Alcoholic liver disease （ALD） poses a serious threat to the health of drinkers worldwide， and establishing appropriate animal models of ALD is an important foundation for conducting disease-related research. Due to the physiological and pathophysiological differences between rodents and humans， alcohol feeding alone is difficult to induce a model that closely matches the disease manifestations in humans， and therefore， the “two-hit” hypothesis （ combining alcohol with another liver injury factor to induce the expected state of liver injury） has been widely used. This article classifies the more commonly used and effective “two-hit” regimens into three major categories of special diets， chemical substances， and genetic engineering， which are divided into high-fat diet， high-iron diet， carbon tetrachloride， lipopolysaccharide， and genetic engineering for further analysis. Although these five “two-hit” models have their own advantages and disadvantages， they can nearly cover the disease spectrum of ALD. In the future， the development of ALD animal models can focus on narrowing the pathophysiological differences in alcohol-induced liver injury between animals and humans and simulating more complex drinking patterns in humans.

BACKGROUND:Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome,but the specific mechanism is not yet clear.OBJECTIVE:To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.METHODS:A total of 70 SD rats were randomly divided into a normal control group(n=10),a model group(n=15),a western medicine group(n=15),a low-dose Huosui Formula group(n=15),and a high-dose Huosui Formula group(n=15).Except for the normal control group,the other four groups were injected with dimethyl benzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models.After modeling,the normal control group and the model group were given normal saline;the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg,and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula,respectively,by intragastric administration once a day for 28 consecutive days.Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation.Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.RESULTS AND CONCLUSION:(1)Compared with the normal control group,peripheral blood leukocyte,neutrophil,hemoglobin,platelet,and CD4+,CD4+/CD8+levels were decreased in the model group significantly(P＜0.05),while CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+expressions were significantly upregulated(P＜0.05).(2)In all dosage groups,myelopoietic proliferation was increased compared with the model group,with no significant difference between the groups(P＞0.05).(3)Compared with the model group,leukocytes,hemoglobin,platelets,and CD4+,CD4+/CD8+were significantly elevated in the high-dose Huosui Formula group(P＜0.05),the expression of CD8+was significantly lower(P＜0.05),and the levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+were down-regulated but not statistically significant(P＞0.05).(4)The western medicine group and the high-dose Huosui Formula group showed similar efficacy.The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group.These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats,increase the levels of CD4+,and CD4+/CD8+while down-regulate the expression levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+.These observations suggest a link to the negative immunoregulation mechanism.

Periodontitis is a common chronic infectious disease resulting from the interaction between oral microorganisms and the host's immune system.The immune system plays a dual role in regulating inflammation.Macrophages,as a component of innate immu-nity,play a crucial role in both the onset and resolution of periodontitis.This article reviews the role of macrophages in periodontitis and the recent advances in targeting macrophages for the treatment of periodontitis.

BACKGROUND:Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome,but the specific mechanism is not yet clear.OBJECTIVE:To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.METHODS:A total of 70 SD rats were randomly divided into a normal control group(n=10),a model group(n=15),a western medicine group(n=15),a low-dose Huosui Formula group(n=15),and a high-dose Huosui Formula group(n=15).Except for the normal control group,the other four groups were injected with dimethyl benzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models.After modeling,the normal control group and the model group were given normal saline;the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg,and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula,respectively,by intragastric administration once a day for 28 consecutive days.Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation.Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.RESULTS AND CONCLUSION:(1)Compared with the normal control group,peripheral blood leukocyte,neutrophil,hemoglobin,platelet,and CD4+,CD4+/CD8+levels were decreased in the model group significantly(P＜0.05),while CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+expressions were significantly upregulated(P＜0.05).(2)In all dosage groups,myelopoietic proliferation was increased compared with the model group,with no significant difference between the groups(P＞0.05).(3)Compared with the model group,leukocytes,hemoglobin,platelets,and CD4+,CD4+/CD8+were significantly elevated in the high-dose Huosui Formula group(P＜0.05),the expression of CD8+was significantly lower(P＜0.05),and the levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+were down-regulated but not statistically significant(P＞0.05).(4)The western medicine group and the high-dose Huosui Formula group showed similar efficacy.The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group.These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats,increase the levels of CD4+,and CD4+/CD8+while down-regulate the expression levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+.These observations suggest a link to the negative immunoregulation mechanism.

Periodontitis is a common chronic infectious disease resulting from the interaction between oral microorganisms and the host's immune system.The immune system plays a dual role in regulating inflammation.Macrophages,as a component of innate immu-nity,play a crucial role in both the onset and resolution of periodontitis.This article reviews the role of macrophages in periodontitis and the recent advances in targeting macrophages for the treatment of periodontitis.

Objective:To understand the current situation of psychological crisis vulnerability among elderly individuals with multimorbidity and analyze the factors that influence it, to provide insights for improving their coping abilities.Methods:A cross-sectional survey design was conducted at Renmin Hospital of Wuhan University from May 1 to November 30, 2022.The attitudes toward aging, sense of meaning of life, and vulnerability to psychological crisis were analysed among outpatients and inpatients.Statistical analysis was performed on the questionnaire results, and the influencing factors of vulnerability to psychological crisis in elderly patients with co-morbidities were analyzed using one-way linear regression and multivariate linear regression.Additionally, the correlation between aging attitudes, sense of meaning of life, and vulnerability to psychological crisis was examined using Pearson correlation analysis.Results:A total of 685 questionnaires were distributed, and 602 valid questionnaires were collected, resulting in a valid recovery rate of 87.9%.The total score for the sense of meaning of life in elderly co-morbid patients was(39.2±8.3), while the total score for aging attitudes was(80.2±13.5).The total score for psychological crisis vulnerability was(69.4±12.8), indicating a medium-high level of vulnerability.The results of multiple linear regression analysis revealed that the factors influencing psychological crisis vulnerability in elderly multimorbidity, in descending order, were residence status, economic situation, marital status, age, type of chronic disease, and hospitalization history in the past six months.Psychological crisis vulnerability in elderly multimorbidity showed a negative correlation with the sense of meaning of life and the attitude of aging( r=-0.315, -0.264, both P<0.01), while the attitude of aging exhibited a positive correlation with the sense of meaning of life( r=0.515, P<0.01). Conclusions:The vulnerability of elderly individuals with multimorbidity to psychological crises is influenced by several factors.Healthcare professionals should prioritize individuals who are elderly, residing in nursing institutions, widowed, financially disadvantaged, experiencing multiple illnesses, and not currently hospitalized.

This study aims to investigate the effect of bovine leukemia virus encoded microRNAs(BLV-miRNAs)on lactoperoxidase(LPO)in bovine mammary epithelial cells(BMECs).Firstly,the LPO content in the milk of BLV-positive cows,categorized by different viral loads,was quanti-fied by enzyme-linked immunosorbent assay(ELISA).Subsequently,BMECs were cultured in vitro and infected with(1 MOI)full-length BLV and BLV lacking miRNAs(BLV-ΔmiRNAs).Va-rious analytical techniques,including fluorescent quantitative PCR and ELISA,were used to assess LPO expression levels in different BMEC cohorts.Ten BLV-miRNAs were computationally predic-ted to target LPO using software tools such as StarMir.Based on these predictions,transfections of BLV-miRNAs were carried out and preliminary verification of their effects on target genes were performed.The results showed that compared to that of BLV-negative counterparts,the LPO levels in the milk of BLV-positive cows,stratified by high and low viral load,decreased by 8.73％and 9.68％,respectively.Invitro experiments further corroborated these trends,revealing a significant increase(P＜0.05)in LPO expression within BMECs following the deletion of BLV-miRNAs compared to the group infected with full-length BLV-infected group.Computational target site pre-dictions implicated BLV-miR-B1-5p,B3-3p,and B4-5p in the collective regulation of the LPO gene.Transfection of BLV-miR-B1-5p into BMECs resulted in a significant downregulation of LPO gene expression(P＜0.05),with the effect intensifying proportionally with the transfection dose.Simi-larly,the transfection of BLV-miR-B4-3p into BMECs significantly reduced LPO gene expression(P＜0.05)without showing a dose-dependent behavior.In conclusion,this research indicates that BLV-miRNAs can suppress LPO expression in BMECs.

Inflammatory bowel disease(IBD)is no cure at present,and only drugs and surgery can relieve symptoms,delay and reduce recurrence.Therefore,it is very important to monitor the disease activity.Glycocalyx,a polyglycoprotein complex covering luminal side of vascular endothelial cells,is supportive in maintaining the intestinal mucosal barrier,and inflammation leads to its structural damage.This review introduces currently available non-invasive biomarkers of clinical importance for IBD in laboratory testing,and analyzes the value of serum glycocalyx injury markers(syndecan-1,HS and HA)in the diagnosis or monitoring of IBD.

Objective To systematically review the epidemiological studies on primary biliary cholangitis (PBC), and to investigate the prevalence rate of PBC in the Chinese general population and its influencing factors. Methods PubMed, Embase, The Cochrane Library, CNKI, and Wanfang Data were searched for articles on the epidemiology of PBC in China published up to 31th March 2022. Two researchers independently performed screening and data extraction, and then related analyses were performed. Results A total of 9 articles were included. The positive rate of AMA was 1 049.05/100 000 (ranging fr om 159.65/100 000 to 2287.40/100 000), and the prevalence rate of PBC was 123.68/100 000 (ranging from 42.70/100 000 to 276.59/100 000). The positive rate of AMA was 636.51/100 000 (ranging from 52.55/100 000 to 1 164.33/100 000) in men and 1 265.47/100 000 (ranging from 225.23/100 000 to 1 704.93/100 000) in women, with a male/female ratio of 1∶1.99 for the prevalence rate of AMA. The prevalence rate of PBC was 40.81/100 000 (ranging from 23.54/100 000 to 75.10/100 000) in men and 148.71/100 000 (ranging from 77.36/100 000 to 214.91/100 000) in women, with a male/female ratio of 1∶3.64 for the prevalence rate of PBC. Conclusion Different studies show great differences in the positive rate of AMA and the prevalence rate of PBC in the Chinese general population, which is mainly affected by sex, age, and region. The positive rate of AMA and the prevalence rate of PBC increase with age, and the patients aged ≥50 years have a significantly higher positive rate of AMA than those aged < 50 years. The positive rate of AMA is significantly higher than the prevalence rate of PBC. There are significantly more women than men in the AMA-positive population and the PBC patients, and the influence of sex on AMA is lower than that on PBC.

This study investigated the potential mechanism of Cordyceps militaris(CM) against non-small cell lung cancer(NSCLC) based on serum untargeted metabolomics. Specifically, Balb/c nude mice were used to generate the human lung cancer A549 xenograft mouse model. The tumor volume, tumor weight, and tumor inhibition rate in mice in the model, cisplatin, Cordyceps(low-, medium-, and high-dose), and CM(low-, medium-, and high-dose) groups were compared to evaluate the influence of CM on lung cancer. Gas chromatography-mass spectrometry(GC-MS) was used for the analysis of mouse serum, SIMCA 13.0 for the compa-rison of metabolic profiles, and MetaboAnalyst 5.0 for the analysis of metabolic pathways. According to the pharmacodynamic data, the tumor volume and tumor weight of mice in high-dose CM group and cisplatin group decreased as compared with those in the model group(P<0.05 or P<0.01). The results of serum metabolomics showed that the metabolic profiles of the model group were significantly different from those of the high-dose CM group, and the content of endogenous metabolites was adjusted to different degrees. A total of 42 differential metabolites and 7 differential metabolic pathways were identified. In conclusion, CM could significantly inhibit the tumor growth of lung cancer xenograft mice. The mechanism is the likelihood that it influences the aminoacyl-tRNA biosynthesis, the metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of glyoxylate and dicarboxylic acid, biosynthesis of phenylalanine, tyrosine, and tryptophan, arginine biosynthesis as well as nitrogen metabolism. This study elucidated the underlying mechanism of CM against NSCLC from the point of metabolites. The results would lay a foundation for the anticancer research and clinical application of CM.
Alanine/metabolism* ; Animals ; Arginine/metabolism* ; Aspartic Acid ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Cisplatin/pharmacology* ; Cordyceps ; Glutamic Acid ; Glutamine ; Glyoxylates/metabolism* ; Humans ; Lung Neoplasms/drug therapy* ; Metabolomics/methods* ; Mice ; Mice, Nude ; Nitrogen/metabolism* ; Phenylalanine/metabolism* ; RNA, Transfer/metabolism* ; Tryptophan/metabolism* ; Tyrosine/metabolism*