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 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 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.

BACKGROUND:Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis. OBJECTIVE:To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair. METHODS:Databases such as CNKI and PubMed were searched.The English key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,electrostatic interaction,covalent crosslinking",and the Chinese key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,physical encapsulation,electrostatic effect,covalent cross-linking".After an initial screening of all articles based on inclusion and exclusion criteria,71 articles with high correlation were retained for review. RESULTS AND CONCLUSION:In cell or animal experiments,nanocomposite hydrogel has the effect of improving osteoarthritis.Nanocomposite hydrogel can promote cartilage repair,improve the internal environment of osteoarthritis,and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints,carrying targeted drugs,and promoting the chondrogenesis of seed cells.At present,the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play.It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments.

Objective To explore the molecular mechanism of Gasdermin B(GSDMB)regulating the fate of intestinal epithelial cells.Methods The human GSDMB plasmid was overexpressed into two human intestinal epithelial cell lines(NCM460 and HT-29 cells)and human colon-derived organoids.Western blotting was used to confirm the efficiency of electroporation.Cell counting kit(CCK8),cell apoptosis,and cell cycle by flow cytometry were performed to analyze the effect of GSDMB overexpression on cell function.Transcriptome sequencing was used to analyze the downstream effector molecules of GSDMB.T test was used to compare the data between the two groups.Results The overexpression of GSDMB protein in the two intestinal epithelial cell lines was successfully reconstructed.The absorbance value(A)of human intestinal epithelial cells overexpressing GSDMB protein[NCM460 cells:(1.17±0.01),HT-29 cells:(0.96±0.06)]was significantly lower than that of blank control cells[NCM460 cells:(1.67±0.12),HT-29 cells:(1.24±0.07)](t=7.24 and 5.46,P＜0.05).The number of apoptotic cells in the GSDMB overexpression group[NCM460 cells:(12.03±1.55),HT-29 cells:(29.30±4.48)]was significantly higher than that in the blank group[NCM460 cells:(4.96±1.74),HT-29 cells:(6.95±3.42)](t=5.26 and 6.97,P＜0.05).Cell cycle analysis showed that the ratio of cells at G0/G1 phase in the GSDMB overexpression group[NCM460 cells:(47.98±5.28)％,HT-29 cells:(38.04±3.45)％]was significantly lower than that in the control group[NCM460 cells:(59.54±3.90)％,HT-29 cells:(63.81±1.76)％](t=3.05 and 11.53,P＜0.05).Transcriptome sequencing results showed that the dual specificity phosphatase 4 and 6(DUSP4 and DUSP6)genes were significantly upregulated after GSDMB protein expression.Fluorescence quantitative PCR results confirmed that the relative expression levels of DUSP4(2.45±0.15)and DUSP6(4.34±0.22)in intestinal epithelial cells transfected with GSDMB were significantly higher than those in the control group(1.06±0.05 and 1.01±0.02)(t=15.08 and 26.52,P＜0.05).After GSDMB-expressing NCM460 cells were treated with the DUSP inhibitor BCI,the BCI treatment group had a significantly increased expression level of p-ERK compared to the control group[(1.14±0.17)vs.(0.58±0.12)](t=5.42,P=0.002);the A value(1.84±0.07)and G0/G1 phase ratio(59.83±2.17)％in the BCI treatment group were significantly higher than those in the non-treatment group[(1.52±0.10)and(52.10±2.23)％],and the number of apoptosis in the BCI treated group(7.60±0.56)was significantly lower than that in the untreated group(12.57±1.00)(t=4.71,4.31,7.52,P＜0.05).TUNEL staining in human colon organoids showed a significant increase in apoptotic cells,and the relative expression level of DUSP6 protein(0.85±0.09)was significantly higher than that of the control group(0.21±0.04),accompanied by a decrease in p-ERK levels[(0.83±0.18)vs.(0.19±0.06)],with statistical significance(t=11.95,P＜0.001;t=6.56,P＜0.001).Conclusion GSDMB may inhibit cell proliferation,induce cell cycle arrest,and promote apoptosis by upregulating dual specificity phosphatase DUSP6-mediated ERK phosphorylation,thus affecting the fate of intestinal epithelial cells.

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 investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.