BACKGROUND:Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke.In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease,it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. OBJECTIVE:To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. METHODS:Sixty male Sprague-Dawley rats were randomly divided into four groups:blank control group(n=12),ischemic stroke group(n=18),disease+syndrome group(n=18),phlegm-heat and Fu-organ excess syndrome group(n=12),all of which were given high-fat diet for 25 days.On the 26th day,the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet,while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days.After gavage,ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group.The changes in diet,water intake,body mass,body temperature,fecal traits,nasal secretions,sputum in the throat,and tongue image were recorded.Neurological deficits,tongue image,blood lipid levels,morphological changes of brain tissue and carotid artery,and the serum levels of motilin and somatostatin were detected. RESULTS AND CONCLUSION:Compared with the control group,the rats in the disease+syndrome group had shortness of breath,listlessness,irritability,bradykinesia,a large number of secretions around the nose,audible and heavy sputum in the throat,decreased diet and water intake,increased body mass,body temperature,and slingual vein score,decreased fecal pellet count,Bristol score and fecal moisture content,increased serum total cholesterol,triglyceride,low-density lipoprotein and somatostatin levels,decreased motilin level,increased neurological deficit score,significant pathological changes of the carotid artery,and significant morphological changes of the brain tissue.The ischemic stroke group only showed pathological changes of ischemic brain tissue,without the characteristics of phlegm-heat and Fu-organ excess syndrome.The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes,without the pathological changes of brain tissue with ischemic stroke.To conclude,the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

ObjectiveTo provide a basis for the establishment of an ideal animal model of allergic asthma by statistically analyzing the modeling characteristics and the selection of indicators of the available models. MethodsWe retrieved the relevant articles from China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， SinoMed， and PubMed with "allergic asthma" as the keyword and the time interval from January 2019 to January 2024. Through integrating the literature and extracting data， we used Excel 2021 to create a personal database and sorted out the animal strains， genders， allergenic substances， modeling routes， and test indicators and methods. Excel 2021， Cytoscape 3.10.2， and SPSS Modeler 18.0 were then used to analyze the relevant characteristics of the animal models. ResultsA total of 418 articles were included in the database， and the comparative analysis showed that the most frequently used animal strain for modeling was BALB/c mice， and female animals were mostly used. The main modeling method was sensitization by intraperitoneal injection of ovalbumin （OVA）， which was combined with intranasal inhalation. The test indicators mainly included appearance signs， cellular analysis， lung histopathology， lung function indicators， and protein and gene expression in the lung. The test methods mainly involved pathological staining， enzyme-linked immunosorbent assay， immunohistochemistry， immunofluorescence， Western blot， and polymerase chain reaction（PCR） assays. ConclusionThere is no recognized modeling method or evaluation standard for the animal models of allergic asthma. Based on the results of data analysis， the OVA-induced allergic asthma model in BALB/c mice is recommended. The main criteria for evaluating the success of modeling are the general behavioral changes， the morphological changes of the airway and inflammatory cell infiltration in the lung tissue， the changes of pro-inflammatory and anti-inflammatory cytokines in the serum， and the alterations of inflammatory cells in the bronchoalveolar lavage fluid.

ObjectiveTo investigate the effect of the nitroglycerin-controlled low central venous pressure （CLCVP） technique on brain metabolic markers and cerebral blood oxygen saturation in patients undergoing laparoscopic hepatectomy for liver cancer， and to reduce the risk of neurological complications. MethodsA total of 105 patients who underwent elective laparoscopic hepatectomy for liver cancer in Haikou Hospital Affiliated to Xiangya Hospital of Central South University from April 2020 to May 2023 were enrolled and randomly divided into CLCVP group with 54 patients and non-CLCVP group with 51 patients. The patients in the CLCVP group were treated with the nitroglycerin CLCVP technique during surgery， while those in the non-CLCVP group were given conventional surgical treatment. The two groups were compared in terms of the following indicators： perioperative indicators； hemodynamic parameters and cerebral oxygen metabolism before anesthesia induction （T0）， at 5 minutes after anesthesia induction （T1）， at 5 minutes after the beginning of liver parenchyma dissection （T2）， at 5 minutes after the end of hepatectomy （T3）， and immediately after the end of surgery （T4）； the changes in liver function parameters after surgery； the incidence rate of adverse reactions. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the analysis of variance with repeated measures was used for comparison between multiple time points. ResultsCompared with the non-CLCVP group， the CLCVP group had significantly lower intraoperative blood loss and intraoperative fluid infusion volume （t=5.408 and 7.220， both P<0.05）， while there were no significant differences between the two groups in time of operation， anesthesia time， extubation time， resuscitation time and intraoperative urine volume （all P>0.05）. Compared with the data at T0， both groups had significant reductions in mean arterial pressure， heart rate， and central venous pressure during surgery （all P<0.05）， and compared with the non-CLCVP group， the CLCVP group had significantly lower mean arterial pressure and central venous pressure （P<0.05） and a significantly higher heart rate （P<0.05） at T2 and T3. Compared with the data at T0， both groups had a significant reduction in Ca-jvDO₂ at T2‍ ‍—‍ ‍T4 time points （all P<0.05）， while there was no significant difference in Ca-jvDO₂ between the two groups at each time point （all P>0.05）. Compared with the data at T0， the CLCVP group had a significant reduction in rSO₂ at T2‍ ‍—‍ ‍T4 time points （all P<0.05）， and the CLCVP group had a significantly lower level of rSO₂ than the non-CLCVP group at T2‍ ‍—‍ ‍T3 time points （both P<0.05）； there were no significant changes in CERO₂ and Djv-aBL in either group at each time point （all P>0.05）. At 3 and 7 days after surgery， both groups had significant increases in the liver function parameters of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and total bilirubin （TBil） （all P<0.05）， and the CLCVP group had significantly lower levels of AST and ALT than the non-CLCVP group （all P<0.05）； there was no significant difference in TBil between the two groups at each time point （all P>0.05）. There was no significant difference in the incidence rate of perioperative complications between the two groups （χ²=0.729， P=0.394）. ConclusionThe application of the nitroglycerin CLCVP technique in laparoscopic hepatectomy for liver cancer can reduce the amount of intraoperative blood loss in patients， but it is necessary to further enhance the monitoring of cerebral blood oxygen saturation during surgery， so as to reduce the risk of neurological complications as much as possible.

Objective:To study the role and preliminary molecular mechanism of TRIM24 regulating macrophage polarization in viral myocarditis(VM).Methods:VM mouse model was established by Coxsackie virus B3(CVB3),and expression of TRIM24 in myocardial tissue was detected.Cardiac inflammation level and polarization phenotype of cardiac infiltrating macrophages in a murine model of cardiac TRIM24 inhibition were detected in vivo.A polarization model of mouse bone marrow-derived macrophages(BMDMs)in vitro was established to observe the role of TRIM24 inhibition in polarizing BMDMs to M1 and M2,as well as its effects on phagocy-tosis and bactericidal function of BMDMs.Effects of TRIM24 inhibition on total STAT6 protein level and phosphorylation were investi-gated.Results:TRIM24 was significantly highly expressed in myocardial tissue of VM mice(P<0.001).Inhibition of TRIM24 expres-sion in myocardium had an attenuating effect on VM and promoted polarization of cardiac infiltrating macrophages to M2.TRIM24 was significantly down-regulated in vitro during the polarization of BMDMs toward M2(P<0.01).Inhibition of TRIM24 expression signifi-cantly promoted macrophage polarization toward M2 type and inhibited polarization toward M1 type,accompanied by a significant increase in STAT6 phosphorylation levels(P<0.01).Conclusion:TRIM24 regulates macrophage M2 polarization via activation of STAT6 signaling pathway to attenuate VM.

This study investigated the characteristics of gut microbiota imbalance in patients with infectious diarrhea caused by various pathogenic infections,and the role of Bacteroides in maintaining homeostasis in the intestinal environment.The gut microbiota in patients with diarrhea caused by pathogenic infections,such as viral and bacterial infections,was determined through full-length 16S rRNA amplicon sequencing.Patients with diarrhea were grouped and analyzed according to the presence of single bacterial infection,single viral infection,mixed infection,or Clostridioides difficile infection.Bacteroides had the highest absolute number and relative abundance in the gut microbiota in healthy people,whereas patients with infectious diar-rhea showed lower relative abundance of Bacteroides at each phylum/order/family/genus taxonomic level.Alpha diversity anal-ysis indicated no significant differences among groups.NMDS and PCoA indicated formation of distinct clusters in the control group compared with the different infectious diarrhea groups.The diversity of the gut microbiota was higher in the control group than the infectious diarrhea groups.Patients with infec-tious diarrhea caused by different pathogens showed differing predominant gut microbiota.Bifidobacterium predominated in the single viral infection group,Streptococcus predominated in the single bacterial infection group,and Lachnoclostridium predominated in the mixed infection group.Escherichia and Klebsiella were the major gut microbiota in the C.difficile infection group.Meanwhile,the dominant gut microbiota in the healthy population was Bacteroides.COG function prediction revealed that the healthy control group formed a distinct cluster from the different infection groups.The functions of defense mechanisms,cell wall synthesis,protein modification,cellular differentiation,and replication and recombination were signifi-cantly diminished in all infectious diarrhea groups.In general,patients with infectious diarrhea caused by different pathogens showed dysbiosis,with diminished gut microbiota diversity and the emergence of related biomarkers.Our findings indicated that Bacteroides has a key role in maintaining the homeostasis of the human intestinal environment,thus providing new ideas for the subsequent treatment of infectious diarrhea and research in other fields.

Objective To investigate the mechanism of Sanguisorbae Radix(SR)in the treatment of ulcerative colitis(UC).Methods Using the GSE92415 dataset from the Gene Expression Omnibus database,we analyzed differentially expressed genes and carried out weighted gene correlation network analysis and FerrDb analysis.Core genes were identified through protein-protein interaction(PPI)network and correlation analysis.UC mouse model induced by dextran sulfate sodium(DSS)was constructed and treated with SR via intragastric administration for 9 days.Disease activity index(DAI)and colon length were recorded.Pathological changes in colon tissue were observed using the HE staining.Levels of inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).Lipid peroxidantion factors such as malondialdehyde(MDA)and glutathione(GSH)were detected using biochemical test kits.Protein expression levels of zonula occludens protein-1(ZO-1)tight junction protein,peroxisome proliferator-activated receptor gamma(PPARG),solute carrier family 7 member 11(SCL7A11),and glutathione peroxidase 4(GPX4)were examined by Western blot or immunofluorescence labeling.Results Nine differentially expressed genes associated with ferroptosis were screened and PPARG was identified as a key gene.Correlation analysis showed a strong correlation between PPARG and ferroptosis.Subsequently,the potential mechanism of SR in improving UC in mice was discussed according to the bioinformatics screening results.The experimental results demonstrated that SR significantly reduced the DAI,prevented colon shortening and improved intestinal mucosal barrier function in the colon.SR decreased TNF-α and IL-6 levels,MDA content and GSH levels in colon tissues.SR also enhanced the expression of PPARG,SLC7A11 and GPX4,which reversed the effect of DSS in mice with colitis.Conclusions Ferroptosis is closely related to UC.SR can inhibit ferroptosis by regulating PPARG and SCL7A11/GPX4 expression,thereby improving colon epithelial injury and dysfunction in UC mice.This provides ideas and directions for UC treatment strategies.

Objective:To serologically and genotypically analyze the pedigree of a case with a new allele c.175_176insGA of B el subtype and preliminarily explore the molecular mechanism of weak expression of glycosyltransferase B. Method:In the descriptive study,a 23-year-old male voluntary blood donor and his family members were selected for the study. The ABO and Le blood types of the proband and his family members was identified by the test tube method. The agglutination inhibition test was applied to detect the B and H antigens in saliva, and the Sanger sequencing and PacBio (Pacific Bioscience) third-generation haplotype sequencing were performed on the study subjects to identify genotypes. Finally, Expasy software were applied to amino acid translation of DNA sequences and prediction of protein length after gene alteration. ORF finder was applied to predict alternative start codons as well as open reading frames of mRNA, and protein expression mechanisms were analyzed.Results:The proband and her sister were B el subtype, her mother was AB el subtype, her father was normal O type, and all members of the family were Le(a+b+) phenotype. Sanger sequencing results showed that a new allele of c.175_176insGA was found in exon 4 of the proband, her mother, and her sister. Third-generation haplotype sequencing detected the haplotypes of the family members, which revealed that the proband was ABO*O.01.02/ABO*BEL.NEW (c.175_176insGA), the father was ABO*O.01.02/ABO*O.01.02, the mother was ABO*A1.02/ABO*BEL.NEW (c.175_176insGA), and the sister was ABO*O.01.02/ABO*BEL.NEW (c.175_176insGA). Analysis of the protein expression mechanism indicated that although the new allele of ABO*BEL.NEW was presumed to cause a frameshift mutation and result in a premature stop codon p.Asp59Glu*fs20 in exon 5, encoding an inactive glycosyltransferase, an alternative start codon could be utilized to initiate translation of B el subtype functional glycosyltransferase. Conclusion:Expression of the new allele of B el subtype is associated with the translation of B el subtype glycosyltransferase initiated by alternative start codons.

Variant acute promyelocytic leukemia (APL) and APL-like leukemia are rare types of APL, with t (16;17) chromosome abnormality being even rarer. An APL-like patient with t (16;17) chromosome abnormality, which was characterized by bone, lymph node, and central nervous system involvement, was admitted to our hospital. He achieved complete remission after several cycles of chemotherapy and subsequently underwent hematopoietic stem cell transplantation. Furthermore, the diagnosis and treatment of this patient were reported and a literature review was conducted.

Objective:To investigate the effect of iron deficiency on the prognosis of elderly patients with ejection fraction preserved heart failure (HFpEF).Methods:The clinical data of old patients (>75 years) with HFpEF from November 2021 to May 2023 in General Hospital of Eastern Theater of the Chinese People′s Liberation Army were retrospectively analyzed. The patients were divided into iron deficiency group (65 cases) and non-iron deficiency group (90 cases) according to serum ferritin (SF) and transferrin saturation (TSAT) at admission. The first hematological indexes and echocardiogram examination results after admission were compared between two groups. The patients were followed up until November 2023, the poor prognosis was recorded. The correlation between iron deficiency, iron metabolism indexes and poor prognosis in elderly patients with HFpEF was analyzed by Spearman correlation analysis. The Kaplan-Meier survival curve was drawn to analyze the effect of iron deficiency on the cumulative survival in elderly patients with HFpEF.Results:There were no statistical difference in triglyceride, total cholesterol, low density lipoprotein cholesterol, C-reactive protein, hemoglobin and echocardiogram indexes between the two groups ( P>0.05). The N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine, procalcitonin (PCT) and interleukin-6 (IL-6) in iron deficiency group were significantly higher than those in non-iron deficiency group: 427.23 (281.00, 736.90) pmol/L vs. 313.50 (182.47, 363.25) pmol/L, (167.93 ± 51.22) μmol/L vs. (121.71 ± 11.99) μmol/L, 0.12 (0.05, 0.22) μg/L vs. 0.07 (0.04, 0.16) μg/L and 25.60 (8.38, 47.01) ng/L vs. 10.15 (4.75, 19.89) ng/L, the SF, serum iron (SI) and TSAT were significantly lower than those in non-iron deficiency group: 75.40 (42.30, 198.00) μg/L vs. 207.00 (281.00, 736.90) μg/L, (6.49 ± 2.66) μmol/L vs. (12.75 ± 4.24) μmol/L and (16.65 ± 6.26)% vs. (33.78 ± 11.16)%, and there were statistical differences ( P<0.01 or <0.05). The patients were followed up for (12.06 ± 7.58) months, the all-cause mortality, cardiovascular mortality, readmission rate and heart failure readmission rate in iron deficiency group were significantly higher than those in non-iron deficiency group: 40.0% (26/65) vs. 20.0% (18/90), 18.5% (12/65) vs. 4.4% (4/90), 90.8% (59/65) vs. 70.0% (63/90) and 66.2% (43/65) vs. 17.8% (16/90), and there were statistical differences ( P<0.01). Spearman correlation analysis result showed that the iron deficiency was positive correlation with all-cause death, cardiovascular death, readmission and heart failure readmission in elderly patients with HFpEF ( P<0.01); the SI and TSAT were negative correlation with all-cause death, cardiovascular death, readmission and heart failure readmission ( P<0.01 or <0.05); and the SF was not correlation with the indexes ( P>0.05). Kaplan-Meier survival analysis result showed that the risk of all-cause death was significantly increased in elderly HFpEF patients with iron deficiency, and the cumulative survival rate was significantly reduced (log-rank χ2 = 6.48, P<0.05). Conclusions:The elderly HFpEF patients with iron deficiency have poor prognosis with high mortality and readmission rate.

Objective:To analyze the correlation between chemokine CX3C ligand 1 (CX3CL1), CX3C chemokine receptor 1 (CX3CR1) and heart function grade, prognosis in patients with chronic heart failure (CHF).Methods:The clinical data of 200 patients with CHF from June 2021 to June 2023 in General Hospital of Eastern Theater of the Chinese People′s Liberation Army and Wuhan Asia Heart Hospital were retrospectively analyzed, and all patients received standardized treatment for heart failure. The baseline clinical data were recorded; the levels of CX3CL1 and CX3CR1 were detected by enzyme linked immunosorbent assay; the heart function grade was evaluated by New York Heart Association (NYHA) heart function grade method. The patients were followed up until December 2023, the patients were divided into poor prognosis group (all-cause death and readmission due to heart failure) and good prognosis group based on their prognosis. Pearson method was used for correlation analysis. Multivariate Logistic regression analysis was used to analyze the independent risk factors of poor prognosis in patients with CHF.Results:Among the 200 patients, NYHA heart function grade Ⅰ to Ⅱ was in 80 cases, Ⅲ to Ⅳ in 120 cases. The levels of CX3CL1 and CX3CR1 in patients with NYHA heart function grade Ⅲ to Ⅳ were significantly higher than those in patients with NYHA heart function grade Ⅰ to Ⅱ: (3.34 ± 0.45) mg/L vs. (2.45 ± 0.26) mg/L and (8.71 ± 0.92) mg/L vs. (2.53 ± 0.35) mg/L, and there were statistical differences ( t = 15.99 and 57.34, P<0.01). The proportion of age<60 years old, rate of coronary heart disease, CX3CL1, CX3CR1, body mass index and high-sensitivity C-reactive protein in poor prognosis group (40 cases) were significantly higher than those in good prognosis group (160 cases): 82.50% (33/40) vs. 10.62% (17/160), 90.00% (36/40) vs. 68.12% (109/160), (3.26 ± 0.77) mg/L vs. (2.25 ± 0.27) mg/L, (8.35 ± 2.01) mg/L vs. (2.48 ± 0.31) mg/L, (26.80 ± 3.55) kg/m 2 vs. (24.74 ± 2.76) kg/m 2 and (9.31 ± 2.19) mg/L vs. (3.58 ± 2.28) mg/L, the rate of smoking history and left ventricular ejection fraction were significantly lower than those in good prognosis group: 37.50% (15/40) vs. 46.88% (75/160) and (30.14 ± 5.77)% vs. (59.40 ± 6.58)%, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that the CX3CL1 and CX3CR1 were positively correlated with NYHA heart function grade ( r = 0.29 and 0.34, P<0.05), and negatively correlated with prognosis ( r = - 0.54 and - 0.36, P<0.05). Multivariate Logistic regression analysis result showed that the CX3CL1 and CX3CR1 were the independent risk factors of poor prognosis in patients with CHF ( OR = 2.110 and 1.566, 95% CI 0.445 to 3.125 and 0.270 to 3.455, P<0.01). Conclusions:The CX3CL1 and CX3CR1 are closely related to the heart function grade in patients with CHF. At the time of CHF patient admission, it may be considered to combine the two indicators for preliminary evaluation of and provide targeted interventions to improve prognosis.