Objective To investigate the safety and effectiveness of Acostream thrombus suction device in the treatment of acute medium-high risk pulmonary embolism(APE).Methods Ten patients with APE medium-high risk treated with Acostream thrombus suction device in Wenzhou Central Hospital from June 2022 to January 2024 were selected as subjects.Clinical observation indicators such as vital signs and auxiliary examination before surgery and 72h after surgery were collected to record the relief of symptoms and complications.The safety and efficacy of the Acostream thrombus suction device for thrombus removal in the pulmonary arteries were evaluated.Respiratory status and complications were assessed at the 1,2 and 3 months.Results All patients completed the operation through the Acostream thrombus suction device.One patient was transferred to the Intensive Care Unit after 3d of automatic discharge because of the septic shock aggravation,and the remaining 9 patients showed significant improvement in strenuous breathing and other symptoms.At 72h after surgery,arterial blood oxygen partial pressure,finger pulse oxygen,heart rate,troponin I,N-terminal prohormone of brain natriuretic peptide,D dimer,and right ventricular ratio to left ventricular diameter of patients were improved compared with preoperative value,and the difference was statistically significant(P＜0.05).During the follow-up period,one patient relapsed due to the withdrawal of anticoagulants.Conclusion Acostream thrombus suction device is safe,effective,and has high clinical application value in the treatment of medium-high risk APE.

Objective To investigate the safety and effectiveness of Acostream thrombus suction device in the treatment of acute medium-high risk pulmonary embolism(APE).Methods Ten patients with APE medium-high risk treated with Acostream thrombus suction device in Wenzhou Central Hospital from June 2022 to January 2024 were selected as subjects.Clinical observation indicators such as vital signs and auxiliary examination before surgery and 72h after surgery were collected to record the relief of symptoms and complications.The safety and efficacy of the Acostream thrombus suction device for thrombus removal in the pulmonary arteries were evaluated.Respiratory status and complications were assessed at the 1,2 and 3 months.Results All patients completed the operation through the Acostream thrombus suction device.One patient was transferred to the Intensive Care Unit after 3d of automatic discharge because of the septic shock aggravation,and the remaining 9 patients showed significant improvement in strenuous breathing and other symptoms.At 72h after surgery,arterial blood oxygen partial pressure,finger pulse oxygen,heart rate,troponin I,N-terminal prohormone of brain natriuretic peptide,D dimer,and right ventricular ratio to left ventricular diameter of patients were improved compared with preoperative value,and the difference was statistically significant(P＜0.05).During the follow-up period,one patient relapsed due to the withdrawal of anticoagulants.Conclusion Acostream thrombus suction device is safe,effective,and has high clinical application value in the treatment of medium-high risk APE.

Objective To compare the safety and tiveness of AngioJet rheolytic thrombectomy(ART)and aspiration thrombectomy(AT)combined with catheterdirected thrombolysis(CDT)in the treatment of early mass inferior vena cava filter-associated thrombosis(IVCFT).Methods A total of 63 patients with IVCFT detected during inferior vena cava filter extraction in Wenzhou Central Hospital from September 2017 to September 2023 were selected as the subject and divided into ART group(n=26)and AT+CDT group(n=37)according to different treatment methods.IVCFT was treated with ART in ART group,IVCFT was treated with AT combined with CDT in AT+CDT group.The removal rate of inferior vena cava filter,changes in hemoglobin level,incidence of related complications and the occurrence of post-thrombotic syndrome(PTS)during follow-up were compared between two groups.Results The filter was all successfully removed in ART group,while 2 patient in AT+CDT group the filter was not removed.There were 12 cases of hemoglobinuria in ART group and 8 cases of hematoma around the blood vessel sheath in AT+CDT group.No significant organ bleeding,pulmonary embolism,or inferior vena cava injury occurred in two groups.Within 1 year of follow-up,1 case occurred PTS in AT+CDT group.Conclusion ART and AT combined with CDT are safe and effective in the treatment of early mass IVCFT.Compared with AT combined with CDT,ART has a considerable clinical effect,which can reduce the thrombus load of inferior vena cava filter,increase the extraction rate of inferior vena cava filter,and reduce the incidence of long-term PTS.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Objective:To establish a method for evaluating the material attributes and skeletal performance of 2208 hydroxypropyl methylcellulose(HPMC),to clarify the influence of different material attributes on the skeletal per-formance of HPMC,to compare the differences between the products of different manufacturers,and to analyze the factors affecting the process.Methods:In this study,the material attributes such as powder chemical properties,viscosity,gelation temperature,thermodynamic properties,weight-average molecular weight,methoxy and hydroxypropoxy contents of different manufacturers were firstly investigated.Then,the water absorption,swelling,and dissolution properties of HPMC blank skeleton tablets were determined using the weighing method.Finally,Principal Component Analysis(PCA)and Orthogonal Partial Least-Squares Discrimination Analysis(OPLS-DA)were used to systematically evaluate the material attributes and skeleton performance of HPMC.The systematic evaluation of each material attribute and skeleton performance of HPMC was carried out to elucidate the intrinsic relationship between each material attribute and skeleton performance of HPMC.Results:The results showed that there were obvious differences in the material attributes of HPMC from different manufacturers,such as the proper-ties of powder,viscosity,and weight-average molecular weight,and that there were differences in the corrosion performance,water absorption,and swelling performance of the skeleton tablets prepared from different manufactur-ers,with the most obvious differences between K4Mand K100M.The results of the PCA and OPLS-DA analyses indicated that these 19 variables showed some correlation with each other.Both mathematical models showed better differentiation and classification effects on HPMC samples,and the OPLS-DA model had better classification effects than the PCA model.Conclusion:Based on the PCA and OPLS-DA models,this study conducted systematical research on HPMC,clarified the degree of influence of different material attributes on the skeletal performance of HPMC,and suggested the addition of HPMC particle size and size distribution,and weight-average molecular weight as the quality standards,which provide a basis for the quality control of the related excipients,the screening of formulation prescriptions,and the improvement of performance.

Objective:To establish a method for evaluating the material attributes and skeletal performance of 2208 hydroxypropyl methylcellulose(HPMC),to clarify the influence of different material attributes on the skeletal per-formance of HPMC,to compare the differences between the products of different manufacturers,and to analyze the factors affecting the process.Methods:In this study,the material attributes such as powder chemical properties,viscosity,gelation temperature,thermodynamic properties,weight-average molecular weight,methoxy and hydroxypropoxy contents of different manufacturers were firstly investigated.Then,the water absorption,swelling,and dissolution properties of HPMC blank skeleton tablets were determined using the weighing method.Finally,Principal Component Analysis(PCA)and Orthogonal Partial Least-Squares Discrimination Analysis(OPLS-DA)were used to systematically evaluate the material attributes and skeleton performance of HPMC.The systematic evaluation of each material attribute and skeleton performance of HPMC was carried out to elucidate the intrinsic relationship between each material attribute and skeleton performance of HPMC.Results:The results showed that there were obvious differences in the material attributes of HPMC from different manufacturers,such as the proper-ties of powder,viscosity,and weight-average molecular weight,and that there were differences in the corrosion performance,water absorption,and swelling performance of the skeleton tablets prepared from different manufactur-ers,with the most obvious differences between K4Mand K100M.The results of the PCA and OPLS-DA analyses indicated that these 19 variables showed some correlation with each other.Both mathematical models showed better differentiation and classification effects on HPMC samples,and the OPLS-DA model had better classification effects than the PCA model.Conclusion:Based on the PCA and OPLS-DA models,this study conducted systematical research on HPMC,clarified the degree of influence of different material attributes on the skeletal performance of HPMC,and suggested the addition of HPMC particle size and size distribution,and weight-average molecular weight as the quality standards,which provide a basis for the quality control of the related excipients,the screening of formulation prescriptions,and the improvement of performance.

Objective To compare the safety and tiveness of AngioJet rheolytic thrombectomy(ART)and aspiration thrombectomy(AT)combined with catheterdirected thrombolysis(CDT)in the treatment of early mass inferior vena cava filter-associated thrombosis(IVCFT).Methods A total of 63 patients with IVCFT detected during inferior vena cava filter extraction in Wenzhou Central Hospital from September 2017 to September 2023 were selected as the subject and divided into ART group(n=26)and AT+CDT group(n=37)according to different treatment methods.IVCFT was treated with ART in ART group,IVCFT was treated with AT combined with CDT in AT+CDT group.The removal rate of inferior vena cava filter,changes in hemoglobin level,incidence of related complications and the occurrence of post-thrombotic syndrome(PTS)during follow-up were compared between two groups.Results The filter was all successfully removed in ART group,while 2 patient in AT+CDT group the filter was not removed.There were 12 cases of hemoglobinuria in ART group and 8 cases of hematoma around the blood vessel sheath in AT+CDT group.No significant organ bleeding,pulmonary embolism,or inferior vena cava injury occurred in two groups.Within 1 year of follow-up,1 case occurred PTS in AT+CDT group.Conclusion ART and AT combined with CDT are safe and effective in the treatment of early mass IVCFT.Compared with AT combined with CDT,ART has a considerable clinical effect,which can reduce the thrombus load of inferior vena cava filter,increase the extraction rate of inferior vena cava filter,and reduce the incidence of long-term PTS.

OBJECTIVE To prepare the Eriodictyol chewable tablet and to evaluate its quality. METHODS The chewable tablet was prepared by the wetting granulation method by using microcrystalline cellulose （MCC） and mannitol as fillers， polyvinylpyrrolidone （PVP） as adhesive， citric acid and sucralose as flavor correction agents， magnesium stearate as lubricant. The comprehensive evaluation was conducted on Eriodictyol chewable tablets with the dosage of each excipient as a factor using the appearance， taste， flavor and texture as indicators. The ratio of excipients was optimized by orthogonal test， and the quality of Eriodictyol chewable tablets prepared by optimized formulation was evaluated in terms of appearance， weight difference， hardness， fragility， eriodictyol content， dissolution and content uniformity. RESULTS The optimal formulation was as follows： 26.4% eriodictyol （50 mg each piece）， 45% mannitol， 25% MCC， 0.3% citric acid， 0.3% sucralose， 1% magnesium stearate， 2% PVP （preparing 5% solution using purified water）. The scores of 3 batches of Eriodictyol chewable tablets in the validation test were 8.76， 8.75 and 8.80 （RSD＝0.30%， n＝3）， respectively. The Eriodictyol chewable tablet had a complete appearance and a smooth surface； the average tablet weight was 192.57 mg， the average hardness was 57.36 N， the fragility was 0.09%， the average content of eriodictyol per tablet was 50.74 mg， the cumulative dissolution within 30 min was exceeding 80%， and the content uniformity was 5.51. CONCLUSIONS Eriodictyol chewable tablet prepared by optimal formulation conforms to the requirements of the 2020 edition of Chinese Pharmacopoeia.

Objective:To investigate the effect of Qideng Mingmu capsule on the formation and remodeling of retinal neovascularization in mice with oxygen-induced retinopathy (OIR).Methods:Thirty-six postnatal day 7 (P7)SPF grade C57BL/6J pups were divided into normal group, OIR group, Qideng Mingmu capsule group and apatinib group by random number table method, with 9 mice in each group.The mice in the normal group were raised in normal environment.The mice in the other three groups were fed in hyperoxic environment of (75±2)% oxygen concentration for 5 days from P7 to P12 and then were fed in normal environment for 5 days from P12 to P17 to establish the OIR model.From P12, mice in Qideng Mingmu capsule group and apatinib group were given intragastric administration of Qideng Mingmu capsule (900 mg/kg) and vascular endothelial growth factor receptor 2 inhibitor apatinib (70 mg/kg) respectively, once a day for 5 consecutive days.On P17, paraffin sections of mouse eyeballs were made and stained with hematoxylin-eosin to count the number of vascular endothelial cells that broke through the internal limiting membrane.The retinal slices were prepared and stained with FITC-dextran to quantify the retinal non-perfusion area, neovascularization density and total vascular density.The distribution and fluorescence intensity of retinal vascular endothelial cell marker CD31 and pericyte marker α-smooth muscle actin (α-SMA) were observed by double immunofluorescence staining.Immunohistochemical staining was used to detect the expression and distribution of retinal hypoxia inducible factor-1α (HIF-1α) and vascular endothelial cadherin (VE-cadherin).The use and care of animals were in accordance with the Regulations on the Management of Laboratory Animals issued by the Ministry of Science and Technology.This study was approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (No.2019-30).Results:The number of vascular endothelial cells breaking through the internal limiting membrane in normal group, OIR group, Qideng Mingmu capsule group and apatinib group were (2.83±4.40), (37.33±5.43), (23.83±6.79) and (14.00±9.34), respectively, with a statistically significant overall difference ( F=28.313, P<0.001).There were more vascular endothelial cells breaking through internal limiting membrane in OIR group than in normal group, Qideng Mingmu capsule group and apatinib group, showing statistically significant differences (all at P<0.05).In the observation of mouse retinal slices, there were large non-perfusion areas, neovascularization buds and disordered distribution of blood vessels in OIR group.The distribution of blood vessels was more uniform and the areas of non-perfusion and neovascularization were smaller in Qideng Mingmu capsule group and apatinib group than in OIR group.The relative area of central retinal non-perfusion area and neovascularization density were significantly lower in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05).The immunofluorescence intensity of CD31 and the absorbance value of HIF-1α were significantly lower, and the immunofluorescence intensity of α-SMA and the absorbance value of VE-cadherin were significantly higher in normal group, Qideng Mingmu capsule group and apatinib group than in OIR group (all at P<0.05). Conclusions:Qideng Mingmu capsule can inhibit retinal neovascularization formation, increase vascular pericyte coverage, relieve retinal hypoxia and increase vascular integrity in OIR mice.It can protect the retinal vessels of OIR mice.

Objective To explore the relationship between methylene tetrahydrofolate reductase(MTHFR)C677T gene polymorphism and serum homocysteine(Hcy)levels with postoperative restenosis in patients with lower limb arteriosclerosis obliterans(ASO)after intervention.Methods A total of 92 patients with lower limb ASO treated in Wenzhou Central Hospital from January 2021 to July 2022 were divided into non-restenosis group and restenosis group according to whether patients with postoperative restenosis.General and surgical data from all patients were collected,and preoperative neutrophils,lymphocytes,platelets,fibrinogen,D-dimer,C-reactive protein,low-density lipoprotein,homocysteine,MTHFR C677T gene polymorphism,etc were tested.x2 test and Logistic regression analysis were used to compare the relationship between lower limb ASO postoperative restenosis after intervention and MTHFR C677T gene polymorphism and serum Hey.A risk scoring system was built to predict postoperative restenosis after intervention and evaluate its effectiveness.Results There were significant differences(P＜0.05)between the two groups in terms of lesion location,stent placement,stent length,serum Hcy,and MTHFR C677T gene polymorphism.Multivariate Logistic regression analysis showed that MTHFR C677T TT type,serum Hey 17.15μmol/L,lesion location in the femoral artery,and no stent placement were independent risk factors for postoperative restenosis in lower limb ASO patients(P＜0.05).The area under the curve(AUC)of receiver operating characteristic curve of the risk scoring system constructed based on independent risk factors was 0.818(95％CI:0.731-0.905),which was significantly higher than those other independent risk factors and had high efficacy.Conclusion The MTHFR C677T gene polymorphism and serum Hcy are closely related to postoperative restenosis in lower limb ASO patients.A risk scoring system based on MTHFR C677T gene polymorphism,serum Hcy,lesion location,and stent placement can help predict the occurrence of restenosis in lower limb ASO patients.