To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Objective To investigate the value of computer-assisted quantification of pulmonary embolism volume(PEV)in identifying mild-to-high-risk acute pulmonary embolism(APE).Methods We retrospectively enrolled 143 patients with suspected APE confirmed by computed tomography pulmonary angiography(CTPA)at Yan'an University Affiliated Hospital from January 2017 to December 2020.According to the 2018 Chinese Guidelines for Diagnosis,Treatment and Prevention of Pulmonary Thromboembolism,all the patients were divided into low-risk group(n=88)and mild-to-high-risk group(n=55).We collected the patients'basic demographic data,clinical manifestations,and serum levels of N-terminal-B type natriuretic peptide precursor(NT-proBNP)and D-dimer.Based on CTPA images,the degree of pulmonary thromboembolism was artificially evaluated to obtain the pulmonary artery occlusion index(PAOI).The thrombus was segmented using the pulmonary embolism detection tool based on digital lung,and PEV was calculated.We compared the differences in clinical and laboratory indicators and PAOI and PEV between the two risk groups.We analyzed the value of PAOI and PEV in identifying mild-to-high-risk APE using receiver operating characteristic(ROC)curves,and used Logistic regression analysis to identify independent risk factors in predicting mild-to-high-risk APE.Different models were established.Results Compared with the low-risk group,APE patients in the mild-to-high-risk group were older(P＜0.05),had lower diastolic blood pressure(P＜0.05),higher levels of D-dimer and NT-proBNP(P＜0.05),lower levels of platelet count,arterial oxygen partial pressure and arterial carbon dioxide partial pressure(P＜0.05),and higher levels of PAOI and PEV(P＜0.001).ROC curve analysis showed that the area under the curve for PEV in identifying mild-to-high-risk APE was 0.809(95％CI:0.734-0.884),while that for PAOI was 0.753(95％CI:0.667-0.839).Logistic regression analysis showed that PEV and NT-proBNP were independent risk factors for mild-to-high-risk APE(P＜0.05).Conclusion PEV and NT-proBNP are independent risk factors for mild-to-high-risk APE.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To analyze the epidemiological characteristics and temporal spatial clustering of hand, foot, and mouth disease in Hubei Province from 2010 to 2023, and to provide evidence for formulating prevention and control measures. Methods Descriptive epidemiological method was used to analyze the surveillance data of hand, foot, and mouth disease of Hubei Province from 2010 to 2023, and spatial clustering analysis was conducted at the district/county level using ArcGIS 10.5 software. Results A total of 1 007 600 cases of hand, foot, and mouth disease were reported from 2010 to 2023, and the average annual incidence rate was 123.60/100 000. Overall , it exhibited a cyclical pattern of high incidence every other year. Except for a few years, two peaks of incidence were observed each year, , with the first peak occurring between April to July and the second occurring in October to December, and the popular season was concentrated from April to July. Children aged < 5 years were primarily affected, with a high incidence in male patients (1.53:1). The incidence of hand, foot, and mouth disease showed a positive spatial autocorrelation（Moran's I was between 0.15 to 0.76, P<0.05）at the district/county level. The hot spots were concentrated in the northwest and southeast of Hubei Province, and the cool spots were concentrated in the east of central Hubei Province. Conclusion The incidence of hand, foot, and mouth disease has obvious seasonality and spatial clustering in Hubei Province. The key prevention and control areas are concentrated in the northwest and southeast of Hubei. Enhanced prevention and control measures should be targeted on children under 5 years old and key areas to effectively reduce the occurrence of cases.

Objective To explore the application of painless diagnosis and treatment technology in children's peripherally inserted central catheter(PICC)guided by ultrasound.Methods Totally 82 children who planned to undergo PICC in the hospital from January 2021 to January 2023 were selected and randomly divided into a control group and an observation group using a random number table method,with 41 cases in each group;The control group underwent conventional ultrasound guided PICC catheterization,while the observation group underwent painless diagnostic and therapeutic techniques using ultrasound guided PICC catheterization;Compare the success rate of catheterization,completion time of catheterization,degree of pain in the child pain[children's pain behavior scale(FLACC)],tolerance[Houpt behavior scale(HBS)],compliance[Frankl scale(FCS)],and family satisfaction between the two groups.Results The success rate of catheterization in the observation group was higher than that in the control group,and the catheterization time was shorter than that in the control group,with a statistically significant difference(P<0.05).The FLACC score of the observation group was lower than that of the control group,while the HBS score and FCS score were higher than those of the control group,with a statistically significant difference(P<0.05);The total satisfaction of family members in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion The use of painless diagnosis and treatment technology in ultrasound-guided PICC catheterization in children can improve the success rate of catheterization,shorten the catheterization time,reduce the degree of pain in children,enhance tolerance and compliance,and improve family satisfaction.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate the role of solute carrier family 7 member 11(SLC7A11)in the pathogenesis and progression of clear cell renal cell carcinoma(ccRCC)and its prognostic significance.Methods Mendelian randomization analysis was employed to identify genes causally associated with the risk of ccRCC.The expression patterns and prognostic relevance of SLC7A11 were assessed using RNA sequencing data and clinical information obtained from the UCSC Xcna pan-cancer cohort.Gene set enrichment analysis(GSEA)was conducted using data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma(TCGA-KIRC)dataset(training set).A prognostic model based on SLC7A11 was then developed using stepwise Cox regression and validated externally in the E-MTAB-1980 cohort(validation set).Results Elevated level of SLC7A11 was associated with an increased risk of ccRCC(HR=1.27,95％CI:1.15-1.40,P＜0.001).SLC7A11 was overexpressed in various tumors and correlated with higher T stage and poorer survival(P＜0.05).GSEA demonstrated that SLC7A11 was enriched in pathways related to proliferation and metastasis,including E2F and epithelial-to-mesenchymal transition signaling pathways.Moreover,the SLC7A11 prognostic model exhibited robust predictive performance in both the training set(1-,3-,and 5-year AUC=0.78,0.73,0.71,respectively)and the external validation set(1-,3-,and 5-year AUC=0.70,0.71,0.72,respectively).Conclusion SLC7A11 can be a potential biomarker and therapeutic target for ccRCC,offering novel perspectives for precision medicine.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.