Objective To optimize the formulation of a new kind of ultrasound contrast agents carrying the sensitizer of hematoporphyrin(HP)with[Poly(lactic-co-glycolic acid),PLGA]for material.Methods The technique of double emulsion was applied to produce HP loaded PLGA ultrasound microbubbles,which was optimized through orthogonal test using encapsulation efficiency for the detected index.Then morphology and distribution of HP-PLGA microbubbles were observed through light microscope and scaning electron microscope.The size,Zeta potential and the properties of releasing behavior and ultrasound imaging in vitro of Hp-PLGA contrast agents were detected.Results The optimization parameters were picked out as 10 mg/ml for concentration of HP,40 mg for PLGA,and 1/5 for volume ratio of water inside to dichloromethane.The optimized HP-PLGA contrast agents were spheric with the mean size of 602.3 nm,and Zeta potentiaI of-(17.1±1.6)mV.The drug loading and encapsulation efficiency of HP-PLGA were(2.15±0.15)%and(63.5±2.6)%,respectively.And the releasing behavior of HP-PLGA contrast agents in vitro was that after an obvious release of about 35.1%in former 24 h,there were 86.5%HP-PLGA released within 14 days.The ultrasound imaging of HP-PLGA could be enhanced obviously in vitro.Conclusions The self-made HP-PLGA ultrasound microbubble might be a useful tool for delivering sensitizer and thus provide a novel strategy for sonodynamic therapy on tumor.

OBJECTIVE: To validate the 2016 ISGPS definition and grading scheme and investigate whether it segregates into distinct subclasses. METHODS: A total of 522 patients undergone pancreaticoduodenectomy in two pancreatic centers were reviewed. The 2016 ISGPS scheme was validated by comparing clinical and economic outcomes between different ISGPS grades. B-POPF were divided into 2 subgroups as B1(without invasive procedures) and B2(with invasive procedures) then outcomes were analyzed across the subgroups. RESULTS: Biochemical leak(BL) did not differ from the non-fistula condition in all outcomes except postoperative hospital stay and cost. Non-fistula/BL,B-POPF and C-POPF condition differed significantly in terms of all clinical and economic outcomes except 30-day readmission rate.B1 differ from B2 subgroup greatly in terms of most critical terms of outcomes such as hemorrhage(15.2% vs. 34.3%,P=0.045),biliary fistula(13.0% vs 34.3%,P=0.023),postoperative hospital stay(32.0 d vs. 39.0 d,P=0.011). CONCLUSION: The present study has confirmed the effectiveness of the 2016 ISGPS definition and grading scheme in identifying three conditions that differ in terms of clinical and economic outcomes. Subclassification of B-POPF according to whether invasive procedures has been used has potential implications for accurate reporting and performance evaluation.

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

This study explored the medication rules of Chinese herbal compound prescriptions for the treatment of angina based on the Chinese herbal compound patents in the patent database of the China National Intellectual Property Administration. The data of eligible Chinese herbal compound patents for the treatment of angina were collected from the patent database of the China National Intellectual Property Administration from database inception to November 10, 2022, and subjected to data modeling, analysis of main syndromes, medication frequency analysis, cluster analysis, association rule analysis, and data visualization by using Excel 2021, IBM SPSS Statistics 26.0, IBM SPSS Modeler 18.0, Cytoscape 3.9.1, and Rstudio R 4.2.2.2 to explore the medication rules for angina. The study included 636 pieces of patent data for angina that met the inclusion criteria, involving 815 drugs, with a total frequency of 6 586. The most common main syndromes were blood stasis obstructing the heart syndrome(222, 34.91%) and Qi deficiency and blood stasis syndrome(112, 17.61%). The top 10 most frequently used drugs were Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoginseng Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Borneolum Syntheticum, and Corydalis Rhizoma. High-frequency drugs included blood-activating and stasis-resolving drugs(1 197, 18.17%) and deficiency-tonifying drugs(809, 12.28%). Cluster analysis identified eight drug combinations, including five new prescriptions suitable for clinical use and new drug development, and three drug pairs. The core drug combination of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Carthami Flos was identified through the complex co-occurrence network analysis of Chinese medicines. Association rule analysis yielded a total of 17 rules, including 13 drug pairs and 4 tripartite combinations. Common drug pairs included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma(support degree 25.79%, confidence coefficient 69.49%, lift 1.30) and Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma(support degree 22.01%, confidence coefficient 61.95%, lift 1.16). Common tripartite combinations included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix(support degree 10.85%, confidence coefficient 73.40%, lift 1.37) and Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Notoginseng Radix et Rhizoma(support degree 10.69%, confidence coefficient 79.07%, lift 1.48). The results showed that the underlying pathogenesis of angina involved blood stasis obstructing the heart and Qi deficiency and blood stasis. The overall nature of the disease was characterized as asthenia in origin and sthenia in superficiality. In the prescription formulation, blood-activating and stasis-resolving drugs, such as Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Carthami Flos were often used to resolve the excess manifestation, which were combined with tonifying drugs such as Astragali Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, and Ginseng Radix et Rhizoma to reinforce the deficiency. The syndrome, pathogenesis, disease nature, and medication were consistent with clinical practice. Additionally, the new compound prescriptions and drug combinations derived from the multiple data mining in this study could provide references and insights for the clinical diagnosis and treatment of angina and the development of new drugs.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Angina Pectoris/drug therapy* ; Prescriptions ; Data Mining ; Drug Combinations