ObjectiveTo analyze the risk factors for long-term cardiovascular events in patients undergoing long-term peritoneal dialysis （PD）， and to construct and validate a visual nomogram prediction model based on multiple parameters. MethodsA prospective cohort study was conducted， consecutively enrolling 248 maintenance PD patients （dialysis duration ≥ 3 months）. Demographic characteristics， clinical indicators， laboratory parameters， and echocardiographic indices （including left ventricular ejection fraction ［LVEF］， ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity （E/e’）， etc.） were collected. The composite endpoint was defined as the occurrence of cardiovascular events or cardiovascular death， with non-cardiovascular death as the competing risk and loss to follow-up or the end of follow-up as censoring events. Fine-Gray competing risks model was used to screen independent predictors， based on which a nomogram model was constructed. Internal validation was performed using the Bootstrap method （1 000 resamplings）， and the concordance index （C-index） and time-dependent receiver operating characteristic （time-dependent ROC） curve were calculated to evaluate the model performance. ResultsWith a median follow-up of 29 months （interquartile range： 24–35 months）， 88 patients （35.48%） reached the composite endpoint， including 80 cases of cardiovascular events and 8 cases of cardiovascular death， and 4 patients died of non-cardiovascular causes. Multivariate Fine-Gray analysis revealed that age， diabetes mellitus， hemoglobin （HGB） level and E/e' ratio were independent influencing factors of the composite endpoint. Specifically， each 1-year increase in age was associated with a 3.0% increase in the risk of the composite endpoint （HR=1.030， P=0.006）； patients with diabetes mellitus had a 167.9% higher risk compared with non-diabetic patients （HR=2.679， P=0.007）； each 1g/L increase in HGB level contributed to a 1.5% reduction in the risk （HR=0.985， P=0.003）； and each 0.1 increase in E/e' ratio led to a 7.2% increase in the risk （HR=1.072， P=0.045）. The nomogram model had a C-index of 0.76 （95% CI： 0.698–0.820）， and the AUC of the time-dependent ROC curve reached 0.849 at 23 months of follow-up. ConclusionIncreased age， complicated with diabetes mellitus， decreased HGB， and elevated E/e' ratio are independent risk factors of long-term occurrence of cardiovascular events and cardiovascular death in patients undergoing long-term PD. The nomogram model constructed based on the above variables has good predictive value and clinical applicability， which can provide a reference for cardiovascular risk stratification and individualized intervention in long-term PD patients.

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.

ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

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.

ObjectiveTo integrate network pharmacology prediction with multi-level experimental verification methods， and to explore in depth the therapeutic efficacy and potential mechanism of luteolin in treating gout. MethodsDatabases were used to obtain potential pharmacodynamic targets of luteolin. Protein-protein interaction （PPI） network construction and network pharmacology analysis techniques were used to screen key core targets of luteolin in gout treatment. Further biological function enrichment analysis and signaling pathway analysis were performed on these targets. Molecular docking simulation was used to calculate the binding energy between luteolin and potential core targets， clarifying the strength of their interactions. In the in vivo experiment for hyperuricemia， 48 mice were randomly divided into a blank group， a model group， an allopurinol group （5 mg·kg^-1）， and low-dose （10 mg·kg^-1）， medium-dose （30 mg·kg^-1）， and high-dose （90 mg·kg^-1） luteolin groups. For the first three days， the blank and model groups were gavaged with an equal volume of normal saline， while the allopurinol group and luteolin groups were gavaged with corresponding drugs. From day 4 onwards， modeling was performed by intraperitoneal injection at 12：00 daily （normal saline for the blank group， and oxonic acid potassium-hypoxanthine mixture for other groups， with 300 mg·kg^-1 for each group）. Gavage intervention was administered at 18：00 daily （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） until day 7. After sampling， levels of serum uric acid （UA）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were measured. Levels of xanthine oxidase （XO） in the liver and kidney， ATP-binding cassette transporter G2 （ABCG2） and malondialdehyde （MDA） in the kidney， and superoxide dismutase （SOD） in the liver were determined. Renal HE staining was also performed. In the pharmacodynamic study of gouty arthritis， 36 rats were randomly divided into a blank group， a model group， a colchicine group （0.315 mg·kg^-1）， and low-dose （7 mg·kg^-1）， medium-dose （21 mg·kg^-1）， and high-dose （63 mg·kg^-1） luteolin groups. The model was established by vertically injecting 100 µL of 25 g·L^-1 monosodium urate suspension into the posterior lateral aspect of the right ankle joint （the blank group was injected with an equal volume of normal saline）， with repeated injections every two days for reinforcement. From day 2 after modeling， daily gavage administration was performed （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） for a total of 16 days. During the experiment， ankle swelling and pain threshold were measured regularly. After sampling， levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined. Ankle joints were subjected to HE， Masson， and safranin O-fast green staining， and HE staining was also performed on ankle synovial tissue and various organs. Western blot was used to determine the expression levels of key proteins in gout-related signaling pathways. ResultsNetwork pharmacology analysis predicted that luteolin may regulate over 20 core targets， such as XO， ABCG2， nuclear factor erythroid 2-related factor 2 （Nrf2）， and SOD， through acting on signaling pathways including NF-κB， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， and ABC transporters， thereby affecting uric acid metabolism and inflammatory responses. In the hyperuricemia model， compared with the blank group， the model group showed significantly increased serum UA level， liver and kidney XO activity， renal ABCG2 expression， and liver SOD activity （P<0.01）. Compared with the model group， the high-dose luteolin group significantly reduced serum UA level （P<0.01）， inhibited liver and kidney XO activity （P<0.01）， and significantly increased renal ABCG2 expression and liver SOD activity （P<0.01）， effectively alleviating renal oxidative stress damage and improving renal histopathological status. In the gouty arthritis model， compared with the blank group， the model group showed significant ankle swelling， decreased pain threshold， and significantly increased levels of IL-6， IL-1β， and TNF-α in serum and synovial tissue （P<0.01）. The high-dose luteolin group significantly reduced ankle swelling， prolonged hot plate pain threshold， effectively decreased the levels of the above inflammatory factors in serum and synovial tissue （P<0.01）， and significantly improved ankle pathological damage， showing good analgesic and anti-inflammatory effects. Western blot results further confirmed that luteolin significantly upregulated Nrf2 protein expression and downregulated XO and nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） expression in animals. ConclusionLuteolin can improve symptoms of hyperuricemia and gouty arthritis， and its potential mechanism may be related to inhibiting XO activity， increasing ABCG2 and SOD levels， and regulating Nrf2-mediated oxidative stress-related pathways.

OBJECTIVE To investigate the molecular mechanism of Tiaozhong huashi decoction in improving gastroesophageal reflux disease （GERD） by regulating endoplasmic reticulum autophagy in rat esophageal interstitial cells of Cajal （ICC） through p62 signaling pathway.METHODS After establishing a rat GERD model via the weak acid intragastric administration and irregular diet， the rats were randomly divided into model group， western medicine group [1.56 mg/（kg·d） of mosapride， 3.125 mg/（kg·d） of lansoprazole] and low-， medium- and high-dose Tiaozhong huashi decoction [4.713， 9.425， 18.85 g/（kg·d）] groups. A blank group was also set up， with 8 rats in each group. The rats in each group were intragastrically administered with corresponding liquid or normal saline twice a day for 14 days. During the intervention period， the general conditions of rats’ hair， spirit， diet and defecation were observed. After the last gavage， the pathological changes of esophageal tissue and the ultrastructure of ICC were observed. The relative expression and positive expression levels of p62， autophagy-related protein 8 （ATG8）， 200 kDa FAK family kinase-interacting protein （FIP200） and Unc-51 like autophagy activating kinase 1 （ULK1） in esophageal tissue were detected.RESULTS Compared with the blank group， rats in the model group exhibited listlessness； thickening of the esophageal basal layer， elongation of lamina propria papillae with inflammatory cell infiltration； markedly dilated endoplasmic reticulum appearing as round vacuolar cisternae with ribosome detachment； and a small number of accumulated autophagosomes. The relative expression and positive expression levels of p62， ATG8， FIP200， and ULK1 were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological injuries in the medium- and high-dose Tiaozhong huashi decoction groups had all improved to varying degrees； the damaged endoplasmic reticulum structure was repaired， and no autophagosome accumulation was observed. In particular， the relative expression levels and positive expression levels of p62， ATG8， FIP200， and ULK1 in esophageal tissue of rats in the medium-dose Tiaozhong huashi decoction group were significantly increased （ P ＜0.05）.CONCLUSIONS Tiaozhong huashi decoction ameliorated esophageal mucosal injury in GERD rats， and its mechanism was possibly associated with activation of the p62 signaling pathway and restoration of the endoplasmic reticulum structure， morphology， and autophagic capacity of ICC.

The 577 nm subthreshold micropulse laser(577 nm SML)is a non-invasive retinal laser treatment technique that selectively acts on the retinal pigment epithelium(RPE), induces heat shock protein expression, regulates inflammatory response, promotes blood retinal barrier repair, downregulates vascular endothelial growth factor(VEGF)levels, improves Müller cell function, promotes retinal metabolism and functional recovery, and avoids thermal damage caused by traditional threshold lasers. In recent years, 577 nm SML has been widely used in the treatment of various fundus diseases, including central serous chorioretinopathy(CSC), diabetes macular edema(DME), macular edema secondary to retinal vein occlusion(RVO-ME), age-related macular degeneration(ARMD), type 2 macular telangiectasia(MacTel2), persistent subretinal fluid after retinal detachment repair, and Irvine-Gass syndrome. Characterized by favorable safety and repeatability, 577 nm SML possesses high clinical application value and serves as a vital adjuvant and complementary strategy for anti-VEGF therapy. This review aims to summarize the therapeutic mechanisms and clinical applications of 577 nm SML in common fundus diseases, and provide a theoretical basis for its further clinical application.

Objective:This study systematically summarized the construction experience of the immunology platform at the Institute of Basic Medical Sciences, Peking University Third Hospital, aiming to provide theoretical references and practical guidance for research-oriented hospitals in building high-quality research platforms.Methods:This study employed case study analysis to elaborate on the platform development initiatives, integrating literature analysis and in-depth interviews to conduct a horizontal comparison of management models among peer research platforms.Results:Through five years of development, the platform had achieved remarkable outcomes via a model integrating ″Talent cultivation-Technological innovation-Equipment procurement″ Research talents had demonstrated breakthroughs in securing national-level research grants, publishing high-impact papers, and obtaining scientific awards. The technical service system had achieved enhancement in both service scope and professional depth, fostering robust interdisciplinary synergy. The platform had effectively expanded its societal engagement capacity.Conclusions:The sustainable advancement of research-oriented hospital immunology platform necessitates establishing standardized flow cytometry databases and implementing high-dimensional data integration. Building upon multidisciplinary convergence, it is imperative to pioneer innovative operational mechanisms characterized by efficiency, open-access, and shared frameworks.

Objective:To explore the adaptability of health resources allocation and the economic development level in Sichuan Province and its influencing factors,so as to provide reference and suggestions for optimizing health resources allocation.Methods:Based on the panel data of 21 cities(states)in Sichuan Province,it analyzes the adaptability of health resources allocation and economic development in Sichuan Province from 2017 to 2021 and its influencing factors through entropy method,coupling coordination model and grey relational model.Results:From 2017 to 2021,the allocation level of health resources in most areas of Sichuan Province showed a gradual upward trend,but the rising speed was obviously lower than the growth rate of economic development;In 2021,the adaptability between the allocation of health resources and the level of economic development in most parts of Sichuan Province is still in a low coordination stage.Conclusion:Different regions should adopt differentiated development strategies based on their actual geographical conditions,optimize the allocation of health resources according to local conditions,and promote the coordinated development of health resource allocation and economic level.

Objective To verify the accuracy of Youssef's formula and evaluate whether fetal biacromial diameter(BA)and other fetal biological diameters estimated by ultrasound can be used to predict macrosomia and shoulder dystocia,so as to provide the possibility for clinical prediction of shoulder dystocia.Methods A total of 200 pregnant women with a gestational period of 37-42 weeks were examined with ultrasound within 3 days before delivery for collecting biparietal diameter(BPD),head circumference(HC),abdominal circumference(AC),humerus length(HL),femur length(FL),thoracic transverse diameter and midpoint diameter of upper arm;and the fetal BA was estimated by Youssef's formula.Neonatal BA,body mass and body length were measured within 1 day after delivery.The above data were analyzed for correlation.Newborns were grouped according to their body mass(macrosomia vs non-macrosomia)and whether they had shoulder dystocia or not(shoulder dystocia vs non-shoulder dystocia).Results(1)The fetal BA estimated by Youssef's formula was consistent with neonatal BA(P>0.05),and the estimated BA was positively correlated with BPD,HC,AC and neonatal body mass(P<0.001).(2)The BA,BA/AC and BA/HC in macrosomia group were different from those in non-macrosomia group(P<0.05).ROC curve showed that the sensitivity and specificity were 92.3%and 88.2%for macrosomia prediction when the estimated BA threshold was 16.05 cm,and those were 61.5%and 77.0%when BA/AC threshold was 0.455,and 76.9%and 72.7%when BA/HC threshold was 0.465.(3)Shoulder dystocia group had neonatal weight close to non-shoulder dystocia group(P>0.05),but higher BA/BPD,BA/HC and BA-BPD(P<0.05).ROC curve showed that the sensitivity and specificity were 100.0%and 66.8%for shoulder dystocia when BA threshold was 15.45 cm,100.0%and 80.6%when BA/BPD threshold was 1.695,100.0%and 81.6%when BA/HC threshold was 0.475,and 100.0%and 76.0%when the threshold difference between BA and BPD was 6.35 cm.Conclusion Fetal BA,BA/BPD,BA/HC,BA/AC and BA-BPD may be effective predictors of shoulder dystocia and macrosomia.