ObjectiveTo investigate the protective effect of artemitin against ozone (O₃)-induced pulmonary inflammation in mice and to explore its underlying mechanism. MethodsThirty-two specific pathogen-free (SPF) male C57BL/6 mice were randomly divided into a blank control group, an artemitin-only control group, an O₃-induced model group, and an artemitin-treated group, with 8 mice in each group. In the artemitin-treated group, animals were injected intraperitoneally with artemitin (20 mg/kg) daily, followed by a 1 h exposure to 0.000 25% O₃. The artemitin-only control group received the same artemitin injection but was exposed to clean air. The O₃-induced model group was injected intraperitoneally with an equal volume of normal saline daily, followed by a 1-h exposure to 0.000 25% O₃. The blank control group received the saline injection and was exposed to clean air. All treatments were administered for 7 consecutive days. Pulmonary function indices of the mice in each group were measured using a whole-body plethysmography system. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in the lung tissue, and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for untargeted metabolomic analysis to examine the changes in overall metabolic pathways in plasma. ResultsCompared with the O₃-induced model group, artemitin treatment significantly improved O₃-induced lung function impairments (P<0.05), lowered the levels of TNF-α and IL-1β in BALF (P<0.05) and alleviated inflammatory cell infiltration and structural damage in lung tissues. Metabolomics results indicated that artemitin treatment compensatorily enhanced energy supply and oxidized lipid signaling, while inhibiting purine metabolism and tryptophan-derived pathways. ConclusionArtemitin exhibits a significant protective effect against O₃-induced pulmonary inflammation in mice. It corrects upstream metabolic disorders by synergistically modulating tryptophan metabolism, energy metabolism, and lipid inflammatory mediators, thereby inhibiting downstream inflammatory responses and airway hyperresponsiveness. This study not only reveals the pleiotropic mechanism of artemitin in treating airway inflammation but also provides potential metabolic biomarkers and a theoretical basis for its clinical translation.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective:To investigate the clinical characteristics and aeromedical assessment conclusions of bronchial asthma in military pilots.Methods:The clinical data of 24 military pilots was retrospectively analyzed who were diagnosed with bronchial asthma and hospitalized at the Air Force Medical Center between January 2010 and March 2024. These pilots were divided into a qualified group and a grounded group based on aeromedical assessment conclusions. The basic information, clinical data, diagnosis and treatment, and aeromedical assessment conclusions were compared between the 2 groups.Results:There were 11 military pilots in the qualified group and 13 in the grounded group. No statistically significant differences were observed between the 2 groups in terms of age at initial asthma diagnosis, body mass index, flying hours, aircraft types, smoking status, or family history of bronchial asthma (all P>0.05). The time intervals between the symptom onset, initial diagnosis and treatment and ground observation were shorter in the qualified group than in the grounded group, with statistically significant differences ( Z=-1.77, -2.73, P=0.047, 0.006). No statistically significant differences were found between the 2 groups in terms of cough variant asthma, concurrent allergic rhinitis, eosinophil count and percentage, and abnormal pulmonary function (all P>0.05). The proportion of military pilots with identified allergens was significantly higher in the grounded group than in the qualified group ( P=0.005). In the qualified group, one fighter pilot was aeromedically assessed as being restricted to dual-seat fighter aircraft. After 3 months of ground observation without disease recurrence, the dual-seat restriction was lifted. The other 2 fighter pilots were qualified for downgraded aircraft types (from fighters to bombers, transporters, or helicopters). Eight non-fighter pilots were aeromedically concluded as eligible for flight. After [43.0(15.8, 66.3)] months of treatment and ground observation, the 13 military pilots in the grounded group were found to be under poor symptom control with recurrent episodes before being grounded. Conclusions:Bronchial asthma in military pilots is closely related to allergic rhinitis, with early clinical symptoms often being atypical and prone to delayed diagnosis and treatment. Patients with bronchial asthma should receive individualized treatment based on their condition. Both the US military and the Chinese military stipulate that pilots with bronchial asthma be ineligible for flight. However, for cases with mild illness, no sudden acute severe attacks, symptom resolution after treatment, normal pulmonary function, and in stable condition after 3-6 months of ground observation, an aeromedical assessment can be conducted based on the aircraft types and flight duties.

Objective To explore the effect of Yinchenhao Decoction plus Zexie Decoction on ferroptosis mediated by IRE1 signaling pathway of endoplasmic reticulum stress in NASH mice.Methods Fifty C57BL/6J mice were randomly divided into blank control group,model group,Yinchenhao decoction group,Zexia decoction group and Hefang group,with 10 mice in each group.Except the blank control group,the other groups were fed with high-fat diet.After 20 weeks,Yinchenhao Tang group,Zexia Tang group and Hefang group were respectively given the corresponding drug by intragastric administration,once a day for 8 weeks.HE staining,oil red O staining and Masson staining were used to observe the pathological changes of liver tissue,automatic biochemical analyzer was used to detect blood lipid and liver function indexes,and RT-qPCR was used to detect the mRNA levels of TFR1,FPN,XBP1,Xbp1s and XBP1-dependent UPR target genes.The expressions of GRP78,P-IRE1α,GPX4,TFR1 and FPN proteins in liver were detected by Western Blot,the contents of Fe2+and MDA were detected by colorimetry,SOD activity was detected by WST-8,ROS content was detected by ELISA,and TG content in mouse liver tissue was detected by GPO-PAP.Results Compared with the model group,the NAS scores of Yinchenhao Tang group,Zexia Tang group and Hefang group were significantly reduced,and the effect of Hefang group was more significant.Compared with the blank control group,the liver lipid deposition of model mice was obvious,and the liver lipid deposition of Yinchenhao Tang group,Zexia group and Hefang group were improved to varying degrees,and the effect of Hefang group was more significant.Masson staining results showed that compared with blank control group,liver fibrosis was obvious in model group,Yinchenhao Decoction group,Zexia group and Hefang group,the degree of liver fibrosis was improved,and the effect of Hefang group was more significant.Compared with the blank control group,the levels of serum TC,HDL-C,LDL-C,AST and ALT in the model group were significantly increased,the contents of TG,Fe2+,MDA and ROS in the liver were significantly increased,and the activity of SOD was significantly decreased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Chop and TFR1were significantly up-regulated,the mrna expression levels of FPN were significantly down-regulated,and the protein expression levels of GRP78,P-IREα,GPX4 and TFR1 in liver were significantly increased.The expression level of FPN protein decreased significantly.Compared with model group,the serum levels of TG,TC,LDL-C,AST and ALT in the combined formula group were significantly decreased,the contents of TG,Fe2+,MDA and ROS in the liver of the combined formula group were significantly decreased,and the activity of SOD was significantly increased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Cho and TFR1 in liver were significantly decreased,the mrna expression level of FPN was significantly increased,and the protein expression levels of GRP78,P-IRE1α,GPX4 and TFR1 in liver were significantly down-regulated.The expression level of FPN protein was significantly up-regulated.Conclusion Yinchenhao Decoction plus Zexie Decoction may ameliorate NASH by inhibiting ferroptosis of hepatocytes through IRE1α pathway of endoplasmic reticulum stress.

Objective:To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2.Methods:Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines.Results:For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity ( t=10.18-16.67, P<0.05), reduced the apoptotic rate ( t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G 2 phase at the same time points ( t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation ( t=2.57-9.39, P<0.05), increased the apoptotic rate ( t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G 2 phase ( t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions:Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways.

Objective:To investigate the clinical characteristics and aeromedical assessment conclusions of bronchial asthma in military pilots.Methods:The clinical data of 24 military pilots was retrospectively analyzed who were diagnosed with bronchial asthma and hospitalized at the Air Force Medical Center between January 2010 and March 2024. These pilots were divided into a qualified group and a grounded group based on aeromedical assessment conclusions. The basic information, clinical data, diagnosis and treatment, and aeromedical assessment conclusions were compared between the 2 groups.Results:There were 11 military pilots in the qualified group and 13 in the grounded group. No statistically significant differences were observed between the 2 groups in terms of age at initial asthma diagnosis, body mass index, flying hours, aircraft types, smoking status, or family history of bronchial asthma (all P>0.05). The time intervals between the symptom onset, initial diagnosis and treatment and ground observation were shorter in the qualified group than in the grounded group, with statistically significant differences ( Z=-1.77, -2.73, P=0.047, 0.006). No statistically significant differences were found between the 2 groups in terms of cough variant asthma, concurrent allergic rhinitis, eosinophil count and percentage, and abnormal pulmonary function (all P>0.05). The proportion of military pilots with identified allergens was significantly higher in the grounded group than in the qualified group ( P=0.005). In the qualified group, one fighter pilot was aeromedically assessed as being restricted to dual-seat fighter aircraft. After 3 months of ground observation without disease recurrence, the dual-seat restriction was lifted. The other 2 fighter pilots were qualified for downgraded aircraft types (from fighters to bombers, transporters, or helicopters). Eight non-fighter pilots were aeromedically concluded as eligible for flight. After [43.0(15.8, 66.3)] months of treatment and ground observation, the 13 military pilots in the grounded group were found to be under poor symptom control with recurrent episodes before being grounded. Conclusions:Bronchial asthma in military pilots is closely related to allergic rhinitis, with early clinical symptoms often being atypical and prone to delayed diagnosis and treatment. Patients with bronchial asthma should receive individualized treatment based on their condition. Both the US military and the Chinese military stipulate that pilots with bronchial asthma be ineligible for flight. However, for cases with mild illness, no sudden acute severe attacks, symptom resolution after treatment, normal pulmonary function, and in stable condition after 3-6 months of ground observation, an aeromedical assessment can be conducted based on the aircraft types and flight duties.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective:To analyze the epidemiological features of pediatric sepsis in the Kashgar region and investigate factors associated with its prognosis, thereby providing evidence for implementing regional public health prevention and control policies.Methods:A single-center, retrospective observational study was conducted on the clinical data of pediatric sepsis patients admitted to the pediatric intensive care unit (PICU) of The First People′s Hospital of Kashgar between January 2022 and December 2023. For the assessment of clinical outcomes, this study utilized a composite endpoint comprising "length of hospital stay and survival status", classifying patients into two groups: Group A (survived with hospital stay <28 days) and Group B (hospital stay ≥28 days or in-hospital mortality). Univariate and binary logistic regression analyses were performed to identify independent risk factors associated with prognosis.Results:This study included a total of 79 pediatric patients with sepsis, with an age range of 1 month to 14 years and a median age of 8 months. Males accounted for 62.0% (49 males, 30 females). The rates of comorbid septic shock, sepsis-associated encephalopathy, and acute kidney injury were 73.4% (58/79), 24.1% (19/79), and 16.5% (13/79), respectively. The primary site of infection was the gastrointestinal tract, accounting for 34.2% (27/79), followed by the respiratory tract at 30.4% (24/79). Pathogens were detected in 59.5% (47/79) of the patients, with Staphylococcus aureus identified in 11 cases, Acinetobacter baumannii and Escherichia coli in 6 cases each, Klebsiella pneumoniae in 5 cases, and Candida albicans in 3 cases. The mechanical ventilation rate was 59.5% (47/79). The total hospital length of stay ranged from 1 to 55 days, with a median of 14 days, while the ICU length of stay ranged from 1 to 29 days, with a median of 6 days. In-hospital mortality occurred in 15 cases (19.0%). Group A comprised 56 patients (70.9%), and Group B comprised 23 patients (29.1%). Univariate analysis revealed that Group A had significantly higher mean arterial pressure (MAP), pediatric critical illness score (PCIS), and Glasgow coma scale (GCS) (all P<0.05), and significantly lower pediatric risk of mortality Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 (PELOD-2), lactate levels, pediatric multiple organ dysfunction score (P-MODS), pediatric sequential organ failure assessment (pSOFA), septic shock rate, and mechanical ventilation rate compared to Group B (all P<0.05). Binary logistic regression analysis identified a high PELOD-2 score ( OR: 1.38, 95% CI: 1.16-1.64, P<0.001) as an independent risk factor for poor prognosis, while a high GCS ( OR: 0.81, 95% CI: 0.74-0.88, P<0.001) served as a protective factor against poor prognosis. The combination of PELOD2 and GCS demonstrated good predictive ability for in-hospital outcomes in pediatric sepsis patients, with an area under the ROC curve of 0.82 (95% CI: 0.72-0.92). Conclusion:In children with sepsis in the Kashgar region, gastrointestinal tract infection represents the most common source of infection. Elevated PELOD-2 scores and reduced GCS are both indicative of a poorer prognosis, and a combined model integrating these two scoring systems may serve as a valuable tool for prognostic assessment.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective To explore the effect of Yinchenhao Decoction plus Zexie Decoction on ferroptosis mediated by IRE1 signaling pathway of endoplasmic reticulum stress in NASH mice.Methods Fifty C57BL/6J mice were randomly divided into blank control group,model group,Yinchenhao decoction group,Zexia decoction group and Hefang group,with 10 mice in each group.Except the blank control group,the other groups were fed with high-fat diet.After 20 weeks,Yinchenhao Tang group,Zexia Tang group and Hefang group were respectively given the corresponding drug by intragastric administration,once a day for 8 weeks.HE staining,oil red O staining and Masson staining were used to observe the pathological changes of liver tissue,automatic biochemical analyzer was used to detect blood lipid and liver function indexes,and RT-qPCR was used to detect the mRNA levels of TFR1,FPN,XBP1,Xbp1s and XBP1-dependent UPR target genes.The expressions of GRP78,P-IRE1α,GPX4,TFR1 and FPN proteins in liver were detected by Western Blot,the contents of Fe2+and MDA were detected by colorimetry,SOD activity was detected by WST-8,ROS content was detected by ELISA,and TG content in mouse liver tissue was detected by GPO-PAP.Results Compared with the model group,the NAS scores of Yinchenhao Tang group,Zexia Tang group and Hefang group were significantly reduced,and the effect of Hefang group was more significant.Compared with the blank control group,the liver lipid deposition of model mice was obvious,and the liver lipid deposition of Yinchenhao Tang group,Zexia group and Hefang group were improved to varying degrees,and the effect of Hefang group was more significant.Masson staining results showed that compared with blank control group,liver fibrosis was obvious in model group,Yinchenhao Decoction group,Zexia group and Hefang group,the degree of liver fibrosis was improved,and the effect of Hefang group was more significant.Compared with the blank control group,the levels of serum TC,HDL-C,LDL-C,AST and ALT in the model group were significantly increased,the contents of TG,Fe2+,MDA and ROS in the liver were significantly increased,and the activity of SOD was significantly decreased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Chop and TFR1were significantly up-regulated,the mrna expression levels of FPN were significantly down-regulated,and the protein expression levels of GRP78,P-IREα,GPX4 and TFR1 in liver were significantly increased.The expression level of FPN protein decreased significantly.Compared with model group,the serum levels of TG,TC,LDL-C,AST and ALT in the combined formula group were significantly decreased,the contents of TG,Fe2+,MDA and ROS in the liver of the combined formula group were significantly decreased,and the activity of SOD was significantly increased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Cho and TFR1 in liver were significantly decreased,the mrna expression level of FPN was significantly increased,and the protein expression levels of GRP78,P-IRE1α,GPX4 and TFR1 in liver were significantly down-regulated.The expression level of FPN protein was significantly up-regulated.Conclusion Yinchenhao Decoction plus Zexie Decoction may ameliorate NASH by inhibiting ferroptosis of hepatocytes through IRE1α pathway of endoplasmic reticulum stress.