To develop a guideline terminology system and promote its standardization, thereby enhancing medical staff's accurate understanding and correct application of guidelines.

[Objective] To analyse and predict the tendencies of using erythrocyte blood in Changsha based on the autoregressive integrated moving average (ARIMA) model, long short-term memory (LSTM) and ARIMA-LSTM combination model, so as to provide reliable basis for designing a feasible and effective blood inventory management strategy. [Methods] The data of erythrocyte usage from hospitals in Changsha between January 2012 and December 2023 were collected, and ARIMA model, LSTM model and ARIMA-LSTM combination model were established. The actual erythrocyte consumption from January to May 2024 were used to assess and verify the prediction effect of the models. The extrapolation prediction accuracy of the models were tested using two evaluation indicators: mean absolute percentage error (MAPE) and root mean square error (RMSE), and then the prediction performance of the model was compared. [Results] The RMSE of LSTM model, optimal model ARIMA(1,1,1)(1,1,1)12 and ARIMA-LSTM combination model were respectively 5 206.66, 3 096.43 and 2 745.75, and the MAPE were 18.78%,11.54% and 9.76% respectively, which indicated that the ARIMA-LSTM combination model was more accurate than the ARIMA model and LSTM model, and the prediction results was basically consistent with the actual situation. [Conclusion] The ARIMA-LSTM model can better predict the clinical erythrocyte consumption in Changsha in the short term.

The emergence of teeth is a complex physiological process characterized by the formation of the tooth crown, its movement towards the occlusal plane, and subsequent penetration through the alveolar bone and oral mucosa to achieve functional positioning for contact with opposing teeth. Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) are critical regulators of calcium and phosphorus metabolism in the body, playing significant roles in tooth emergence. Their regulatory functions exhibit intricate temporal and spatial dynamics, with underlying mechanisms that remain incompletely understood. In recent years, an increasing number of researchers both domestically and internationally have investigated the role and mechanisms of PTH/PTHrP in tooth emergence, primarily focusing on aspects such as dental sac formation, basal alveolar bone development, coronal alveolar bone resorption, root formation, and periodontal ligament development. Literature reviews indicate that PTH and PTHrP regulate bone metabolism, coordinate various signaling pathways including OPG/RANK/RANKL, cAMP/PKA, and Wnt/β-catenin, and are allosterically modulated by Ca2+ and ATP. These processes contribute to the development of dental sacs, which transmit signals to recruit osteoclasts and promote the resorption of crown alveolar bone, thereby forming an eruption pathway. Additionally, PTH/PTHrP plays a role in the formation of basal alveolar bone, root development, and the periodontal ligament, generating the force necessary for tooth eruption. Through precise spatiotemporal regulation and coordinated efforts, alveolar bone remodeling is achieved, facilitating the intricate process of tooth eruption. Through stringent temporal regulation and multi-faceted cooperation, remodeling of the alveolar bone occurs to complete this intricate developmental process of tooth emergence. Future research should further elucidate the mechanisms underlying PTH/PTHrP actions while also considering optimal dosage regimens regarding timing and frequency for therapeutic applications.

OBJECTIVE To explore the expression,regulation,and downstream pathways of miR-21-5p in nasal type 2 inflammatory diseases.METHODS The expression levels of miR-21-5p were evaluated in nasal mucosa of patients with chronic rhinosinusitis with nasal polyps(CRSwNP)and healthy controls,as well as in nasal mucosa of CRSwNP and allergic rhinitis(AR)mouse models by real-time PCR.Human primary nasal epithelial cells were cultured and treated with different cytokines.The expression of miR-21-5p were then detected after 48 hours treatment.miR-21-5p lentivirus were used for overexpression in nasal epithelial cells.After 72 hours,cells were collected,and RNA was extracted for transcriptome analysis.Differentially expressed genes were further analyzed for pathway enrichment.RESULTS Compared with healthy controls,the expression of miR-21-5p was significantly increased in the nasal mucosa of CRSwNP patients(P<0.01).The expression of miR-21-5p was also significantly increased in mouse models of CRSwNP and AR respectively,compared to the control groups(P<0.01,respectively).The type 2 inflammation cytokines IL-4 and IL-13 can significantly upregulate miR-21-5p expression in nasal epithelial cells(P<0.01,respectively).Overexpression by lentivirus can significantly increase the expression of miR-21-5p in nasal epithelial cells,and lead to 118 differentially expressed genes.Those genes are significantly enriched in pathways associated with posttranscriptional gene silencing,WNT signaling and MAPKinase signaling.CONCLUSION miR-21-5p is upregulated in nasal type 2 inflammatory diseases partially controlled by IL-4 and IL-13.Overexpression of miR-21-5p lead to the changes of downstream pathways associated with WNT signaling and MAPKinase signaling in nasal epithelial cells.

Objective:To characterize the clinical and genetic features of 2 patients with interleukin-1 receptor associated kinase (IRAK) 4 deficiency and to assess the pathogenicity of their genetic variants.Methods:This case series included two patients diagnosed with IRAK4 gene deficiency at Shenzhen Children′s Hospital and the University of Hong Kong-Shenzhen Hospital between 2019 and 2024. Six healthy children without recent infections or immunodeficiency served as controls. Peripheral blood mononuclear cells were stimulated in vitro with Toll-like receptor 4 (TLR4) agonists, and cytokine levels were quantified using a protein chip assay.Results:The 2 patients, a 5-year-old boy and a 10-year-old girl, presented with recurrent invasive or non-invasive bacterial infections and impaired acute-phase inflammatory responses. Genetic testing identified a homozygous frameshift variant (c.540delT, p.F180Lfs*26) in Patient 1 and compound heterozygous frameshift variants (c.166delT, p.F56fs and c.629delG, p.R210fs) in Patient 2, all predicted to result in truncated IRAK4 proteins. Both patients received regular infection prophylaxis with favorable clinical outcomes. Controls consists of 3 males and 3 females, aged 5-17 years. Following TLR4 stimulation, cytokine levels in Patient 1, Patient 2, and controls (tumor necrosis factor-α 68.6, 103.0, 618.7 (392.7, 824.1); interleukin (IL)-1β 39.8, 10.8, 1 975.5 (1 556.0, 2 096.5); interferon-γ 8.6, 6.2, 13.5 (12.7, 14.9); granulocyte colony-stimulating factor 17.6, 15.9, 2 890.0 (1 622.0, 4 692.8); IL-6 140.1, 352.7, 7 222.5 (5 768.5, 8 043.5); and IL-17 47.5, 44.5, 59.7 (43.4, 69.5), respectively.Conclusions:IRAK4 deficiency should be suspected in patients with early-onset recurrent bacterial infections and attenuated inflammatory response. Homozygous and compound heterozygous frameshift variants in IRAK4 gene lead to truncated IRAK4 proteins and impared innate immune signaling.

Objective:To observe the tumor control and the degree of radiation-induced lung injury (RILI) between FLASH irradiation and conventional dose rate (CONV) irradiation, and compare the changes in plasma proteomic profiles of mice following whole-lung FLASH and CONV irradiation using proteomics method.Methods:A mouse model with metastatic lung cancer was established. After whole-lung irradiation, changes in normal lung capacity were monitored using CT scans. Then, a RILI model was constructed to examine pathological alterations in lung tissues following whole-lung CONV and FLASH irradiation. Plasma samples were collected from mice receiving whole-lung CONV irradiation ( n = 5) and whole-lung FLASH irradiation ( n = 5), followed by comparison with samples from the control group of healthy mice (also referred to as the healthy control group). These plasma samples were analyzed using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics, followed by the screening and identification of differentially expressed proteins using high-throughput bioinformatics. Moreover, protein-protein interaction (PPI) network analysis was conducted to identify hub genes using the STRING database and Cytoscape software. Results:Whole-lung FLASH and CONV irradiation produced consistent tumor control, with the former significantly reducing RILI compared to the latter. A total of 609 proteins were identified through proteomic analysis. Among them, 89 differentially expressed proteins were detected in the whole-lung FLASH group. Gene Ontology (GO) enrichment analysis indicated that up-regulated genes were primarily associated with stress and inflammatory responses, whereas down-regulated genes were related to ATP metabolism and angiogenesis regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that up-regulated genes were predominantly enriched in unfolded protein response pathways, while down-regulated genes were mainly involved in metabolic pathways and oxidative phosphorylation. Integrated PPI analysis and subsequent validation via reverse transcription-polymerase chain reaction (RT-PCR) revealed four key genes.Conclusions:Compared to the whole-lung CONV irradiation, whole-lung FLASH irradiation reduces the RILI of normal lung tissues while maintaining equivalent tumor control in metastatic lung cancer. Proteomic analysis of differentially expressed proteins in plasma after whole-lung FLASH and CONV irradiation provides valuable insights into the molecular mechanisms underlying the FLASH effect.

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.

In recent years,FLASH radiotherapy(FLASH-RT),as a cutting-edge radiotherapy technology,has developed rapidly in basic research and clinical trials.FLASH-RT can deliver ultra-high dose rate(average dose rate≥40 Gy/s,instantaneous dose rate≥100 Gy/s)irradia-tion in a very short time(usually≤500 ms).Under the premise of maintaining equivalent tumor control rates,the normal tissue injury is less than that of conventional irradiation at the same dose,that is known as the FLASH effect.FLASH-RT has unique advantages and is currently the frontier field of radiation oncology.The research and development of FLASH-RT have progressed rapidly in China,this paper elucidated the new challenges and opportunities of FLASH-RT in China.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Objective To observe the effects of four different modeling method on the hypothalamus-pituitary-adrenal(HPA)axis,blood rheology,platelet aggregation rate,and myocardial ischemia in rats,and to provide new ideas for the establishment of a rat model of"double heart"disease in line with clinical diagnosis and treatment characteristics.Methods Sixty-nine male Sprague-Dawley rats were divided randomly into a Control group(unstimulated),chronic unpredictable mild stimulation(CUMS)group,isoproterenol(ISO)group(intraperitoneal injection of ISO),high-fat diet(HFD)group(fed high-fat chow),and composite model(CUMS+ISO+HFD)group(n=12 rats in the Control and HFD groups;n=15 rats in the other three groups,respectively).Modeling procedures were carried out for a total of 8 weeks,with ISO injection started from week 6 of the experiment for a total of 3 weeks.At the end of modeling,rats in each group were subjected to absent-field and sugar-water preference behavioral tests.Electrocardiography(ECG)was performed to observe changes in ECG lead Ⅱ in each group.Serum levels of adrenocorticotropic hormone(ACTH),cortisol(Cor),corticosterone(CORT),endothelin-1(ET-1),and soluble intercellular adhesion molecule-1(sICAM-1)were detected by enzyme-linked immunosorbent assay.Myocardial histopathological changes were detected by hematoxylin/eosin(HE)staining.Serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an enzyme labeling instrument.Whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were assessed using an automatic blood rheology analyzer.The maximum platelet aggregation rate(MAR)and average platelet aggregation rate(AAR)induced by arachidonic acid and adenosine diphosphate were detected using a whole-blood platelet aggregometer.Results Compared with the Control group,all four model groups had significantly lower absenteeism distance and number of entries into the central region in the absent-field test,and a lower sugar-water preference ratio(P＜0.01).ECG revealed ST-segment elevation in the ISO and CUMS+ISO+HFD groups,tachycardia in the CUMS group,and mild ST-segment elevation in the HFD.Serum ACTH,Cor,CORT,ET-1,and sICAM-1 were all significantly elevated in the four model groups(P＜0.01).HE staining showed that myocardial tissue was severely damaged in rats in the ISO and CUMS+ISO+HFD groups,with pathological changes such as localized fibrosis and inflammatory infiltration of the myocardium,while mild cardiomyocyte disarrangement and fracture was seen in the CUMS and HFD groups.Rats in the HFD group had increased serum TC and LDL(P＜0.01)and decreased HDL contents(P＜0.01).Compared with the Control group,whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were all increased in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01,P＜0.05),while whole blood high-cut viscosity(200 V/S),whole blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen levels were decreased in rats in the ISO group(P＜0.01,P＜0.05).MAR and AAR were significantly higher in rats in the CUMS,HFD,and CUMS+ISO+HFD groups(P＜0.01),while the platelet aggregation rate was decreased in the ISO group compared with the Control group(P＜0.01,P＜0.05).Conclusions These result showed that the rat CUMS+ISO+HFD model better reflected the complexity of clinical double heart disease than the other three models.