Research progress of airway inflammation in asthma: A bibliometric analysis.

BACKGROUND: In recent years, the prevalence of asthma has gradually increased and the number of asthmatics worldwide has reached 358 million, which has caused huge economic loss. Airway inflammation is an important feature of asthma, and international research in this field has a high degree of heat. Therefore, this paper uses the bibliometric method to systematically review and visualize the literature in this field, aiming to provide some reference value for follow-up related research. METHODS: To retrieve the research literature on airway inflammation in asthma from 2003 to 2022 in the Web of Science Core Collection database. The bibliometric method was used to systematically analyze the included literature data by using visualization analysis software such as CiteSpace (6.2. R4) and VOSviewer (1.6.19). RESULTS: A total of 1892 articles published in 423 journals were included in this study, from 1912 institutions in 62 countries/regions. The number of articles published between 2003 and 2022 showed a trend of fluctuating growth. The country with the largest number of articles published was China (558,29.49 %), followed by the United States (371,19.61 %) and Korea (212,11.21 %). Gibson, Peter G is the author with the highest number of publications, and Journal of Allergy and Clinical Immunology is the most published journal. CONCLUSION SUBSECTIONS: This study systematically reveals the state of the literature in the field of airway inflammation in asthma over the past 20 years. The exploration of inflammatory cell components, pathway molecules and biological agents are research hotspots in this field and should be further studied.

Characterization and In vivo Evaluation of Polymorphic Valnemulin Hydrogen Fumarate.

AIMS: In the present study, a valnemulin hydrogen fumarate prodrug was characterized, its stability was compared with valnemulin hydrochloride, and the efficacy was evaluated in Actinobacillus pleuropneumoniae-induced pneumonia in mice. METHOD: Optical microscopy, X-ray powder diffraction, infrared spectroscopy, and hydrogen nuclear magnetic resonance spectroscopy were used to study the physical and chemical properties of the prodrug. The thermal stability was investigated in comparison with valnemulin hydrochloride to improve the preparation process of valnemulin hydrogen fumarate soluble powder and maximize its drug effect. Additionally, the efficacy of valnemulin hydrogen fumarate was evaluated in a challenge-treatment trial in mice using an in vitro antimicrobial susceptibility test. RESULTS: The valnemulin hydrogen fumarate had high crystallinity. After light irradiation for 20 days, valnemulin hydrogen fumarate did not degrade, whereas valnemulin hydrochloride did. These results showed that the valnemulin hydrogen fumarate was stable. At the same dose in drinking water, the valnemulin hydrogen fumarate was more effective than the reference drug (tiamulin fumarate) in an Actinobacillus pleuropneumoniae challenge-treatment trial. CONCLUSION: Valnemulin hydrogen fumarate shows excellent potential for application as a veterinary drug.

Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Glyphosate exposure affected longevity-related pathways and reduced survival in asian honey bees (Apis cerana).

Glyphosate (N-(phosphonomethyl)glycine, GLY) ranks among the most extensively used and effective herbicides globally. However, excessive GLY utilization poses a substantial threat to the survival of honey bees (Apis cerana). Here we monitored the survival status of A. cerana treated with GLY, and conducted transcriptome sequencing of the bee gut and head to further explore potential GLY influences at the molecular level. We observed that the mortality rate of bees increased as GLY concentration escalated. Pivotal pathways emerged in response to the GLY treatment, with a substantial number of differentially expressed genes enriched in the longevity regulating pathway - multiple species. This strongly suggested that GLY may influence the physiological behavior of bees by impacting this particular pathway. Moreover, our analysis revealed a notable reduction in the enzymatic activities of CYP450 and AChE in both the bee head and intestines of when exposed to GLY. Conversely, the enzymatic activity of superoxide dismutase (SOD) in the head remained unaffected, whereas in the intestines, it exhibited a significant increase. Additionally, prophenol oxidase (PPO) and glutathione-S-transferases (GSTs) displayed contrasting trends in enzymatic activity in both organs. This study offers valuable insights into how GLY impacted the survival of A. cerana.

Berberine interferes with RSV infection of HEp-2 cells by inducing mitophagy autophagy / 中国药理学通报

Aim To explore the effect of berberine (B E) on RSV infected HEp-2 cells and the related mechanism. Methods HEp-2 cells were infected with RSV and treated with BE. Cell viability was assessed using the CCK-8 assay. Protein expression levels of NLRP3, ASC, caspase-1, PINK1, Parkin, Beclinl, p62, LC3 I,LC3 II,and BNIP3 in HEp-2 cells were detected by Western blot. The secretion level of IL-1 p in HEp-2 cells was measured using ELISA. Apoptosis rate and mitochondrial membrane potential of HEp-2 cells were examined by flow cytometry. Mitochondrial ROS (mtROS) in HEp-2 cells was detected through MitoSOX staining. Colocalization of mitochondria and autophagosomes in HEp-2 cells was investigated using immunofluorescence staining. Cyclosporin A was used for validation experiments. Results BE could significantly improve the activity of RSV-infected HEp-2 cells,reduce the apoptosis rate (P < 0. 05), and decrease the activation level of NLRP3 inflammasomes and IL-lp level (P <0. 05); BE improved mitochondrial function by increasing mitochondrial membrane potential and ATP levels,and reduced mtROS. BE significantly promoted the colocalization of mitochondria-autophagosome in RSV infected cells, inducing PINK1/ Parkin and BNIP3 to mediate mitochondrial autophagy; cyclosporine A aggravated RSV infection. Conclusions BE has protective effects on HEp-2 cells infected by RSV. The mechanism may be related to the inhibitory effect of BE on the production of mtROS and the activation of NLRP3 inflammasomes by inducing PINK1/ Parkin and BNIP3-mediated mitochondrial autophagy.

Construction of Knowledge Graph Based on Literature Data by Taking Treatment of Diabetic Peripheral Neuropathy with Traditional Chinese Medicine as An Example / 中国实验方剂学杂志

ObjectiveTo systematically sort out the knowledge framework and conceptual logic relationship of "disease-syndrome-treatment-prescription-medicine" in the existing literature on traditional Chinese medicine（TCM） treatment of diabetic peripheral neuropathy（DPN）， to construct of the knowledge map of TCM treatment of DPN， and to promote the explicitation of the implicit knowledge in the literature on the treatment of DPN with TCM. MethodTaking the literature of China National Knowledge Infrastructure about TCM treatment of DPN as the main data source， TCM-related concepts and entities were constructed by manual citation， and the corresponding relationships between the entities were established. Structured data were formed by processing with Python 3.7， and the knowledge graph was constructed based on Neo4j 3.5.34 graph database. ResultThe resulting knowledge graph with TCM diagnosis and treatment logic， defined 12 node labels such as prescriptions， Chinese medicines and syndrome types at the schema layer， as well as 4 types of relationships， such as inclusion， correspondence， selection and composition. It could support the query and discovery of nodes（syndrome elements， syndrome types and treatment methods）， as well as the relationship between each node. ConclusionBased on the literature data， this study constructed a knowledge map for TCM treatment of DPN， which brought together various methods of TCM treatment of DPN， including internal and external treatment. The whole chain knowledge structure of syndrome differentiation and classification for DPN treatment is formed from syndrome element analysis， syndrome type composition to treatment method selection， which can provide new ideas and methods for literature data to serve clinical and scientific research work， as well as reference for visualization of TCM literature knowledge， intellectualization of TCM knowledge services and the standardization of TCM diagnosis and treatment.

Current Situation of Health Technology Assessment in Traditional Chinese Medicine Hospitals / 中国实验方剂学杂志

ObjectiveThis study aims to understand the recognition of practitioners in traditional Chinese medicine （TCM） hospitals on hospital-based health technology assessment （HB-HTA）， assessment needs， challenges， and suggestions， so as to provide references for the future work. MethodThe convenient sampling method was adopted to survey the relevant practitioners in TCM hospitals. The questionnaire included 39 questions in 4 dimensions and was distributed through the online platform Weijuanxing. ResultA total of 244 questionnaires were recovered， and the obtained data were analyzed in SPSS. The results showed that 137 practitioners were very familiar with HB-HTA and there was no significant difference in the recognition of practitioners in different occupations （F=0.251； P=0.778）. The practitioners in Hong Kong， Macao， and Taiwan had lower recognition than those in other regions. In terms of the assessment needs， 127 practitioners believed that it was very necessary to carry out HB-HTA in TCM hospitals in the future. Chinese patent medicines/Chinese herbal medicine decoction pieces （5.91） and TCM appropriate technology （5.57） had higher assessment priority scores. The assessment needs were high for the effectiveness （235 practitioners） and safety （224 practitioners） of health technology. The lack of specialized organization and standardized evaluation process system and the shortage of talents were considered to be the major challenges for the future development in this field. ConclusionThe stakeholders carrying out the health technology assessment in TCM hospitals had certain awareness of HB-HTA. Most practitioners believed that it was necessary to carry out HB-HTA in TCM hospitals in the future， while the work might face challenges such as the lack of organizations and system and the shortage of talents， which requires policy support.

Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury transforming growth factor beta1 signaling and metabolic reprogramming.

OBJECTIVE: To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis (RA) based on the transforming growth factor beta1 (TGF-ß1)/Smads signaling pathway. METHODS: One hundred rats were treated with saline [normal control (NC) group] or complete Freund's adjuvant (CFA) by right plantar injection for the RA model group, and the latter were randomly divided into 4 groups. Tripterygium wilfordii polyglycoside tablets (, TPT) have anti-inflammatory and are widely used in the clinical treatment of RA, therefore serving as a positive control group. Three days post injection rats were given TPT tablet (TPT group), acupuncture therapy (APT group), and moxibustion treatment (MOX group) for 15 consecutive days, while NC group and model group were equally grasped and fixed and received normal saline. Rat joint swelling scores and arthritis index (AI) were evaluated in each group before the CFA challenge, therapy and after receiving therapy. Myocardial ultrastructure was observed by electron microscope. Enzyme-linked immunosorbent assay was used to detect cardiac troponin I (cTnI) levels in rat myocardial tissue. Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-ß signaling molecules including TGF-ß1, Smad2, Smad3, Smad4, and Smad7. Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer. RESULTS: Compared with model group, RA model rats receiving TPT, acupuncture, or moxibustion therapy all showed reduced joint swelling scores and AI (all P < 0.01) and improved myocardial damage, whereas rats treated with moxibustion were found to be more marked. Consistently, the expressions of cTnI, TGF-ß1, Smad2, Smad3, and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT, APT and MOX group when compared with model group, while the levels of Smad7 showed the opposite result (all P < 0.01). Moreover, the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate, dihydroxyacetone phosphate, arachidonic acid, etc was defined and implicated in amino acid, glucose, and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis. CONCLUSION: Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions. The protective effects might be associated with its role in TGF-ß1 inactivation and metabolic reprogramming.

Efficacy of bioactive compounds of Chaihu () on glaucomatous optic atrophy through interleukin-6/hypoxia inducible factor-1α signal pathway.

OBJECTIVE: To investigate the bioactive compounds of Chaihu (Radix Bupleuri Chinensis) (RB) on glaucomatous optic atrophy (GOA), and to study the pharmacological mechanism. METHODS: We collected information on the bioactive compounds of RB from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to bioactive compounds and GOA were also obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses were performed to investigate the potential mechanism of RB against GOA. Subsequently, the main bioactive compounds of RB and targets of GOA were docked by Autodock software. Moreover, a GOA model of retinal ganglion cells (RGCs) induced by cobalt chloride was established to verify the effect of RB on GOA. RESULTS: There were 17 main bioactive compounds and 46 key targets were screened as potential players in GOA. The compound-target network mainly contained 17 compounds and 46 corresponding targets, and the key targets consisted of interleukin-6 (IL-6), hypoxia inducible factor-1α (HIF1A), Caspase-3, estrogen receptor alpha (ESR1), MYC proto-oncogene (MYC), and vascular endothelial growth factor A (VEGFA). Forty-nine significantly enriched GO terms, and 134 KEGG signaling pathways were identified (P < 0.05), including HIF-1, tumor necrosis factor, VEGF, prolaction, and other signaling pathways. Molecular docking results showed that the main bioactive compounds of RB exhibited the strongest binding activity with IL-6. Furthermore, experimental validation showed that the RB extract inhibited the activity and promoted apoptosis of RGCs in a dose-dependent manner. The RB extract also suppressed the expression of Bax, Caspase-3, and Caspase-9 and regulated malonaldehyde, superoxide dismutase, and glutathione peroxide by inhibiting the IL-6/HIF-1α signaling pathway. CONCLUSIONS: The present study provided insights into the mechanism of RB on GOA. RB mainly reverses GOA by inhibiting the IL-6/HIF-1α signaling pathway.

Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma.

Pulmonary nodules with part-solid imaging features manifest during the progression from preinvasive to invasive lung adenocarcinoma. To define the spatial composition and evolutionary trajectories of early-stage lung adenocarcinoma, we combined spatial transcriptomics (ST) and pathological annotations from 20 part-solid nodules (PSNs), four of which were matched with single-cell RNA sequencing. Two malignant cell populations (MC1 and MC2) were identified, and a linear evolutionary relationship was observed. Compared to MC2, the pre-existing malignant MC1 exhibited a lower metastatic signature, corresponding to the preinvasive component (lepidic) on pathology and the ground glass component on PSN imaging. Higher immune infiltration was observed among MC1 regions in ST profiles, and further analysis revealed that macrophages may be involved in this process through the CD74 axis. This work provides deeper insights into the evolutionary process and spatial immune cell composition behind PSNs and highlights the mechanisms of immune escape behind this adenocarcinoma trajectory.

Neoadjuvant immunotherapy in patients with pulmonary lymphoepithelioma-like carcinoma.

OBJECTIVES: Neoadjuvant immunotherapy can be used to treat early-stage non-small-cell lung cancer; however, their effects on pulmonary lymphoepithelioma-like carcinomas (LELC) remain unclear. MATERIALS AND METHODS: Thirty-nine patients with stages I-III LELC were treated with chemotherapy (Chemo) or neoadjuvant immune-checkpoint inhibitors (ICIs) with or without chemo (IO) before radical-intent surgery. Short-term outcomes included objective response rate (ORR), major pathologic response (MPR), pathologic complete response (PCR), and event-free survival. For comparison, we used IO to treat 63 patients with pulmonary squamous cell carcinomas (SQC) and 47 with adenocarcinomas (ADC). Propensity score matching was analyzed to minimize bias. RESULTS: ORRs of the LELC-IO and LELC-Chemo groups were 62.5% and 42.9%, respectively (odds ratio, 2.2, 95% confidence interval, 0.423-11.678, p = 0.346). Seven (21.9%) and zero patients in LELC-IO and LELC-Chemo groups, respectively, reached PCR. MPR was identified in five (15.6%) of the 32 patients with LELC-IO. The 1-year progression-free survival rates were 96.9% and 71.4% in IO and Chemo groups, respectively (p > 0.05). However, no difference was observed in ORR, PCR, and MPR between LELC and SQC groups (ORR, 63.2% vs. 68.4%, p > 0.05; PCR, 21.1% vs. 47.4, p > 0.05; MPR, 42.1% vs. 57.9%, p > 0.05) and LELC and ADC groups (ORR, 58.8% vs. 41.2%, p > 0.05; PCR, 17.6% vs. 23.5%, p = 0.672; MPR, 29.4% vs. 47.1%, p > 0.05). The plasma Epstein-Barr virus (EBV) DNA level in a patient was altered posttreatment. CONCLUSION: Patients with LELC could be benefit from neoadjuvant immunotherapy. Distinct histological subtypes demonstrated comparable efficacy with respect to neoadjuvant immunotherapy.

Morphology and deformity of the shoulder and pelvis in the entire spine radiographs of adolescent idiopathic scoliosis.

Background: To investigate the deformity and asymmetry of the shoulder and pelvis in adolescent idiopathic scoliosis (AIS) patients. Methods: This retrospective cross-sectional study enrolled 223 AIS patients with a right thoracic curve or left thoracolumbar/lumbar curve who underwent spine radiographs at the Third Hospital of Hebei Medical University between November 2020 and December 2021. The following parameters were measured: Cobb angle, clavicular angle, glenoid obliquity angle, acromioclavicular joint deviation, femoral neck-shaft projection angle, iliac obliquity angle, acetabular obliquity angle, coronal trunk deviation distance, and spinal deformity deviation distance. The Mann-Whitney U test, Kruskal-Wallis H test were used for inter-group comparisons, and Wilcoxon signed-rank test were used for intra-group left and right sides comparisons. Results: Shoulder and pelvic imbalances were found in 134 and 120 patients, respectively, and there were 87, 109, and 27 cases of mild, moderate, and severe scoliosis, respectively. Compared with mild scoliosis patients, the difference in the acromioclavicular joint offset on bilateral sides was significantly increased in moderate and severe scoliosis [11.04, 95% confidence interval (CI): 0.09-0.14 for mild, 0.13-0.17 for moderate, and 0.15-0.27 for severe scoliosis, P=0.004], and the difference in the femoral neck-shaft projection angle on bilateral sides was significantly enhanced with scoliosis aggravation (14.14, 95% CI: 2.34-3.41 for mild, 3.00-3.94 for moderate, and 3.57-6.43 for severe scoliosis, P=0.001). The acromioclavicular joint offset was significantly larger on the left than that on the right in patients with a thoracic curve or double curves (thoracic curve -2.75, 95% CI: 0.57-0.69 for the left and 0.50-0.63 for the right, P=0.006; double curve -3.27, 95% CI: 0.60-0.77 for the left and 0.48-0.65 for the right, P=0.001). The femoral neck-shaft projection angle was significantly larger on the left than right in patients with a thoracic curve (-4.46, 95% CI: 133.78-136.20 for the left and 131.62-134.01 for the right, P<0.001), but larger on the right than left in patients with thoracolumbar/lumbar curve (thoracolumbar -2.98, 95% CI: 133.75-136.70 for the left and 135.13-137.82 for the right, P=0.003; lumbar -3.24, 131.97-134.56 for the left and 133.76-136.26 for the right, P=0.001). Conclusions: In AIS patients, shoulder imbalance has a greater impact on coronal balance and spinal scoliosis above the lumbar segment, whereas pelvic imbalance has a greater impact on sagittal balance and spinal scoliosis below the thoracic segment.

Aquaporin 5 maintains lens transparency by regulating the lysosomal pathway using circRNA.

The lens is transparent, non-vascular, elastic and wrapped in a transparent capsule. The lens oppacity of AQP5-/- mice was increased more than that of wild-type (AQP5+/+ ) mice. In this study, we explored the potential functional role of circular RNAs (circRNAs) and transcription factor HSF4 in lens opacity in aquaporin 5 (AQP5) knockout (AQP5-/- ) mice. Autophagy was impaired in the lens tissues of AQP5-/- mice. Autophagic lysosomes in lens epithelial cells of AQP5-/- mice were increased compared with AQP5+/+ mice, based on analysis by transmission electron microscopy. The genetic information of the mice lens was obtained by high-throughput sequencing, and then the downstream genes were analysed. A circRNA-miRNA-mRNA network related to lysosomal pathway was constructed by the bioinformatics analysis of the differentially expressed circRNAs. Based on the prediction of the TargetScan website and the validation by dual luciferase reporter assay and RNA immunoprecipitation-qPCR, we found that circRNA (Chr16: 33421321-33468183+) inhibited the function of HSF4 by sponging microRNA (miR-149-5p), and it downregulated the normal expression of lysosome-related mRNAs. The accumulation of autophagic lysosome may be one of the reasons for the abnormal development of the lens in AQP5-/- mice.

Therapeutic effect evaluation of leonurine,polygonatum polysaccharide and deoxynojirimycin in combination on antithrombosis and hypoglycaemia / 中国药理学通报

Aim To evaluate the efficacy of the combination of leonurine(SCM),polygonatum polysaccharide(PSP)and deoxynojirimycin(DNJ)in hypoglycemic and antithrombotic aspects by establishing and using zebrafish type II diabetes combined with thrombosis model. Methods On the basis of the zebrafish type II diabetes model established by streptozotocin,phenylhydrazine(PH),arachidonic acid(AA)and ponatinib(PT)were used respectively to establish thrombosis models,which were divided into control group,model group,metformin+aspirin group,and the high,medium and low concentration groups of the combination drugs. After drug intervention in the experimental group,the thrombosis of tail vein was observed. Kit was used to determine the sugar content of juvenile fish tissues in each group. Quantitative analysis of cardiac erythrocytes by o-dianisidine staining method was used to calculate the inhibition rate of thrombus. Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of related genes in zebrafish. Results Compared with the model group,the combined drug could significantly increase the staining intensity of erythrocytes in zebrafish hearts,inhibit thrombosis,down-regulate the expression of thrombosis-related genes,and reduce tissue glucose content. Conclusions The combined use of the three drugs can effectively reduce the tissue sugar content and have antithrombotic effect,which show great potential in the development of drugs for the treatment of type II diabetes and thrombosis.

miR-509-3p promotes oxidized low-density lipoprotein-induced apoptosis in mouse aortic endothelial cells / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of microRNA-509-3p (miR-509-3p) on the apoptosis of atherosclerotic vascular endothelial cells.@*METHODS@#Mouse aortic endothelial cells (MAECs) were divided into normal control group, oxidized low-density lipoprotein (ox-LDL) group, miR-509-3p overexpression group, miR-509-3p overexpression control group, miR-509-3p inhibitor + ox-LDL group, and miR-509-3p inhibitor control + ox-LDL group. MAEC were induced with 100 mg/L ox-LDL for 24 hours, and then transfected with miR-509-3p overexpression/inhibitor and corresponding control for 48 hours. The miR-509-3p expression in MAECs exposed to ox-LDL was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Flow cytometry was used to detect the level of apoptosis, and cell counting kit (CCK-8) was used to detect the proliferation activity of MAECs. The direct gene targets of miR-509-3p were predicted using bioinformatics analyses and confirmed using a dual luciferase reporter assay. The expression of Bcl-2 mRNA and protein was detected by RT-qPCR and Western blotting, respectively.@*RESULTS@#Compared with the normal control group, miR-509-3p was significantly upregulated in ox-LDL-stimulated MAECs (1.68±0.85 vs. 1.00±0.30, t = 2.398, P < 0.05). After transfection of MAECs with miR-509-3p overexpression, the luciferase activity of the BCL2 3'UTR WT reporter gene was significantly lower than that of miR-509-3p overexpression control group (0.83±0.06 vs. 1.00±0.07, t = 4.531, P = 0.001). The luciferase activity of the BCL2 3'-UTR mutant (MUT) reporter gene was not significantly different from that of miR-509-3p overexpression control group (0.94±0.05 vs. 1.00±0.08, t = 1.414, P = 0.188). Compared with the normal control group and miR-509-3p mimics control group, the cell proliferation activity was decreased [(0.60±0.06)% vs. (1.00±0.09)%, (0.89±0.04)%, both P < 0.01], the percentage of apoptotic cells were increased [(23.46±2.02)% vs. (7.66±1.52)%, (10.40±0.78)%, both P < 0.05], and the mRNA and protein expression of Bcl-2 were significantly downregulated (Bcl-2 mRNA: 0.52±0.13 vs. 1.00±0.36, 1.10±0.19, Bcl-2 protein: 0.42±0.07 vs. 1.00±0.11, 0.93±0.10, both P < 0.01) in miR-509-3p overexpression group. Compared with the ox-LDL group, inhibition of miR-509-3p expression could increase the proliferation activity of MAECs induced by ox-LDL [(0.64±0.35)% vs. (0.34±0.20%)%, P < 0.05], and reduce the apoptosis rate [(13.59±2.22)% vs. (29.84±5.19)%, P < 0.01], and up-regulated the expression of Bcl-2 mRNA and protein in MAECs induced by ox-LDL (Bcl-2 mRNA relative expression: 0.82±0.09 vs. 0.52±0.10, Bcl-2 protein relative expression: 0.83±0.17 vs. 0.40±0.07, both P < 0.05).@*CONCLUSIONS@#Bcl-2 was one of the target genes of miR-509-3p. miR-509-3p can reduce the proliferation activity of endothelial cells, reduce the expression of Bcl-2, and promote cell apoptosis, thereby promoting the occurrence and development of atherosclerosis. Inhibition of miR-509-3p expression may be a potential therapeutic target for atherosclerosis.

Practice and benefit of national standardized management of type 2 diabetes in Yulin City / 西安交通大学学报(医学版)

【Objective】 To investigate the practice and benefit of national standardized management of type 2 diabetes in Yulin City. 【Methods】 We recruited the adult type 2 diabetes patients who sought medical help at our hospital from May 2020 to October 2022 as subjects. We collected their basic information (sex and age); measured height, weight, waist and hip circumference, and blood pressure; calculated body mass index (BMI); and detected blood glucose, c-peptide, HbA1c, biomarkers, urinary microalbumin, sensory nerve conduction velocity of lower limbs, ABI, and subcutaneous and visceral fat at the time of MMC recruited and the end of six months. T test and Mann-Whitney U rank sum test were used for measurement data and χ2 test or Fisher’s exact probability method for counting data to analyze the data. 【Results】 After 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, and visceral and subcutaneous fat in all the patients decreased, but the level of fasting c-peptide increased compared with the baseline (all P<0.05). Secondly, compared with the baseline, the control rate of HbA1c (35.21% vs. 13.71% ) and the comprehensive control rate (13.97% vs. 7.26% ) were both significantly increased at six months (P<0.05). Thirdly, after 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, TG, TC, and UA were decreased more, while the fasting c-peptide and postprandial c-peptide were increased more in the patients of the HbA1c standard group (HbA1c<7% ) than those of the non-standard group. 【Conclusion】 The multiple benefits of blood glucose, blood lipid, uric acid and islet function can be achieved by taking type 2 diabetes patients into MMC. Meanwhile, the rates of HbA1c control and comprehensively reaching the standard are significantly increased. Therefore, MMC can explore a new way for the management of type 2 diabetic patients in this area.

Mitigating of the interference of anti-CD47 monoclonal antibody on transfusion compatibility detection / 中国输血杂志

【Objective】 To evaluate the interference of anti-CD47 monoclonal antibody on transfusion compatibility detection, in order to establish methods for removing interference and evaluate its efficacy. 【Methods】 Blood samples from 8 patients in our clinical trial who were treated with anti-CD47 monoclonal antibody from Tianjing and Xinda were collected. ABO and Rh blood group antigen identification, direct anti-human globulin test, unexpected antibody screening test and cross-matching test were performed by ZZAP, Gamma-clone(an anti-globulin reagent lacking IgG4) and Immucor Capture-R solid phase agglutination kit. 【Results】 ABO blood group identification of 5 subjects were interfered after treatment with anti-CD47 monoclonal antibody. All 8 subjects showed 2+ to 4+ agglutination intensity on direct anti-human globulin test and 3+ to 4+ on unexpected antibody screening. The results of unexpected antibody screening by Gamma-clone and Immucor Capture-R solid phase agglutination kit were all negative, while the cross-matching test were compatible. Patients with anemia caused by CD47 monoclonal antibody treatment were transfused with 2 U suspension red blood cells, and the evaluation showed that the transfusion was effective. 【Conclusion】 The CD47 monoclonal antibody can interfere with transfusion compatibility detection, and the use of antiglobulin reagents lacking IgG4 and Immucor Capture-R solid phase agglutination kit can remove the interference, with good transfusion efficacy in patients.

A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns / 中华烧伤杂志

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities / 中草药·英文版

OBJECTIVE@#Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury.@*METHODS@#PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments.@*RESULTS@#Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3.@*CONCLUSION@#Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Practice and analysis of clinical pharmacist participating in the treatment of a case of acanthoma caused by navulizumab / 中国药房

This paper reports the clinical pharmacist participated in the diagnosis and treatment of a patient with acanthoma caused by nivolumab. This patient developed acanthoma 2 weeks after medication， involving scalp， neck， trunk， back of hand， sole of foot and other parts， with moderate pruritus. The clinical pharmacist determined it as “yes” according to the causality evaluation method of adverse reactions. After reviewing the literature， clinical pharmacists found that acanthoma caused by immune checkpoint inhibitors was more commonly seen in male elderly patients with malignant melanoma， and mainly involved the trunk， extremities and hands. Under the general principle of considering the effectiveness， safety， economy and accessibility of therapeutic drugs， the clinical pharmacist finally decided to give the patient a comprehensive treatment scheme of Halometasone cream for external use + oral administration of Retinoic acid capsules + oral administration of Ebastine tablets after discussion with the doctor， with maximum respect for the patient’s wishes，and continued to use navulizumab for immunotherapy. At the same time， pharmaceutical care and psychological counseling were conducted by clinical pharmacist. Finally， the patient successfully completed the treatment， and the acanthoma gradually subsided after the end of navulizumab treatment. The diagnosis and treatment process of this patient indicated that the participation of clinical pharmacists is helpful to improve the continuity and safety of immunotherapy.