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.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) originator and biosimilars in the treatment of Crohn′s disease (CD).Methods:From January 2020 to January 2023, the clinical data of 73 patients who were diagnosed as CD and received ADA treatment at the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University were retrospectively analyzed. Among them, 30 patients received ADA originator treatment (National Medicine Approval Number SJ20181019; originator group), 23 patients received biosimilar A treatment (Medicine Medicine Approval Number S20190038; biosimilar A group), and 20 patients received biosimilar B (Medicine Medicine Approval Number S20190043; biosimilar B group). At 12 and 48 weeks after treatment, the clinical data of clinical remission (Crohn′s disease activity index(CDAI) score <150), clinical response (CDAI score decreased ≥ 70 from baseline), endoscopic remission (simple endoscopic score for Crohn′s disease (SES-CD) ≤ 2 or Rutgeerts score ≤ 1), endoscopic response (SES-CD decreased > 50% from baseline), and adverse drug reaction (ADR) were collected. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:After 12 weeks of ADA treatment, the overall clinical remission rate was 69.9% (51/73), which of the biosimilar A group was 69.6% (16/23), the biosimilar B group was 75.0% (15/20), and the originator group was 66.7% (20/30). The overall clinical response rate was 83.6% (61/73), which of the biosimilar A group was 82.6% (19/23), the biosimilar B group was 80.0% (16/20), and the originator group was 86.7% (26/30). The overall endoscopic remission rate was 42.5% (31/73), which of the biosimilar A group was 52.2% (12/23), the biosimilar B group was 45.0% (9/20), and the originator group was 33.3% (10/30). The overall endoscopic response rate was 63.0% (46/73), which of the biosimilar A group was 73.9% (17/23), the biosimilar B group was 70.0% (14/20), and the originator group was 50.0% (15/30). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). After 48 weeks of treatment, the overall clinical remission rate was 54.2% (32/59), which of the biosimilar A group was 8/18, the biosimilar B group was 9/15, and the originator group was 57.7% (15/26). The overall clinical response rate was 71.2% (42/59), which of the biosimilar A group was 10/18, the biosimilar B group was 12/15, and the originator group was 76.9% (20/26). The overall endoscopic remission rate was 25.4% (15/59), which of the biosimilar A group was 5/18, the biosimilar B group was 3/15, and the originator group was 26.9% (7/26). The overall endoscopic response rate was 40.7% (24/59), which of the biosimilar A group was 7/18, the biosimilar B group was 5/15, and the originator group was 46.2% (12/26). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). The overall incidence of ADR was 32.9% (24/73), which of the biosimilar A group was 30.4% (7/23), the biosimilar B group was 30.0% (6/20), and the originator group was 36.7% (11/30); and there was no statistically significant difference among the 3 groups ( P=0.847). Conclusion:ADA biosimilars A and B demonstrate comparable efficacy and safety to the originator medication in the treatment of CD.

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.

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: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.

Objective:To evaluate the efficacy and safety of adalimumab (ADA) originator and biosimilars in the treatment of Crohn′s disease (CD).Methods:From January 2020 to January 2023, the clinical data of 73 patients who were diagnosed as CD and received ADA treatment at the Department of Gastroenterology, the Tenth People′s Hospital of Tongji University were retrospectively analyzed. Among them, 30 patients received ADA originator treatment (National Medicine Approval Number SJ20181019; originator group), 23 patients received biosimilar A treatment (Medicine Medicine Approval Number S20190038; biosimilar A group), and 20 patients received biosimilar B (Medicine Medicine Approval Number S20190043; biosimilar B group). At 12 and 48 weeks after treatment, the clinical data of clinical remission (Crohn′s disease activity index(CDAI) score <150), clinical response (CDAI score decreased ≥ 70 from baseline), endoscopic remission (simple endoscopic score for Crohn′s disease (SES-CD) ≤ 2 or Rutgeerts score ≤ 1), endoscopic response (SES-CD decreased > 50% from baseline), and adverse drug reaction (ADR) were collected. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:After 12 weeks of ADA treatment, the overall clinical remission rate was 69.9% (51/73), which of the biosimilar A group was 69.6% (16/23), the biosimilar B group was 75.0% (15/20), and the originator group was 66.7% (20/30). The overall clinical response rate was 83.6% (61/73), which of the biosimilar A group was 82.6% (19/23), the biosimilar B group was 80.0% (16/20), and the originator group was 86.7% (26/30). The overall endoscopic remission rate was 42.5% (31/73), which of the biosimilar A group was 52.2% (12/23), the biosimilar B group was 45.0% (9/20), and the originator group was 33.3% (10/30). The overall endoscopic response rate was 63.0% (46/73), which of the biosimilar A group was 73.9% (17/23), the biosimilar B group was 70.0% (14/20), and the originator group was 50.0% (15/30). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). After 48 weeks of treatment, the overall clinical remission rate was 54.2% (32/59), which of the biosimilar A group was 8/18, the biosimilar B group was 9/15, and the originator group was 57.7% (15/26). The overall clinical response rate was 71.2% (42/59), which of the biosimilar A group was 10/18, the biosimilar B group was 12/15, and the originator group was 76.9% (20/26). The overall endoscopic remission rate was 25.4% (15/59), which of the biosimilar A group was 5/18, the biosimilar B group was 3/15, and the originator group was 26.9% (7/26). The overall endoscopic response rate was 40.7% (24/59), which of the biosimilar A group was 7/18, the biosimilar B group was 5/15, and the originator group was 46.2% (12/26). And in the above data, there were no statistically significant differences among the 3 groups (all P>0.05). The overall incidence of ADR was 32.9% (24/73), which of the biosimilar A group was 30.4% (7/23), the biosimilar B group was 30.0% (6/20), and the originator group was 36.7% (11/30); and there was no statistically significant difference among the 3 groups ( P=0.847). Conclusion:ADA biosimilars A and B demonstrate comparable efficacy and safety to the originator medication in the treatment of CD.

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Objective: To investigate the effect of a Passy-Muir speaking valve (PMV) on the biomechanics of swallowing and on aspiration among persons tracheotomized after brain damage. Methods: Twenty tracheotomized patients with aspiration after brain injury were selected and randomly divided into a non-PMV intervention group and a PMV intervention group, each of 10. Both groups were given routine swallowing training, while the PMV intervention group was additionally provided with a PMV and trained to use it. The treatment ended when the tracheal tube was removed or after 2 weeks. High-resolution manometry and videofluoroscopy were used to evaluate the maximum pressure in the velopharynx (VP-Max), the maximum post-deglutitive upper esophageal sphincter (UES) pressure (UES-Max) and Rosenbek penetration aspiration (PAS) scores for both groups before and after the treatment. Results: Before the treatment there was no significant difference between the two groups in terms of average VP-Max, UES-Max or PAS score. After the treatment, the average VP-Max and UES-Max had increased significantly in both groups, and the average PAS score of the PMV intervention group had decreased significantly. There was a significant positive correlation between the increases in VP-Max and the decrease in PAS scores. Conclusion Inserting a PMV can improve velopharynx contraction and post-deglutitive UES among persons tracheotomized after a brain injury. The increase in maximum velopharynx pressure is positively correlated with decreases in aspiration.

Ohjective To explore the impact of constraint-induced aphasia therapy (CIAT) on language function and neural activity in patients with chronic Broca's aphasia.Methods Two chronic aphasics whose use of language was recovering after standard language therapy were selected to receive 1.5 h of CIAT twice daily for two weeks (30 hours in total).Before and after the CIAT they were tested using a block-designed picture-naming task,fMRIs were taken and their use of language was examined.Results The language function assessments showed relatively large improvements in the subjects' use of language after 4 weeks of conventional language training,but not much further change after 8 and 12 weeks.After the two weeks of CIAT,their language function improved further to a certain extent.fMRI showed increased activation in the left inferior frontal gyrus with or without enhanced activation in the left hemisphere,and reduced activation in the right inferior frontal gyrus.Conclusions Functional reorganization induced in the brain by CIAT was associated with up-regulation of the left inferior frontal gyrus or down-regulation of the right inferior frontal gyrus.Even the whole language network may have been modified.