Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

OBJECTIVE To explore the potential mechanism of ketamine-induced cognitive impairment in mice based on metabolomics. METHODS Male C57BL/6 mice were randomly divided into control group and ketamine group （25 mg/kg）， with 12 mice in each group. Each group of mice was intraperitoneally injected with normal saline or corresponding drugs， 4 times a day， for 10 consecutive days. On the last 2 days of drug administration， the cognitive behavior was evaluated by Y maze and novel object recognition test， and the histopathological changes in the prefrontal cortex （PFC） were observed. Ultra-high performance liquid chromatography-tandem mass spectrometry technology was used to analyze the changes of metabolites in PFC， screen for differential metabolites， and perform pathway enrichment analysis. RESULTS Compared with the control group， the morphology of PFC neurons in the ketamine group of mice was inconsistent. There were cavities around the nucleus， and the number of deeply stained cells increased. The mean optical density value of the Nissl staining positive area was significantly reduced， and the alternation rate and discrimination index were significantly reduced （P＜0.05 or P＜0.01）. In the PFC tissue samples of mice of the two groups， there were a total of 114 differential metabolites， including 73 up-regulated and 41 down-regulated metabolites， including glutamine， succinic acid， ketoglutarate， and choline， etc. The differential metabolites mentioned above were mainly enriched in metabolism of alanine， aspartate and glutamate， metabolism of arginine and proline， γ aminobutyric acid synapses， pyrimidine metabolism， cholinergic synapses pathways， etc. CONCLUSIONS Ketamine can induce cognitive impairment in mice. Its neurotoxicity is related to abnormal synaptic transmission and energy metabolism， and neuroimmune regulation disorders.

Dry eye disease is a multifactorial chronic ocular surface disorder that is challenging to manage because its pathogenesis is not well understood. The gut-eye axis theory provides insights into its pathogenesis to guide prevention and treatment. Intestinal flora dysbiosis induces dry eye disease through complex mechanisms involving inflammation, ocular surface microbiota, nerve damage, and microbial metabolites. This article reviews the immunometabolic regulation of the gut-eye axis and summarizes gut flora-targeted interventions(fecal microbiota transplantation, probiotic supplementation, and dietary modification)to provide a theoretical basis for dry eye disease prevention and treatment.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

The ethical basis of public health policy is relatively weakness, which is mainly reflected in the conflict between individual rights and public interests, the lack of moral norm, the short of ethical review, the low level of relevant legislation, the weak of ethical consciousness and so on. Therefore, it is necessary to take measures to improve relevant ethical policies and regulations, establish an ethical framework for evaluating public health policies, highlight ethical values and strengthen ethical awareness in public health policy-making. Make it carry a certain ethical dimension to achieve the purposes of maintaining and improving health.

The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.

BACKGROUND:Minipigs are often used in research fields such as skin injury,vascular trauma and cosmetic medicine because they are highly similar to human beings in terms of skin tissue structure and cardiovascular system.Hydrogel as a wound repair drug possesses a variety of excellent physicochemical properties such as strong water retention and adhesion,which can provide isolation moisturization and drug release for wounds. OBJECTIVE:To summarize and conclude the progress of the application of trauma models for different experimental purposes of hydrogel therapy for minipigs,to reveal the development status of various types of minipig trauma models,to analyze the deficiencies of minipig trauma models at the present stage. METHODS:The relevant articles published in Web of Science database and CNKI database from the establishment of each database to 2023 were checked,using"piglet,miniature pig,minipig,miniature pig;gel,hydrogel;trauma,injury,wound,lesion,incision"as Chinese search terms and"Miniature Swine,Miniature pig,minipig;gel,hydrogel;injury,wound,lesion,incision"as English search terms.A total of 438 Chinese and English documents were retrieved,and 59 documents were included in the study through the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)At present,the main models used clinically for trauma repair are large animal species(dogs and pigs),rabbits,and rodents(rats and mice).Because the skin structure of the minipig is more like that of humans,the minipig is the most ideal animal model for trauma repair.(2)In the in-vitro skin injury model,skin defect model is the basic wound model,which can be divided into full skin defect model and medium-thickness skin defect model according to the depth of the wound defect.Burn wound model and infected wound model are multidimensional models with hot metal scald and bacterial culture imposed on the basis of the skin defect model,which have the advantages of high safety coefficient and low operation difficulty.(3)In the in-vivo trauma repair model,mini-pigs are used as esophageal cricothyrotomy model which is more in line with the pathological state of clinical diseases.Mini-pigs are used in the gastric perforation and vascular hemostasis model,which can visually demonstrate the stronger organ adhesion,hemostatic properties and tissue regeneration-promoting effects of the hydrogel.(4)The specific parts of the pig also has the corresponding mode of use:pig ear is usually used to evaluate the hydrogel drug delayed-release effect.Porcine cellular proteins and pig skin collagen are mostly used to prepare composite hydrogels of tissue origin.

Objective To observe the effect of electroacupuncture on corneal Toll-like receptor 4(TLR4)-mediated inflammatory signaling pathway in diabetic dry eye rats and to explore the mechanism of electroacupuncture in the treat-ment of diabetic dry eye.Methods A type 2 diabetic rat model was established in 32 healthy male Sprague-Dawley(SD)rats by intraperitoneal injection of streptozotocin(30 mg·kg-1)for 12 weeks after feeding with high-sugar and high-fat di-et for 4 weeks.Twenty-five successfully modeled diabetic dry eye rats were randomly divided into the model group(non-in-tervention),electroacupuncture group(the"Jingming","Cuanzhu","Sizhukong","Taiyang"and"Tongziliao"acupoints were treated with acupuncture,and then"Cuanzhu"and"Tongzilao"acupoints were treated with electroacupuncture,15 min for each time,once a day),sham acupuncture group(blunt-tip needle pricking was performed at the same acupoints as the electroacupuncture group),and fluorometholone group(1 g·L-1fluorometholone eye drops were used in both eyes at 8 o'clock,13 o'clock,and 18 o'clock,1 drop each time),with 6 rats in each group,lasting for 2 weeks.Another 6 healthy male SD rats were selected as a blank group.Random blood glucose,tear film breakup time(BUT),tear secre-tion,corneal fluorescein staining(FL)score,and corneal touch threshold(CTT)of rats in each group were detected be-fore modeling,after modeling,and after the intervention.Hematoxylin and Eosin(HE)staining was performed to observe the corneal morphologic changes in each group.Immunofluorescence histochemical staining was adopted to detect the cor-neal TLR4-positive expression in each group.The TLR4,phosphorylated nuclear factor-kappa P65(P-NF-KB P65),inter-leukin(IL)-1β,and IL-18 expression levels in the cornea were detected by Western blot.Results After modeling,com-pared with the blank group,BUT,tear secretion and CTT decreased and FL increased in all experimental groups,and the differences were statistically significant(all P＜0.01).After the intervention,compared with the model group,FL de-creased,and BUT,tear secretion and CTT increased in the electroacupuncture group,and the differences were statistically significant(all P＜0.05).Corneal HE staining showed that after the intervention,the corneal surface of rats in the model group and sham acupuncture group was not smooth,and the corneal epithelial cells were thickened and disorganized;the corneal surface of rats in the electroacupuncture group and fluorometholone group was smooth,and the corneal epithelial cells were arranged neatly.After the intervention,compared with the blank group,the corneal TLR4 expression of rats in all other groups was elevated,and the differences were statistically significant(all P＜0.05);compared with the model group,the corneal TLR4 expression of rats in the electroacupuncture group and fluorometholone group was reduced(both P＜0.01).Compared with the blank group,corneal TLR4,P-NF-κBP65,IL-1β and IL-18 protein expressions increased in the model group and sham acupuncture group(all P＜0.05);compared with the model group,these expressions decreased in the electroacupuncture group and the fluorometholone group(all P＜0.05).Conclusion Electroacupuncture can im-prove the ocular surface signs and inhibit the expressions of TLR4,P-NF-κB P65,IL-1 β,and IL-18 in the cornea of type 2 diabetic dry eye rats,and its mechanism of action may be related to the regulation of TLR4-mediated inflammatory signaling pathway,which inhibits ocular surface inflammation in diabetic dry eye rats.

Objective To reveal the potential mechanism of electroacupuncture regulating the neuroinflammatory signaling pathway mediated by triggering receptor expressed on myeloid cells 2(TREM2)in trigeminal ganglion(TG)and caudate nucleus of spinal trigeminal nucleus(SpVc)of rats with type 2 diabetes and dry eyes and alleviating ocular surface sensory abnormalities.Methods Healthy male Sprague-Dawley(SD)rats were induced by intraperitoneal injection of 10 g·L-1 streptozotocin to establish a type 2 diabetes dry eye rat model after 4 weeks of high-glucose and high-fat diets.In the 12th week of the experiment,successfully modeled rats were randomly divided into the model group,electroacupunc-ture group,sham-acupuncture group and fluorometholone group,and healthy male SD rats fed with normal diets were se-lected as the blank group.Rats in all groups were intervened for 2 weeks.The corneal fluorescein sodium staining(FL),tear secretion[detected by phenol red thread(PRT)test],tear film break-up time(BUT),and corneal touch threshold(CTT)in each group were measured before,after modeling,and after the intervention.The changes in tissue morphology of TG and SpVc and TREM2 positive expression sites in each group were observed.The messenger ribonucleic acid(mR-NA)expression of TREM2,interleukin-18(IL-18)and interleukin-1β(IL-1β)of TG and Sp Vc in each group were detec-ted.Results After modeling,compared with the blank group,the FL scores of rats significantly increased and PRT,BUT and CTT significantly decreased in other groups(all P＜0.01).After the intervention,compared with the model group,the electroacupuncture group and fluorometholone group showed significant reductions in FL scores and significant increases in PRT,BUT and CTT(all P＜0.01);there was no statistically significant difference in these indicators in the sham-acupuncture group(all P＞0.05).Compared with the electroacupuncture group,the PRT and CTT of rats in the flu-orometholone group and sham-acupuncture group were significantly reduced,the FL score significantly increased and BUT significantly decreased in the sham-acupuncture group(all P＜0.01),and there was no statistically significant difference in FL score and BUT of rats in the fluorometholone group(both P＞0.05).Compared with the sham-acupuncture group,the fluorometholone group showed a decrease in FL score and an increase in PRT,BUT and CTT in rats,with statistically dif-ferent significances(all P＜0.05).The immunofluorescence double-labeling assay showed a positive expression of TREM2 in activated microglia of TG and SpVc in the model group.The reverse transcription-polymerase chain reaction of TG and SpVc showed that compared with the blank group,the TREM2 mRNA expression in the TG and SpVc of the model group,electroacupuncture group,fluorometholone group and sham-acupuncture group decreased,the IL-18 and IL-1β mRNA in TG and SpVc of the model group,IL-18 and IL-1β mRNA in TG and IL-1β mRNA in SpVc of the sham-acupuncture group increased(all P＜0.05);compared with the model group,the TREM2 mRNA expression increased and IL-18 and IL-1β mR-NA expression decreased in the TG and SpVc of the electroacupuncture group and fluorometholone group(all P＜0.05).Compared with the electroacupuncture group,the TREM2 mRNA expression decreased and IL-18,IL-1β mRNA expression increased in TG and SpVc of the sham-acupuncture group(all P＜0.05),and no significant difference was found in TREM2,IL-18 and IL-1β mRNA expression in TG and SpVc of the fluorometholone group(all P＞0.05).Compared with the sham-acupuncture group,the TREM2 mRNA expression in TG and SpVc increased in the fluorometholone group,while the IL-18 mRNA expression in SpVc decreased(all P＜0.05);the IL-1β mRNA in TG and SpVc and the IL-18 mRNA in TG of the fluorometholone group showed no statistically significant difference(all P＞0.05).Conclusion Electroacupunc-ture can effectively alleviate the ocular surface sensory abnormalities of rats with type 2 diabetes and dry eyes by regulating the inflammatory signaling pathway mediated by TREM2 in TG and SpVc.

Objective To observe the effects of brain-computer interface-controlled pedal training system on bal-ance function and serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels in ischemic stroke pa-tients.Methods Forty patients with ischemic stroke who were hospitalized from September 2022 to September 2023 were selected as observation subjects.The patients were equally divided into stroke control group and stroke experimental group according to the random number table method.At the same time,20 healthy subjects with similar gender and age were recruited as the healthy control group to collect relevant plantar pressure data.Patients in the stroke control group received conventional rehabilitation training including the upper and lower extremity active and passive motor training system,and the stroke experimental group replaced the upper and lower extremity active and passive motor training system in the stroke control group with the brain-computer interface-controlled pedal training system for rehabilitation treatment,and other things remained unchanged.Bilateral plantar pressure symmetry index(SI)and center of body pressure(COP)swing area were collected from both groups of stroke patients with eyes open and closed using the plantar pressure assessment system before and after 4 weeks of treatment.Fugl-meyer low-er extremity motor function score(FMA-LE)and berg balance scale(BBS)were used to evaluate the two groups of stroke patients.Serum IL-6 and TNF-α levels were also compared between the two groups before and after treat-ment.Results ① The SI value and COP swing area in the eyes open and closed state improved in both groups of stroke patients after treatment compared with that before admission,and the results of the stroke experimental group were better than those of the stroke control group(P＜0.05),but there was still a gap with the healthy control group(P＜0.05).②The BBS and FMA-LE scores of stroke patients in both groups were higher after treatment than before treatment,and the scores of the stroke experimental group were greater than those of the stroke control group,with statistically significant differences(all P＜0.05).③Serum IL-6 and TNF-α levels decreased in both groups of stroke patients after treatment compared with before,and the degree of decrease in serum IL-6 and TNF-αlevels in the stroke experimental group was greater than that in the stroke control group,and the difference was sta-tistically significant(P＜0.001,P＜0.05).Conclusion Brain-computer interface-controlled pedal training sys-tem has a facilitating effect on the recovery of balance function in hemiplegic patients with ischemic stroke,and its mechanism may be related to the reduction of serum IL-6 and TNF-α levels.