ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

ObjectiveTo explore the mechanism by which Sini San （SNS） inhibits ferroptosis， alleviates inflammation and myocardial injury， and improves myocardial infarction （MI）. MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， its target sites were predicted using the SwissTargetPrediction Database， and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards， Online Mendelian Inheritance in Man （OMIM） database， DrugBank， Therapeutic Target Database （TTD）， FerrDb database and literature review， respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction （PPI） network was constructed using the STRING database， and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in， and the biological functions were clustered by the MCODE plug-in. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group， the model group， the SNS group， and the trimetazidine （TMZ） group. The mice were subcutaneously injected with isoprenaline （ISO， 5 mg·kg^-1·d^-1） to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram （ECG）， and the tissue morphology changes were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， reduced glutathione （GSH）， and malondialdehyde （MDA） levels were detected by biochemical assay. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of interleukin （IL）-6 and 4-hydroxynonenal （4-HNE）. Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 （p-STAT3） in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6， IL-18， solute carrier family 7 member 11 （SLC7A11）， arachidonic acid 15-lipoxygenase （ALOX15）， and glutathione peroxidase 4 （GPx4） in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained， and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation， and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 （P0.01）， down-regulated the expression of ALOX15 mRNA （P0.01）， up-regulated the level of serum GSH， and the expressions of SLC7A11 and GPx4 mRNA， reduced MDA and 4-HNE levels （P0.05， P0.01）. Additionally， SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis， reduced the area of MI， alleviated inflammation and myocardial injury， lowered the levels of serum CK， CK-MB， LDH， IL-6， and the mRNA expression levels of IL-16 and IL-18 （P0.05）， and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels， inhibit ferroptosis in cardiomyocytes， alleviate inflammation and myocardial injury， thereby improving MI.

The early life period is a rapid period, as well as a critical/sensitive period for brain development. Proteins, long-chain polyunsaturated fatty acids (LCPUFAs), iron, zinc, iodine, folate, choline, vitamins A, D, B6, and B12, all play a role in key neural development processes and thus influence brain development. Different brain regions or circuits have specific critical periods during different stages of development that depend on specific nutrients. Any nutrient deficiency during this period, even if corrected with supplementation, may still affect the trajectory of brain development and result in long-term cognitive and behavioral impairment. This article elucidates the effects of major nutrient deficiencies during early life on brain development, the possible sensitive/critical timing, and the impacts on long-term cognitive and behavioral development, providing insights for the prevention and intervention of nutritional diseases and psychiatric developmental disorders, and the promotion of early childhood development.

An analysis was conducted on the clinical manifestations, auxiliary examinations, diagnosis and treatment process, treatment, and prognosis of a child with neurobrucellosis. 408 relevant literature on neurobrucellosis from January 2012 to December 2022 were searched through Chinese and English databases such as CNKI, Wanfang Data, and Biomedical Literature Database (PubMed). Literature was screened based on inclusion and exclusion criteria, A total of 14 children with neurobrucellosis were selected for analysis, with an average age of onset of 10 years old. Among the patients, there were 3 cases of middle cranial nerve injury, 2 cases of ataxia, 1 case of myelitis, 2 cases of mental symptoms, 1 case of optic disc edema, 1 case of sagittal sinus thrombosis, and the rest were manifested as meningitis and encephalitis. The imaging results suggested that there was often no specific area of invasion, with magnetic resonance imaging (MRI) commonly involving the cortex, central half oval, and basal ganglia. Extensive white matter changes were also frequently observed, which is consistent with the findings of this case report. Neurobrucellosis has diverse clinical manifestations and lacks specificity. It is mainly diagnosed based on comprehensive analysis of neuropsychiatric symptoms, cerebrospinal fluid and serological results, imaging characteristics, etc. Early diagnosis and treatment are of great significance in preventing complications of neurobrucellosis.

OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore-ductase(NR)and bioactivate aristolochic acid Ⅰ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS① Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC50)was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25 μmol·L-1)+AA-Ⅰ 0.2 and 1.0 μmol·L-1 for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L-1 small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0 μmol·L-1 for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L-1 human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS ①The IC50 of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42 μmol·L-1,respec-tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).② Luteolin≥5 μmol·L-1 significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰ under anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU-SION AKR1A1 is involved in AA-Ⅰ bioactivation,providing a reference for elucidation of the carcino-genic mechanism of AA-Ⅰ.

Objective:To conduct a series case study on hospitalized anthrax cases in five hospitals in North China, to share clinical experiences in the diagnosis and treatment of cutaneous and pulmonary anthrax.Methods:A retrospective, multicenter cohort study was conducted on the anthrax patients admitted to five hospitals in North China from August 2018 to March 2022. Forty patients were divided into severe and mild groups. The clinical features, treatment and prognosis of the patients were collected and analysed. Statistical evaluations included independent sample t test, Mann-Whitney U test, and chi-square test. Results:Among the 40 patients with anthrax, 10(25.0%) were severely ill and 30(75.0%) were mildly ill. According to the sites of infection, 40 patients were classified as 39 cutaneous anthrax cases (one case had secondary pulmonary anthrax) and one pulmonary anthrax case. The rates of chills and fever, lymphadenopathy, liver dysfunction and hypoalbuminemia in the severe group were all higher than those in the mild group, with statistically significant differences ( χ2=5.71, 6.54, 4.68 and 9.22, respectively, all P<0.05). The peripheral white blood cell count, neutrophil count, neutrophil/lymphocyte ratio and C-reactive protein were (11.8±4.9)×10 9/L, (9.5±5.1)×10 9/L, 8.6±7.3, 27.9(8.6, 167.7) mg/L, respectively, which were all higher than those in mild disease group ((7.5±2.4)×10 9/L, (5.0±2.1)×10 9/L, 3.2±2.3, 3.5(1.2, 14.7) mg/L), with statistically significant differences ( t=2.66, t=2.71, t=2.32 and Z=-3.01, respectively, all P<0.05). The albumin level in the severe group was (35.5±8.1) g/L, which was lower than that of the mild group ((43.7±3.2) g/L), and the difference was statistically significant ( t=-3.13, P=0.011). The severe cases were more likely to have skin lesions greater than four centimetre in diameter, multiple, vesicular, or edematous, with a significant difference ( χ2=6.01, P=0.014). Among 39 patients with cutaneous anthrax, 28(71.8%) in the mild group were treated with penicillin alone, and nine (23.1%) in the severe group were treated with penicillin, ofloxacin, piperacillin/tazobactam combined with one of linezolid, doxycycline, or clindamycin for anti-infection treatment. The two patients with pulmonary anthrax were treated with closed thoracic drainage for pleural effusion and pneumothorax, and were treated with two bactericidal and one protein synthesis inhibitor antibiotics. All 40 anthrax patients were cured and discharged from hospital. Conclusions:Patients with mild cutaneous anthrax can generally be treated with single penicillin, and patients with severe cutaneous anthrax and pulmonary anthrax should be treated with combined antibiotics.

ObjectiveTo investigate the effects of Buyang Huanwutang （BYWHT） on reducing inflammatory injury and improving neurological function after cerebral ischemia-reperfusion in rats via activating the adiponectin （APN） pathway. MethodMale SD rats were randomized into sham， model， BYHWT （16 g·kg^-1， twice a day）， and BYHWT + APN inhibitor （GW9662） groups. In the sham group， blood vessels were isolated. The rat model of middle cerebral artery occlusion （MCAO） was established. The rats in the BYHWT+GW9662 group was treated with subcutaneous injection of GW9662 at 4 m·kg^-1 30 min before MCAO surgery and BYHWT at 16 g·kg^-1 by gavage after MCAO surgery， once in the morning and once in the evening. The immunofluorescence （IF） assay was employed to observe the expression of adiponectin receptor 1 （AdipoR1） and the colocalization of AdipoR1 with neuronal nuclei （NeuN） and ionized calcium binding adaptor molecule 1 （Iba1） in the brain. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the expression of APN in the serum and brain. The balance beam test was carried out to examine the balance ability， and the grasping test to assess the recovery of limb strength. The immunofluorescence assay was used to detect the expression of myeloperoxidase （MPO）. Western blot was employed to determine the expression of tumor necrosis factor-alpha （TNF-α）， interleukin （IL）-1β， IL-6， and IL-10 and in the brain. ResultCompared with the sham group， the modeling promoted the expression of AdipoR1 （P<0.01）， lowered the APN levels in the serum and brain （P<0.05， P<0.01）， increased the score in the balance beam test （P<0.01）， and decreased the grasping strength of forepaw （P<0.01）， which were accompanied with increased MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and decreased IL-10 level （P<0.01）. Compared with the model group， BYHWT promoted the expression of AdipoR1 （P<0.01）， elevated APN levels in the serum and brain （P<0.05， P<0.01）， and increased the grasping strength of forepaw （P<0.01）， which were accompanied with lowered MPO， TNF-α， IL-1β， and IL-6 levels （P<0.01） and elevated IL-10 level （P<0.01）. All the above effects were partially blocked by GW9662. ConclusionBYHWT can reduce inflammatory injury and improve neurological function in the rat model of cerebral ischemia-reperfusion by activating the APN pathway.

Objective:To investigate the clinical effect of minimally invasive catheterization based on computer 3D-Slicer software system in the treatment of hypertensive intracerebral hemorrhage (HICH).Methods:Three hundred and fifty patients with HICH treated in People′s Hospital of Lanling County in Shandongfrom June 2019 to June 2020 were selected as the research object. According to the operation method, they were divided into 3D-Slicer group (175 cases) and CT group (175 cases). They were treated with 3D-Slicer software-assisted minimally invasive catheterization and minimally invasive soft-channel drainage under CT localization, respectively. The general conditions of the surgery, hematoma clearance rate and laboratory indexes, oxidative stress index and prognosis were compared between the two groups.Results:The intraoperative blood loss, the hospitalizationtimein the 3D-Slicer group were lower than those in the CT group: (81.42 ± 12.33) ml vs. (101.54 ± 11.71) ml, (15.67 ± 3.71) d vs. (17.22 ± 3.52) d; the success rate of one-time successful puncture to preset position in the 3D-Slicer group was higher than that in the CT group: 100.00%(175/175) vs. 81.14%(142/175), there were statistical differences ( χ 2 = 34.26, P<0.05). The hematoma clearance rate after the surgery for 1, 3 and 7d in the 3D-Slicer group were higher than those in the CT group:(87.93 ± 8.54)% vs. (66.43 ± 7.99)%, (92.48 ± 10.31)% vs. (89.52 ± 11.74)%, (96.37 ± 10.22)% vs. (94.30 ± 9.25)%, there were statistical differences( P<0.05). After the surgery for 7 d, the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the 3D-Slicer group were higher than those in the CT group: (121.36 ± 10.59)U/L vs. (109.14 ± 9.05) U/L, (92.80 ± 8.63) μg/L vs. (81.45 ± 9.11) μg/L, (24.64 ± 5.43) U/L vs. (20.84 ± 3.47) U/L; while the level of malondialdehyde (MDA) was lower than that in the CT group: (4.42 ± 0.57)μmol/L vs. (5.19 ± 0.51) μmol/L, there were statistical differences ( P<0.05). After the surgery for 3 months, the rate of favorable prognosis in the 3D-Slicer group was higher than that in the CT group 73.71%(129/175) vs. 62.29%(199/175), there was statistical difference ( χ2 = 5.25, P<0.05). Conclusions:Minimally invasive catheterization based on 3D-Slicer software system in the treatment of HICH can not only improve the clinical efficacy, but also shorten the hospitalization time, reduce intraoperative blood loss, and improve the prognosis.

In recent years, the aging process of China′s population has accelerated, and the number of disabled people has skyrocketed. It is urgent to improve the health benefits of family bed services. The author found that there was a lack of synergy in policies, service subjects and content, and service concepts in the practical process of family bed services in various regions of China, which limited the effectiveness of services. The author put forward the theoretical framework of integrated family bed service, combined the service practice experience of six cities, namely Guangzhou, Shanghai, Beijing, Shenzhen, Nanjing and Hohhot, and put forward specific suggestions on building integrated family bed service. Among them, department collaboration could be the source power of system integration, institutional linkage could improve service continuity, service concept and incentive mechanism could promote each other, and modern technology could promote functional integration.