrence and development of insulin resistance.However,the potential mechanism of Nrf2-targeting exercise therapy strategies in alleviating insulin resistance remains unclear.OBJECTIVE:Based on the relationship between Nrf2,insulin resistance and exercise,to analyze the mechanism and influence of different exercise modes on the activation of Nrf2,thereby elucidating the potential mechanism of Nrf2-targeting exercise therapy strategies in the process of alleviating insulin resistance.METHODS:"Diabetes mellitus,insulin,insulin resistance,nuclear factor E2 related factor 2,oxidative stress,ferroptosis,autophagy,inflammatory response,exercise"were used as search terms in Chinese and English.WanFang Database,CNKI,Google Scholar and PubMed database were searched for relevant literature from inception to October 2024,and a total of 127 core related articles were obtained according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Keap1/Nrf2 signaling pathway,as an important endogenous antioxidant stress pathway,plays an important role in insulin resistance.Activation of Keap1/Nrf2 signaling pathway can enhance the antioxidant capacity of cells,reduce oxidative stress and inflammation,improve insulin signaling,and thus protect insulin resistance.(2)A variety of exercise methods(including aerobic exercise,resistance exercise and high-intensity intermittent exercise)can effectively activate Nrf2 signal,improve the activity of antioxidant kinase and enhance the antioxidant capacity of cells,so as to alleviate oxidative stress damage to a certain extent.(3)By activating Nrf2 signaling pathway,exercise can up-regulate the activity of antioxidant enzymes such as Heme oxygenase 1,superoxide dismutase,catalase,glutathione peroxidase,glutathione,and enhance the antioxidant capacity of cells.In addition,it can also regulate the key enzymes and proteins in the ferroptosis pathway,such as glutathione peroxidase 4,membrane iron transport protein 1,and ferritin heavy chain 1,inhibit the ferroptosis pathway and promote the balance of iron metabolism.In autophagy,the expression of autophagy related genes p62 and ATG5/7 can be enhanced,and the level of microtubule-associated protein 1 light chain 3 is increased,thus regulating autophagy process.At the same time,the activity of tumor necrosis factor-α,nuclear factor-κB,interleukin-6,interleukin-1β and other pro-inflammatory cytokines is decreased,and the inflammatory response can be effectively inhibited.These combined effects can reduce oxidative stress damage,increase insulin sensitivity and improve insulin signaling,and thus have a positive effect on improving insulin resistance.(4)Given that the Keap1/Nrf2 signaling pathway plays an important role in the pathogenesis and treatment of insulin resistance,exercise therapy strategies targeting the Keap1/Nrf2 signaling pathway will help promote the development of"exercise+drug"precision medicine for insulin resistance.

BACKGROUND:Exercise interventions play a key role in disease prevention and treatment,which can effectively activate the nuclear factor erythroid2-related factor 2(Nrf2)signaling pathway to prevent the occurrence and development of insulin resistance.However,the potential mechanism of Nrf2-targeting exercise therapy strategies in alleviating insulin resistance remains unclear.OBJECTIVE:Based on the relationship between Nrf2,insulin resistance and exercise,to analyze the mechanism and influence of different exercise modes on the activation of Nrf2,thereby elucidating the potential mechanism of Nrf2-targeting exercise therapy strategies in the process of alleviating insulin resistance.METHODS:"Diabetes mellitus,insulin,insulin resistance,nuclear factor E2 related factor 2,oxidative stress,ferroptosis,autophagy,inflammatory response,exercise"were used as search terms in Chinese and English.WanFang Database,CNKI,Google Scholar and PubMed database were searched for relevant literature from inception to October 2024,and a total of 127 core related articles were obtained according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Keap1/Nrf2 signaling pathway,as an important endogenous antioxidant stress pathway,plays an important role in insulin resistance.Activation of Keap1/Nrf2 signaling pathway can enhance the antioxidant capacity of cells,reduce oxidative stress and inflammation,improve insulin signaling,and thus protect insulin resistance.(2)A variety of exercise methods(including aerobic exercise,resistance exercise and high-intensity intermittent exercise)can effectively activate Nrf2 signal,improve the activity of antioxidant kinase and enhance the antioxidant capacity of cells,so as to alleviate oxidative stress damage to a certain extent.(3)By activating Nrf2 signaling pathway,exercise can up-regulate the activity of antioxidant enzymes such as Heme oxygenase 1,superoxide dismutase,catalase,glutathione peroxidase,glutathione,and enhance the antioxidant capacity of cells.In addition,it can also regulate the key enzymes and proteins in the ferroptosis pathway,such as glutathione peroxidase 4,membrane iron transport protein 1,and ferritin heavy chain 1,inhibit the ferroptosis pathway and promote the balance of iron metabolism.In autophagy,the expression of autophagy related genes p62 and ATG5/7 can be enhanced,and the level of microtubule-associated protein 1 light chain 3 is increased,thus regulating autophagy process.At the same time,the activity of tumor necrosis factor-α,nuclear factor-κB,interleukin-6,interleukin-1β and other pro-inflammatory cytokines is decreased,and the inflammatory response can be effectively inhibited.These combined effects can reduce oxidative stress damage,increase insulin sensitivity and improve insulin signaling,and thus have a positive effect on improving insulin resistance.(4)Given that the Keap1/Nrf2 signaling pathway plays an important role in the pathogenesis and treatment of insulin resistance,exercise therapy strategies targeting the Keap1/Nrf2 signaling pathway will help promote the development of"exercise+drug"precision medicine for insulin resistance.

BACKGROUND:Activation of nuclear factor-κB/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling leads to endothelial dysfunction,oxidative stress,and plays a key role in the initiation of lipid metabolism disorders and arteriosclerosis.However,currenty,the effect of walnut oil and peanut oil on skeletal muscle inflammatory factors in arteriosclerotic rats remains unclear.OBJECTIVE:To discuss the effect and mechanism of walnut oil and peanut oil on atherosclerosis.METHODS:Forty 8-week-old SD male rats were randomly divided into normal control group(n=10)and high fat group(n=30)after 1 week of adaptive feeding.The atherosclerosis model was established by high-fat diet combined with vitamin D3 injection.The rats with successful modeling were randomly divided into model group(n=10),peanut oil group(n=8)and walnut oil group(n=8).The latter two groups were gavaged with peanut oil or walnut oil for 4 weeks(5 days/week,1.2 g/kg per day).After the intervention,ELISA was used to detect the related indexes of blood lipids in rats.The morphological changes of aorta were observed by hematoxylin-eosin staining.The RT-qPCR and western blot assay were used to detect nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,interleukin-18 mRNA and nuclear factor-κB,NLRP3,interleukin-1β protein expression levels in skeletal muscle.The protein expressions of nuclear factor-κB and NLRP3 were detected by immunofluorescence immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the aortic wall of rats in the model group was thickened,the damage and lipid precipitation were more serious,the blood lipid levels and arteriosclerosis index were significantly increased(P＜0.01).The mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18,and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly increased(P＜0.01).(2)Compared with model group,the vulnerable area of aortic tissue in peanut oil group and walnut oil group was significantly reduced,the levels of total cholesterol,triglyceride,low density lipoprotein cholesterol in serum,and atherosclerosis index were decreased(P＜0.01),and the mRNA expressions of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18 and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly decreased(P＜0.01 or P＜0.05).(3)Compared with peanut oil group,the serum total cholesterol,triglyceride,and low density lipoprotein cholesterol levels in walnut oil group were significantly decreased(P＜0.01 or P＜0.05),and the mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-18,and the protein levels of nuclear factor-κB,NLRP3,interleukin-1β decreased significantly in skeletal muscle(P＜0.01 or P＜0.05).It is concluded that both peanut oil and walnut oil have ameliorative effect on atherosclerotic damage,which may be related to nuclear factor-κB/NLRP3 signaling pathway,and walnut oil has better ameliorative effect than peanut oil.

This article summarized Professor Liu Qiquan's clinical experience in the treatment of acne from the perspective of"internal retention and stagnation of heat pathogen".Professor Liu believes that the core pathogenesis of acne lies in the internal retention and stagnation of heat pathogen,which manifests as external skin inflammation,with the primary focus being on the heat pathogen.With the pathogen inside the body,the progress of disease and syndrome is related to"toxin,depression,blood stasis and deficiency".At the same time,the disease is also closely related to the dysfunction of the five-zang organs.Professor Liu points out that"to resist the outside,one must first settle the inside",and treats acne from the five internal organs.Based on the idea of"internal retention and stagnation of heat pathogen",according to the symptoms of the patients,the comprehensive use of methods to guide the treatment,such as penetrating turbidity,removing pathogenic factors and detoxifying heat,promoting qi and dispersing stagnant heat,cooling collaterals to control blood and breaking stasis heat,and restraining qi,softening yin and supporting deficiency heat,has been proved to have a good clinical effect.One medical case was attached as evidence.

Objective: To analyze the key control points of pathogenic microbial contamination during the food processing of school canteens, so as to provide a basis for effectively preventing the occurrence of campus food safety incidents. Methods: In March 2023, 10 school canteens from Zhengzhou City, Henan Province were selected by convenient sampling method. A total of 300 samples were collected from the storage equipment of raw materials, production tools, staff hands, infrastructure, dining utensils and other facilities in the school canteens during the food processing process.The rapid detection method of foodborne pathogens based on isothermal multiple selfmatchinginitiated amplification (IMSA) technology was used to analyze the possible risk of pathogenic microorganism contamination. Fisher exact probability method was applied for the statistical analysis. Results: Among the 300 samples collected, pathogenic microorganisms including Staphylococcus aureus, Salmonella and Listeria monocytogenes were detected in 5 samples, distributed in the food preparation utensils such as cutting boards, operating tables, knives and staff hands, while no pathogenic microorganisms were detected in dining utensils, raw material storage equipment and canteen infrastructure.There was no statistically significant difference between the IMSA rapid detection method and the national standard method for testing Staphylococcus aureus, Salmonella and Listeria monocytogenes(P>0.05). Compared to international method, the positive coincidence of pathogenic microorganism detected by IMSA rapid inspection system was 83.3%(5/6), the negative coincidence was 100%(n=294), and the overall consistency rate was 99.7%. Conclusions The key control points of pathogenic microbial contamination in the food processing process of school canteens mainly are the utensils in the food production process, such as cutting boards, operating tables, knives and staff hands in the food processing process of the school canteen, which could be accurately identified by the rapid detection method of pathogenic microorganism established based on IMSA technology. The quality and efficiency campus food safety supervision should be promoted to prevent the food safety events in school canteen.

Objectives:To explore the impact of inositol-requiring enzyme 1(IRE1)signaling pathway on autophagy flux and cardiac function in mice with myocardial ischemia/reperfusion(I/R)injury. Methods:H9c2 cells were divided into control group,IRE1 group,oxygen glucose deprivation/reoxygenation(OGD/R)group,OGD/R+IRE1 group,chloroquine group,IRE1+chloroquine group,OGD/R+IRE1+chloroquine group,OGD/R+chloroquine group,OGD group,OGD+chloroquine group,OGD+IRE1+RNAi X-box binding protein 1(si-XBP1)group and OGD+IRE1+XBP1 overexpression(XBP1-OE)group.Autophagy flux of cells in each group was evaluated by autophagy double-labeled adenovirus(Adv-RFP-GFP-LC3).The nuclear translocation of X-box binding protein 1(XBP1)was analyzed by immunofluorescence and western blot.Adult male C57BL/6 J mice were randomly divided into sham operation group,I/R group,IRE1 group and I/R+IRE1 group(n=8 each).Cardiac function was evaluated by echocardiography.Quantitative western blot analysis was used to detect protein expression of autophagy-related molecules. Results:(1)Compared with OGD/R group,the expression level of IRE1 protein was significantly upregulated(P<0.001),and the expressions of microtubule-associated proteins light chain 3B(LC3Ⅱ)and sequestosome 1(p62)proteins were significantly decreased in IRE1+OGD/R group(all P<0.05).Compared with OGD/R+chloroquine group,the expression of LC3Ⅱ and p62 protein was significantly increased in OGD/R+IRE1+chloroquine group(all P<0.05).Compared with control group,the fluorescence intensity ratio of IRE1 nucleus/cytoplasm was significantly increased in OGD/R group(P<0.001),and further increased in IRE1+OGD/R group(P<0.001).The level of XBP1 in the nuclear protein was significantly higher in IRE1+OGD/R group than in OGD/R group(P<0.01).Compared with OGD/R+IRE1 group,the yellow punctures was significantly decreased in OGD/R+IRE1+si-XBP1 group(P<0.01),and significantly increased in OGD/R+IRE1+XBP1-OE group(P<0.05).(2)Compared with Sham group,the left ventricular ejection fraction(LVEF)and fractional shortening(FS)were significantly decreased in I/R group(both P<0.05),LVEF and FS reduction could be partly reversed in I/R+IRE1 group.Compared with Sham group,the number of autophagic vacuoles and the expressions of IRE1,LC3Ⅱ and p62 were significantly increased in I/R group(P<0.05).The number of autophagic vacuoles and the expression of p62 were significantly downregulated(both P<0.05),and the expressions of IRE1 and LC3Ⅱ in myocardial tissue were further increased in I/R+IRE1 group as compared to the I/R group(all P<0.05). Conclusions:IRE1 restores the blocked autophagy flux induced by OGD/R and I/R by promoting the nuclear translocation of XBP1,and the recovery of autophagy flux is associated with cardiac function improvement post I/R injury in mice.

BackgroundCompared with adult-onset schizophrenia， patients with adolescent-onset schizophrenia experience a high genetic susceptibility， severe negative symptoms， high recurrence rate， poor prognosis and social function recovery. And clarifying the brain functional alterations in adolescent-onset schizophrenia is of great significance for further elucidating the pathogenesis of the disease and exploring personalized and precise treatment. ObjectiveTo investigate the altered functional and effective connectivity of bilateral precuneus in first-episode patients with adolescent-onset schizophrenia based on resting-state functional magnetic resonance imaging （rs-fMRI）， thus providing reliable imaging evidence in guiding the study on mechanism involved in adolescent-onset schizophrenia. MethodsTwenty-one drugnaïve first-episode patients with adolescent-onset schizophrenia who met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） criteria for schizophrenia were enrolled， and another 21 psychiatrially healthy controls matched on age， educational background and gender were concurrently selected. The schizophrenic subjects were evaluated using the Psychotic Symptom Rating Scales （PSYRATS） and Positive and Negative Symptom Scale （PANSS）. All participants underwent rs-fMRI scans， and the whole-brain seed-based functional and effective connectivity analyses were conducted in bilateral cuneus region. Then the correlation between functional connectivity strength and clinical symptoms of patients was discussed. ResultsIn terms of functional connectivity， the functional connectivity of bilateral precuneus and left middle temporal gyrus was increased in patient group compared with healthy control group ［P<0.01， family-wise error （FWE） correction at cluster level， P<0.05］. In terms of effective connectivity， patient group responded to negative feedback with greater activation of seed region and left middle frontal gyrus than healthy control group. Correlation analysis within patient group denoted that the decreased effective connectivity of bilateral precuneus and left middle frontal gyrus was positively correlated with the total PANSS score （r=0.450， P<0.05）. ConclusionThe resting-state functional and effective connectivity of bilateral precuneus is abnormally alerted in drugnaïve first-episode patients with adolescent-onset schizophrenia， and the decreased effective connectivity of bilateral precuneus and left middle frontal gyrus may be related to the development of clinical symptoms. ［Funded by National Key Research and Development Program of China （number， 2022YFC2009901， 2022YFC2009900）］