BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

Objective:To analyze the morphology and molecular biology of Rhodococcus erythropolis isolated from blood culture, and clarify its microbiological characteristics, clinical diagnosis and treatment. Methods:Strain F1069 was isolated and cultured. Then, it was analyzed by morphology, physiological tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS), 16S rRNA gene sequencing, and whole-genome sequencing analysis.Results:The colonies of Rhodococcus erythropolis were light yellow, moist, round, and raised, and had neatly-edged margins after being cultured for 48 h. They could turn orange-red after a prolonged cultivation time. The strain was gram-positive bacillus without spores and was negative in acid-fast staining. The strain was identified as Rhodococcus erythropolis by MALDI-TOF MS, and the result was confirmed by 16S rRNA gene sequencing. The F1069 strain contained the RbpA resistance gene and multiple virulence genes. Conclusions:Cases of Rhodococcus erythropolis infection are rare. The diagnosis of such cases depends on the pathogen detection results, especially molecular biology methods. A definitive diagnosis enables rapid guidance for clinical anti-infection treatment.

Objective:To explore the risk factors and prediction model of lateral lymph node metastasis(LLNM)in Hashimo-to's thyroiditis(HT)combined with papillary thyroid carcinoma(PTC).By investigating its risk factors in a multi-dimensional and sys-tematic manner,a precise prediction model with clinical application value will be constructed to provide a basis for clinical diagnosis and treatment,prognosis assessment,and surgical practice decision evaluation.Methods:A retrospective analysis was conducted on the clinical data of 201 patients with HT combined with PTC who were admitted to the Thyroid Surgery Department of the First Affiliated Hospital of Jinzhou Medical University from April 2022 to June 2024.According to whether the patients had LLNM,they were divided into a metastasis group(n=82)and a non-metastasis group(n=119).The relevant clinical indicators of the two groups of patients were compared.Univariate and multivariate analyses were used to identify the independent risk factors affecting the occurrence of LLNM in patients.A logistic regression was employed to establish a prediction model and evaluate its predictive value.Results:The results of univariate analysis showed that there were statistically significant differences between the two groups in terms of TSH value,nodule lo-cation,nodule echo,shape,boundary,aspect ratio,tumor diameter,multifocality,microcalcification,rich blood supply of nodules,ELN,CLNM,capsule invasion,and ETE(P<0.05).The results of multivariate logistic regression analysis indicated that tumor diam-eter,CLNM,rich blood supply of nodules,multifocality,and TSH were all independent risk factors for LLNM(P<0.05).The receiv-er operating characteristic(ROC)curve analysis demonstrated that the areas under the curve(AUC)of tumor diameter,multifocality,CLNM,rich blood supply of nodules,and TSH were 0.613(95%CI:0.533～0.693),0.656(95%CI:0.578～0.733),0.694(95%CI:0.619～0.768),0.622(95%CI:0.543～0.701)and 0.588(95%CI:0.510～0.667),respectively.The sensitivities were 72.20%,69.60%,65.80%,60.80%and 41.80%,respectively and the specificities were 45.90%,62.30%,73.80%,60.70%and 83.60%,respectively.Conclusion:Tumor diameter,multifocality,CLNM,rich blood supply of nodules and TSH are significantly associated with the occur-rence of LLNM in patients with HT combined with PTC.Among them,tumor diameter and multifocality had relatively high sensitivities in predicting LLNM and has a certain predictive value for the occurrence of LLNM in patients with HT combined with PTC.

Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.

Objective To establish and evaluate a mouse model of acute myocardial infarction(AMI)with coronary heart disease(CHD)that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.Methods Forty-eight ICR mice were randomly divided into four groups using a random number table:sham-operated,normal diet,high-choline,and trimethylamine N-oxide(TMAO).From weeks 1 to 8,each group received corresponding dietary and water interventions.From the 9th week,the normal diet,high-choline,and TMAO groups underwent coronary artery ligation(left anterior descending artery,LAD).In contrast,the sham-operated group only had suture placement without ligation,maintaining the same dietary and water interventions.Data on general signs,body weight,food and water intake,urine and feces,auricle and paw conditions,and behavioral patterns were collected and compared macroscopically and microscopically to determine the syndrome type of the high-choline-induced AMI mouse model and observe changes in the"deficiency-stagnation-toxicity"syndrome indicators.After 12 weeks,echocardiography,hematoxylin-eosin(HE)staining,and Masson′s trichrome staining were used to assess cardiac function,myocardial tissue cellular morphology changes,and myocardial fibrosis levels,respectively.The stability and reliability of the model were evaluated by observing the fluorescence intensity of inflammatory cytokines in the myocardial tissues of each group using immunofluorescence.Results Mice in all groups post-AMI surgery exhibited significant weight loss,dull fur,lethargy,and reduced activity.Mice in the high-choline and TMAO groups showed more sluggish responses to stimuli.The high-choline and TMAO groups displayed increased food intake but slow weight gain from weeks 1 to 4,developing into a trend of"increased food and water intake with weight loss"from 5 to 8 weeks,accompanied by yellowish urine and dry stools(P<0.01).Postoperatively(9-12 weeks),body weight significantly decreased,with the most prominent weight loss observed in the high-choline group.The high-choline and TMAO groups exhibited abnormal RGB values in auricles and paws(P<0.01),and behavioral tests showed a significant decline in open-field activity(P<0.01).Cardiac function and pathological examinations revealed that,compared with the sham-operated and normal diet groups,mice in the high-choline and TMAO groups had increased left ventricular end-diastolic and end-systolic volumes(P<0.01),decreased left ventricular ejection fraction and fractional shortening(P<0.01),and elevated heart indices(P<0.05).HE staining of myocardial tissues indicated more pyknotic nuclei and inflammatory cell infiltration in the high-choline and TMAO groups.Masson′s trichrome staining showed extensive blue-stained collagen fiber distribution in the infarct border zones of the high-choline and TMAO groups,with aggravated fibrosis(P<0.05).Immunofluorescence revealed elevated interleukin-1 beta and tumor necrosis factor-alpha levels in the high-choline and TMAO groups compared with the sham-operated and normal diet groups(P<0.01).Conclusion A high-choline diet combined with LAD ligation successfully established an animal model of AMI with CHD that integrates syndrome differentiation with disease diagnosis,based on the"deficiency-stagnation-toxicity"pathogenesis.This model not only embodies the traditional Chinese medicine theory′s understanding of the pathogenic features of"deficiency-stagnation-toxicity",but also serves as a reference for assessing the interventional effects of Chinese herbal compound prescriptions and facilitating research on syndrome patterns in traditional Chinese medicine.

Objective:To study the risk factors of thyroid nodules in patients with type 2 diabetes.Methods:Data of patients with type 2 diabetes with normal thyroid function admitted to the Department of Endocrinology of Heze Municipal Hospital from January to June 2024 were collected. Binary logistic regression was used to analyze the influencing factors of thyroid nodules in patients with type 2 diabetes, and the receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of each influencing factor.Results:Among 162 patients with type 2 diabetes, 96 had thyroid nodules, accounting for 59.3%. The incidence of thyroid nodules in women was significantly higher than that in men (χ 2 = 4.56, P = 0.034). Multivariate logistic regression analysis showed that age (≥50 years old), overweight and obesity [body mass index (BMI)≥24.0 kg/m 2], high glycated hemoglobin (≥10%), and high total cholesterol ( > 6.5 mmol/L) were independent risk factors for thyroid nodules in patients with type 2 diabetes ( OR = 1.83, 1.67, 1.08, 3.65, P < 0.05), and men was an independent protective factor ( OR = 0.63, P = 0.039). The ROC curve results showed that total cholesterol and total cholesterol combined with glycated hemoglobin could distinguish patients with thyroid nodules from those without thyroid nodules, with AUC = 0.64 and 0.68, respectively, and the differences were statistically significant ( P < 0.05). Conclusions:The incidence of thyroid nodules in patients with type 2 diabetes is relatively high. Age, overweight and obesity, high glycated hemoglobin, and high total cholesterol are independent risk factors for thyroid nodules in patients with type 2 diabetes, and total cholesterol has the ability to distinguish patients with thyroid nodules.

Objective:To explore the associations of temperature, relative humidity, and their interaction effect with fall risk.Methods:Data on fall cases were collected using the national injury surveillance system from May to September, in 2006-2022 in Hubei Province. Combined with the meteorological and air pollution data, we conducted a time-stratified case-crossover design and used conditional logistic regression models and distributed lag nonlinear models to examine the exposure-response relationships between temperature, humidity, and fall risk. We further divided the low and the high temperature groups and the low and the high relative humidity groups and analyzed the excess risk ( ER) of falls attributed to dry-hot or wet-hot events. Finally, we calculated the additive interactions of temperature and humidity on fall risk. Results:A total of 55 401 fall cases were included. With the increase in temperature and relative humidity decrease, the exposure-response curves of fall showed nonlinear upward trends among all populations. Gender and age differences were found in temperature-fall and relative humidity-fall risk relationships. Compared with wet-non-hot (normal temperature and high relative humidity) events, the ER of fall in dry-hot (high temperature and low relative humidity) events was 14.80% (95% CI: 9.69%- 20.15%), and the ER of wet-hot (high temperature and high relative humidity) events was 9.59% (95% CI: 2.52%-17.13%). However, there was no statistically significant difference between dry-hot and wet-hot events in the fall, and no statistically significant difference between different genders, ages, occupations, and fall occurred place (all P>0.05). No significant synergistic additive interaction was found between temperature and relative humidity on fall risk (relative excess risk due to interaction=-0.08, 95% CI: -0.19-0.02). Conclusions:Higher temperatures and lower relative humidity were associated with increased fall risk. Both dry-hot and wet-hot events had a higher risk of fall, while high temperature and low humidity have no synergistic effect on fall risk.

Objective:To analyze the morphology and molecular biology of Rhodococcus erythropolis isolated from blood culture, and clarify its microbiological characteristics, clinical diagnosis and treatment. Methods:Strain F1069 was isolated and cultured. Then, it was analyzed by morphology, physiological tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS), 16S rRNA gene sequencing, and whole-genome sequencing analysis.Results:The colonies of Rhodococcus erythropolis were light yellow, moist, round, and raised, and had neatly-edged margins after being cultured for 48 h. They could turn orange-red after a prolonged cultivation time. The strain was gram-positive bacillus without spores and was negative in acid-fast staining. The strain was identified as Rhodococcus erythropolis by MALDI-TOF MS, and the result was confirmed by 16S rRNA gene sequencing. The F1069 strain contained the RbpA resistance gene and multiple virulence genes. Conclusions:Cases of Rhodococcus erythropolis infection are rare. The diagnosis of such cases depends on the pathogen detection results, especially molecular biology methods. A definitive diagnosis enables rapid guidance for clinical anti-infection treatment.