OBJECTIVE To systematically evaluate risk prediction models for chemotherapy-induced myelosuppression in breast cancer， and provide a scientific reference for clinical healthcare workers in selecting or developing effective predictive models. METHODS A systematic search was conducted for studies on predictive models of the risk of chemotherapy-induced myelosuppression in breast cancer across the CNKI， VIP， Wanfang， PubMed， Web of Science， Cochrane Library， Embase， and Scopus databases， with a time frame of the establishment of the database to May 7， 2024. Literature was independently screened by 2 investigators， data were extracted according to critical appraisal and data extraction for systematic reviews of predictive model studies， and the risk of bias evaluation tool for predictive model studies was used to analyze the risk of bias and applicability of the included studies. RESULTS There were totally 7 studies， comprising 12 models. Among them， 11 models indicated an area under the subject operating characteristic curve of 0.600-0.908； 2 models indicated calibration. The common predictor variables of the included models were age， pre-chemotherapy neutrophil count， pre-chemotherapy lymphocyte count， and pre-chemotherapy albumin. The overall risk of bias of the 7 studies was high， which was mainly attributed to the flaws in the study design， insufficient sample sizes， inappropriate treatment of variables， non-reporting of missing data， and the lack of indicators for the assessment of the models， but the applicability was good. CONCLUSIONS The predictive performance of risk predictive models for chemotherapy-induced myelosuppression in breast cancer remains to be further enhanced， and the overall risk of model bias is high. Future studies should follow the specifications of model development and reporting， then combine machine learning algorithms to develop risk predictive models with good predictive performance， high stability， and low risk of bias， so as to provide a decision-making basis for the clinic.

OBJECTIVE To construct a prediction model for the efficacy of serotonin-norepinephrine reuptake inhibitor （SNRI） in inpatients with moderate and severe depression by using a machine learning method. METHODS The case records of inpatients with moderate and severe depression treated with SNRI antidepressants were collected from a third-grade class-A hospital in Xinjiang from January 2022 to October 2024； those patients were divided into effective group and ineffective group based on the Hamilton depression scale-24 score reduction rate. After screening the characteristic variables related to the therapeutic efficacy of SNRI drugs through LASSO regression， five prediction models including support vector machine， k-nearest neighbor， random forest， lightweight gradient boosting machine and extreme gradient boosting were constructed using the training set. Bayesian optimization was used to adjust the hyperparameters of these models. The performance of the models was evaluated in the validation set to select the optimal model. The Shapley additive explanations method was used to perform explainable analysis on the best model. RESULTS The medical records from 355 hospitalized patients with moderate and severe depression were collected， comprising 285 cases in the effective group and 70 cases in the ineffective group， resulting in an overall therapeutic response rate of 80.28%. After feature variable screening， five characteristic variables for therapeutic efficacy were obtained， including Hamilton anxiety scale， blood urea nitrogen， combination of anti-anxiety drugs， drinking history， and first onset of the disease. Compared with other models， the random forest model performed the best. The area under the receiver operating characteristic curve was 0.85， the area under the precision-recall curve was 0.87， the accuracy was 0.74， and the recall rate value was 0.75. CONCLUSIONS The random forest model constructed based on five characteristic variables demonstrates potential for predicting the therapeutic efficacy of SNRI antidepressants in hospitalized patients with moderate and severe depression.

RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG＜8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P＜0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P＜0.001),and triglyceride level(P＜0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95％confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.

Objective To investigate the safety and effectiveness of endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion(AIS-LVO)over 24 h after onset.Methods The clinical data of AIS-LVO patients who received endovascular treatment in Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2022 were retrospectively analyzed,including baseline characteristics,imaging findings,treatment,degree of vascular recanalization(modified thrombolysis in cerebral infarction grade 2b and 3 for successful recanalization)and prognosis.Results A total of 57 patients were included,including 42 males and 15 females,aged from 30 to 84 years old.The most common risk factors were hypertension(39 cases,68.4%),followed by smoking history(24 cases,42.1%),diabetes mellitus(17 cases,29.8%),previous stroke history(16 cases,28.1%),and atrial fibrillation(9 cases,15.8%).Before treatment,the National Institutes of Health stroke scale score was 12.84±7.04,and the Alberta Stroke Program early computed tomography score was 9.00(7.00,10.00).Vascular occlusion sites included middle cerebral artery occlusion in 27(47.4%)cases,internal carotid artery occlusion in 24(42.1%)cases,and tandem lesions in 6(10.5%)cases.The time from onset to femoral artery puncture was 38.30(28.17,53.71)h,and the time from femoral artery puncture to vascular recanalization was 52.00(38.50,92.50)min.General anesthesia was the main anesthesia method,accounting for 64.9%(37/57).The etiological types of stroke were mainly large artery atherosclerosis(38 cases,66.7%),cardiogenic embolism(9 cases,15.8%),unknown causes(6 cases,10.5%),and other clear causes(4 cases,7.0%).Mechanical thrombectomy was the first choice in 41(71.9%)cases,balloon dilatation/stenting was used in 35(61.4%)cases,of which 15(26.3%)cases were the first choice.Finally,53(93.0%)cases were recanalized successfully.In terms of complications,1(1.8%)case had symptomatic intracranial hemorrhage.The 90-d prognosis rate was 59.6%(34/57),and 3(5.3%)cases died.Conclusion Endovascular treatment for AIS-LVO patients over 24 h after onset has high recanalization rate and good safety,but it still needs to be further verified by randomized controlled trials.

OBJECTIVE To determine the species,quantity,and dispersion patterns of airborne pollen in two districts and five counties of Handan City,Hebei Province.METHODS The gravity sedimentation method was employed from October 1,2023,to September 30,2024,for daily and consecutive pollen exposure slides in two districts(Congtai District and Yongnian District)and five counties(Qiu County,Daming County,Cheng'an County,Cixian County,and She County)of Handan City,Hebei Province.The types of pollen were counted and identified under an optical microscope,and the pollen data were statistically analyzed.RESULTS The annual pollen quantity in the two districts and five counties of Handan City ranged from 24 031 grains/1 000 mm2 to 85 131 grains/1 000 mm2.The dissemination of major allergenic pollen presented two peaks.The first peak occurred in spring(March to April),mainly composed of Platanus(25.15％),Broussonetia(13.61％),Pinus(8.48％);the second peak occurred in(August to September),mainly consisting of Humulus/Cannabis(13.71％)and Artemisia(8.44％).Pollen in spring was significantly higher than that in summer and autumn.CONCLUSION The major allergenic airborne pollen in the two districts and five counties of Handan City exhibited two peaks in spring and summer-autumn,with Platanus pollen,Broussonetia pollen,Pinus pollen,Humulus/Cannabis pollen,and Artemisia pollne being the dominant pollen types.Among them,Platanus pollen was the absolute dominant pollen in this region.

AIM:To investigate the effects of adipose-derived stem cells(ADSCs)with overexpression or si-lencing of long noncoding RNA(lncRNA)SNHG8 on the viability,migration,angiogenesis,and the expression of vasoac-tive factors in human umbilical vein endothelial cells(HUVECs).METHODS:Identification of ADSCs derived from morbidly obese patients(O-ADSCs)was conducted using flow cytometry and induction of lipogenesis and osteogenesis.The expression of lncRNA SNHG8 in healthy human ADSCs(H-ADSCs)and O-ADSCs was detected by RT-qPCR.Tran-swell method was used to establish the indirect co-culture system of ADSCs and HUVECs for 48 h,and the cells were di-vided into O-ADSCs+HUVECs group,H-ADSCs+HUVECs group,and HUVECs alone group.The mRNA and protein ex-pression levels of angiotensin Ⅱ(Ang Ⅱ),endothelin-1(ET-1)and endothelial nitric oxide synthase(eNOS)in HUVECs were detected by RT-qPCR and Western blot.The lncRNA SNHG8 overexpression and silencing lentiviruses were con-structed and used to infect O-ADSCs.The indirect co-cultured ADSCs and HUVECs were divided into O-ADSCs-OE-SNHG8+ HUVECs group,O-ADSCs-OE-NC+HUVECs group,O-ADSCs-sh-SNHG8+HUVECs group,and O-ADSCs-sh-NC+HUVECs group.After co-culture for 48 h,the viability,migration and tubule formation of HUVECs were detected by CCK-8,scratch and angiogenesis assays,respectively.The mRNA and protein expression levels of Ang Ⅱ,ET-1 and eNOS in HU-VECs were detected by RT-qPCR and Western blot,respectively.The nitrate reductase method was used to detect the con-tent of NO in HUVECs.RESULTS:(1)The cultured cells were identified as ADSCs.(2)Compared with H-ADSCs,ln-cRNA SNHG8 expression was significantly up-regulated in O-ADSCs(P<0.01).(3)Compared with H-ADSCs+HUVECs group and HUVECs group,the mRNA and protein expression levels of Ang Ⅱ and ET-1 in HUVECs in O-ADSCs+HU-VECs group were up-regulated(P<0.01).(4)Overexpression of lncRNA SNHG8 in O-ADSCs enhanced the viability,mi-gration and tube formation ability of HUVECs,up-regulated the mRNA and protein expression levels of Ang Ⅱ and ET-1,down-regulated the mRNA and protein expression levels of eNOS,and decreased the content of NO in HUVECs(P<0.05).However,silencing of lncRNA SNHG8 in O-ADSCs exerted opposite results(P<0.05).CONCLUSION:(1)The O-ADSCs can promote endothelial cell viability,migration and tubule formation through paracrine effects.(2)The O-ADSCs with overexpression of lncRNA SNHG8 promote the imbalance of diastolic and contractile factors secreted by endo-thelial cells,and induce the dysfunction of vascular endothelial cells.

Objective:To construct and purify four respiratory syncytial virus (RSV) PreF proteins through gene sequence design and optimization and evaluate their immunogenicity.Methods:Coronin-1A and T4 trimer protein gene sequences were optimized with Human and CHO codons, and then added to RSV F protein sequence. The above plasmids were transfected into Expi293F cells for protein expression. After purification by nickel column, four trimer proteins were prepared. SDS-PAGE and Western blot were performed for protein identification. BALB/c mice were immunized at week 0 and week 3, and blood samples were collected to measure the activities of binding and neutralizing antibodies in serum.Results:SDS-PAGE and Western blot showed that the four proteins had stable trimer structure. Antigen-antibody affinity test showed that the four trimer proteins had strong affinity with RSV-specific monoclonal antibodies 8897, D25, Motavizumab, AM14 and Palivizumab. The titers of antibodies induced by the two T4 trimers were higher after the initial immunization, while there was a substantial increase in the titers of antibodies induced by Human codon-optimized trimer protein after the second immunization.Conclusions:PreF trimer protein can be prepared by adding any of the two different heterotrimer motifs, and induce effective binding and neutralizing antibodies in mice.

Objective:To compare the immunogenicity of the prefusion (PreF) and postfusion (PostF) conformations of the respiratory syncytial virus (RSV) F protein.Methods:The expression of PreF and PostF recombinant proteins was analyzed by SDS-PAGE and Western blot. The binding affinity between F protein and its specific antibodies was detected by Octet. The binding antibodies and neutralizing antibodies in immune serum were detected after immunizing mice with PreF or PostF recombinant protein.Results:PreF protein was stable in the form of a trimer after modification with higher binding affinity with monoclonal antibodies such as D25, 8897, AM14, Palivizumab and Motavizumab. PostF protein lacked the antigenic site ? and showed a monomer conformation. Besides, it was unable to bind to D25, 8897 and AM14 antibodies. Animal experiments showed that AS01 adjuvant was better than aluminum adjuvant in inducing binding antibodies and neutralizing antibodies against RSV Long strains. The binding antibodies induced by PreF and PostF recombinant proteins had similar binding ability to PreF protein, while the binding antibodies induced by PostF recombinant protein showed stronger binding ability to PostF than to PreF.Conclusions:PreF has more epitopes and the trimer form of PreF recombinant protein after modification is more stable and can induce stronger neutralizing antibodies. Moreover, the immunopotentiating effect of AS01 adjuvant is better than that of aluminum adjuvant. Therefore, stabilization-based trimer structure modification of PreF and the development of adjuvants are crucial for the development of RSV vaccines.