Metabolic dysfunction-associated fatty liver disease （MAFLD）， as one of the most common chronic liver diseases in the world， poses a severe challenge to precision diagnosis and treatment due to its complex pathogenesis and highly heterogeneous disease progression. Existing clinical classification systems cannot meet the needs for comprehensively analyzing the complexity of the disease and the heterogeneity of its adverse outcomes. In recent years， data-driven prognostic risk classification methods have gradually emerged， optimizing the ability for predicting adverse outcomes and enhancing the accuracy of identifying different endpoint outcomes. However， such paradigm of “classify first， associate outcomes later” suffers from a “black-box” nature， and there are various indicators for classification， leading to limited stability and generalizability in clinical application. Future research needs to integrate or establish large-scale population cohorts， develop outcome-oriented prognostic risk classification models， incorporate dynamic data， refine classification algorithms， and validate their generalizability across multiple populations， thereby providing reliable support for the precision diagnosis and treatment of MAFLD.

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.

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.

BACKGROUND:Dysfunction of macrophage efferocytosis can induce local and systemic inflammatory damage and is associated with a variety of obesity-related metabolic diseases.Moreover,compounds targeting efferocytosis have shown good therapeutic effects. OBJECTIVE:By reviewing the effects of obesity on macrophage efferocytosis,to analyze the key mechanism by which obesity inhibits efferocytosis,to summarize the research progress in compounds targeting efferocytosis to treat obesity-related metabolic diseases,so as to provide new ideas for fully understanding efferocytosis and its relationship with metabolic diseases,aiming to provide new strategies for disease prevention and treatment. METHODS:The English search terms were"efferocytosis,metabolism,obesity,obese,atherosclerosis,non-alcoholic steatohepatitis,neurodegeneration,tumor,osteoarthritis,diabetes,compound,medicine,treatment,"which were used for literature retrieval in PubMed and Web of Science.The Chinese search term was"efferocytosis,"which was used for literature retrieval in CNKI,VIP and WanFang datebases.Ninety-nine papers were finally included in the review analysis after a rigorous screening process. RESULTS AND CONCLUSION:In the process of efferocytosis,the"Find me"and"Eat me"processes involving a large number of apoptotic cell derived factors are mainly regulated by apoptotic cells.The efferocytosis factor involved in cytoskeletal remodeling and digestion are mainly derived from macrophages,which are crucial for efferocytosis activity.These results suggest that the"Find me"and"Eat me"factors mainly reflect the condition of apoptosis,and it is more scientific to select the expression of factors involved in cytoskeletal remodeling and digestion when evaluating the efferocytosis activity of macrophages.Obesity inhibits efferocytosis,and shows an inhibitory effect on most digestive factors,but has a stress-induced activation effect on most"Find me,""Eat me"and cytoskeletal recombination factors,which further indicates the decisive effect of digestive stage on efferocytosis and suggests that it is not reliable for some studies to evaluate the efferocytosis based on the increased expression of"Find me"and"Eat me"factors.Targeting cytokines in the digestive phase may be more effective when discussing future intervention strategies targeting macrophages efferocytosis.The efferocytosis activators of macrophages are effective in the treatment of various metabolic diseases,but the efferocytosis inhibitors in tumor tissue show good anticancer effects,suggesting that the role of efferocytosis should be rationally evaluated according to the characteristics of tissue inflammation.Efferocytosis is a relatively new concept proposed in 2003,with a short research history and complex efferocytosis factors.Current studies on obesity and efferocytosis only involve a tip of the iceberg and most of them are at a superficial level and a large number of scientific experiments are needed to further validate the mechanisms.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE T o explore the clinical characteristics and risk factors for plastic bronchitis(PB)in the chil-dren with Mycoplasma pneumoniae pneumonia(MPP).METHODS A retrospective case-control study was con-ducted for the medical data of the children with MPP who hospitalized in pediatrics department of Affiliated Hos-pital of Jining Medical College and underwent bronchoscopy and bronchoalveolar lavage from Jan.2023 to Dec.2024.The enrolled children were divided into the PB group and the non-PB group according to the status of complication with PB.The baseline data,clinical characteristics,laboratory test indexes,imaging features,bron-choscopy findings and treatment outcomes were observed and compared between the two groups of children.RESULTS A total of 734 children with MPP were included in the study,131 of whom were assigned as the PB group,and 603 were assigned as the non-PB group.The children were younger[4.83(1.88,7.00)years],the du-ration of fever was longer,the peak temperature was higher[39.50(39.20,39.80)℃],the percentage of compli-cation with pleural effusion was higher(33.59％),the percentage of extrapulmonary organs involved was higher(27.48％),the levels of white blood cells,neutrophils percentage,C-reactive protein(CRP),lactic dehydrogen-ase(LDH),D-dimer(DD)and alanine aminotransferase(ALT)were higher in the PB group than in the non-PB group,and there were significant differences(P＜0.05).There were significant differences in the percentage of mucosal necrosis under bronchoscopy,number of times of treatments assisted by bronchoscopy and length of hospital stay between the two groups(P＜0.05).CONCLUSIONS The MPP children with PB are characterized by younger rage,longer duration of fever,higher peak temperature,higher percentage of complication with pleural effusion,extrapulmonary organs more likely to be involved,more intensive inflammatory reactions and higher percentage of mucosal necrosis under bronchoscopy.Some of the children need to be treated repeatedly with assis-tance of bronchoscopy,and the length of hospital stay is long.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To investigate the influencing factors of airway mucosal erosion occurrence in child Mycoplasma pneumoniae pneumonia.Methods The medical record data of 162 children patients with Mycoplasma pneumoniae pneumonia hospitalized in the pediatric department of this hospital from February 2023 to February 2024 were analyzed retrospectively.The patients were divided into the mucosal erosion group(n=43)and non-mucosal erosion group(n=119)according to whether or not the mucosal erosion was ob-served by the bronchoscope.The general data,laboratory examination and lung ultrasound images data in the two groups were collected.The pulmonary ultrasound(LUS)was scored.The clinical characteristics,experi-mental indexes and LUS score were compared between the two groups.The stepwise logistic regression was used to analyze the influencing factors of airway mucosal erosion occurrence in Mycoplasma pneumoniae pneu-monia.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficiency.Results There were statistically significant differences in the fever duration,fever peak,pleural effusion,hos-pitalization duration,neutrophil ratio,levels of C-reactive protein(CRP),lactate dehydrogenase(LDH)and D-dimer,and LUS score had statistical differences between the two groups(P<0.05).The multivariate logistic regression analysis results showed that the fever duration,neutrophil ratio,LDH,D-dimer and LUS score were the influencing factors for airway mucosal erosion occurrence in Mycoplasma pneumoniae pneumonia.The fe-ver duration,neutrophil ratio,LDH,D-dimer and LUS score all had certain predictive value for airway mucosal erosion occurrence in Mycoplasma pneumonae pneumonia,in which the area under the curve(AUC)of LDH,D-dimer and LUS score was larger,and the predictive value was higher(P<0.05).Conclusion The influen-cing factors of airway mucosal erosion in children patients with Mycoplasma pneumoniae pneumonia should be vigilant to improve their prognosis.

BACKGROUND:Macrophage subtypes exhibit tissue heterogeneity,and the adipose tissue macrophage phenotype is largely influenced by obesity.Local and systemic inflammatory responses caused by obese adipose tissue macrophages are considered a vital pathological mechanism of obesity-associated metabolic diseases.OBJECTIVE:To summarize the inflammatory characteristics of different macrophage subtypes in adipose tissue and their relationship with obesity-associated metabolic diseases,aiming to provide a reference basis for targeting specific macrophage subtypes to explore preventive and treatment strategies for obesity-associated metabolic diseases.METHODS:Literature retrieval was conducted in CNKI and PubMed using Chinese and English search terms "obesity,adipose tissue,adipose tissue macrophage,macrophage polarisation,metabolic diseases." The search results were accepted or excluded according to the inclusion criteria.Ninety-one papers that met the criteria were finally included for review.RESULTS AND CONCLUSION:(1) Macrophages have tissue heterogeneity.Under normal conditions,adipose tissue macrophages are mainly composed of anti-inflammatory M2 resident macrophages,which maintain tissue inflammation homeostasis.Under obese conditions,a large number of foreign infiltrating macrophages surround hypertrophic adipocytes,and most of them exhibit pro-inflammatory characteristics.Therefore,it is believed that adipose tissue macrophages of pro-inflammatory M1 type may actually be a collection of multiple pro-inflammatory subtypes.Further understanding of the characteristics of various pro-inflammatory subtypes helps us to gain a deeper understanding of the mechanisms underlying inflammatory disorders in obese adipose tissue.(2) In obesity,foreign infiltrating macrophages form crown-like structures around hypertrophic adipocytes.Currently,six different subtypes of the crown-like structure have been identified,most of which exhibit pro-inflammatory properties and a few of which possess anti-inflammatory characteristics.Thus,taking full advantage of the anti-inflammatory subtypes while inhibiting the differentiation of the pro-inflammatory subtypes may be a new target for alleviating inflammatory damage in obese adipose tissue.(3) M3,Mme,CD9+and LAM adipose tissue macrophage subtypes have been found to be involved in the occurrence and development of metabolic diseases such as atherosclerosis,diabetes,insulin resistance,and cancer.DARC+and Mfehi adipose tissue macrophage subtypes play a vital role in the treatment of non-alcoholic fatty liver disease,obesity insulin resistance,iron death,and other related metabolic diseases.The above studies further suggest that inflammatory disorders caused by externally infiltrated macrophages in obese adipose tissue are an important pathological basis for obesity-induced metabolic diseases.Further in-depth research on the characteristics of various subtypes has important theoretical and practical significance.