Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

OBJECTIVE: To investigate the risk factors, clinical characteristics, and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease, so as to provide a reference for infection control. METHODS: The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected. The clinical characteristics, susceptibility factors, and antibiotic resistance of the children were retrospectively analyzed. RESULTS: Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children (≤14 years old) with hematological diseases was the highest (19.91%) and significantly higher than other bacteria, accounting for 38.64% of Gram-positive cocci, and presented as an increasing trend year by year. A total of 427 children tested positive blood cultures, including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever. Most children experienced a recurrent high fever in the early and middle stages (≤6 d) of neutropenia and persistent fever for more than 3 days. After adjusting the antibiotics according to the preliminary drug susceptibility results, the body temperature of most children (63.5%) returned to normal within 4 days. The 85 children were mainly diagnosed with acute myeloid leukemia (AML), accounting for 84.7%. The proportion of children in the neutropenia stage was 97.7%. The incidence of oral mucosal damage, lung infection, and gastrointestinal injury symptoms was 40%, 31.8%, and 27.1%, respectively. The ratio of elevated C-reactive protein (CRP) and procalcitonin was 65.9% and 9.4%, respectively. All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid, and the resistance rate to penicillin, cefotaxime, levofloxacin, and quinupristin-dalfopristin was 10.6%, 8.2%, 9.4%, and 14.1%, respectively. None of children died due to bloodstream infection caused by Streptococcus mitis. CONCLUSION The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases, especially in children with AML. Among them, neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors. The common clinical symptoms include persistent high fever, oral mucosal damage, and elevated CRP. Penicillin and cephalosporins have good sensitivity. Linezolid, as a highly sensitive antibiotic, can effectively control infection and shorten the course of disease.
Humans ; Child ; Streptococcal Infections/microbiology* ; Retrospective Studies ; Hematologic Diseases/complications* ; Streptococcus mitis ; Drug Resistance, Bacterial ; Risk Factors ; Microbial Sensitivity Tests ; Anti-Bacterial Agents ; Female ; Male ; Bacteremia/microbiology* ; Child, Preschool ; Adolescent

OBJECTIVE: To investigate the effect of aquaporin 5 (AQP5) on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in Sjögren syndrome (SS) rats. METHODS: The SS gene expression data sets GSE406611 and GSE84844 were extracted from the Gene Expression Omnibus (GEO), and the AQP5 mRNA expression was analyzed by R software. The rat SS model was constructed. The successfully modeled rats were divided into SS group, SS+NC group, and SS+pc group, 10 rats in each group; and 10 rats were set as Normal group. The rats in the SS+NC group were injected with 10 μg of rno-pcDNA3.1-AQP5-NC at the submandibular gland, subcutaneously every day for 28 days. The rats in the SS+pc group were injected with 10 μg of rno-pcDNA3.1-AQP5 at the submandibular gland, subcutaneously every day for 28 days. The enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum. High-throughput sequencing was used to identify the target genes. Quantitative real-time PCR (qPCR) and Western blot were used to detect the mRNA and protein expressions of AQP5, TLR4, MyD88, and NF-κB in the rat submandibular gland tissue. RESULTS: In the SS dataset GSE406611 and GSE84844, the mRNA expression of AQP5 in SS was significantly reduced. Compared with the Normal group, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS group were significantly increased, the mRNA and protein expressions of AQP5 were significantly decreased. After overexpression of AQP5, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS+pc group were significantly decreased, the mRNA and protein expressions of AQP5 were significantly increased. The differences were statistically significant (all P < 0.05). CONCLUSION The expression of AQP5 is involved in the progression of SS. Increasing the expression of AQP5 can significantly inhibit inflammatory stress and reduce the pathological damage of submandibular gland tissue. This may be related to the inhibition of TLR4/MyD88/NF-κB conduction.
Animals ; Toll-Like Receptor 4/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Aquaporin 5/metabolism* ; Sjogren's Syndrome/genetics* ; Signal Transduction ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Interleukin-1beta/metabolism* ; Female

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Objective:To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022.Methods:Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed.Results:A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024.Conclusion:The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To evaluate the reliability and clinical application of a self-established classification system for the lower 1/3 humeral fractures in adults.Methods:A retrospective study was performed to analyze the 88 patients with lower 1/3 humeral fracture who had been admitted to Department of Orthopedics, The Second Hospital of Fuzhou between January 2013 and December 2020. There were 61 males and 27 females with an age of (34.6±12.7) years. The lower 1/3 humeral fractures were classified according to the location of the fracture line, displacement, and bone mass into 3 types: type Ⅰ: transverse and short oblique ones; type Ⅱ: oblique and spiral ones; type Ⅲ: oblique and spiral ones with butterfly-shaped bone mass. After a junior orthopedic surgeon, an intermediate orthopedic surgeon, a senior orthopedic surgeon, and a radiologist had learned this novel classification system, they were asked to classify the lower 1/3 humeral fractures in this cohort independently to assess the reliability of the classification system. Our treatments were based on this novel classification. Open reduction and internal fixation with a unilateral plate through a lateral approach was performed for type Ⅰ fractures, internal fixation with a unilateral plate plus compression screws through a lateral approach for type Ⅱ fractures, and double plate internal fixation through the ulnar and anterolateral approaches for type Ⅲ fractures. The functions of the radial, ulnar, and musculocutaneous nerves and fracture healing time were observed postoperatively. The shoulder and elbow functions were evaluated using Neer shoulder function score and Mayo elbow function score.Results:Of the 88 patients in this cohort, 20 were type Ⅰ, 25 type Ⅱ, and 43 type Ⅲ. The mean Kappa value for inter-observer reliability was 0.878 at the first stage and 0.914 at the second stage, and the mean Kappa value for intra-observer reliability was 0.950. All patients were followed up for (14.1±3.7) months. Iatrogenic injury to the radial nerve was observed in 2 patients, but no injury to the ulnar nerve, the musculocutaneous nerve or important blood vessels or failure of internal fixation was reported. All patients achieved bony union after (12.7±2.0) weeks. The maximum elbow flexion was 137.8°±4.8°, and the maximum elbow extension 2.4°±1.6°. The Mayo elbow function score was (92.0±3.1) points and the Neer shoulder function score (92.2±3.2) points.Conclusions:Our classification system for the lower 1/3 humeral fractures in adults is reliable. As the treatments corresponding to the novel classification system can achieve satisfactory clinical outcomes, the classification system has a clinical value.

【Objective】 To establish a blood quality monitoring indicator system, in order to continuously improve blood quality and standardized management. 【Methods】 Based on the research of literature and standards, and guided by the key control points of blood collection and supply process, the blood quality monitoring indicator system was developed. Through two rounds of Delphi expert consultation, the indicator content was further revised and improved according to expert opinions after six months of trial implementation. The indicator weight was calculated by questionnaire and analytic hierarchy process. 【Results】 A blood quality monitoring indicator system covering the whole process of blood collection and supply was constructed, including five primary indicators, namely blood donation service, blood component preparation, blood testing, blood supply and quality control, as well as 72 secondary indicators, including definitions, calculation formulas, etc. Two rounds of expert consultation and two rounds of feasibility study meeting were held to revise 17 items and the weight of each indicator was obtained through the analytic hierarchy process. After partial adjustments, a blood quality monitoring indicator system was formed. 【Conclusion】 A blood quality monitoring indicator system covering the whole process of blood collection and supply has been established for the first time, which can effectively evaluate the quality management level of blood banks and coordinate blood quality control activities of blood banks in Shandong like pieces in a chess game, thus improving the standardized management level