This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

OBJECTIVE: To investigate the feasibility of varicocele ligation with mobile phone microscope. METHODS: The high-performance mobile phone and mobile phone stand were combined to act as a mobile phone microscope. And the varicocele ligation was performed under the mobile phone microscope. RESULTS: All five patients successfully underwent varicocelectomy under the guidance of a mobile phone microscope. The average operation time was （112.8 ± 52.2）with ranged from 74.0 to 195.0 minutes. Three patients completed the follow-up after the operation with the proportion of improved sperm quality reaching 100.0% (3/3). CONCLUSION High- performance mobile phone microscope can be used for varicocele ligation.
Humans ; Male ; Ligation/methods* ; Cell Phone ; Adult ; Varicocele/surgery* ; Microscopy ; Young Adult

Objective:To explore the application of virtual augmented reality (AR) technology combined with transcranial Doppler ultrasound (TCD) in nursing teaching of cerebrovascular diseases.Methods:Eighty-six nursing students who interned in the Department of Neurology of The First Affiliated Hospital of Army Medical University from January 2021 to November 2022 were assigned into control group (students of grade 2021) and research group (students of grade 2022). The control group received traditional teaching with AR technology about the anatomy of the cerebral arterial circle, its composition, and adjacent structures. The research group was given AR-assisted teaching combined with TCD-based demonstration and interpretation. At the end of internship, the assessment scores, satisfaction with teaching, clinical decision-making ability, self-learning ability, and problem-solving ability were compared between the two groups. SPSS 23.0 was used to perform the non-parametric test, t test, and chi-square test. Results:The theoretical, practical, and comprehensive ability assessment scores of the research group [90 (89, 96), 95 (90, 96), and 93 (90, 96), respectively] were significantly higher than those of the control group [89 (87, 91), 90 (89, 92), and 91 (89, 94), respectively]. In terms of satisfaction with teaching effects, teaching methods, teaching content, and teaching style, the scores of the research group [16 (15, 18), (5.98±0.91), (3.38±0.52), and 13 (11, 14), respectively] were significantly higher than those of the control group [14 (13, 16), (4.23±0.65), (2.37±0.36), and 13 (10, 14 ), respectively]. The research group showed significantly better independent learning abilities than the control group in information seeking [(4.66±0.71) vs. (4.00±0.61)] and solution seeking [(4.43±0.68) vs. (4.41±0.67)], with no significant differences in the other dimensions between the two groups. The research group was significantly superior to the control group in all problem-solving dimensions: positive orientation [12 (10, 12) vs. 10 (9, 11)], rationality [26 (23, 28) vs. 21 (21, 24)], negative orientation [15 (13, 20) vs. 20 (17, 20)], avoidance style [17 (15, 18) vs. 19 (17, 20)], and impulsivity/neglect style [16 (15, 18) vs. 18 (16, 20)]. For rounds assessment, the research group showed significantly higher scores than the control group in all the items except " communication with patients" [(9.21±0.39) vs. (9.04±0.53)] and "patient satisfaction with nursing students" [(8.92±0.53) vs. (8.73±0.56)].Conclusions:The teaching method based on AR combined with TCD can improve nursing students' knowledge of cerebrovascular diseases, clinical nursing ability, and satisfaction with teaching.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Coronary atherosclerotic heart disease(CHD)is an ischemic cardiovascular condition caused by the narrowing or blockage of the vascular lumen due to coronary atherosclerosis.Clinically,it presents as angina pectoris,heart failure,or sud-den cardiac death,and stands as one of the primary causes of mortality among both urban and rural populations in China.Cir-cRNA,classified as non-coding RNAs,can function as upstream regulatory molecules for miRNA or RNA-binding proteins.They actively participate in various pathological processes associated with CHD,including endothelial cell dysfunction,smooth mus-cle cell migration,macrophage-derived foam cell formation,an-giogenesis,myocardial injury,and repair,as well as post-in-farction heart failure.The expression pattern of these molecules is highly specific to the illness and tissue,indicating their poten-tial as therapeutic targets for disease management and as biomar-kers.Furthermore,they also open up new avenues for drug tar-get development in the field of traditional Chinese medicine.This article aims to provide an overview of the recent research progress on circRNA in the regulation of coronary heart disease,as well as the mechanisms involved in traditional Chinese medi-cine.It serves as a valuable reference for future research on cor-onary heart disease.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective To study the efficacy and safety of different dual antiplatelet therapy(DAPT)in patients with acute myocardial infarction(AMI)undergoing percutaneous coronary intervention(PCI)treatment.Methods AMI patients receiving PCI treatment were randomly divided into treatment group and control group.The treatment group was given clopidogrel(50 mg,bid)combined with ticagrelor(90 mg,bid)after PCI,while the control group was given aspirin(100 mg,qd)combined with clopidogrel(75 mg,qd)after PCI.The treatment course for both groups was 6 months.Platelet activation and endothelial function-related indicators were compared between the two groups,and major adverse cardiovascular events(MACE)and adverse drug reactions were followed up during the treatment period.Results During the trial,5 cases dropped out,and finally,98 cases and 97 cases were included in the treatment group and control group,respectively.After treatment,the incidence of stent restenosis in the treatment group and control group were 2.04％(2 cases/98 cases)and 9.27％(9 cases/97 cases),respectively;the incidence of MACE were 4.08％(4 cases/98 cases)and 13.40％(13 cases/97 cases),respectively,with significant differences between the two groups(P＜0.05).After treatment,the inhibition of platelet aggregation(IPA)in the treatment group and control group were(54.97±6.43)％and(52.38±6.12)％,respectively;the serum nitric oxide(NO)levels were(64.29±8.12)and(59.61±8.45)μmol·L-1,respectively;the prostacyclin(PGI2)levels were(42.15±3.94)and(38.46±3.71)ng·L-1,respectively;the maximum platelet aggregation rate(MPAR)were(31.65±3.86)％and(32.97±4.25)％,respectively;the platelet count(PC)were(169.84±36.71)× 109·L-1 and(172.63±38.94)× 109·L-1,respectively;the positive rates of P-selectin(CD62P)were(24.58±5.34)％and(27.13±5.82)％;the positive rates of platelet activated complex-1(PAC-1)were(7.63±2.15)％and(8.45±2.69)％;serum endothelin-1(ET-1)levels were(61.03±5.97)and(65.39±7.14)ng·L-1,which were significantly reduced compared with those before treatment(all P＜0.05).The adverse drug reactions in treatment group were mainly headache,dyspnea and bleeding events,and the adverse drug reactions in control group were mainly dyspnea and bleeding events.The total incidence rates of adverse drug reactions in treatment group and control group were 11.22％(11 cases/98 cases)and 9.28％(9 cases/97 cases),respectively(P＞0.05).Conclusion Cilostazol combined with ticagrelor in patients with AMI after PCI is beneficial to inhibiting the platelet aggregation and activation,relieving the vascular endothelial function injury and reducing the risk of in-stent restenosis and MACE,and it has obvious advantages over aspirin combined with clopidogrel.

Aim To explore the effect of baicalin on respiratory syncytial virus in vitro and its effect on cell metabolism. Methods The anti-RSV effect of baicalin in vitro was verified by antiviral cell experiment, and the cellular metabolic mechanism of baicalin against RSV was explored by cell metabolomics. Results Baicalin had an inhibitory effect on all stages of RSV infection, and the condition of CPE was significantly improved, which may mainly play a role in the adsorption and proliferation of RSV. A total of 19 differential metabolites were screened by cell metabolomics, which were mainly glycerol phospholipids, nucleosides and fatty acids. Seven metabolic pathways were obtained by enrichment analysis, which were mainly related to glycerol-phospholipid metabolism, fatty acid metabolism (arachidonic acid metabolism, α-linolenic acid metabolism, linoleic acid metabolism), amino acid metabolism and purine metabolism. Conclusions Baicalin has significant inhibitory effect on the adsorption and proliferation of RSV, which may be related to fatty acid metabolism, glycerol phospholipid metabolism, amino acid and purine metabolism.

ObjectiveTo investigate whether hsa_circ_0002316 （circOMA1） is involved in drug resistance in prolactinoma and its mechanism. MethodsRT-qPCR was used to dectect the expression of circOMA1 in clinical prolactinoma specimens including 5 dopamine receptor agonists （DAs）-sensitive prolactinomas and 12 DAs-resistant prolactinomas. MMQ cell lines with stable expression of exogenous circOMA1 were constructed by lentivirus vector infection for in vitro experiment， and were divided into MMQ NC group and MMQ OMA1 group. Xenograft tumor models in nude mice were established for in vivo experiment， and were divided into MMQ NC+cabergoline （CAB） group， MMQ NC+bromocriptine （BRC） group， MMQ OMA1+CAB group and MMQ OMA1+BRC group. CCK8， Western blot and ELISA were performed to detect the effects of circOMA1 on cell proliferation and secretion of prolactin （PRL） in drug resistance mechanism. Western blot， ELISA and immunohistochemistry were used to examine the effect of circOMA1 on dopamine receptor expression. The mechanism of circOMA1 regulating dopamine receptor was explored by TargetScan， CircInteractome and microRNA-145-5p （miR-145-5p） minic remediation experiment. ResultsRT-qPCR showed that circOMA1 expression was increased in DAs-resistant prolactinomas （P < 0.01）. Compared with MMQ NC group， MMQ OMA1 group had lower DAs sensitivity and increased cell proliferation and prolactin secretion （P < 0.05） in vivo and in vitro. Western blot and immunohistochemical analysis showed that in MMQ OMA1 group， the expression of dopamine receptor type 2 （DRD2） was down-regulated， and the expression of dopamine receptor type 5 （DRD5）， the cyclic 3 'and 5' -adenosine monophosphine （cAMP） was up-regulated （P < 0.05）. In MMQ OMA1 group， miR-145-5p expression was down-regulated， kelch repeat sequence and BTB domain-containing protein 7 （KBTBD7） mRNA and protein expression was up-regulated （P < 0.05）. After transfected with miR-145-5p minic， MMQ OMA1 group exhibited down-regulated KBTBD7 expression and up-regulated DRD2 expression （P < 0.05）， which indicated that overexpression of miR-145-5p reversed the promoting effect of circOMA1 on KBTBD7. ConclusionCircOMA1 down-regulated DRD2 expression through miR-145-5p/KBTBD7 pathway to reduce the sensitivity of prolactinoma to DAs， and regulated the expression of dopamine receptors to activate the cAMP pathway and promote the synthesis and release of prolactin， thus promoting the drug resistance in prolactinoma.

This study aims to explore the mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis(RA) with syndrome of internal obstruction and cold-dampness and the compatibility characteristics based on the "disease-syndrome-formula" association network. A gene set associated with the clinical symptoms of RA was collected from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0(TCMIP v2.0). The different expression gene set of RA with syndrome of internal obstruction and cold-dampness was screened out by transcriptomic expression profile detection and bioinformatics data mining of the comparison of RA patients with syndrome of internal obstruction and cold-dampness and healthy volunteers. The chemical composition information of 35 Chinese medicines from Tianhe Zhuifeng Ointment was collected from TCMIP v2.0 and Traditional Chinese Medicine Bank(TCMBank). The candidate targets were predicted based on the similarity principle of compounds structure. The interactive network of "related gene of RA with syndrome of internal obstruction and cold-dampness-candidate target of Tianhe Zhuifeng Ointment" was constructed. The core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome Pathway Database. The compatibility mechanisms of various efficacy groups of Tianhe Zhuifeng Ointment were further explored. The results showed that the candidate targets of Tianhe Zhuifeng Ointment were mainly involved into the modules of "immune-inflammation" regulation, nervous system function, cell function, and substance and energy metabolism, etc. The mechanisms of various efficacy groups emphasized on different aspects. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, and the group of pungent analgesia regulated "immune-inflammation" system by warming meridians and dissipating cold. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated "immune-inflammation" system by activating blood and dredging channels. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, the group of activating blood and resolving stasis, the group of strengthening sinews and bones, and the group of clearing heat and draining water affected the nervous system by invigorating Qi-blood and benefiting spirit. The group of dispelling wind and removing dampness-dredging channels and activating collaterals and the group of extinguishing wind and stopping convulsions regulated cell function and substance and energy metabolism by dispelling wind and eliminating cold-dampness. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated the cell function and substance and energy metabolism by activating blood and strengthening sinews and bones. The results showed that Tianhe Zhuifeng Ointment exerted the comprehensive efficacy of dispelling wind, removing dampness, activating blood, removing stasis, warming meridians, dredging channels, and strengthening sinews and bones through adjusting the imbalance of "immune-inflammation", regulating nervous system, cell function, and interfering with substance and energy metabolism, thus improving the syndrome of internal obstruction and cold-dampness. The findings of this study laid foundations for clarifying the therapeutic characteristics and clinical orientation of Tianhe Zhuifeng Ointment.
Arthritis, Rheumatoid/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Inflammation/drug therapy* ; Medicine, Chinese Traditional ; Ointments ; Seizures ; Syndrome