AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

Objective To explore the correlation between different syndromes of sepsis and laboratory parameters,SOFA score,and APACHE Ⅱ score,providing reference for improving the objectivity of traditional Chinese medicine syndrome differentiation.Methods Based on the cross-sectional survey,information of the four diagnostic methods of traditional Chinese medicine,laboratory parameters,and disease assessment scales were collected from sepsis patients admitted to ICUs in 8 hospitals across the country.ANOVA,non-parametric tests,and Logistic regression analysis were used to screen for sepsis syndrome related factors.Results A total of 905 sepsis patients were included,and the distributions of traditional Chinese medicine syndromes were as follows:163(18.01%)of phlegm heat obstructing the lungs syndrome,141(15.58%)of blood stasis and toxin obstruction(damage)syndrome,130(14.36%)of intense exuberant heat toxin syndrome,129(14.25%)of Yin exhaustion and Yang deficiency syndrome,124(13.70%)of Yangming fu-organ excess syndrome,96(10.61%)of lung Qi deficiency syndrome,68(7.51%)of Yin deficiency and internal heat syndrome,and 54(5.97%)of Qi and blood deficiency syndrome.The results of ANOVA and non-parametric tests showed that there were differences in 14 indicators,including body temperature,heart rate,WBC,NE%,PCT,CRP,PLT,D-D,APTT,Lac,HCT,Hb,SOFA score,APACHE Ⅱ score among 8 common syndromes(P<0.05);Using the 14 indicators mentioned above as independent variables,and syndrome as the dependent variable,Logistic regression analysis was conducted.The results showed that in the excess syndrome category:①Phlegm heat obstructing lung syndrome was positively correlated with heart rate and WBC,and negatively correlated with Lac and APACHE Ⅱ scores;②Intense exuberant heat toxin syndrome was positively correlated with body temperature,WBC,NE%,PCT,CRP,and negatively correlated with PLT and SOFA scores;③Yangming fu-organ excess syndrome was positively correlated with body temperature and negatively correlated with PCT;④Blood stasis and toxin obstruction(damage)syndrome was positively correlated with body temperature,NE%,PLT,CRP,and D-D,and negatively correlated with heart rate,WBC,PCT,and APTT.Deficiency syndrome category:①Lung Qi deficiency syndrome was positively correlated with Hb,and negatively correlated with body temperature,WBC,and HCT;②Yin deficiency and internal heat syndrome were negatively correlated with NE%and CRP;③Qi and blood deficiency syndrome was positively correlated with APACHE Ⅱ score,and negatively correlated with body temperature,Hb,PLT,D-D;④Yin exhaustion and Yang deficiency syndrome was positively correlated with heart rate,PCT,Lac,SOFA score,and APACHE Ⅱ score,and negatively correlated with body temperature.Conclusion Patients with sepsis with excess syndrome category have higher WBC,NE%,PCT,CRP scores,which suggests a drastic inflammatory response.Among them,Blood stasis and toxin obstruction(damage)syndrome have highest PLT,D-D,and lowest APTT,suggesting a more severe disorder of coagulation function.Deficiency syndrome category,especially patients with Yin exhaustion and Yang prostration syndrome has higher Lac and SOFA score and APACHE Ⅱ score than other patients with sepsis of other syndromes,suggesting a worse condition and poor prognosis.

Objective To explore the correlation between different syndromes of sepsis and laboratory parameters,SOFA score,and APACHE Ⅱ score,providing reference for improving the objectivity of traditional Chinese medicine syndrome differentiation.Methods Based on the cross-sectional survey,information of the four diagnostic methods of traditional Chinese medicine,laboratory parameters,and disease assessment scales were collected from sepsis patients admitted to ICUs in 8 hospitals across the country.ANOVA,non-parametric tests,and Logistic regression analysis were used to screen for sepsis syndrome related factors.Results A total of 905 sepsis patients were included,and the distributions of traditional Chinese medicine syndromes were as follows:163(18.01%)of phlegm heat obstructing the lungs syndrome,141(15.58%)of blood stasis and toxin obstruction(damage)syndrome,130(14.36%)of intense exuberant heat toxin syndrome,129(14.25%)of Yin exhaustion and Yang deficiency syndrome,124(13.70%)of Yangming fu-organ excess syndrome,96(10.61%)of lung Qi deficiency syndrome,68(7.51%)of Yin deficiency and internal heat syndrome,and 54(5.97%)of Qi and blood deficiency syndrome.The results of ANOVA and non-parametric tests showed that there were differences in 14 indicators,including body temperature,heart rate,WBC,NE%,PCT,CRP,PLT,D-D,APTT,Lac,HCT,Hb,SOFA score,APACHE Ⅱ score among 8 common syndromes(P<0.05);Using the 14 indicators mentioned above as independent variables,and syndrome as the dependent variable,Logistic regression analysis was conducted.The results showed that in the excess syndrome category:①Phlegm heat obstructing lung syndrome was positively correlated with heart rate and WBC,and negatively correlated with Lac and APACHE Ⅱ scores;②Intense exuberant heat toxin syndrome was positively correlated with body temperature,WBC,NE%,PCT,CRP,and negatively correlated with PLT and SOFA scores;③Yangming fu-organ excess syndrome was positively correlated with body temperature and negatively correlated with PCT;④Blood stasis and toxin obstruction(damage)syndrome was positively correlated with body temperature,NE%,PLT,CRP,and D-D,and negatively correlated with heart rate,WBC,PCT,and APTT.Deficiency syndrome category:①Lung Qi deficiency syndrome was positively correlated with Hb,and negatively correlated with body temperature,WBC,and HCT;②Yin deficiency and internal heat syndrome were negatively correlated with NE%and CRP;③Qi and blood deficiency syndrome was positively correlated with APACHE Ⅱ score,and negatively correlated with body temperature,Hb,PLT,D-D;④Yin exhaustion and Yang deficiency syndrome was positively correlated with heart rate,PCT,Lac,SOFA score,and APACHE Ⅱ score,and negatively correlated with body temperature.Conclusion Patients with sepsis with excess syndrome category have higher WBC,NE%,PCT,CRP scores,which suggests a drastic inflammatory response.Among them,Blood stasis and toxin obstruction(damage)syndrome have highest PLT,D-D,and lowest APTT,suggesting a more severe disorder of coagulation function.Deficiency syndrome category,especially patients with Yin exhaustion and Yang prostration syndrome has higher Lac and SOFA score and APACHE Ⅱ score than other patients with sepsis of other syndromes,suggesting a worse condition and poor prognosis.

AIM:A mouse model of acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF)was estab-lished.METHODS:One hundred and twenty male C57BL/6 mice were randomly divided into a negative control group,an IPF group,and an acute exacerbation of interstitial fibrosis(AE-IPF)group.The IPF group received a low dose(3 mg/kg)of bleomycin(BLM)by endotracheal drip on days 0,14,and 28.The AE-IPF group received a high dose(5 mg/kg)of BLM by endotracheal drip on day 56.The control group received an equal volume of saline at different time points.The AE-IPF group was injected with a high dose(5 mg/kg)of BLM via tracheal drip on day 56 on top of the initial IPF induction,while the control group received equal amounts of saline at different time points.Experiments were con-ducted on the 57th,59th,63rd,and 70th days after the initial modeling.Mice were observed for general conditions,CT imaging changes,HE,and Masson staining to assess the degree of alveolitis and fibrosis in lung tissues.Lung function,hydroxyproline(HYP)content in lung tissues,and interleukin-6(IL-6)content in bronchoalveolar lavage fluid(BALF)were also measured.RESULTS:Mice in the AE-IPF group exhibited wheezing,shortness of breath,dyspnea,and weight loss.CT imaging revealed that IPF group mice showed patchy,subpleural reticular fuzzy shadows with irregular thickening of interlobular septa and intralobular linear shadows,along with tractional bronchiectasis.In the AE-IPF group,new ground-glass shadows and solid shadows appeared in addition to the IPF features.AE-IPF group mice demon-strated decreased lung function,elevated lung index,and acute pulmonary edema.HE and Masson staining of AE-IPF group mice showed consistent pathological manifestations of AE-IPF.HYP content in lung tissues,total cell count in BALF,and IL-6 concentration were significantly higher in the AE-IPF group compared to the control group(P<0.05).CONCLUSION:The use of multiple tracheal drip administrations of bleomycin successfully established an AE-IPF ani-mal model in mice.The 63rd day of the experiment was identified as the optimal observation point,as it exhibited the most significant pathological features and clinical symptoms.This model provides ideal conditions for studying AE-IPF patho-genesis and evaluating therapeutic efficacy.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of patients with adrenal diffuse large B-cell lymphoma(DLBCL).Methods·From March 2002 to December 2022,a total of 105 patients with adrenal DLBCL admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival outcomes,and prognostic factors.Patients'gene mutation profiles were evaluated by targeted sequencing of 152 lymphoma-related genes.Results·The median age of the patients was 62(15?82)years and the male-to-female ratio was 2.3∶1.Among them,63 patients(60.0%)were over 60 years old,22 patients(21.0%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or higher,87 patients(82.9%)were staged Ann Arbor Ⅲ?Ⅳ,92 patients(87.6%)had elevated serum lactate dehydrogenase(LDH)levels(above the upper limit of reference),84 patients(80.0%)had extranodal invasion in at least two organs,67 patients(63.8%)were of non-germinal center B-cell(non-GCB)origin,and 95 patients(90.5%)had an international prognosis index(IPI)scored over 2.With a median follow-up of 28.3(0.7?191.9)months,the estimated 2-year overall survival(OS)rate and progression-free survival(PFS)rate were 68.3%and 53.1%,respectively.The estimated 5-year OS rate and PFS rate were 52.6%and 44.0%,respectively.Among 93 patients who could be evaluated for clinical outcomes,62(66.7%)got a complete response(CR).Univariate analysis and multivariate Cox analysis revealed that age over 60 years was an adverse prognostic factor for PFS,and ECOG performance status of two or higher was an adverse prognostic factor for both OS and PFS.Targeted gene sequencing in 46 adrenal diffuse DLBCL patients showed high mutation frequencies in lysine methyltransferase 2D(KMT2D;n=17,37%),Pim-1 proto-oncogene,serine/threonine kinase(PIM1;n=17,37%),MYD88 innate immune signal transduction adaptor(MYD88;n=15,33%),CD79b molecule(CD79B;n=13,28%),and BTG anti-proliferation factor 2(BTG2;n=10,22%).Conclusion·Age over 60 years is an adverse prognostic factor for PFS,and ECOG performance status of two or higher is an adverse prognostic factor for both OS and PFS in patients with adrenal DLBCL.Patients exhibited high frequencies of KMT2D,PIM1,MYD88,CD79B,and BTG2 mutations,as well as an increased proportion of the MCD-like subtype.

Objective·To investigate the clinicopathologic features,gene mutation profile,and real-world survival prognosis of diffuse large B-cell lymphoma(DLBCL)with pulmonary involvement.Methods·The clinical data of 110 patients with newly diagnosed,pathologically confirmed DLBCL and pulmonary involvement at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between August 2003 and December 2022 were retrospectively collected and analyzed.Evaluation of the efficacy of treatment,survival analyses,and univariate and multivariate analyses were performed in 88 patients who received a first-line regimen based on rituximab in combination with cyclophosphamide,doxorubicin/epirubicine,vincristine,and prednisone(R-CHOP).A total of 74 patients underwent targeted DNA sequencing of 55 lymphoma-related genes and were evaluated for mutations.Results·Among the 110 patients,72(65.5%)were>60 years old,52(47.3%)were female,92(83.6%)presented with Ann Arbor stage Ⅲ?Ⅳ,20(18.2%)had ECOG scores≥2,75(68.2%)had elevated lactate dehydrogenase(LDH)levels,79(71.8%)had≥2 extranodal involvements,32(31.4%)were classified as germinal center B-cell subtype,22(26.8%)were diagnosed with double expressor lymphoma,and 4(4.6%)with double-hit lymphoma.Among the patients treated with R-CHOP-based first-line regimens,the objective response rate(ORR)was 68.2%,the 5-year progression-free survival(PFS)rate was 43.7%,and the 5-year overall survival(OS)rate was 65.4%.Univariate analysis showed that elevated LDH and ECOG score≥2 were poor prognostic factors for PFS and OS,and mutations in PIM1 and CD79B were poor prognostic factors for PFS among high-frequency mutations.Multivariate analysis showed that elevated LDH was an independent adverse prognostic factor for PFS(HR=2.47,95%CI 1.28?4.77)and OS(HR=2.71,95%CI 1.21 ? 6.07).Targeted sequencing results showed that PIM1(25.7%),MYD88(24.3%),TP53(18.9%),CD79B(17.6%),KMT2D(17.6%),and TNFAIP3(16.2%)were the high-frequency mutations with mutation rates over 15%.Conclusion·Elevated LDH is an independent adverse prognostic factor for PFS and OS in DLBCL with pulmonary involvement.Mutations in PIM1,MYD88,TP53,CD79B,KMT2D,and TNFAIP3 are frequently observed in this population.

Following the evidence-based diagnosis and treatment guideline development method for common pediatric diseases,the The Guideline for the Diagnosis and Treatment of Pediatric Food Accumulation and Stagnation in Chinese Medicine was formed through literature retrieval,expert questionnaire survey,expert discussion meeting,and solicitation of opinions.The revised content includes the scope of the guideline,normative reference documents,terms and definitions,diagnosis,syndrome differentiation,treatment,pre-vention and nursing suggestions,etc.,aiming to update the clinical diagnosis and treatment plan of Chinese medicine for accumulation and provide important clinical decision-making references for clinical physicians to rationally apply the diagnosis and treatment plan of Chinese medicine in the prevention and treatment of accumulation and stagnation in Children.

Objective:To explore the clinical efficacy of three different surgical timings of modified cervical cerclage in twin pregnant women with cervical insufficiency.Methods:The clinical data of 73 twin pregnant women who underwent modified cervical cerclage and had pregnancy outcomes in Qilu Hospital of Shandong University (Qingdao) from April 2014 to July 2023 were retrospectively analyzed. According to the different timings of surgery, they were divided into prophylactic cerclage group, ultrasound-indicated cerclage group (further divided into cervical length (CL)≤15 mm and 15 mm10 mg/L was a risk factor for preterm birth before 34 weeks of gestation ( OR=5.230, 95% CI: 1.616-16.929; P=0.006). Conclusions:In twin pregnant women with cervical insufficiency, prophylactic cerclage has the same surgical effect as ultrasound-indicated cerclage, while both prophylactic cerclage and ultrasound-indicated cerclage could significantly improve maternal and fetal outcomes compared with emergency cerclage. Twin pregnancies with CL≤15 mm might benefit from cervical cerclage. Postoperative CRP>10 mg/L is an independent risk factor for preterm birth before 34 weeks of gestation.

Reporting guidelines are structured checklists for researchers to follow when reporting spe-cific types of studies.As researches conducted in real-world settings to address practical issues,implementa-tion research has stringent requirements for the replicability of result and the transparency of reporting,making its reporting guidelines particularly important.This paper systematically introduces the reporting guidelines in the field of implementation science,outlines their classification systems and scopes of applica-tion,and focuses on explaining the core characteristics and functions of five key reporting guidelines,inclu-ding the Standards for Reporting Implementation Studies(StaRI),Reporting guidelines for implementation and operational research,the Template for Intervention Description and Replication(TIDieR),the Frame-work for Reporting Adaptations and Modifications-Enhanced(FRAME),and recommendations for specifying and reporting implementation strategies.Furthermore,combined with the PEDALs research paradigm in im-plementation science,this paper further clarifies the specific application pathways for reporting guidelines and discusses directions for refinement,aiming to provide references for researchers to select appropriate reporting guidelines.

Cell ablation has recently emerged as a valuable technique for investigating cell lineage and function during the development of organisms.The nervous system contains diverse cellular populations,whose roles under physiological and pathological conditions are still not fully understood.Various cell ablation methods have been reported to specifically ablate different types of cell populations in the nervous system and have also been used to study cellular functions under physiological conditions as well as the pathogenesis of neurologi-cal system diseases.In this article,we have summarized common cell ablation techniques and focus on their applications in neurobio-logical and neurological system disease research.