OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Objective To understand the current status of work-related musculoskeletal disorders (WMSDs) among operating room doctors,thereby analyzing its effect on mental health. Methods A total of 1013 doctors in the operating rooms of 30 hospitals in 24 provinces from September to December 2022 were selected by cross-sectional survey method. The domestic musculoskeletal disease questionnaire was used to investigate the occurrence of WMSDs in operating room doctors,the symptom check list-90 (SCL-90) was used to evaluate the psychological status of operating room doctors,the relationship between WMSDs related items and SCL-90 scores was analyzed,the correla-tion between the rest time of each shift and SCL-90 factors was analyzed by Pearson method,and the influencing factors of mental health of operating room doctors were analyzed by multivariate Logistic regression.Results A total of 1100 questionnaires were distributed and 1013 valid questionnaires were recovered,with an effective rate of 92.10％. The incidence of WMSDs among operating room doctors in the past 1 year was 95.06％. The body parts with incidences of WMSDs from high to low were as follows:waist (36.92％),neck (35.54％),shoulder (33.56％),and upper back (32.77％). In the past 1 year,the SCL-90 scores and total scores of patients with musculoskeletal pain in various body parts,keeping the same back posture for a long time while work,bending the back at the same time of turning frequently while working,bowing the head for a long time while working,and bending the knee for a long time while working were significantly higher than those who were without the above conditions (P<0.05). Shorter rest time of each shift and longer periods of keeping the same back posture were the risk factors for the development of mental illness in operating room doctors. Conclusion The incidence of WMSDs in operating room doctors is high,which can influence the mental health of operating room doctors. Therefore,operating room doctors should avoid keeping the same back posture for a long time,bending the back at the same time of turning frequently,bowing the head for a long time,and bending the knee for a long time while working,and increase the rest time of each shift,in order to improve the mental condition of the operating room doctors.

Objective To understand the current status of work-related musculoskeletal disorders (WMSDs) among operating room doctors,thereby analyzing its effect on mental health. Methods A total of 1013 doctors in the operating rooms of 30 hospitals in 24 provinces from September to December 2022 were selected by cross-sectional survey method. The domestic musculoskeletal disease questionnaire was used to investigate the occurrence of WMSDs in operating room doctors,the symptom check list-90 (SCL-90) was used to evaluate the psychological status of operating room doctors,the relationship between WMSDs related items and SCL-90 scores was analyzed,the correla-tion between the rest time of each shift and SCL-90 factors was analyzed by Pearson method,and the influencing factors of mental health of operating room doctors were analyzed by multivariate Logistic regression.Results A total of 1100 questionnaires were distributed and 1013 valid questionnaires were recovered,with an effective rate of 92.10％. The incidence of WMSDs among operating room doctors in the past 1 year was 95.06％. The body parts with incidences of WMSDs from high to low were as follows:waist (36.92％),neck (35.54％),shoulder (33.56％),and upper back (32.77％). In the past 1 year,the SCL-90 scores and total scores of patients with musculoskeletal pain in various body parts,keeping the same back posture for a long time while work,bending the back at the same time of turning frequently while working,bowing the head for a long time while working,and bending the knee for a long time while working were significantly higher than those who were without the above conditions (P<0.05). Shorter rest time of each shift and longer periods of keeping the same back posture were the risk factors for the development of mental illness in operating room doctors. Conclusion The incidence of WMSDs in operating room doctors is high,which can influence the mental health of operating room doctors. Therefore,operating room doctors should avoid keeping the same back posture for a long time,bending the back at the same time of turning frequently,bowing the head for a long time,and bending the knee for a long time while working,and increase the rest time of each shift,in order to improve the mental condition of the operating room doctors.

Objective To develop an effective treatment strategy to simultaneously avoid fatal adverse effects in the treatment of oral cancer, combination therapy has been explored because of its multiple functions. This work aims to develop a novel type of gold-nanorod-based nanomaterials decorated with tetrahedral DNA nanostructures (TDN) carrying antitumor drugs, namely, GNR@TDN-DOX nanocomposites. Methods In the designed structure, TDN, with a three-dimensional geometry composed of DNA strands, can provide GC base pairs for binding with the anticancer drug doxorubicin (DOX). The photothermal heating properties, biocompatibility properties, and antitumor performance of obtained GNR@TDN-DOX nanocomposites were investigated to assess their application potential in tumor treatment. Results Systematic studies have shown that the obtained GNR@TDN-DOX nanocomposites have high photothermal conversion under the illumination of an 808-nm infrared laser, leading to effective antitumor applications. In addition, the cell viability study shows that GNR@TDN-DOX nanocomposites have good biocompatibility. In vitro studies based on A375 cells show that the GNR@TDN-DOX nanocomposites can effectively eliminate cancer cells because of the combination of photothermal therapy induced by GNRS and chemotherapy induced by TDN-carrying DOX. The result shows that the obtained GNR@TDN-DOX nanocomposites have efficient cellular uptake and lysosome escape ability, together with their nuclear uptake behavior, which results in a significant antitumor effect. Conclusion This work has demonstrated a potential nanoplatform for anticancer applications.

Circular RNA(circRNA)is a novel type of endogenous non-coding RNA.Most circRNAs act as microRNA(miRNA)sponges to regulate the expression of functional genes.In addition,some circRNAs can be translated and interact with RNA-binding proteins to perform biological functions.The expression of circRNAs is prevalent in tissues and body fluids,and their abnormal expression is related to tumor progression.circRNAs are stable even under the treatment of RNase R because of their circular conformation.As circRNAs have construct stability,wide variety,specific regulation of tumor progression and high expression in body fluids,it is potential for circRNAs to serve as candidate diagnostic,prognostic and therapeutic targets.However,the knowledge about circRNAs remains poor.In addition to the not completely resolved functions and generation mechanisms of circRNAs,the annotations of circRNAs are also waiting for expanding.Here,we review the generation mechanisms,biological functions,and application of circRNAs in tumor research,aiming to provide integrated information for the future research.
Biomarkers, Tumor/genetics* ; MicroRNAs ; Prognosis ; RNA, Circular

Objective: To evaluate the auditory efficacy and subjective satisfaction of adhesive bone conduction hearing aid in children with unilateral congenital aural atresia (UCAA). Methods: Ten subjects (5 males and 5 females) diagnosed with UCAA with an average age of 8.3 years old (ranged from 5 to 15) were included in Beijing Tongren Hospital, Capital Medical University from January to August 2019. The free sound field hearing threshold, word recognition score in quiet, speech reception threshold in noise and sound localization ability (results were measured by RMS error) tests were performed in unaided and aided situation, respectively. Subjective satisfaction questionnaires were also distributed to subjects. Paired t test and Wilcoxon signed rank test were used as statistical analysis methods. Results: The average hearing threshold in aided condition was improved by (21.9±4.4) dB (t=15.8，P<0.05). Speech recognition abilities were generally improved both under quiet and noise (P<0.05);however, when the binaural summation, squelch and head shadow effects were analyzed respectively, the binaural squelch effect was not statistically improved (P>0.05), while the other effects were improved in aided condition (P<0.05). In sound localization test, there was no significant difference of the RMS error value between the unaided and aided situation (P>0.05). The subjects got high satisfaction rates in three subjective questionnaires. Conclusion: The adhesive bone conduction hearing aid can provide significant audiological benefit for children with UCAA as well as raising the quality of their life.
Adhesives ; Adolescent ; Bone Conduction ; Child ; Child, Preschool ; Female ; Hearing Aids ; Hearing Loss, Conductive ; Humans ; Male ; Speech Perception ; Treatment Outcome

Objective:To establish the fingerprint of standard decoction of Citri Reticulatae Pericarpium and evaluate its quality. Method:According to the preparation conditions of the standard decoction,15 batches of standard decoction of Citri Reticulatae Pericarpium were prepared.HPLC was employed to determine the content of hesperidin in this standard decoction.Ultraviolet spectroscopy(UV) and infrared spectroscopy(IR) were used to establish the fingerprint of standard decoction of Citri Reticulatae Pericarpium.The correlation coefficient method and double index sequence analysis method were used to compare and analyze the spectra of different batches of this standard decoction. Result:The content of hesperidin in 15 batches of this standard decoction were 0.82%-2.60%,and the measured value of dry extract rate was 32.02%-46.11%.Compared with ultraviolet and infrared control fingerprint,the fingerprint similarities of the standard decoction of each batch were > 0.897 and > 0.942,respectively.The double index analysis results showed that the common peak ratio was more than 62.50%,variation peak ratio was less than 46.67%. Conclusion:The quality evaluation method established in this study can be used for systematic evaluation of standard decoction of Citri Reticulatae Pericarpium,and it can provide theoretical reference for the formulation of quality standard of Citri Reticulatae Pericarpium dispensing granules and other related preparations.

Andrographolide is a main active ingredient in traditional Chinese medicine Andrographis paniculata，with a variety of pharmacological activity，widely used in clinical practice. However its biosynthetic pathway has not been resolved. Cytochrome P450 reductase provides electrons for CYP450 and plays an important role in the CYP450 catalytic process. In this study，the coding sequence of A. paniculata CPR was screened and cloned by homologous alignment，named ApCPR4. The ApCPR4 protein was obtained by prokaryotic expression. After isolation and purification，the enzyme activity was identified . The results showed that ApCPR4 could reduce the cytochrome c and ferricyanide in NADPH-dependent manner. In order to verify its function，ApCPR4 and CYP76AH1 were co-transformed into yeast engineering bacteria. The results showed that ApCPR4 could help CYP76AH1 catalyze the formation of rustols in yeast. Real-time quantitative PCR results showed that the expression of ApCPR4 increased gradually in leaves treated with methyl jasmonate (MeJA). The expression pattern was consistent with the trend of induction and accumulation of andrographolide by MeJA，suggesting that ApCPR4 was associated with biosynthesis of andrographolide.
Acetates ; Andrographis ; enzymology ; genetics ; Biosynthetic Pathways ; Cloning, Molecular ; Cyclopentanes ; Diterpenes ; metabolism ; NADPH-Ferrihemoprotein Reductase ; genetics ; Oxylipins ; Plant Leaves ; enzymology ; Plant Proteins ; genetics

Protein complexes are involved in the synthesis of multiple secondary metabolites in plants, and their separation is essential to elucidate plant secondary metabolism and improve in vitro catalytic efficiency. In this study, the transgenic hairy roots of CYP76AH1, a key enzyme of tanshinone synthesis pathway, was constructed and the transgenic hairy roots of Danshen overexpressing CYP76AH1 protein were screened by Western blotting and used as a tissue culture material for the subsequent extraction of protein complex in tanshinone synthesis pathway. By optimizing the type and concentration of the detergent in the protein extraction buffer, the buffer containing 0.5% Triton X-100 was selected as the best extraction buffer, and a relatively large amount of soluble CYP76AH1 protein was isolated. This study lays the foundation for the further separation and purification of protein complexes interacting with CYP76AH1, and provides the idea for deep analysis of tanshinone metabolic pathway.

Objective To observe the effect of different concentration netrin-1 on retinal vascular permeability in diabetes mellitus (DM) rats.Methods Eighty adult Sprague-Dawley rats were randomly divided into 8 groups,10 rats in each group,including normal control group (group A),normal+balanced salt solution (BSS) group (group B),normal+netrin-1 (500 μg/ml) group (group C) and DM group (50 rats in 5 subgroups).DM rats were induced by intraperitoneal injection of streptozocin.Three months after intraperitoneal injection,10 DM rats in the control group were injected with BSS (group D).Forty DM rats were injected with 5 μl of different concentrate netrin-1,and were divided into DM+netrin-1 10 μg/ml group (group E),DM+netrin-1 50 μg/ml group (group F),DM+netrin-1 100 μg/ml group (group G),DM+netrin-1 500 μg/ml group (group H)according to the different concentration.Non-DM rats in group C were injected with netrin-1 500 μg/ml.The expression of occludin was determined by immunohistochemistry for protein,and by real-time fluorescence quantitative reverse transcription polymerase chain reaction for mRNA level.Retinal vascular permeability was measured by Evans blue infusion.Results The expression of occludin protein and mRNA in group D were less than group A (t=27.71,8.59;P=0.00,0.00).However,the retinal vascular permeability increased in group D (t=-42.72,P=0.00).The expression of occluding protein,occludin mRNA and retinal vascular permeability showed significant differences between group D,E,F,G and H (F=146.31,16.54,67.77;P=0.00,0.00,0.00).Compared the group B with group C,there was no significant differences between the expression of occludin protein,occludin mRNA and the retinal vascular permeability (t=-1.13,0.93,1.04;P=0.27,0.36,0.31).The concentrate of netrin-1 showed a significant positive correlation to the expression level of occludin and occludin mRNA (r=0.73,0.81;P=0.00,0.00),but negative correlation to the vascular permeability (r=-0.61,P=0.00).Conclusion Netrin-1 can reduce the DM rats' retinal vascular permeability,which depended on the concentration of netrin-1.