Exploration of potential active ingredients and mechanism of action of Xihuang pill-medicated serum against glioma based on HPLC-Q-TOF-MS/MS, network pharmacology and experimental verification / 药学学报

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC50 of 30.96 μmol·L-1, and KBA (30 μmol·L-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway.@*METHODS@#Different doses (12.5-800 µg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC50) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside.@*RESULTS@#Asperuloside of 325, 650, and 1300 µg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions (P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (P<0.05), and 650 µg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3, -4 and GRP78 protein expressions (P<0.05).@*CONCLUSION@#Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

The Ubiquitin Ligase SMURF1 Catalyzes the Polyubiquitination of ADAR1 / 中国生物化学与分子生物学报

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

Effect of Atglistatin on PA-induced VSMCs proliferation and ATGL expression / 中国临床药理学与治疗学

AIM: With building a proliferation model of PA-induced VSMC, the effect of ATGL, a key fat metabolism enzyme, on the phenotype transformation of VSMC was preliminarily explored. METHODS: 40 μmol/L Atglistatin was added to the proliferation model of VSMC induced by PA (50 μmol/L, 100 μmol/L, and 200 μmol/L, respectively) at separately administered concentrations, and cell viability and cell proliferation were detected by CCK-8 and EDU; cell migration ability was detected by scratch assay; oil red staining was used to detect the accumulation of lipid droplets in VSMC was detected by oil red staining; the effects of PA on ATGL as well as the effects of smooth muscle contraction phenotype proteins were examined by Western blot. RESULTS: PA at a concentration of 100 μmol/L could significantly induce VSMC proliferation, promote lipophagy and increase lipid droplet accumulation in VSMC; meanwhile, Atglistatin could exacerbate these changes caused by PA and increase lipid droplet accumulation in VSMC. CONCLUSION: Atglistatin exacerbates PA-induced VSMC proliferation and increases VSMC lipid droplet accumulation, and exacerbates transformation of proliferative phenotype of VSMC.

Mediation of mitochondrial translocator protein by tanshinone ⅡA in apoptosis of HepG2 cells / 中国药理学通报

Aim To investigate the role of mitochondrial translocator protein(TSPO)in the apoptosis of HepG2 cells induced by tanshinone IIA(Tan II A)and the involved mechanism. Methods Following the HepG2 cells treated with Tan ⅡA at 2.5, 5 and 10 μmol·L-1, the cell viability was determined by MTT assay, and intracellular ATP content was determined by luciferin-luciferase method. Oxygen utilization was measured polarographically with a Clark oxygen electrode. Cell apoptosis was determined by Hoechst 33342 staining and flow cytometry. The mitochondrial membrane potential was assessed with JC-1 staining. The intracellular distribution of TSPO was examined by TSPO immunostaining, and the expressions of TSPO, Cyto C, caspase-3, caspase-9 were determined by immunoblotting analysis. Results Tan II A inhibited the proliferation of HepG2 cells in a dose-and time-dependent manner. The treatment with Tan II A inhibited ATP production and oxygen utilization of mitochondria. In addition, Tan ⅡA enhanced TSPO expression and accumulation in nuclei and up-regulated the expression of Cyto C, caspase-3 and caspase-9. Conclusions Tan II A induces the apoptosis of HepG2 cells, which may be related to the TSPO-mediated mitochondrial dysfunction.

Research progress of reversion multi-drug resistance in tumor by berberine / 中国药理学通报

Tumor is a kind of disease with high morbidity, high mortality and poor prognosis. Chemotherapy is the main treatment of tumor, but the problem of chemotherapy resistance is becoming increasingly prominent, so finding ways to overcome chemotherapy resistance and improve the therapeutic effect has become an urgent problem to be solved. At present, with the development of research, the anti-tumor effect of some traditional Chinese medicine has attracted extensive attention. Berberine, traditionally used in the treatment of digestive system diseases, has been proved to have the effect of anti-tumor and reversing tumor multi-drug resistance. This review summarizes the recent researches on the reversion multi-drug resistance in tumor by berberine, in order to explore the means to improve the therapeutic effect and prognosis of tumor drug resistance.

Malignant gastrointestinal neuroectodermal tumor: a clinicopathological analysis of three cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.

Screening of small molecule inhibitors of IL-15Rα using molecular docking and surface plasmon resonance technology / 生理学报

The study aims to explore the active molecules of traditional Chinese medicine that specifically bind to interleukin-15 receptor α (IL-15Rα) using molecular docking and surface plasmon resonance (SPR) technology. AutoDock molecular docking software was used to perform simulated docking of more than 3 000 compounds from 48 traditional Chinese medicines at IL-15Rα and screen the specific binding compounds. Then Biocore T200 biomolecular interaction analysis system of SPR was used to confirm the binding specificity of the selected target compounds. Finally, the biological effects of the target compounds on IL-15Rα were verified by cell biological experiments. The results showed that neoprzewaquinone A (Neo) possessed the highest specific binding affinity among the active molecules from traditional Chinese medicine, and the dissociation constant (KD) value was (0.62 ± 0.20) µmol/L. The results of cell experiment showed that Neo significantly inhibited the proliferation of Mo7e cells induced by IL-15, and the IC50 was 1.075 µmol/L, approximately 1/120 of the IC50 of Cefazolin (IL-15 specific antagonist). These results suggest that Neo is a specific inhibitor of IL-15Rα and may be a potential active drug for the treatment of diseases related to the dysfunction of the IL-15Rα signaling.

Characteristics and phylogenetic analysis of chloroplast genome of a new type of fruit Rubus rosaefolius / 生物工程学报

The genomic DNA of Rubus rosaefolius was extracted and sequenced by Illumina NovaSeq platform to obtain the complete chloroplast genome sequence, and the sequence characteristics and phylogenetic analysis of chloroplast genes were carried out. The results showed that the complete chloroplast genome of the R. rosaefolius was 155 650 bp in length and had a typical tetrad structure, including two reverse repeats (25 748 bp each), a large copy region (85 443 bp) and a small copy region (18 711 bp). A total of 131 genes were identified in the whole genome of R. rosaefolius chloroplast, including 86 protein coding genes, 37 tRNA genes and 8 rRNA genes. The GC content of the whole genome was 36.9%. The genome of R. rosaefolius chloroplast contains 47 scattered repeats and 72 simple sequence repeating (SSR) loci. The codon preference is leucine codon, and the codon at the end of A/U is preferred. Phylogenetic analysis showed that R. rosaefolius had the closest relationship with R. taiwanicola, followed by R. rubraangustifolius and R. glandulosopunctatus. The chloroplast genome characteristics and phylogenetic analysis of R. rosaefolius provide a theoretical basis for its genetic diversity research and chloroplast development and utilization.

Chloroplast genomic characterization and phylogenetic analysis of Pellionia scabra / 生物工程学报

Pellionia scabra belongs to the genus Pellionia in the family of Urticaceae, and is a high-quality wild vegetables with high nutritional value. In this study, high-throughput techniques were used to sequence, assemble and annotate the chloroplast genome. We also analyzed its structure, and construct the phylogenetic trees from the P. scabra to further study the chloroplast genome characteristics. The results showed that the chloroplast genome size was 153 220 bp, and the GC content was 36.4%, which belonged to the typical tetrad structure in P. scabra. The chloroplast genome encodes 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes in P. scabra. Among them, 15 genes contained 1 intron, 2 genes contained 2 introns, and rps12 had trans-splicing, respectively. In P. scabra, chloroplast genomes could be divided into four categories, including 43 photosynthesis, 64 self-replication, other 7 coding proteins, and 4 unknown functions. A total of 51 073 codons were detected in the chloroplast genome, among which the codon encoding leucine (Leu) accounted for the largest proportion, and the codon preferred to use A and U bases. There were 72 simple sequence repeats (SSRs) in the chloroplast genome of P. scabra, containing 58 single nucleotides, 12 dinucleotides, 1 trinucleotide, and 1 tetranucleotide. The ycf1 gene expansion was present at the IRb/SSC boundary. The phylogenetic trees showed that P. scabra (OL800583) was most closely related to Elatostema stewardii (MZ292972), Elatostema dissectum (MK227819) and Elatostema laevissimum var. laevissimum (MN189961). Taken together, our results provide worthwhile information for understanding the identification, genetic evolution, and genomics research of P. scabra species.

The role of inflammation in heart failure with preserved ejection fraction / 生理学报

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.

A glass micropipette vacuum technique of cerebrospinal fluid sampling in C57BL/6 mice / 生理学报

The purpose of this study was to establish a suitable method for extracting cerebrospinal fluid (CSF) from C57BL/6 mice. A patch clamp electrode puller was used to draw a glass micropipette, and a brain stereotaxic device was used to fix the mouse's head at an angle of 135° from the body. Under a stereoscopic microscope, the skin and muscle tissue on the back of the mouse's head were separated, and the dura mater at the cerebellomedullary cistern was exposed. The glass micropipette (with an angle of 20° to 30° from the dura mater) was used to puncture at a point 1 mm inboard of Y-shaped dorsal vertebral artery for CSF sampling. After the first extraction, the glass micropipette was connected with a 1 mL sterile syringe to form a negative pressure device for the second extraction. The results showed that the successful rate of CSF extraction was 83.33% (30/36). Average CSF extraction amount was (7.16 ± 0.43) μL per mouse. In addition, C57BL/6 mice were given intranasally ferric ammonium citrate (FAC) to establish a model of brain iron accumulation, and the CSF extraction technique established in the present study was used for sampling. The results showed that iron content in the CSF from the normal saline control group was not detected, while the iron content in the CSF from FAC-treated group was (76.24 ± 38.53) μmol/L, and the difference was significant. These results suggest that glass micropipette vacuum technique of CSF sampling established in the present study has the advantages of simplicity, high success rate, large extraction volume, and low bleeding rate, and is suitable for the research on C57BL/6 mouse neurological disease models.

The effect and mechanism of Xihuang pill inhibits the formation of vasculogenic mimicry in human glioblastoma cells by down-regulating HIF-1α/VEGFA/VEGFR2 signaling pathway / 药学学报

Our studies were aimed to explore the effect and mechanism of the inhibition of the formation of vasculogenic mimicry (VM) in human glioblastoma cells by Xihuang pill (XHP) medicated serum through regulating the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. The medicated serum of XHP was prepared by gavage for 7 days to male SD rats (approval number of animal experiment ethics: 202105A051). The hypoxia model of U251 cells was established using 200 μmol·L-1 of CoCl2. After treatment with XHP-medicated serum, cell viability and proliferation of U251 cells were detected by CCK-8 and cell cloning experiment. Cell apoptosis and cell cycle of U251 cells were determined by flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell invasion assay. The formation of VM was assessed by three-dimensional cell culture of U251 cells. The protein expression levels of HIF-1α, VEGFA, VEGFR2, phosphorylated-VEGFR2 (p-VEGFR2), vascular endothelial-cadherin (VE-cadherin), Eph receptor tyrosine kinases A2 (EphA2), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 14 (MMP14) and laminin γ2 in U251 cells were detected by Western blot. The results showed that 10% XHP-medicated serum had little effect on the cell viability, proliferation, apoptosis and cell cycle of U251 cells under hypoxia. Compared with the model group, 10% XHP-medicated serum at 1.0, 1.5 and 2.0 h significantly decreased the migration rate (P < 0.01) and the number of invading U251 cells (P < 0.01). 10% XHP-medicated serum at 2.0 h significantly suppressed the formation of VM tubular structures in U251 cells under the condition of hypoxia (P < 0.01). Western blot experiment showed that 10% XHP-medicated serum significantly down-regulated the expression of HIF-1α, VEGFA, phospho-VEGFR2, VE-cadherin, EphA2 and MMP14 proteins (P < 0.05). In conclusion, XHP could inhibit the formation of VM in human glioblastoma U251 cells to suppress the angiogenesis by down-regulating the HIF-1α/VEGFA/VEGFR2 signaling pathway.

Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices. @*Materials and Methods@#Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated. @*Results@#Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia. @*Conclusion@#TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

Effect of miR-125b on T Cell Activation in Aplastic Anemia by Targetting B7-H4 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of miR-125b on T cell activation in patients with aplastic anemia (AA) and its molecular mechanism.@*METHODS@#A total of 30 AA patients were enrolled in department of hematology, Binzhou Medical University Hospital from January 2018 to October 2021, as well as 15 healthy individuals as healthy control (HC) group. Peripheral blood mononuclear cells (PBMCs) were isolated, in which the levels of miR-125b and B7-H4 mRNA were detected by RT-qPCR. Immunomagnetic beads were used to separate naive T cells and non-naive T cells from AA patients and healthy people to detect the levels of miR-125b and B7-H4 mRNA. Lentivirus LV-NC inhibitor and LV-miR-125b inhibitor were transfected into cells, and T cell activation was detected by flow cytometry. The dual-luciferase reporter gene assay was used to detect the targetting relationship between miR-125b and B7-H4. RT-qPCR and Western blot were used to detect the levels of miR-125b, CD40L, ICOS, IL-10 mRNA and B7-H4 protein.@*RESULTS@#Compared with HC group, the expression of miR-125b was up-regulated but B7-H4 mRNA was down-regulated in PBMCs of AA patients (P <0.05), and the proportions of CD4+CD69+ T cells and CD8+CD69+ T cells in PBMCs of AA patients were higher (P <0.05). The expression of miR-125b was significantly up-regulated but B7-H4 mRNA was down-regulated in both naive T cells and non-naive T cells of AA patients (P <0.05), and non-naive T cells was more significant than naive T cells (P <0.05). Compared with NC inhibitor group, the expression of miR-125b was significantly decreased, the expression level of CD69 on CD4+ and CD8+ T cells in PBMCs was also significantly decreased, while the luciferase activity was significantly increased after co-transfection of miR-125b inhibitor and B7-H4-3'UTR-WT in the miR-125b inhibitor group (P <0.05). Compared with NC inhibitor group, the mRNA and protein levels of B7-H4 were significantly increased in the miR-125b inhibitor group (P <0.05). Compared with miR-125b inhibitor+shRNA group, the expression levels of CD69 on CD4+ and CD8+ T cells were significantly increased, and the levels of CD40L, ICOS and IL-10 mRNA were also significantly increased in the miR-125b inhibitor+sh-B7-H4 group (P <0.05).@*CONCLUSION@#MiR-125b may promote T cell activation by targetting B7-H4 in AA patients.

Research advances in genetic polymorphisms in Kawasaki disease / 中国当代儿科杂志

Kawasaki disease (KD) is a systemic inflammatory vascular disorder that predominantly affects children and is the leading cause of acquired heart disease in children. Although the etiology of this disease remains unclear, genome-wide association and genome-wide linkage studies have shown that some susceptible genes and chromosomal regions are associated with the development and progression of KD. With the advancement of high-throughput DNA sequencing techniques, more and more genomic information related to KD is being discovered. Understanding the genes involved in the pathogenesis of KD may provide novel insights into the diagnosis and treatment of KD. By analyzing related articles and summarizing related research advances, this article mainly discusses the T cell activation-enhancing genes that have been confirmed to be closely associated with the development and progression of KD and reveals their association with the pathogenesis of KD and coronary artery lesions.

25G pars plana vitrectomy combined with Dexamethasone intravitreal implants for the treatment of vitreous hemorrhage and diabetic macular edema secondary to proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical effect of 25G pars plana vitrectomy(PPV)combined with dexamethasone intravitreal implant(DEX)on the treatment of vitreous hemorrhage and diabetic macular edema(DME)secondary to proliferative diabetic retinopathy(PDR).METHODS: Prospective clinical case study. A total of 40 patients(40 eyes)with vitreous hemorrhage and DME secondary to PDR who treated in Tianjin Eye Hospital from July 2020 to January 2022 were included in the study. All eyes underwent 25G PPV and cataract phacoemulsification. The patients were randomly divided into PPV group(20 eyes)and PPV+DEX group(20 eyes). Best corrected visual acuity(BCVA), intraocular pressure, and central macular thickness(CMT)of the patients before and 1, 3, 6mo after the operation were compared.RESULTS: All patients were followed up for 6mo. The BCVA of the patients in the PPV+DEX group improved better than that of the PPV group at 1, 3 and 6mo after surgery(P&#x003C;0.05). CMT of the PPV+DEX group was lower than that of the PPV group at 1mo after operation(P&#x003C;0.05). Retinal neovascularization or CMT regression with less than 5% was found in 8 eyes in the PPV group, who were supplemented with anti-vascular endothelial growth factor, while it was found in only 1 eye in the PPV+DEX group(P&#x003C;0.05).CONCLUSION: PPV combined with DEX could yield synergies, which provide better therapeutic effect for the patients with vitreous hemorrhage and DME secondary to PDR.

Investigation of medical humanistic practice ability of nurses and factors affecting their practices: a questionnaire-based analysis of 1196 cases in a general hospital in Hunan Province / 南方医科大学学报

OBJECTIVE@#To investigate humanistic practice ability of nurses in a general hospital in Hunan Province and analyze the factors affecting their practices to provide evidence for interventions to improve humanistic practice ability of the nurses.@*METHODS@#A total of 1196 nurses were surveyed using a self-designed questionnaire and a nurse humanistic practice ability assessment scale questionnaire for assessment of their abilities for humanistic care practice, psychological adjustment, interpersonal communication, self-management, ethics and legal practice. Univariate and multivariate analyses were performed for analysis of the factors affecting the practice abilities of the nurses.@*RESULTS@#The total score of humanistic practice ability of the 1196 nurses was 105.69±16.45 (the full score of the scale was 130), and the scores of humanistic care practice ability, psychological adjustment ability, interpersonal communication ability, self-management ability, ethics and legal practice ability were 40.95±6.46, 16.41±2.66, 16.41±2.66, 11.32±2.05 and 12.43±2.00, respectively. Univariate analysis and multiple linear regression analysis showed that gender (P=0.033), age (P < 0.001), department (P=0.015), working years (P < 0.001), professional title (P < 0.001), first academic degree (P < 0.001), highest academic degree (P < 0.001), family location (P=0.010), marital status (P=0.023), number of patients to care for (P=0.022), number of children (P=0.001), previous humanities related training (P < 0.001), training times (P < 0.001), and care received from family members (P < 0.001) and colleagues (P < 0.001) were all the factors affecting humanistic practice ability of the nurses. Among these factors, age, working in department of obstetrics and gynecology and emergency department, professional title, humanities training, and care from family and colleagues explained 20.7% of the variance.@*CONCLUSION@#The humanistic practice ability of nurses in this general hospital is above the average level, but their self-management ability needs to be improved. Intervention measures should be implemented to improve the nurses' humanistic practice ability including more attentions to the key groups and departments, strengthening the training of humanistic practice ability, and improving the promotion assessment system.

A long-term evaluation of periodontal phenotypes before and after the periodontal-orthodontic-orthognathic combined treatment of lower anterior teeth in patients with skeletal Angle class Ⅲ malocclusion / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the changes of periodontal phenotype (width of keratinized gingiva, thickness and height of alveolar bone) of lower anterior teeth in patients with skeletal class Ⅲ malocclusion before and after the periodontal-orthodontic-orthognathic combined treatment.@*METHODS@#In the study, 20 patients with skeletal class Ⅲ malocclusion (6 males and 14 females) completed the periodontal-orthodontic-orthognathic combined treatment were included from March 2017 to June 2022, with 39 central incisors, 40 lateral incisors and 40 canines. The mean age was (25.40±4.27) years (20-34 years). The mean follow-up time was (3.70±1.05) years from the beginning of periodontal corticotomy regenerative surgery (PCRS) to the end of the combined treatment. Cone-beam computed tomography (CBCT) was used to measure the thickness, area and height of alveolar bone by the same researcher, taken before the PCRS (T0), 6 months after the PCRS (T1), 12 months after the PCRS (T2), before the orthognathic surgery (T3), and after the periodontal-orthodontic-orthognathic combined treatment (T4). The periodontal clinical parameters were used to evaluate changes in the soft tissue by another researcher, measured before the PCRS (T0) and after the combined treatment (T4). Changes of soft and hard tissue were evaluated by the periodontal phenotype.@*RESULTS@#The width of keratinized gingiva increased significantly (all P < 0.001) in lower anterior teeth, the central incisors, lateral incisors and canines increased by (1.82±1.57) mm, (2.03±1.48) mm and (2.05±1.27) mm, respectively. The proportion of thick periodontal biotype in the central and lateral incisors increased significantly (all P < 0.001), while the changes of periodontal biotypes in the lower canines were not obvious. The thickness of labial alveolar bone of lower anterior teeth all increased significantly after periodontal corticotomy regenerative surgery and the combined treatment (all P < 0.001). The area of labial alveolar bone of lower anterior teeth also increased significantly after the combined treatment (all P < 0.001). The whole area of labial and lingual alveolar bone of central and lateral incisors increased (P < 0.001), while the whole area of canines remained the same. All The height of the alveolar bone increased (all P < 0.001) on the labial side after the treatment.@*CONCLUSION@#The periodontal phenotypes of lower anterior teeth were significantly improved after the periodontal-orthodontic-orthognathic combined treatment in patients with skeletal Angle class Ⅲ malocclusion. The improvement was long-termly stable, and the periodontal risk was reduced.

Changes and significance of type 2 innate lymphoid cells and their related factors in bronchopulmonary dysplasia / 中国当代儿科杂志

OBJECTIVES@#To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD).@*METHODS@#A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth.@*RESULTS@#The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05).@*CONCLUSIONS@#Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.