Objective To explore the promoting effect of long-term administration of nicotiflorin on the recovery of neurological function in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods The CIRI model was established and nicotiflorin was injected intraperitoneally after 1 hour of obstruction for 8 weeks. Tail suspension deflection experiment, balance beam experiment and water maze test were performed in the 2nd, 4th and 8th weeks. After 8 weeks, TTC staining was used to observe the volume of infarct atrophy, transcriptome sequencing was employed to screen differential expressed genes （DEGs） and highly enriched pathways were analyzed, Western-bloting and Elisa were used to assess proteins expression related to the pyroptosis pathway and inflammatory cytokines IL-1β and IL-18. Results By long-term administration of nicotiflorin, the contralateral deflection rate was significantly reduced and beam experiment score of CIRI rats was balanced, the number of crossing the platform in water maze test was increased （P<0.05）, the volume of cerebral infarction atrophy was decreased （P<0.01）, which significantly promoted the recovery of neurological function in rats. Transcriptome sequencing found that the expression of genes in the pyroptosis-related signaling pathways in the brain tissue of rats in the nicotiflorin group was significantly down-regulated （P<0.05）. Western-blot and Elisa experiments showed that nicotiflorin reduced the expression levels of Caspase-1 and GSDMD-N and other pyroptosis-related proteins, and at the same time, the release of inflammatory factors IL-1β and IL-18 was significantly reduced （P<0.05）, indicating that nicotiflorin could inhibit the inflammatory process of pyroptosis. Conclusion Nicotiflorin exhibited a significant long-term promotion effect on the recovery of neurological function in CIRI rats, which potentially attributed from its ability to inhibit pyroptosis.

Objective To develop and validate a model to predict the risk of radiation-induced lung injury (RILI) and assess its clinical feasibility. Methods Clinical data from 125 patients with non-small cell lung cancer (NSCLC) were included in the study. The patients were divided into training group (88 cases) and validation group (38 cases). Key predictive factors were identified using univariate and multivariate logistic regression analyses combined with least absolute shrinkage and selection operator (LASSO) regression. A predictive model was constructed and evaluated using a nomogram, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results The key variables identified by the model were tumor volume (P = 0.017), Eastern Cooperative Oncology Group performance status score (P = 0.035), 95% of the minimum dose to the target volume (P = 0.028), percentage of bilateral lung volume receiving 20 Gy of radiation (P < 0.001), and neutrophil-to-lymphocyte ratio (P = 0.021). The ROC curve showed that the areas under the curve (AUC) for the model in the training and validation groups were 0.987 and 0.992, respectively, indicating good predictive ability. The calibration curve and decision curve further confirmed the accuracy and clinical practicability of the model. Conclusion The predictive model proposed in this study can accurately assess the risk of developing RILI in patients with NSCLC who have undergone radiotherapy, demonstrating its potential value in clinical practice.

OBJECTIVE To prepare nanoparticle-based targeting preparation loaded with triptolide （TP）， and evaluate its quality， targeting ability and cytotoxic effects. METHODS Polymer nanoparticles carrying TP-targeted folic acid （FA） receptor （TP@PLGA-PEG-FA） were fabricated using poly （lactic-co-glycolic acid）/polyethylene glycol/FA （PLGA-PEG-FA） as the carrier by emulsion and volatilization technique. The morphology and distribution were observed， and their particle size， Zeta potential， polydispersity index （PDI）， drug loading capacity and encapsulation efficiency were measured. Their stability， blood compatibility， in vitro drug release， uptake by RAW264.7 cells （localization with fluorescent dye Cy3.5）， and in vitro cytotoxicity were evaluated. RESULTS TP@PLGA-PEG-FA exhibited spherical shape and uniform distribution， with particle size of （122.60±0.02） nm， Zeta potential of （－17.6±0.6）mV， and PDI of 0.26±0.02； drug loading capacity and encapsulation efficiency of TP were measured to be （7.78±0.05）% and （68.62±0.03）%， respectively. The hemolysis rates of 100， 200， 300， 400 µg/mL TP@PLGA- PEG-FA were 0.77%， 0.92%， 1.34% and 1.63%， respectively. There were no significant changes in particle size， PDI and Zeta potential when TP@PLGA-PEG-FA were placed in 4 ℃ water for 14 days and in DMEM culture medium containing 10% fetal bovine serum at 37 ℃ for 12 h. The cumulative release rate of TP@PLGA-PEG-FA was （84.83±0.29）% in phosphate buffer at pH5.5 for 72 h， which was significantly higher than the cumulative release rates in phosphate buffer solutions at pH7.4 and 6.5 for 72 h （[ 42.37±0.35）% and （63.83±0.29）% ， respectively] （P＜0.05）. Activated RAW264.7 cells took up significantly more Cy3.5@PLGA-PEG-FA than they took up Cy3.5@PLGA-PEG-FA+free FA and Cy3.5@PLGA-PEG. When the mass concentration of TP was≥15.63 ng/mL， the survival rates of activated cells in the TP@PLGA-PEG-FA groups were significantly lower than those of the same mass concentration of free TP groups （P＜0.05）. CONCLUSIONS The prepared TP@PLGA-PEG-FA has high stability， good blood compatibility， active targeting and cytotoxicity to inflammatory cells.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

OBJECTIVE Aimed to investigate the impact of comorbid asthma on chronic rhinosinusitis with nasal polyps(CRSwNP)and identify key proteins and signaling pathways.METHODS Proteomic methods were employed to analyze differentially expressed proteins(DEPs)in nasal lavage fluid(NLF)from control,CRSwNP,and CRSwNP with asthma groups.DIA quantitative analysis technology was used to assess the gradient changes of DEPs among the three groups to determine key proteins affected by comorbid asthma in CRSwNP.RESULTS Compared to the control group,1 377 and 1 006 DEPs were identified in the CRSwNP and CRSwNP with asthma groups,respectively.Peroxiredoxin-5(PRDX5),Ran-Binding Protein 1(RanBP1)(upregulated),and Keratin 9(KRT9)(downregulated)were identified as key proteins affecting CRSwNP with asthma.CONCLUSION Comorbid asthma may promote the occurrence and development of nasal polyps through specific key proteins and signaling pathways,providing new molecular insights into the interaction between CRSwNP and asthma.

This article summarizes Professor Shang Lili's experience in diagnosing and treating recurrent respiratory tract infections(RRTIs)in children based on the theory of"internal deficiency and external injury".Professor Shang believes that children are in the stage of growth and development,with delicate organs and insufficient vital energy,which is called"internal deficiency";external pathogens repeatedly invade the human body,resulting in clinical manifestations of both cold and heat,ultimately damaging the body's qi,blood,essence,and spirit,known as"external injury"."Internal deficiency and external injury"leads to repeated infections of pathogens in children and causes physical and mental distress,affecting their growth and development.The theory of"internal deficien-cy and external injury"emphasizes the influence of internal and external factors on RRTIs in children,reflecting the evolution of patho-genesis and guiding clinical staging treatment.During the acute infection period,the treatment of wind heat syndrome is based on the Xin Liang and Qing San methods,while the treatment of wind cold syndrome is based on the Xin Wen and Kai Bi methods.For the mixed deficiency and excess syndrome,various methods such as attacking,supplementing,harmonizing,and supporting should be used,and treatment should be based on syndrome differentiation,with adjustments made according to the symptoms;during the inter-mittent period of infection,Professor Shang aims to assist the righteous qi,taking into account the upper,middle,and lower Jiao,and adopting treatment principles such as nourishing the lungs,spleen,and kidneys.Professor Shang's experience provides useful ideas and methods for the treatment of RRTIs in children.

Objective To explore the relationships between headache and pulmonary function,chronic lung disease(CLD)in middle-aged and elderly people in China.Methods This cross-sectional study collected data from participants aged 45 and above in the 2015 China Health and Retirement Longitudinal Study(CHARLS).Headache was diagnosed based on self-report,and CLD and asthma were defined by self-reported doctor diagnoses or a combination of health assessments and medication use.Peak expiratory flow(PEF)was used as an indicator of pulmonary function.Multivariable logistic regression model was used to analyze the correlations between PEF,asthma,CLD,and headache.Relationship between PEF and headache was analyzed by restricted cubic spline(RCS)analysis and subgroup analysis.Results Among 12 661 middle-aged and elderly participants,the prevalence of headache was 14.42%(1 826/12 661),with a prevalence of 9.07%(558/6 151)in males and 19.48%(1 268/6 510)in females.After full adjustment for covariates,each 1 L/s increase in PEF was associated with a 7%reduction in the risk of headache(odds ratio[OR]=0.93,95%confidence interval[CI]0.90-0.96,P＜0.001).Categorizing PEF into quartiles(Q1-Q4),as the increase of PEF,the risk of headache significantly decreased(ORs for Q2,Q3,and Q4 were 0.92,0.82,and 0.72,respectively,Ptrend＜0.001).Additionally,asthma(OR=1.78,95%CI 1.43-2.20,P＜0.001)and CLD(OR=2.21,95%CI 1.92-2.53,P＜0.001)were positively associated with the risk of headache.RCS analysis indicated a negative linear correlation between PEF and the risk of headache(Poverall＜0.001,Pnon-linear=0.57).Subgroup analysis revealed that a history of hypertension had a significant impact on the negative association between PEF and headache(Pinteraction＜0.001).Conclusion There is a significant negative correlation between PEF and headache among middle-aged and elderly people in China,while asthma and CLD are positively associated with headache.Improving lung function in middle-aged and elderly populations may be an effective strategy for preventing or alleviating headache.

Red blood cells(RBCs)are the primary mediators of oxygen transport in the human body,and their function is mainly achieved through conformational changes of hemoglobin(Hb).Hb is a tetramer composed of four subunits,with HbA being the predominant Hb in healthy adults,existing in two forms:tense state(T state)and relaxed state(R state).Endogenous regulators of Hb conformation include 2,3-diphosphoglyceric acid,carbon dioxide,protons,and chloride ions,while exogenous regulators include inositol hexaphosphate,inositol tripyrophosphate,benzabate,urea derivative L35,and vanillin,each with different mechanisms of action.The application of Hb conformational regulators provides new insights into the study of hypoxia oxygen supply issues and the treatment of sickle cell disease.

Dura mater is a tough collagen connective tissue attached to inner surface of skull and wrapped around brain.As a buffer bridge between brain tissue and skull,its physiological function and role in skull development and repair have always been a focus of research.Recent studies have found that dura mater not only directly participates in skull development during skull growth,but also secretes a variety of cytokines that control the development of central nervous system.There are abundant material exchange and cell communication between the two.This article reviews the role of dura in development and repair of skull,and provides clues for further discovery of the relevant mechanisms of dura in development and repair of skull.

Objective:To conduct a systematic evaluation of prognostic factors for retreatment of esophageal cancer patients with locoregional recurrence after radical chemoradiotherapy, and provide a clinical reference for selecting individualized retreatment schemes and improving their survival.Methods:A retrospective analysis was performed on the clinical data of 85 patients with esophageal cancer who experienced locoregional recurrence at least 1 year after radical radiotherapy or chemotherapy at the Department of Radiation Oncology in the Fourth Hospital of Hebei Medical University from January 2008 to December 2017. The effects of different nutritional and immune status and retreatment schemes on survival were compared, and the prognostic factors for retreatment were subjected to comprehensive subgroup analysis.Results:As of December 2021, the follow-up rate for all patients was 93%. The 1-, 2-, 3-, and 5-year overall survival rates of all patients after retreatment were 31.5%, 18.6%, 10.6%, and 6.6%, respectively. For patients who received radiotherapy or chemoradiotherapy, the 1-, 2-, 3-, and 5-year overall survival rates were 36.8%, 22.3%, 13.0% and 9.3%, respectively. Multivariable analysis showed that the time interval between the first treatment and recurrence, the retreatment schemes after recurrence, the level of serum albumin before retreatment, and the prognostic nutritional index before retreatment were independent prognostic factors for survival after retreatment ( P<0.05). Subgroup analysis was performed on the combinations of peripheral blood hemoglobin level, albumin level, and prognostic nutritional index before retreatment, as well as systemic immune inflammation index and short-term curative effect after retreatment. The results showed that the comprehensive analysis of blood routine and serum albumin indicators could accurately predict the survival after retreatment. Conclusions:The nutritional and immune status of patients with locoregional recurrence of esophageal cancer after chemoradiotherapy can be used to predict the prognosis of retreatment. The time interval between the first treatment and recurrence and the retreatment scheme significantly affect the survival after retreatment. The retreatment scheme should be rigorously evaluated and appropriately selected to improve the benefit-risk ratio.