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 investigate whether Tuina alleviates fibrotic symptoms in myofascial trigger points (MTrPs) by regulating transforming growth factor (TGF)-β1/Smad3 signaling pathway, thereby deactivating these points. Methods: This study comprised two experimental phases. In phase 1, 27 specific pathogen-free (SPF) grade female Sprague-Dawley (SD) rats were randomized into three groups: control 1, model 1, and Tuina 1 groups. Model 1 and Tuina 1 groups underwent an 8-week MTrPs modeling protocol involving blunt impact and eccentric exercise. After successful modeling, rats in Tuina 1 group received manual pressing on nodules or cord-like taut bands on the medial aspect of the left hindlimb. Pain sensitivity and tissue stiffness were evaluated via pressure pain threshold (PPT) and soft tissue tension (STT). Muscle histopathology and fibrosis were observed using hematoxylin and eosin (HE) and Masson staining. Inflammatory factors in muscle were measured by enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) and Western blot (WB) were used to detect the expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ, and TGF-β1. In phase 2, 45 SPF female SD rats were randomized into five groups: control 2, model 2, Tuina 2, TGF-β1 inhibitor (TI), and Tuina + TGF-β1 agonist (Tuina + TA) groups. All groups except control 2 underwent standardized MTrPs modeling. Rats in Tuina 2 group received consistent pressing manipulation. TI group received intraperitoneal injections of oxymatrine, while Tuina + TA group received intraperitoneal injections of SRI-011381 hydrochloride followed by the same pressing protocol as Tuina 2 group. WB was used to detect the expression of collagen I, collagen III, TGF-β1, and phosphorylated-Smad3 (p-Smad3)/Smad3. Results: In phase 1, Tuina significantly improved PPT and STT in MTrPs of rats (P < 0.01), reversed pathological damages including disorganized muscle fiber arrangement, abnormal myocyte morphology, and exacerbated fibrosis. In addition, in MTrPs of rats in model 1 group, expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and fibrosis markers (α-SMA, collagen I, and collagen III) were upregulated, and all exhibited a significant downward trend after Tuina intervention (P < 0.05 or P < 0.01). This indicates that the therapeutic effects of Tuina are directly associated with reduced local inflammation and fibrosis in MTrPs. In phase 2, compared with model 2 group, rats in TI and Tuina 2 groups had decreased expression levels of TGF-β1 and p-Smad3/Smad3 in MTrPs, alongside reduced levels of inflammatory factors (IL-1β, IL-6, NF-κB, and TNF-α) and fibrosis markers (α-SMA, collagen I, and collagen III) (P < 0.05 or P < 0.01). When co-administered with TGF-β1 agonist, the therapeutic effects of Tuina were significantly attenuated, with rebounded TGF-β1 expression and p-Smad3/Smad3 in local MTrPs, and fibrosis and inflammatory responses were re-exacerbated (P < 0.05 or P < 0.01). Conclusion Tuina can effectively reduce inflammatory responses and fibrosis in MTrPs tissue, and its mechanism is closely related to the inhibition of the TGF-β1/Smad3 signaling pathway, which plays a critical role in Tuina-mediated regulation of MTrPs fibrosis.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

To investigate the infection status of two arboviruses,akabane orthobunyavirus(AKAV)and bluetongue virus(BTV),in cattle herds of Guizhou Province,we employed the indirect ELISA method to detect AKAV and BTV antibody levels in the present experiment.A total of 1504 bovine serum samples from 37 large-scale farms and 88 free-range households from 26 districts or coun-ties of 7 cities(prefectures)of Guizhou Province were collected to detect AKAV antibody levels.Additionally,1 241 serum samples from 30 large-scale farms and 15 free-range households in 19 districts or counties of 3 cities(prefectures)were tested for BTV antibody levels.Moreover,two influencing factors,breeding mode and sampling season,were statistically analyzed for their effects.The results showed that the overall positive rate of AKAV antibodies was 11.64％(175/1 504),with individual positive rates of 13.20％(123/934)and 9.12％(52/570)in large-scale farms and free-range households,respectively.No significant differences were observed between the two groups.However,the farm positive rate(64.86％,24/37)in large-scale farms was significantly higher than that(26.14％,23/88)in free-range households.Seasonal statistics showed that the positive rate was highest during the summer season at 60.00％(12/20).The total positive rate of BTV antibodies was 25.42％(222/1 241).The farm positive rate and individual positive rate in free-range households were 66.67％(10/15)and 41.91％(57/136),respectively.For large-scale farms,these rates were 60.00％(18/30)and 14.93％(165/1 105),respectively.The individual pos-itive rate in free-range households was significantly higher than that in large-scale farms.Seasonal statistics showed that the positive rates in summer and autumn seasons were 50.00％(5/10)and 72.41％(21/29),respectively,both of which were significantly higher than those in winter and spring seasons.All these findings indicated that both AKAV and BTV were present to a certain ex-tent in Guizhou Province,with seasonality.Furthermore,differences were observed between the different breeding modes.Our results could provide a data reference for the formulation of preven-tion and control measures for the two insect-borne diseases.

Objective:To identify and summarize the best evidence for pelvic floor muscle exercises (PFME) in preventing pelvic floor dysfunction (PFD) during pregnancy.Methods:A systematic search was conducted in databases including UpToData, Cochrane Library, PubMed, Web of Science, Embase, China National Knowledge Infrastructure, VIP, Wanfang Data, SinoMed, Yiigle, and Joanna Briggs Institute Evidence Based Healthcare Center Database and so on. The search spanned from January 1, 2018, to March 16, 2023. Two researchers independently evaluated the quality of clinical decision-making articles, expert consensus, and systematic reviews, while four researchers appraised the quality of guidelines. Evidence extraction and grading were performed independently by two researchers.Results:A total of nine documents were included: three guidelines, two clinical decision-making articles, one expert consensus, and three systematic reviews. A total of 20 evidence-based recommendations were summarized in six categories: indications and contraindications, assessment, implementation plans, supervision and follow-up, management, and outcome evaluation.Conclusions:PFME during pregnancy is effective in preventing PFD. Healthcare providers should integrate best evidence into clinical practice to develop tailored PFME plans for pregnant women, aiming to prevent PFD.

To investigate the infection status of two arboviruses,akabane orthobunyavirus(AKAV)and bluetongue virus(BTV),in cattle herds of Guizhou Province,we employed the indirect ELISA method to detect AKAV and BTV antibody levels in the present experiment.A total of 1504 bovine serum samples from 37 large-scale farms and 88 free-range households from 26 districts or coun-ties of 7 cities(prefectures)of Guizhou Province were collected to detect AKAV antibody levels.Additionally,1 241 serum samples from 30 large-scale farms and 15 free-range households in 19 districts or counties of 3 cities(prefectures)were tested for BTV antibody levels.Moreover,two influencing factors,breeding mode and sampling season,were statistically analyzed for their effects.The results showed that the overall positive rate of AKAV antibodies was 11.64％(175/1 504),with individual positive rates of 13.20％(123/934)and 9.12％(52/570)in large-scale farms and free-range households,respectively.No significant differences were observed between the two groups.However,the farm positive rate(64.86％,24/37)in large-scale farms was significantly higher than that(26.14％,23/88)in free-range households.Seasonal statistics showed that the positive rate was highest during the summer season at 60.00％(12/20).The total positive rate of BTV antibodies was 25.42％(222/1 241).The farm positive rate and individual positive rate in free-range households were 66.67％(10/15)and 41.91％(57/136),respectively.For large-scale farms,these rates were 60.00％(18/30)and 14.93％(165/1 105),respectively.The individual pos-itive rate in free-range households was significantly higher than that in large-scale farms.Seasonal statistics showed that the positive rates in summer and autumn seasons were 50.00％(5/10)and 72.41％(21/29),respectively,both of which were significantly higher than those in winter and spring seasons.All these findings indicated that both AKAV and BTV were present to a certain ex-tent in Guizhou Province,with seasonality.Furthermore,differences were observed between the different breeding modes.Our results could provide a data reference for the formulation of preven-tion and control measures for the two insect-borne diseases.

This article reports the diagnosis and treatment process of a case with secondary infective femoral artery pseudoaneurysm after intervention surgery for cerebral infarction,who improved after anti-infection and surgical treatment and was discharged.The patient was a 52-year-old female who underwent percutaneous balloon dilatation of basilar artery due to basilar artery stenosis.After surgery,she developed secondary methicillin-resistant Staphy-lococcus aureus(MRSA)bloodstream infection and infective femoral artery pseudoaneurysm.After treatment with vancomycin and linezolid,femoral artery pseudoaneurysm resection,and autovascular replacement,the patient re-covered well after the surgery and discharged from hospital.CT angiography(CTA)re-examination showed artifi-cial blood vessel patency.This study is expected to provide experience for the diagnosis and treatment of such pa-tients in clinical work.

To summarize the clinical practice of continuous medical service for patients at Shanghai Children′s Medical Center, affiliated with Shanghai Jiao Tong University School of Medicine, from September 2023 to December 2024, following the approval of its extended care qualification. This study utilized a mixed-methods research design that integrates quantitative and qualitative approaches. The quantitative study included a total of 117 subjects, with an age range of 18 to 35 years, an average age of 21.56 years, and a median age of 19 years; there were 59 males and 58 females. The disease types covered four major categories: childhood leukemia and solid tumors (68 cases), congenital structural malformations (25 cases), congenital hereditary metabolic diseases (4 cases), and rare diseases (20 cases). Among the subjects, 57.26% (67 cases) were first-time visitors to SCMC. The patients came from 20 provinces, autonomous regions, and municipalities across the country, with 88.03% (103 cases) from outside Shanghai. The treatment outcomes showed improvement or cure in 80.34% (94 cases) of the subjects, and there were no medical complaints. In addition, a qualitative study was conducted to deeply explore the experiences, confusions, and challenges of receiving or implementing continuous medical services from the perspectives of patients and their families, as well as medical staff. According to the inclusion and exclusion criteria, a total of 44 subjects were included in the study, among them, there were 12 patients, 12 family members who were taking care of the patients in SCMC, and 20 corresponding medical staff members. The results of the qualitative study showed that trust in the attending physicians of the children′s specialty hospital, a good doctor-patient relationship, satisfactory treatment outcomes, and support from medical insurance policies are the main driving forces for patients over 18 years old to receive continuous treatment at children′s specialty hospitals. The medical staff of the hospital also believed that this model can promote patient benefits. In conclusion, under the policy support of the Shanghai Municipal Health Commission, the "Six Fixed" Model for continuous treatment established by SCMC has achieved certain positive results in practice. This provides practical references for the development of continuous treatment in China and offers new strategies for the application of preventive medicine in the field of children′s health.

Objective:To evaluate the risk of developing pulmonary tuberculosis (PTB) among individuals with latent tuberculosis infection (LTBI) in schools and the protective effect of tuberculosis preventive treatment (TPT).Methods:A retrospective cohort study was conducted to collect data on 15 school outbreaks that occurred in Guangdong Province from 2017 to 2021. Baseline information on tuberculin skin test (TST) or interferon-gamma release test (IGRA) was obtained during contact surveys, as well as baseline information such as TPT. The incidence of PTB between 2017 and 2022 was queried using the Chinese Center for Disease Control and Prevention Information System. Poisson regression analysis was used to compare the incidence risk of PTB in the LTBI population under different TST states at baseline. Current cases, new cases and all cases (the sum of the two) were used as dependent variables. Cox regression models were used to analyze various risk factors affecting the risk of PTB in the LTBI population and evaluate the protective effect of TPT.Results:A total of 6 550 contacts were included in this study, of which 409 received TPT. Within 0-3 months after baseline survey, 119 cases were diagnosed as current cases [19.4‰, 119/(6 550-409)]. A total of 17 221.65 person-years of follow-up were conducted, during which 71 new cases were diagnosed (4.1/1 000 person-years, 71/17 221.65). The incidence density of PTB was 47.7/1 000 person-years, 6.6/1 000 person-years, 1.4/1 000 person-years, and 0.9/1 000 person-years, respectively, in TST strong/IGRA positive, TST moderate positive, TST generally positive, and TST and IGRA negative populations. The difference in PTB incidence density was statistically significant [likelihood ratio test LRT=153.16, P<0.001]. TPT was performed for individuals with strong TST or IGRA positivity, and the protection rate could reach 93% ( HR=0.07, 95% CI: 0.02-0.23). Conclusion:After the outbreak of the school epidemic, individuals with strong TST/IGRA positivity have a higher risk of developing PTB in the future. Targeted implementation of TPT can achieve better protection effects. In addition, the risk of developing PTB in individuals with moderate TST positivity is also worth noting.