ObjectiveTo investigate the possible mechanisms of modified Xiaoyao Powder （逍遥散） in the treatment of hyperprolactinemia （HPRL） with liver constraint and spleen deficiency. MethodsNinety-six female SD rats were randomly divided into a normal group （n=16） and a modeling group （n=80）. In the modeling group， rats were subjected to chronic unpredictable stress combined with intraperitoneal injection of metoclopramide to establish a rat model of HPRL with liver constraint and spleen deficiency. The 80 successfully modeled rats were randomly divided into a model group， a high， medium， and low-dose group of modified Xiaoyao Powder， and a bromocriptine group， with 16 rats in each group. The high， medium， and low-dose groups of modified Xiaoyao Powder were orally administered doses of 60， 30， and 15 g/（kg·d） respectively， the bromocriptine group was orally administered bromocriptine tablets at a dose of 1 mg/（kg·d）， and the normal group and model group were orally administered 10 ml/（kg·d） of normal saline for 14 consecutive days. ELISA was used to detect serum prolactin （PRL） level； immunohistochemistry was used to determine the expression of tumor necrosis factor-alpha （TNF-α） and tyrosine hydroxylase （TH） in the hypothalamus； Western blot was used to detect the protein expression of tumor necrosis factor receptor 1 （TNFR1） in the hypothalamus； Real-time PCR was used to detect the mRNA expression of receptor interacting protein kinase 3 （RIP3） in the hypothalamus； immunofluorescence was used to detect the co-expression of RIP3 and dopamine neurons in the hypothalamus. ResultsCompared with the normal group， the serum PRL levels were increased in the model group， and the expression of hypothalamic TNF-α， TNFR1， RIP3 mRNA， and the co-expression of RIP3 with dopamine neurons were significantly increased， while TH expression was decreased （P＜0.05 or P＜0.01）. Compared with the model group， the expression of hypothalamic TNF-α was decreased in the bromocriptine group and low-dose group of modified Xiaoyao Powder， and the expression of TH was significantly increased in the medium and high-dose groups of modified Xiaoyao Powder and the bromocriptine group. The serum PRL levels， hypothalamic TNFR1 and RIP3 mRNA expression， and the co-expression of RIP3 with dopamine neurons were significantly decreased in all dose groups of modified Xiaoyao Powder and the bromocriptine group （P＜0.05 or P＜0.01）. Compared with the bromocriptine group， the serum PRL level were significantly increased in the high and low-dose groups of modified Xiaoyao Powder， TH expression was significantly increased in the medium-dose group of modified Xiaoyao Powder， hypothalamic RIP3 mRNA expression was decreased in the low-dose group of modified Xiaoyao Powder， and the co-expression of RIP3 with dopamine neurons was significantly increased in the high-dose group of modified Xiaoyao Powder （P＜0.01）. ConclusionModified Xiaoyao Powder can regulate the programmed cell death of hypothalamic dopamine neurons， affect DA expression， and regulate PRL levels， which may be one of its mechanisms in the treatment of HPRL with liver constraint and spleen deficiency.

Objective To research the effectiveness of deep learning techniques in intelligently diagnosing dental caries and periapical periodontitis and to explore the preliminary application value of deep learning in the diagnosis of oral diseases.Methods A dataset containing 2 298 periapical films,including healthy teeth,dental caries,and peri-apical periodontitis,was used for the study.The dataset was randomly divided into 1 573 training images,233 valida-tion images,and 492 test images.By comparing various neural network models,the MobileNetV3 network model with better performance was selected for dental disease diagnosis,and the model was optimized by tuning the network hyper-parameters.The accuracy,precision,recall,and F1 score were used to evaluate the model's ability to recognize dental caries and periapical periodontitis.Class activation map was used to visualization analyze the performance of the net-work model.Results The algorithm achieved a relatively ideal intelligent diagnostic effect with precision,recall,and accuracy of 99.42%,99.73%,and 99.60%,respectively,and the F1 score was 99.57%for classifying healthy teeth,den-tal caries,and periapical periodontitis.The visualization of the class activation maps also showed that the network model can accurately extract features of dental diseases.Conclusion The tooth lesion detection algorithm based on the Mo-bileNetV3 network model can eliminate interference from image quality and human factors and has high diagnostic accu-racy,which can meet the needs of dental medicine teaching and clinical applications.

Objective:To explore the association between the variability of triglyceride glucose index (TyG) and the risk of type 2 diabetes mellitus(T2DM).Methods:This study was a retrospective cohort study. A total of 22 929 community-dwelling elderly (aged≥60 years) who received annual health check-ups in Kunshan city of Suzhou Municipality during 2014 to 2021 were enrolled in the study. Fasting triglycerides and blood glucose were measured during annual physical check-ups and the TyG was calculated, the standard deviation of TyG measurements in three consecutive physical check-ups was used as the indicatior of TyG long-term variability. According to the quartile of TyG long-term variability, the study subjects were divided into four groups, namely Q 1 (0-0.14), Q 2 (>0.14-0.22), Q 3 (>0.22-0.33), Q 4 (>0.33-1.90). The outcome variable was the occurrence of T2DM. The relationship between TyG variability and T2DM incidence was analyzed by multivariate Cox regression. Results:In the study cohort 11 518 (50.2%) were females and the mean age was (67.42±5.35) years. By the end of follow-up, 2 934 cases of new T2DM were diagnosed, with an oveall incidence rate of 12.8%. After adjusting for multiple confounders and average TyG, long-term variability of TyG was significantly associated with T2DM risk ( HR=1.83, 95% CI: 1.51-2.20). The risk of T2DM in Q 4 group was significantly higher than that in Q 1 group ( HR=1.33, 95% CI: 1.19-1.47). Kaplan-Meier survival curve showed that long-term variability of TyG was significantly correlated with the cumulative risk of T2DM incidence ( P<0.001). Conclusions:TyG variability is an independent risk factor for T2DM, suggesting that attention should be paid not only to specific time-point TyG levels but also to TyG fluctuation for early identification of T2DM risk.

Objective This study aims to analyze the clinical epidemiology,diagnostic and treatment characteristics of minor patients with maxillofacial fracture and provide a reference for the prevention and treatment.Methods The clinical data of minor patients with maxillofacial fracture in Department of Traumatic and Plastic Surgery,West China Hospital of Stomatology,Sichuan University,from January 1,2015 to December 31,2020 were retrospectively studied and statistically analyzed in terms of age,gender,etiology,anatomic sites and treatment modalities.Results The mean age of the patients was(10.65±5.15)years,and the male-to-female ratio was 1.91∶1.High fall was the primary cause of maxillofacial fractures in minors aged 0-6 years.Traffic accident injuries were the main cause of maxillofacial fractures in minors aged 7-12 and 13-17 years.About 65.13%of the midface and 83.08%non-condylar fractures were mainly treated by surgery,and condylar fractures were treated conservatively in 74.73%and by surgical treatment in 25.27%.Conclusion The etiology of maxillofacial fractures in minors differs at different ages,so prevention strategies should be adjusted according to age.Surgical treatment has become the preferred treatment modality for midface and non-condylar fractures.Conservative treatment is still the main treatment method for condylar fractures,but the proportion of surgical treatment increases.

Objective·To explore the molecular regulatory mechanism of neural tube defect(NTD)induced by retinoic acid(RA)in mouse embryos,and reveal the gene expression regularity of neural tube closure in mice.Methods·Based on the high-quality brain vesicle transcriptome data of mouse embryo during the critical period of neural tube closure[embryonic day 8.5(E8.5),E9.5 and E10.5],the gene expression trend data of the NTD group and the control group were obtained by using Short Time-series Expression Miner(STEM)software.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for genes with different expression trends between the NTD group and the control group.Some candidate genes were screened for validation.Pregnant mice were divided into the NTD group and control group,with 9 mice in each group.Pregnant mice in the NTD group were treated with RA and those in the control group were treated with sesame oil by gavage at E7.5.Foetal rat brain vesicle tissues were collected at E8.5,E9.5 and E10.5 for experiments.Based on the above animal tissues,the screened candidate genes were validated by quantitative real-time PCR(RT-PCR).Results·A total of 18 255 genes were detected in the transcriptome data of the control group,and the expression patterns of these genes could be summarized into 7 significant profiles.A total of 19 037 gene expression data were detected in the transcriptome data of the NTD group,and gene expression patterns could be summarized into 6 profiles with significant significance.A total of 46 genes in the control group showed an upward trend but a downward trend in the NTD group.They were enriched in the positive and negative regulation of organ development,neuronal apoptosis,oligodendrocyte proliferation,and fibroblast growth factor signaling pathway at the biological process level.At the cellular component level,they were mainly involved in the basic structure of cells and neurons;At the molecular functional level,they were mainly related to the binding of fibroblast growth factor receptor.A total of 61 genes showed a downward trend in the control group but an upward trend in the NTD group.These genes were enriched in functions such as cell lysis and amino acid/ion transport at the biological process level.At the cellular component level,they were enriched in intracellular molecules,particles,extracellular region,intercellular space,etc.At the molecular function level,they were related to the activity of a series of enzymes and transporters.The results of RT-qPCR showed that the transcriptome sequencing data were authentic and reliable.Conclusion·RA intervention causes abnormal cellular activities and stress responses during mouse embryo development,leading to abnormal embryo development,activation of signalling pathways related to organismal self-protection,and suppression of genes that maintain normal embryo development.

Virtual reality technology is an emerging technology that integrates multiple disciplines. It has the advantages of immersion, interactivity and imagination, which provides convenience for intelligent nursing in the field of rehabilitation treatment. This paper summarizes the application research of virtual reality technology in patients with kinetophobia, focusing on classification, application mechanism, application status, limitations and future development of virtual reality technology in various diseases of kinetophobia, so as to provide reference and basis for the rehabilitation nursing of patients with kinetophobia based on virtual reality technology in the future.

Objective To investigate the effect of the monoamine oxidase A(MAOA),Maoa c.1409 T＞C synonymous mutation on anxiety,fear,and other emotional behaviors in mice.Methods In this study,CRISPR/Cas9 technology was used to construct a mouse model of a single nucleotide polymorphism(SNP)synonymous mutation.We evaluated the differential effect of this gene between males and females through animal behavior and gene expression studies in animal models.In terms of animal behavior,an open field test,elevated plus maze test,defensive burial experiment,forced swimming test,and 3D behavioral analysis were used.Other method were used to evaluate behavioral differences between male and female mice with polymorphisms in Maoa synonymous mutant genes.Results The result of the open field experiment showed that the residence time of female SNP mice in the central area was significantly higher than that of male SNP mice(P＜0.001).In the elevated cross maze experiment,the EPM result showed that the time and frequency of male SNP mice entering the open arm were higher than those of female SNP mice,but there was no significant difference.The defensive burial test showed that the number and duration of excavations by female SNP mice in response to rat urine were significantly reduced(P＜0.01).The FST showed that SNP females had shorter immobility time and longer swimming time(P＜0.05),and thus their depression was lower than males.3D-AI fine behavior analysis showed no significant male and female differences,except for the movement trajectory and climbing behavior of mice.The MAOA enzyme content of female SNP mice was significantly lower than that of male SNP mice(P＜0.001),but there was no significant difference in enzyme activity between male and female SNP mice.Conclusions The synonymous mutation of Maoa c.1409 T＞C acts by affecting the expression of MAOA and may have different fear,anxiety,and mood effects in male and female SNP mice.

Objective:To observe the clinical efficacy of neck Gongfa exercise in intervening people at high risk for cervical spondylosis. Methods:A total of 212 participants from 8 companies at high risk for cervical spondylosis were divided into two groups using the random number table method,with 105 participants in the control group receiving health education and 107 participants in the trial group receiving an additional neck Gongfa exercise.After successive 3-month interventions,the two groups were compared in terms of cervical soft tissue tension and neck disability index(NDI)score.The incidence of cervical spondylosis was observed 3 months later. Results:During the process,10 cases dropped out in the trial group,and the control group had 9 dropout cases.After the intervention,the cervical soft tissue tension value and NDI score improved in both groups(P<0.05)and showed significant differences between the two groups(P<0.05).At the 3-month follow-up,the trial group had a lower incidence rate of cervical spondylosis than the control group(P<0.05). Conclusion:For people at high risk for cervical spondylosis,neck Gongfa exercise can effectively improve cervical soft tissue tension and motor dysfunction and lower the incidence of cervical spondylosis in the short run.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

Objective To establish a quality traceability evaluation method for the whole honeysuckle oral solution process by identifying and screening its anti-inflammatory quality markers.Methods UPLC/-TOF-MS was used to analyze the iridoids and phenolic acids in oral solution,and the correlations were constructed by molecular network technology.The HPLC fingerprints of multiple batches of oral solution were established,and similarity analyses were performed to identify key pharmacodynamic molecules.The key anti-inflammatory quality markers were confirmed by the NF-κB dual luciferase assay system.Further,the quantification of 12 quality markers of iridoids and phenolic acids in oral solution was established separately based on the dual-wavelength HPLC technique.The quality of the oral solution was evaluated by examining the extraction and transfer rate of quality markers during the processing of raw materials and preparations and thermal stability.Results A total of 9 iridoids and 6 phenolic acids were identified in the oral solution,and the possible conversion relationships between their components were depicted.Fingerprint analysis of 11 batches of oral liquids showed that the composition of their main peaks was the same,with a similarity of more than 90%.Among them,6 iridoids(loganic acid,secologanoside,secologanic acid,sweroside,secoxyloganin,secologanin)and 6 phenolic acids(neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,isochlorogenic B,isochlorogenic A,isochlorogenic C)exhibited NF-κB inhibitory activity,which were the main pharmacological components and could be used as quality markers.The traceability of the above 12 quality markers was investigated in a multi-batch process based on the dual-wavelength HPLC method.The thermal stability studies of the raw materials revealed that the contents of their total iridoids and phenolic acids remained stable.Still,some of them would be transformed between components.The production process of the oral solution was stable,and the transfer rates of the iridoids and phenolic acids during the extraction,concentration and preparation were over 76%and 63%,respectively.Conclusion The method is stable,reliable,easy to operate and can evaluate the full honeysuckle oral solution process,which provides an effective means for the quality control of honeysuckle herbs and preparations.