OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

Objective:To examine the regulatory effects of a potential antifibrotic tetrapeptide called N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the expression of epidermal growth factor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in lung tissues with fibrosis induced by silicosis in rats. This study aims to explore the potential therapeutic benefits of Ac-SDKP in the prevention and treatment of fibrotic lung diseases associated with silicosis.Methods:In January 2024, disease targets and Ac-SDKP active ingredients were predicted through GeneCards (https://www.genecards.org) and OMIM (https://www.omim.org) databases. Using R 4.2.1 software, we identified overlapping targets between pulmonary fibrosis and AC-SDKP. Cytoscape 3.10.2 was employed to visualize interactions between active chemical components and these targets, followed by GO enrichment analysis and KEGG pathway analysis using R 4.2.1. Forty healthy adult Wistar rats were selected to establish silicosis models through single-dose gavage with 50 mg/ml silica suspension (1. 0 ml per rat). The rats were randomly divided into four groups: model control group (4 weeks), silicosis model group (4 weeks), Ac-SDKP preventive treatment group (acquired via intraperitoneal injection of a micro-release pump containing Ac-SDKP [800 μg/ (kg·d) ] during modeling, maintained for 4 weeks), and Ac-SDKP anti-fibrosis treatment group (acquired via intraperitoneal injection of the same pump after 2 weeks of modeling, continued maintenance for 2 weeks). Each group contained 10 rats. The pathological changes in rat lung tissues were observed. Western blot technology was used to detect the protein expression levels of α-smooth muscle actin (α-SMA), epidermal growth factor receptor (EGFR), signal transduction and activation transcription factor 3 (STAT 3), caspase 3, and caspase 8 in lung tissues. Immunohistochemical techniques were employed to assess the expressions of EGFR, STAT3, caspase 3, and caspase 8. Overall differences between groups were compared using one-way ANOVA.Results:Compared with the control group in the silicosis model, rats in the 4-week group exhibited significant fibrotic nodules. The lung tissues of these rats showed statistically significant increases in α-SMA, EGFR, STAT 3, Caspase 3, and Caspase 8 protein expression ( P<0.05). In contrast, the Ac-SDKP prevention and anti-fibrosis treatment group demonstrated markedly reduced expression levels of these proteins compared to the 4-week silicosis model group, with statistically significant differences ( P<0.05). Immunohistochemical staining revealed that brownish-yellow expression of EGFR, STAT3, Caspase3, and Caspase8 was significantly enhanced in silicotic nodules within the silicosis model group. Conversely, this brownish-yellow expression was notably decreased in the Ac-SDKP prevention and anti-fibrosis treatment group compared to the 4-week silicosis model group. Conclusion:Ac-SDKP may exert antifibrotic effects on the lungs of rats with silicosis by regulating the EGFR/STAT3 pathway.

Strangles,caused by Streptococcus equi subsp.equi,remains one of the most prevalent and high-incidence infectious diseases in intensive donkey farms,posing a significant threat to the healthy development of the donkey industry.Vaccination serves as an effective measure for the pre-vention and control of the disease,however,there is currently no attenuated vaccine against this disease in China.To provide a candidate strain for the development of a live attenuated strangles vaccine,this study focused on a wild-type S.equi subsp.equi strain isolated from donkeys.Using homologous recombination gene knockout technology,the aroA gene(encoding 5-enolpyru-vylshikimate-3-phosphate synthase)and the sag A gene(encoding the precursor of streptolysin S toxin)were sequentially deleted to construct a double-gene-deletion strain(ΔsagA/aroA).The virulence and key biological characteristics of the mutant strain were systematically evaluated.TheΔsagA/aroA strain was successfully generated,exhibiting complete loss of hemolytic activity and maintaining stable genetic inheritance over 60 consecutive passages.Electron microscopy revealed that the mutant retained morphological characteristics compared to the wild-type strain,and its growth rate was significantly slower(P＜0.000 1).Virulence assessment using a challenge dose of 1× 105 CFU/0.2 mL(the minimum fully lethal dose of the wild-type strain)demonstrated markedly attenuated virulence in the mutant.Immunization trials with 1 ×104 CFU/0.2 mL of theΔsagA/aroA strain revealed a increase in ELISA antibody titers by day 7 post-vaccination,and higher levels at days 14 and 21.Notably,antibody levels in the experimental group were significant-ly higher than those in the control group(P＜0.000 1).These findings confirm that the double-gene-deletion strain S.equi subsp.equi ΔsagA/aroA exhibits reduced virulence while retaining im-munogenicity,which suggested it can be used as a promising candidate strain for further develop-ment of a live attenuated strangles vaccine.

Objective To explore the changes in symptom clusters and core symptoms at different stages in col-orectal cancer patients undergoing postoperative chemotherapy,and to provide a reference for developing precise symptom management strategies in clinical practice.Methods 300 colorectal cancer patients who underwent post-operative chemotherapy at 2 tertiary hospitals in Tianjin from August 2023 to May 2024 were conveniently selected as the study subjects.General information questionnaires and the Chinese version of the MD Anderson Symptom In-ventory for Colorectal Cancer were used to survey patients during the first chemotherapy cycle(T1)and the third chemotherapy cycle(T2).Exploratory factor analysis was used to extract symptom clusters;R language was used to construct symptom networks.Results 300 questionnaires were distributed and collected at T1,and 264 question-naires were distributed and collected at T2,with a recovery rate of 88.00％.Colorectal cancer patients undergoing postoperative chemotherapy had 5 symptom clusters at T1,and 4 symptom clusters at T2.In the symptom network,distress was the symptom with the highest strength(rs=1.188),closeness centrality(rc=0.004),and betweenness centrality(rb=36)at T1.Distress was the symptom with the highest strength(rs=1.397),while decreased appetite had the highest closeness centrality(rc=0.004)and betweenness centrality(rb=39)at T2.Conclusion The symptom clusters in colorectal cancer patients undergoing postoperative chemotherapy remain stable over time.Distress is a stable core symptom during chemotherapy,while decreased appetite is a bridging symptom in the mid-chemotherapy phase.Healthcare providers should prioritize interventions for decreased appetite while addressing emotional symptoms to improve the efficiency of symptom management.

Objective:To examine the regulatory effects of a potential antifibrotic tetrapeptide called N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on the expression of epidermal growth factor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in lung tissues with fibrosis induced by silicosis in rats. This study aims to explore the potential therapeutic benefits of Ac-SDKP in the prevention and treatment of fibrotic lung diseases associated with silicosis.Methods:In January 2024, disease targets and Ac-SDKP active ingredients were predicted through GeneCards (https://www.genecards.org) and OMIM (https://www.omim.org) databases. Using R 4.2.1 software, we identified overlapping targets between pulmonary fibrosis and AC-SDKP. Cytoscape 3.10.2 was employed to visualize interactions between active chemical components and these targets, followed by GO enrichment analysis and KEGG pathway analysis using R 4.2.1. Forty healthy adult Wistar rats were selected to establish silicosis models through single-dose gavage with 50 mg/ml silica suspension (1. 0 ml per rat). The rats were randomly divided into four groups: model control group (4 weeks), silicosis model group (4 weeks), Ac-SDKP preventive treatment group (acquired via intraperitoneal injection of a micro-release pump containing Ac-SDKP [800 μg/ (kg·d) ] during modeling, maintained for 4 weeks), and Ac-SDKP anti-fibrosis treatment group (acquired via intraperitoneal injection of the same pump after 2 weeks of modeling, continued maintenance for 2 weeks). Each group contained 10 rats. The pathological changes in rat lung tissues were observed. Western blot technology was used to detect the protein expression levels of α-smooth muscle actin (α-SMA), epidermal growth factor receptor (EGFR), signal transduction and activation transcription factor 3 (STAT 3), caspase 3, and caspase 8 in lung tissues. Immunohistochemical techniques were employed to assess the expressions of EGFR, STAT3, caspase 3, and caspase 8. Overall differences between groups were compared using one-way ANOVA.Results:Compared with the control group in the silicosis model, rats in the 4-week group exhibited significant fibrotic nodules. The lung tissues of these rats showed statistically significant increases in α-SMA, EGFR, STAT 3, Caspase 3, and Caspase 8 protein expression ( P<0.05). In contrast, the Ac-SDKP prevention and anti-fibrosis treatment group demonstrated markedly reduced expression levels of these proteins compared to the 4-week silicosis model group, with statistically significant differences ( P<0.05). Immunohistochemical staining revealed that brownish-yellow expression of EGFR, STAT3, Caspase3, and Caspase8 was significantly enhanced in silicotic nodules within the silicosis model group. Conversely, this brownish-yellow expression was notably decreased in the Ac-SDKP prevention and anti-fibrosis treatment group compared to the 4-week silicosis model group. Conclusion:Ac-SDKP may exert antifibrotic effects on the lungs of rats with silicosis by regulating the EGFR/STAT3 pathway.

Strangles,caused by Streptococcus equi subsp.equi,remains one of the most prevalent and high-incidence infectious diseases in intensive donkey farms,posing a significant threat to the healthy development of the donkey industry.Vaccination serves as an effective measure for the pre-vention and control of the disease,however,there is currently no attenuated vaccine against this disease in China.To provide a candidate strain for the development of a live attenuated strangles vaccine,this study focused on a wild-type S.equi subsp.equi strain isolated from donkeys.Using homologous recombination gene knockout technology,the aroA gene(encoding 5-enolpyru-vylshikimate-3-phosphate synthase)and the sag A gene(encoding the precursor of streptolysin S toxin)were sequentially deleted to construct a double-gene-deletion strain(ΔsagA/aroA).The virulence and key biological characteristics of the mutant strain were systematically evaluated.TheΔsagA/aroA strain was successfully generated,exhibiting complete loss of hemolytic activity and maintaining stable genetic inheritance over 60 consecutive passages.Electron microscopy revealed that the mutant retained morphological characteristics compared to the wild-type strain,and its growth rate was significantly slower(P＜0.000 1).Virulence assessment using a challenge dose of 1× 105 CFU/0.2 mL(the minimum fully lethal dose of the wild-type strain)demonstrated markedly attenuated virulence in the mutant.Immunization trials with 1 ×104 CFU/0.2 mL of theΔsagA/aroA strain revealed a increase in ELISA antibody titers by day 7 post-vaccination,and higher levels at days 14 and 21.Notably,antibody levels in the experimental group were significant-ly higher than those in the control group(P＜0.000 1).These findings confirm that the double-gene-deletion strain S.equi subsp.equi ΔsagA/aroA exhibits reduced virulence while retaining im-munogenicity,which suggested it can be used as a promising candidate strain for further develop-ment of a live attenuated strangles vaccine.

Objective To explore the changes in symptom clusters and core symptoms at different stages in col-orectal cancer patients undergoing postoperative chemotherapy,and to provide a reference for developing precise symptom management strategies in clinical practice.Methods 300 colorectal cancer patients who underwent post-operative chemotherapy at 2 tertiary hospitals in Tianjin from August 2023 to May 2024 were conveniently selected as the study subjects.General information questionnaires and the Chinese version of the MD Anderson Symptom In-ventory for Colorectal Cancer were used to survey patients during the first chemotherapy cycle(T1)and the third chemotherapy cycle(T2).Exploratory factor analysis was used to extract symptom clusters;R language was used to construct symptom networks.Results 300 questionnaires were distributed and collected at T1,and 264 question-naires were distributed and collected at T2,with a recovery rate of 88.00％.Colorectal cancer patients undergoing postoperative chemotherapy had 5 symptom clusters at T1,and 4 symptom clusters at T2.In the symptom network,distress was the symptom with the highest strength(rs=1.188),closeness centrality(rc=0.004),and betweenness centrality(rb=36)at T1.Distress was the symptom with the highest strength(rs=1.397),while decreased appetite had the highest closeness centrality(rc=0.004)and betweenness centrality(rb=39)at T2.Conclusion The symptom clusters in colorectal cancer patients undergoing postoperative chemotherapy remain stable over time.Distress is a stable core symptom during chemotherapy,while decreased appetite is a bridging symptom in the mid-chemotherapy phase.Healthcare providers should prioritize interventions for decreased appetite while addressing emotional symptoms to improve the efficiency of symptom management.

Objective:To study the risk factors of venous thromboembolism(VTE)and the predictive value of the improved VTE score model to identify the risk of VTE in gynecological surgery patients.Methods:From Janu-ary 1,2020 to December 31,2022,41 patients with VTE after gynecological surgery were selected as the VTE group,and a total of 164 patients with adjacent gynecological surgeries during the same period were selected as the non-VTE group with a ratio of 1 :4.Univariate and multivariate Logistic regression analysis were used to ana-lyze the risk factors of VTE after gynecological surgery,and a modified VTE risk factor rapid assessment model(referred to as the improved VTE score model)was constructed.The receiver operating characteristic(ROC)curve was used to study the predictive value for VTE for in gynecological surgery,and compared with the Caprini score model(Caprini table for short).Results:①Multivatiate Logistic regression analysis showed that there were independent risk factors for postoperative VTE in gynecology surgery(OR＞1,P＜0.05),including age≥60 years,BMI≥28 kg/m2,malignant tumors,surgery time＞3 hours,history of thrombosis,and the increased D-di-mer difference before and after surgery.②The Area under Curve(AUC)of ROC was 0.963 in the improved VTE score model with a Youden index 81.10％,sensitivity 87.80％and specificity 93.29％.The AUC of the Caprini score model was 0.888 with Youden index 63.41％,sensitivity 73.17％and specificity 90.24％.The improved VTE score model the Caprini score model identified 92.68％and 85.37％of VTE patients as high-risk or ex-tremely high-risk,respectively,but the difference was not statistically significant(P＜0.05).Conclusions:More attention should be paid to the six independent risk factors for postoperative VTE in gynecology surgery.The two score models showed a similar identified level.However,the improved VTE score model is more simple and easier to operate,has better practicality,and has certain clinical promotion value.

Objective:To explore the evaluation of dual-parameter three dimension arterial spin labelling(3D-ASL)perfusion imaging on blood-supply situation of patients with chronic middle cerebral artery occlusion(CMCAO)and the relationship between that and cerebral infarction area.Methods:A total of 112 patients with unilateral CMCAO admitted to Handan Central Hospital from April 2019 to December 2021 were selected,and all of them were divided into a compensatory group(50 cases)with anterior cerebral artery(ACA)leptomeningeal anastomoses(LMA)and an uncompensated group(62 cases)according to the results of digital subtraction angiography(DSA)examination.The results of diffusion weighted imaging(DWI),magnetic resonance angiography(MRA)and dual-parameter 3D-ASL detection were respectively analyzed,and the clinical data,3D-ASL parameters and the incidence of cerebral infarction between the two groups were compared.The influence factors of compensation were further analyzed.The receiver operating characteristics(ROC)curve of LMA diagnostic value of CMCAO patients was drawn according to cerebral blood flow values[post label delay(PLD)=1.5 s,2.5 s)].The 3D-ASL parameters of patients with different cerebral infarction areas were compared,and the relationship between 3D-ASL parameters and cerebral infarction area was compared.Results:The apparent diffusion coefficient(ADC)at the side of lesion of CMCAO patients was(0.31±0.10),and cerebral blood flow values at 1.5s and 2.5s were respectively(25.67±4.25)and(54.09±4.49),which were significantly lower than those at the side of healthy,and the differences were statistically significant(t=27.591,34.210,3.913,P<0.05),respectively.The differences of cerebral blood flow values(1.5s and 2.5s)between compensatory group and uncompensated group were significant(t=5.584,4.090,P<0.05),respectively.The results of logistic regression analysis showed that age,stroke,cerebral infarction area and cerebral blood flow values(1.5 s and 2.5 s)were influencing factors on LMA compensation of CMCAO patients(OR=4.187,6.604,0.482,5.681,5.807,P<0.05),respectively.The ROC values showed that the area under curve(AUC)of 3D-ASL were respectively 0.720 and 0.812 in diagnosing LMA when PLD were respectively 1.5s and 2.5s.The proportion of normal and lacunar infarctions in the compensatory group was significantly higher than that in the uncompensated group,while the proportions of middle and small infarction,and large area infarctions of the compensatory group were significantly lower than those of the uncompensated group,and the difference was statistically significant(t=28.062,P<0.05).The difference in cerebral blood flow values(1.5s)among patients with different infarct areas was statistically significant(t=0.202,P<0.05).The cerebral blood flow value(1.5s)of 3D-ASL was negatively correlated with the area of cerebral infarction(r=-0.261,P<0.05).Conclusion:Dual parameter 3D-ASL can non-invasively and visually assess the compensatory status of LMA of patients with unilateral CMCAO.The blood flow perfusion of middle cerebral artery(MCA)at the side of lesion is related to the area of cerebral infarction.When the PLD is 1.5s,the sensitive response can be conducted on this,so as to provide objective and reliable basis for clinical diagnosis and treatment and curative effect.