Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Xuanfuhua Decoction （旋覆花汤） is considered as the theoretical prototype of the method of unbloc-king collaterals with acrid and moistened medicinals. Guided by the theories of "chronic disease entering the collaterals" and "collaterals performing their functions when there is free flow"， YE Gui further developed this approach into a systematic method. The core of this approach lies in dispersing and opening constraint with acrid medicinals， nourishing and harmonizing collaterals with moistened medicinals， eliminating pathogens and unblocking collaterals with insect medicinals. The disease course of idiopathic pulmonary fibrosis （IPF） is prolonged， with a complex of deficiency and excess， and chronic disease entering the collaterals. The core pathogenesis involves lung collaterals obstruction， fluid depletion with blood stasis， and chronic disease entering the collaterals. Treatment can be guided by the method of unblocking collaterals with acrid and moistened medicinals based on Xuanfuhua Decoction， following a strategy of "dispersing and unblocking， moistening and nourishing， penetrating and venting". Specifically， for lung collaterals obstruction， acrid medicinals can be used to disperse lung qi and open bi （痹）. In case of fluid depletion and blood stasis， moistened medicinals for nourishing lung collaterals are suggested to restore vitality. For chronic disease ente-ring collaterals， it is advised to search and eliminate collateral pathogens in order to dissipate masses.

BACKGROUND:Coptis chinensis can clear heat,dry dampness,relieve fire,and detoxify.Coptis chinensis and its components have a significant protective effect on cerebral ischemia.The action mechanism of anti-cerebral ischemia of Coptidis Rhizoma Alkaloids was explored based on network pharmacology and transcriptome sequencing. OBJECTIVE:Based on the study of the protective effects of Coptidis Rhizoma Alkaloids on cerebral ischemia of rats,the action mechanism of Coptidis Rhizoma Alkaloids intervention in cerebral ischemia was investigated by using network pharmacology and transcriptome sequencing technology. METHODS:The SD rats were randomly divided into sham operation group,ischemia/reperfusion group,positive drug group,and Coptidis Rhizoma Alkaloids group.The ischemia/reperfusion model of middle cerebral artery occlusion was prepared by modified thread method in the latter three groups.No thread was inserted and the other operations were the same in the sham operation group.TTC staining,Longa 5 neurological deficient score,hematoxylin and eosin staining,and Nissl staining were used to evaluate the protective effect of Coptidis Rhizoma Alkaloids on ischemia/reperfusion model rats.Transcriptome sequencing was performed on the brain tissues of rats in sham operation group,ischemia/reperfusion group,and Coptidis Rhizoma Alkaloids group.Differentially expressed genes,gene Ontology analysis,Kyoto encyclopedia of genes and genomes analysis,and Correlation Analysis of Transcriptomics and Network Pharmacology were used to elucidate the effect of Coptidis Rhizoma Alkaloids on cerebral ischemia.Finally,ELISA and immunofluorescence staining were used to verify the key targets of Coptidis Rhizoma Alkaloids in the intervention of cerebral ischemia. RESULTS AND CONCLUSION:(1)Coptidis Rhizoma Alkaloids treatment decreased the Longa 5 neurological deficit scores and cerebral infarction area of ischemia/reperfusion model rats,increased the number of neurons and Nissl bodies.(2)Differentially expressed gene after Coptidis Rhizoma Alkaloids treatment analyzed by functional enrichment analysis of gene ontology includes biological processes such as inflammatory reaction and positive regulation of mitogen-activated protein kinase cascade.The enrichment analysis of Kyoto gene and genome encyclopedia analysis pathway mainly involves interleukin-17 signaling pathway,neuroactive ligand-receptor interaction,cyclic adenosine-3′,5′-mconophosphate signaling pathway and so on.(3)Analysis of transcriptomics showed that the main genes regulated by Coptidis Rhizoma Alkaloids were prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(4)Network pharmacology analysis revealed that nine components in Coptidis Rhizoma Alkaloids may exert their effects by associating with 87 targets related to prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(5)ELISA and immunofluorescence staining results further confirmed that Coptidis Rhizoma Alkaloids regulated the expression of prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(6)It is concluded that Coptidis Rhizoma Alkaloids treatment can significantly improve the injury in ischemia/reperfusion model rats,possibly by regulating prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.

Objective To analyze the epidemiological characteristics of acute respiratory infections(ARIs)during the autumn-winter season in Beijing,providing evidence for the prevention,control,diagnosis,and treatment of ARIs.Methods A convenience sampling method was employed,enrolling patients who visited Peking Union Medical College Hospital(PUMCH)between September 2023 and February 2024 due to ARIs.Na-sopharyngeal swabs were collected,and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus(FluA),influenza B virus(FluB),human rhinovirus(HRV),Myco-plasma pneumoniae(MP),respiratory syncytial virus(RSV),and adenovirus(ADV)],as well as SARS-CoV-2 infection.The distribution patterns of pathogen infections were analyzed.Results A total of 5556 eligible patients were included.The overall positivity rate for the six common respiratory pathogens was 63.7％,with sin-gle-pathogen positivity at 54.0％,dual-pathogen positivity at 8.9％,and triple or more pathogen positivity at 0.7％.The predominant pathogens detected were FluA(16.1％)and RSV(15.7％),followed by ADV(11.1％),MP(11.1％),HRV(10.0％),and FluB(10.0％).No significant difference in overall pathogen positivity was observed between genders.However,significant differences were found between autumn and winter(x2=34.617,P＜0.001)and among pediatric,young/middle-aged,and elderly patients(x2=422.38,P＜0.001).Specifically,MP(x2=8.647,P=0.003),FluA(x2=131.932,P＜0.001),and HRV(x2=174.199,P＜0.001)exhibited significantly higher positivity rates in autumn than in winter,whereas FluB was more prevalent in winter(x2=287.894,P＜0.001).In pediatric patients,MP,RSV,HRV,and ADV positivity rates were significantly higher than in young/middle-aged and elderly patients(all P＜0.001),whereas FluB was more common in young/middle-aged patients(both P＜0.001).The positivity rates of the six common respiratory pathogens significantly declined during the SARS-CoV-2 epidemic period,exhibiting an asynchronous seasonal pattern.Conclusions The prevalence of respiratory pathogens in Beijing is associated with age and season.Tar-geted preventive measures should be implemented in different seasons and for key populations.

OBJECTIVE: To assess the diagnostic value of whole exome sequencing (WES) for fetuses undergone induced abortion due to structural abnormalities. METHODS: A retrospective analysis was carried out on 43 aborted fetuses with negative results for copy number variation (CNV) testing from January 2023 to June 2024 at Northwest Women's and Children's Hospital. Trio-WES was carried out on the tissues from the aborted fetuses. This study has been approved by the Ethics Committee of the Hospital (Ethics No. 21-036). RESULTS: Among the 43 abortic fetuses, WES has detected pathogenic variants in 15 cases, with a total of 9 pathogenic variants, 5 suspected pathogenic variants, and 5 variants of uncertain significance. No definite pathogenic variants were detected in the remaining 28 cases. CONCLUSION For fetuses with structural abnormalities and negative results from CNV testing, WES can increase the diagnostic rate and facilitate etiological diagnosis and genetic counseling.
Humans ; Female ; Exome Sequencing/methods* ; Pregnancy ; DNA Copy Number Variations/genetics* ; Retrospective Studies ; Adult ; Prenatal Diagnosis/methods* ; Abortion, Induced ; Fetus/abnormalities* ; Congenital Abnormalities/diagnosis* ; Genetic Testing ; Aborted Fetus/abnormalities*

With the rapid advancements in pancreatic cancer diagnosis and treatment research,the Chinese Society of Clinical Oncology(CSCO)has released two editions of pancreatic cancer diagnosis and treatment guidelines in 2022 and 2024.The present article systematic-ally compares the differences between the two editions in terms of diagnostic stratification,treatment pathways,and supportive manage-ment.By integrating insights from cutting-edge international research,the scientific rationale and clinical value of the underlying guideline revisions are explored.Clinicians are encouraged to adopt the new guidelines to dynamically assess the biological characteristics and treat-ment tolerance of patients,thereby formulating personalized diagnosis and treatment plans that ultimately lead to the synergistic enhance-ment of both survival benefits and quality of life for patients.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To evaluate the clinical efficacy of left ventricular assist device(LVAD) in the treatment of end-stage heart failure.Methods:This is a retrospective case series study. Data were retrospectively analyzed from 48 patients treated at eight domestic cardiac surgery centers in China between March 2022 and September 2024, who underwent LVAD implantation due to end-stage heart failure. All surgeries were led by the cardiovascular surgery team from Nanjing First Hospital. The study included 42 male and 6 female patients, aged (59.1±12.3) years (range:28 to 73 years). All patients had a preoperative New York Heart Association(NYHA) functional class of Ⅳ. General preoperative data, intraoperative extracorporeal circulation time, cross-clamp time, postoperative ICU stay, hospital stay, pump parameters at discharge, intraoperative and postoperative left ventricular end-diastolic diameter, left ventricular ejection fraction, and follow-up results post-discharge were collected. The generalized estimation equation was used to compare the difference of cardiac function indexes in patients with different follow-up time points. The Tukey′s Honestly Significant Difference test was used for pairwise comparison within the group.Results:The surgery was successfully completed for 47 patients, and 1 perioperative death. The extracorporeal circulation time was (122.4±21.6) minutes (range: 101 to 200 minutes), the cross-clamp time was (70.1±18.3) minutes (range: 101 to 200 minutes), the postoperative ICU length of stay was (6.9±3.2) days (range: 2 to 23 days), and the hospital length of stay was (28.1±4.2) days (range: 23 to 42 days). At discharge, the blood bump flow rate was (3.4±0.6) L/min(range: 3.1 to 3.6 L/min), and speed was (2 791.3±142.0) r/min(range: 2 680 to 3 250 r/min). The follow-up period was (12.2±0.78) months (range:2 to 24 months) of 47 patients. One case underwent heart transplantation during the follow-up period, and 3 cases died, with no major device malfunction events. Three months post-surgery, the patients showed a significant reduction in left ventricular end-diastolic diameter compared to pre-surgery ((69.1±8.3) mm vs. (77.3±8.3) mm, q=6.73, P<0.01); the left ventricular ejection fraction significantly increased ((29.6±8.0)% vs. (23.2±5.8)%, q=6.49, P<0.01); and the 6-minute walk distance significantly improved ((382.0±12.8)metres vs. (114.8±18.4)metres, q=116.56, P<0.01). Six months postoperatively, all patients′ cardiac function had recovered to NYHA class Ⅰor Ⅱ. Conclusions:Preliminary research findings indicate that left ventricular assist device therapy yields favorable outcomes in the treatment of end-stage heart failure. serving as a bridge to transplantation, recovery, or a destination therapy.