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 explore the early effects of birth weight at different gestational ages on blood pressure trajectory among primary school students, so as to provide evidence for incorporating gestational age birth weight into individualized early warning and intervention strategies for childhood hypertension. Methods: From May to November 2023, a purposeful sampling method was used to recruit 1 676 students in grade 1-3 from three primary schools in a certain urban district of Chongqing. Follow up assessments were conducted in May 2024(T1), November 2024(T2), and May 2025(T3). General demographic and birth related information were collected via self administered questionnaires, while height, weight and blood pressure were obtained through physical examinations. Linear mixed effects model was used to analyze the associations between birth weight at different gestational ages and blood pressure trajectories. Results: During the T1-T3 period, the systolic blood pressure of boys were 98.5 (93.0, 104.5 ),98.5 (93.5, 105.0), and 97.5 (92.5, 103.5)mmHg, respectively, while the diastolic blood pressure were 60.5 (56.5, 65.0), 61.5 ( 57.0 , 65.5), and 60.0 (56.0, 64.0)mmHg, respectively. For girls, the systolic blood pressure were 95.5 (90.0, 102.0),95.5 (90.5, 101.5), and 96.0 (90.5, 101.5)mmHg, respectively, and the diastolic blood pressure were 60.5 (56.0, 64.5 ),61.5 (57.5, 65.5), and 59.5 (56.0, 63.0)mmHg, respectively. Through Friedman test within both boys and girls, diostolic blood pressure were statistically significant across three measurements( χ 2=48.85，81.54，both P <0.01). The proportion of normal blood pressure increased , and the proportion of prehypertension and hypertension decreased with time( χ 2=39.72，25.62，both P < 0.01 ). Linear mixed effects model analysis revealed that after adjusting for age, sex, household income monthly, parental education, family history of hypertension and maternal pregnancy complications, large for gestational age had significantly higher trajectories of systolic ( β = 1.50) and diastolic( β =0.94) blood pressure compared to appropriate for gestational age(both P <0.01). Conclusion Large for gestational age is associated with elevated blood pressure trajectories during school age, and it may be considered as an early indicator for individualized screening and intervention for childhood hypertension.

ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

Objective To explore the optimal warning threshold of motor evoked potentials(MEP)in decompression surgery for ossification of the posterior longitudinal ligament(OPLL)at cervical and thoracic segments,and the predictive role of different MEP parameters on postoperative lower extremity motor function.Methods A retrospective analysis was conducted on the clinical data of 227 patients diagnosed with cervical or thoracic OPLL and underwent decompression surgery from January 2022 to January 2024 in the hospital.There were 131 males and 96 females,with an average age of(60±10)years.All patients underwent continuous neuro-physiological monitoring during the operation,and the minimum ratio of MEP amplitude change to the baseline at the beginning of the operation(Dmax)and the ratio of MEP terminal amplitude change to the baseline at the end of the operation(Dend)were recorded.The correlations between these two ratios and the lower extremity motor func-tion immediately after the operation and at 1 year were compared.According to the Medical Research Council muscle strength score(MRC)standard,a postoperative score increase of≥1 point compared to preoperative was defined as postoperative motor dysfunction.Pearson correlation coefficients were used to evaluate the correlations between Dmax and Dend and the lower extremity motor function immediately after the operation and at 1 year.Receiver operating characteristic(ROC)curves were drawn to predict postoperative lower extremity motor dysfunc-tion using Dmax and Dend.Results Among the 227 patients,186 had cervical OPLL and 41 had thoracic OPLL.The incidence of lower extremity motor dysfunction immediately after the operation and at 1 year was 7 cases(3.76%)and 2 cases(1.08%)in the cervical group,and 9 cases(21.95%)and 3 cases(7.32%)in the thoracic group,respectively.The incidence of lower extremity motor dysfunction in the thoracic group was higher than that in the cervical group(P<0.001).The baseline induction rate of bilateral lower extremity MEPs was 98.92%(368/372)in the cervical group and 96.34%(79/82)in the thoracic group.The Pearson correlation coefficients of Dend with the bilateral lower extremity motor function immediately after the operation in the cervical and thoracic groups were both greater than those of Dmax,and the differences were statistically significant(cervical group:r=0.669,0.517,P=0.001 2;thoracic group:r=0.882,0.727,P=0.003 6),while the differences in the Pearson corre-lation coefficients of Dend and Dmax with the bilateral lower extremity motor function at 1 year were not statistically significant(cervical group:r=0.457,0.352,P=0.088;thoracic group:r=0.760,0.625,P=0.098).The cut-off values of Dend for the cervical group were 0.853 immediately after the operation and at 1 year,and the cut-off values of Dmax were 0.881 and 0.978,respectively.For the thoracic group,the cut-off values of Dend were 0.532 immediately after the operation and 0.639 at 1 year,and the cut-off values of Dmax were 0.532 and 0.640,respec-tively.Conclusions In OPLL surgery,the MEP monitoring strategy should be adjusted according to the surgical segment.For the cervical segment,Dmax should be emphasized to balance high sensitivity and specificity,while for the thoracic segment,Dmax or Dend can be flexibly selected.Higher MEP warning thresholds are required for cervical OPLL surgery(Dmax:0.881 immediately after the operation and 0.978 at 1 year;Dend:0.853),while significantly lower thresholds are needed for thoracic OPLL(Dmax/Dend:0.532 immediately after the operation and 0.640 at 1 year).

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

AIM:To analyze the expression of se-creted phosphoprotein 1(SPP1)and programmed cell death-ligand 1(PD-L1)in SMARCA4-deficient non-small cell lung cancer,and to provide a scientif-ic basis for the study of the follow-up treatment of this rare pathological type of lung cancer.METH-ODS:The clinical and pathological characteristics of 12 patients with this disease were analyzed retro-spectively,and the patients were divided into two groups of adenocarcinomas and poorly differentiat-ed carcinomas according to their morphological characteristics,and the relationship between the expression of SPP1 and PD-L1 was analyzed in the two groups.RESULTS:SPP1 expression was detect-ed in all patients and Its expression level was signif-icantly higher in the poorly differentiated carcino-ma group compared with the adenocarcinoma group(P=0.015);PD-L1 expression was found in 6/7 patients(5 cases were not measured),compared with the adenocarcinoma group,PD-L1 was also highly expressed in the poorly differentiated carci-noma group(P=0.048)and the PD-L1 difference be-tween the two groups suggested that the results were similar to those of SPP1.CONCLUSION:SMARCA4-deficient non-small cell lung cancer has high positive expression of SPP1 and PD-L1.It was more pronounced in patients with poorly differenti-ated carcinoma.There may be a positive correla-tion between SPP1 and PD-L1 expression in SMAR-CA4-deficient non-small cell lung cancer and the mechanism of the correlation needs to be further verified in subsequent studies.

OBJECTIVE To conduct the epidemiological survey for 4 patients with carbapenem-resistant Klebsiella pneumoniae(CRAB)that gathered to emerge in intensive care unit(ICU)within a short period so as to find out the sources of suspected CRAB.METHODS The clinical data and epidemiological history of the 4 patients with hospital-associated infection with CRAB who were treated in Shandong Provincial Hospital Affiliated to Shandong First Medical University from Mar.31,2023 to Apr.7,2023 were retrospectively analyzed.The whole genome second-generation sequencing was carried out for the CRAB strains isolated from the patients and their surround-ings,and the sources of the CRAB strains were traced by means of the whole genome sequencing.RESULTS The result of the epidemiological survey showed that the case 1,2,3 and 4 were close in spatial position and had the similar drug resistance spectrum,and there might be cross infection.With the combination of the result of genome analysis,it was found that the strain from the case 1 was brought from the community and was the evolutionary branch different from other CRAB strains causing nosocomial infection;the strains from the case 2,3 and 4 had the close original sources with the CRAB strains from surroundings.CONCLUSIONS The CRAB strain from the case 1 is brought from community,which differs in the evolution branch with the strains from the cases of hospi-tal-associated CRAB infection.The transmission of CRAB leading to the incident of suspected hospital-associated infection outbreak is multiple sources.It is an effective measure to early identify the outbreak of hospital-associated infection and take targeted prevention measures so as to control the outbreak of hospital-associated infection.

Objective To explore the optimal warning threshold of motor evoked potentials(MEP)in decompression surgery for ossification of the posterior longitudinal ligament(OPLL)at cervical and thoracic segments,and the predictive role of different MEP parameters on postoperative lower extremity motor function.Methods A retrospective analysis was conducted on the clinical data of 227 patients diagnosed with cervical or thoracic OPLL and underwent decompression surgery from January 2022 to January 2024 in the hospital.There were 131 males and 96 females,with an average age of(60±10)years.All patients underwent continuous neuro-physiological monitoring during the operation,and the minimum ratio of MEP amplitude change to the baseline at the beginning of the operation(Dmax)and the ratio of MEP terminal amplitude change to the baseline at the end of the operation(Dend)were recorded.The correlations between these two ratios and the lower extremity motor func-tion immediately after the operation and at 1 year were compared.According to the Medical Research Council muscle strength score(MRC)standard,a postoperative score increase of≥1 point compared to preoperative was defined as postoperative motor dysfunction.Pearson correlation coefficients were used to evaluate the correlations between Dmax and Dend and the lower extremity motor function immediately after the operation and at 1 year.Receiver operating characteristic(ROC)curves were drawn to predict postoperative lower extremity motor dysfunc-tion using Dmax and Dend.Results Among the 227 patients,186 had cervical OPLL and 41 had thoracic OPLL.The incidence of lower extremity motor dysfunction immediately after the operation and at 1 year was 7 cases(3.76%)and 2 cases(1.08%)in the cervical group,and 9 cases(21.95%)and 3 cases(7.32%)in the thoracic group,respectively.The incidence of lower extremity motor dysfunction in the thoracic group was higher than that in the cervical group(P<0.001).The baseline induction rate of bilateral lower extremity MEPs was 98.92%(368/372)in the cervical group and 96.34%(79/82)in the thoracic group.The Pearson correlation coefficients of Dend with the bilateral lower extremity motor function immediately after the operation in the cervical and thoracic groups were both greater than those of Dmax,and the differences were statistically significant(cervical group:r=0.669,0.517,P=0.001 2;thoracic group:r=0.882,0.727,P=0.003 6),while the differences in the Pearson corre-lation coefficients of Dend and Dmax with the bilateral lower extremity motor function at 1 year were not statistically significant(cervical group:r=0.457,0.352,P=0.088;thoracic group:r=0.760,0.625,P=0.098).The cut-off values of Dend for the cervical group were 0.853 immediately after the operation and at 1 year,and the cut-off values of Dmax were 0.881 and 0.978,respectively.For the thoracic group,the cut-off values of Dend were 0.532 immediately after the operation and 0.639 at 1 year,and the cut-off values of Dmax were 0.532 and 0.640,respec-tively.Conclusions In OPLL surgery,the MEP monitoring strategy should be adjusted according to the surgical segment.For the cervical segment,Dmax should be emphasized to balance high sensitivity and specificity,while for the thoracic segment,Dmax or Dend can be flexibly selected.Higher MEP warning thresholds are required for cervical OPLL surgery(Dmax:0.881 immediately after the operation and 0.978 at 1 year;Dend:0.853),while significantly lower thresholds are needed for thoracic OPLL(Dmax/Dend:0.532 immediately after the operation and 0.640 at 1 year).