Objective:To conduct a comparative analysis of the oxygen depletion and oxygen effect of FLASH irradiation and conventional irradiation by direct measurement of oxygen content.Methods:The oxygen content in different tissues and organs of mice was measured using a phosphorescent probe. A subcutaneous xenograft tumor model in mice was established, to receive electron-beam irradiation at different doses and dose rates. The oxygen depletion of tumor and normal tissue was analyzed, and tumor control was evaluated. The oxygen depletion of conventional irradiation and FLASH irradiation was further analyzed using an in vitro model. The survival fraction (SF) of normal cells after conventional irradiation and FLASH irradiation was calculated using colony formation assay under different partial pressures of oxygen, and the data were fitted to the oxygen enhancement ratio (OER) curve. Results:The mean oxygen content of subcutaneous xenograft tumor in mice was 1.28%, suggesting hypoxia. The mean oxygen content of normal tissue ranged from 3.51% to 6.53%, suggesting physioxia. In animal experiments, oxygen depletion was not observed during conventional irradiation. High-dose-rate (20 Gy/s) and ultra-high-dose-rate (FLASH, 40 Gy/s) irradiation produced oxygen depletion. During FLASH irradiation, with the increase of oxygen content, the oxygen depletion was 0.1-0.2 mm Hg/Gy for tumor tissue and 0.19-0.21 mm Hg/Gy for skin tissue, which tended to stabilize. FLASH irradiation maintained equivalent tumor control compared to conventional irradiation. The tumoricidal effect was significantly enhanced with the increase of oxygen content in the tissue ( t=3.46, P<0.01). In in vitro experiments, the mean oxygen depletion rate was about 0.16 mm Hg/Gy for conventional irradiation and 0.16-0.18 mm Hg/Gy for FLASH irradiation, which did not change significantly with the increase of oxygen content. FLASH irradiation was associated with an oxygen effect. When the partial pressure of oxygen decreased from physioxia to hypoxia, the OER value significantly reduced. Conclusions:Normal tissues and organs are in physioxia, which exhibits a lower oxygen content than that in the air. FLASH irradiation can consume a proportion of oxygen, producing an oxygen effect. When oxygen content decreases, the oxygen depletion rate slows down after FLASH irradiation.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

With the development of manned space technology,long-term space missions have gradually become a reality,but the problem of sleep disorders faced by astronauts has become increasingly prominent.The combined effects of microgravity,abnormal circadian rhythm,confined space pressure and psychological stress in space environment lead to the significant decline of sleep quality of astronauts,which is manifested as difficulty falling asleep,sleep fragmentation and reduction of deep sleep.Based on the theory of traditional Chinese medicine,this paper systematically analyzes the etiology and pathogenesis of astronaut sleep disorders,and reveals the unique advantages of transcutaneous electrical acupoint stimulation in space medicine,which provides a new idea for the construction of non-pharmacological sleep intervention system.Although there are technical difficulties,non-pharmacological therapy such as transcutaneous electrical acupoint stimulation is still a key breakthrough to solve sleep disorders in astronauts.It is expected to become an important part of space medicine and provide safe and efficient health protection for long-term space missions.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To study the medication law of TCM compounds for ischemic stroke using data mining methods;To provide reference for clinical medication.Methods Literature about TCM treatment for ischemic stroke was retrieved from CNKI,VIP,Wanfang Data and SinoMed from May 31,2014 to May 31,2024.Drug frequency analysis,dosage analysis,property and taste attribution analysis,association rule analysis,factor analysis and clustering analysis were performed using Excel 2019,SPSS Modeler 18,SPSS 25 software.Results A total of 180 prescriptions for the treatment of ischemic stroke were included,involving 208 kinds of Chinese materia medica,with a total frequency of 1 996 times,of which 20 were high-frequency medicines(≥24 times),with Chuanxiaong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix,Paeoniae Radix Rubra and Carthami Flos being the most frequent;the efficacy of the medicines included activating blood circulation and removing blood stasis,tonifying the deficiency,pacifying the liver,calming the wind and clearing away heat;the main properties were warm,cold and neutral;the main tastes were bitter,sweet and pungent;the main meridians were liver,spleen,heart and lung meridians;among the drug dosages of drugs with frequency≥24,the mean dosage of Chuanxiong Rhizoma,Angelicae Sinensis Radix,Pheretima,Astragali Radix and Paeoniae Radix Rubra were 12.24,12.91,10.52,40.00,12.13 g,respectively.In the systematic clustering and complex network analysis,it was suggested that the core TCM prescriptions were:Xuefu Zhuyu Decoction with modified Banxia Baizhu Tianma Decoction,modified Chaihu Shugan Powder,Buyang Huanwu Decoction with modified Huangqi Guizhi Wuwu Decoction and modified Liujunzi Decoction.Conclusion TCM treatment for ischemic stroke mostly uses the methods of activating blood circulation and expelling phlegm,nourishing blood to promote blood circulation,clearing heat and cooling blood,and benefiting qi and neutralizing qi,which provides ideas and methods for following research.

Objective To investigate the differences in pathological changes and immune responses of human airway organoids at different stages of differentiation following respiratory syncytial virus(RSV)infection.Methods Models of human fetal lung organoids(FLO)and induced airway organoids(iAO)were established to simulate immature and mature airway epithelium.Immunofluorescence staining,electron microscopy,and quantitative polymerase chain reaction(Q-PCR)were used to confirm the successful construction of the lung organoid models.Human lung organoids were infected with RSV,and samples were collected at 6 and 48 hours post-infection.The immune characteristics of immature and mature RSV-infected organoids were assessed using immunofluorescence staining,droplet digital PCR(DDPCR),and Q-PCR.Results We successfully generated FLO expressing both the progenitor markers sex determining region Y-box transcription factor 2(SOX2)and sex determining region Y-box transcription factor 9(SOX9),as well as iAO containing basal cells,ciliated cells,club cells,and goblet cells.In addition,organoid models of RSV infection were established.DDPCR results showed that,at the initial stage of RSV infection,the viral load in iAO was significantly higher than that in FLO(P＜0.001).However,at 48 hours post-infection,the viral load in iAO was lower than that in FLO(P＜0.05).Q-PCR results indicated that the expression of RSV infection receptor genes,including epidermal growth factor receptor(EGFR),insulin-like growth factor 1 receptor(IGF1R),and nucleolin(NCL),was significantly higher in iAO compared to that in FLO(P＜0.001).RSV infection led to an increase in the expression levels of immune factors,including interleukin 6(ILL-6),interleukin 8(CXCL8),interferon α(IFN-α),granulocyte colony-stimulating factor(G-CSF),granulocyte-macrophage colony-stimulating factor(GM-CSF),and tumor necrosis factor α (TNF-α),in iAO compared to those in FLO,and the differences were statistically significant(P＜0.05).Conclusion The expression of RSV infection receptor proteins increases with airway maturation,and mature airway epithelial cells exhibit a stronger immune response than immature ones do,effectively inhibiting RSV replication.

Objective:To investigate the clinical characteristics, prognosis, and the impact of different secondary prevention strategies on stroke recurrence in patients with carotid web (CaW)-associated acute anterior circulation large vessel occlusion (LVO).Methods:A retrospective analysis was conducted on 401 patients with acute anterior circulation LVO who underwent mechanical thrombectomy at 2 advanced stroke centers, Xingtai Central Hospital and Xingtai People′s Hospital, from January 2018 to June 2024. CaW was identified using digital subtraction angiography (DSA) and other imaging modalities. Based on the presence of CaW, patients were divided into CaW group and non-CaW group. Differences between the 2 groups in baseline characteristics, clinical features, and clinical outcomes were compared, and long-term follow-up was conducted for the CaW group.Results:Among the 401 patients, the CaW group consisted of 16 patients (4.0%), while the non-CaW group included 385 patients (96.0%). Compared to the non-CaW group, patients in the CaW group were younger [53 (46, 58) years vs 65 (56, 76) years, Z=-3.811, P<0.001], had a higher proportion of M1 segment middle cerebral artery occlusion [13/16 vs 54.0% (208/385), χ2=4.602, P=0.032] and a lower proportion of internal carotid artery terminus occlusion [1/16 vs 40.0% (154/385), χ2=6.024, P=0.014]; the 90-day modified Rankin Scale (mRS) score was significantly lower in the CaW group [1.00 (0, 1.75) vs 3.00 (1.00, 4.00), Z=14.210, P<0.001], and the proportion of patients with favorable functional independence (mRS score 0-2) was significantly higher [15/16 vs 45.7% (176/385), χ2=12.350, P<0.001] in the CaW group; the incidence of pneumonia in the CaW group was significantly lower [2/16 vs 42.6% (164/385), χ2=4.562, P=0.033]. Among the 16 CaW patients, 10 received antiplatelet therapy, 4 underwent carotid artery stenting (CAS), and 2 underwent carotid endarterectomy (CEA). During a median follow-up of 29 months, patients who underwent CAS and CEA had no stroke recurrence, while 2 patients who received antiplatelet therapy had stroke recurrence and subsequently underwent CAS and CEA. Conclusions:The proportion of CaW among patients with acute anterior circulation LVO was 4.0%. The patients with CaW were younger and had a higher proportion of M1 segment middle cerebral artery occlusion. Following mechanical thrombectomy, patients in the CaW group had good functional outcomes. Simple drug therapy may be insufficient to prevent stroke recurrence in CaW patients, and CAS and CEA may be effective therapeutic options.

Objective To investigate the effect of the rs3765467 polymorphism of glucagon-like peptide-1 receptor(GLP-1R)gene on the efficacy of Liraglutide(Lir)in patients with type 2 diabetes mellitus(T2DM)and metabolic associated fatty liver disease(MAFLD).Methods A total of 281 patients with T2DM from May 2022 to May 2023 were selected,including 125 patients with simple T2DM(T2DM group)and 156 patients with T2DM combined with MAFLD(T2DM+MAFLD group).120 healthy individuals during the same period were selected as the control(NC)group.The related indexes of glucose and lipid metabolism were detected.The polymorphism of GLP-1R gene rs3765467 was detected.Results BMI,FPG,HbA1c,HOMA-IR and TG in each group increased in turn(P<0.05),while the distribution frequency of genotype GG and allele G decreased in turn(P<0.05).TC and LDL-C in T2DM and T2DM+MAFLD groups were higher than those in NC group(P<0.05).TC and TG levels in genotype GA/AA patients were significantly higher than those in genotype GG patients(P<0.05).Compared with before treatment,the levels of BMI,FPG,HbA1c,HOMA-IR,TC,TG and LDL-C in T2DM patients with MAFLD were significantly decreased after Lir treatment(P<0.05).There was no significant difference in BMI and related indexes of glucose and lipid metabolism in GG and GA/AA patients before and after Lir treatment(P>0.05).Conclusions The distribution frequency of GG and G allele at rs3765467 of GLP-1R gene is reduced in T2DM patients with MAFLD.The carrying of allele A was associated with increased TC and TG levels,but did not affect the efficacy of Lir in reducing weight and improving glycolipid metabolism.