ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

OBJECTIVE To establish a multi-dimensional value assessment framework for new antidiabetic drugs based on multi-criteria decision analysis theory， thus providing a theoretical framework and methodology for evidence-informed medical insurance decision-making. METHODS Firstly， multi-dimensional evidence was searched and obtained to provide reliable data for the establishment of the framework. Secondly， in terms of the obtained evidence， the value assessment framework was preliminarily constructed. Its structure， main core criteria， and contextual criteria were determined through focus group discussion. Finally， the criteria and sub-criteria of the framework and their weights were further determined， reasons for inclusion of sub-criteria and the reasonableness of rating scores were evaluated， and methods of assessment were optimized through expert consultation. RESULTS The multi-dimensional value assessment framework for new antidiabetic drugs was composed of core criteria and contextualized criteria， which could be used for quantitative and qualitative value assessment of new drugs， respectively. The core criteria consisted of five dimensions， with affordability （6.31） having the highest weighting score， followed by comparative effectiveness （6.20）， comparative safety （6.01）， cost-effectiveness （5.89）， and quality of evidence （5.46）. After the normalization of weight within sub-criteria， the budget impact on medical insurance had the highest standardized weight， followed by the control of glycated hemoglobin and patient affordability. The contextual criteria included two dimensions， i. e.， innovation and equity. CONCLUSIONS The assessment framework integrates evidence， stakeholders’ values， and decision contexts to enable a multi- dimensional and evidence-based assessment of the value of new antidiabetic drugs.

ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

BACKGROUND: Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. METHODS: The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI). RESULTS: The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356-128,645,155 cases), 693,444 cases (95% UI = 567,765-850,490 cases), and 17,672 cases (95% UI = 13,932-21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26-1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94-1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0-2235.14) in 1990 to 964.70 (801.26-1175.09) per 100,000 people in 2021. CONCLUSIONS Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.
Humans ; Urolithiasis/mortality* ; Male ; Female ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Adult ; Middle Aged ; Risk Factors ; Sex Factors

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To explore the clinical effect of clinical observation of supplemented wendan decoction combined with Western medicine in treating insomnia accompanied by anxiety and depression in phlegm-heat internal disturbance syndrome.Methods A total of 120 cases of insomnia with anxiety and depression comorbiditis with phlegm heat disturbance syndrome were randomly divided into control group and treatment group,60 cases in each group.The control group was given escitalopram oxalate tablet combined with dexzopiclonone tablet,and the observation group was given added Wendan decoction on the basis of the control group.Both groups were treated continuously for 6 weeks.Polysomnography monitoring parameters and heart rate variability were compared between the two groups during baseline period and visit 2(baseline period+3 months).Scale scores of the two groups were compared during baseline period,visit 1(baseline period+6 weeks)and visit 2.The content of heart rate variability includes:time domain analysis(standard deviation of normal interval(SDNN),square root of the square sum of the mean of the difference between adjacent normal interval(RMSSD)and frequency domain analysis(LF,HF,LF/HF).The scale scores included the Pittsburgh Sleep Quality Index(PSQI)and Insomnia Severity Index(ISI)to assess sleep status,and the Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Self-assessment Scale for Depression(PHQ-9)and Generalized Anxiety Disorder Scale(GAD-7)to assess anxiety and depression status.Results(1)Polysomnography monitoring:the wake time of observation group was significantly shorter than that of control group,the number of awakenings was significantly less than that of control group,and the percentage of N3 and REM was significantly higher than these of control group(P＜0.05).(2)Heart rate variability:RMSSD and HF values in the observation group were significantly higher than those in the control group,and LF/HF values were significantly lower than those in the control group(P＜0.05).(3)In terms of sleep:during the interview,PSQI total score,sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group(P＜0.05);At the 3 months,the sleep quality,hypnotic drugs and daytime dysfunction in the observation group were significantly lower than those in the control group(P＜0.05).In terms of emotion:HAMA,HAMD and GAD-7 scores were significantly lower than those of control group at 6 weeks(P＜0.05);At the 3 months,HAMA and GAD-7 scores were significantly lower than those of control group(P＜0.05).Conclusion Supplemented Wendan decoction combined with western medicine can obviously optimize the sleep structure of insomnia patients with anxiety and depressionof phlegm-heat disturbance syndrome,improve sleep continuity and deepen sleep depth,and improve parasympathetic functional activities,contribute to sympathetic parasympathetic balance,can improve insomniaand depression symptoms recently,and significantly improve anxiety symptoms in the short term,with good safety.

Objective To analyze the effects of miR-181a-5p overexpression on metabolites in the small intestines of mice with subcutaneous oral cancer by detecting changes in metabolites and metabolic pathways.Methods Three groups were included in study:Control group,negative control and miR-181a-5p overexpression group.To establish a subcutaneous oral cancer model in mice,variously treated cell suspensions were subcutaneously injected into the upper right of the groin in female M-NSG severely immunodeficient mice.Changes in pathology and small intestinal tissues were assessed by HE staining.Changes in mouse body weight were also assessed.Tandem orbitrap mass spectrometry and ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry,were used to examine metabolites in the small intestines.By pre-analyzing the original data and quality rating sample data,XCMS was able to assess which metabolites were different among the groups.To identify unique metabolic pathways,KEGG enrichment analysis was used.Results A total of 170 distinct metabolites were found in the small intestinal tissues of Control and NC groups.Choline metabolism,alanine,aspartate,and glutamate metabolism,GABA synaptic metabolism,glycerophospholipid metabolism,cAMP signaling route,cancer center carbon metabolism,and niacin and niacin amine metabolic pathways were important signaling pathways for metabolite enrichment.In the NC group,16 distinct metabolites with VIP values larger than 2 were found in the small intestines compared with the OE group overexpressing miR-181a-5p.Glycerin phosphorylcholine,palmitic acid,3-hydroxybutyl carnitine,and β-hydroxybutyric acid were among the metabolites that significantly varied.The primary enhanced metabolic pathway was the choline pathway.Conclusions Mouse small intestines underwent slight changes from subcutaneous oral cancer with the greatest effect on metabolites critical for energy metabolism.The choline metabolic pathway was the pathway that selected absolutely metabolites in mouse small intestines with subcutaneous grafts of oral cancer.

Objective:To investigate symptoms of anxiety and depression among primary and middle school students quarantined in hotels during the COVID-19 epidemic.Methods:Anxiety and depression symptoms among 726 primary and middle school students quarantined in hotels were investigated with The Screen for Child Anxiety Related Emotional Disorders(SCARED)and Depression Self-rating Scale for Children(DSRSC)from September to October 2022 in Chifeng City,Inner Mongolia Autonomous Region.There were 624 students completed investi-gation with response rate of 86％.The positive score of SCARED was ≥23 and DSRSC was ≥ 15.Results:The detection rates of anxiety and depression were 17.9％and 15.4％respectively.The detection rates of anxiety and depression were higherin middle school students than inprimary school students(Ps＜0.05).The scores of general-ized anxiety and social phobia factors were higher in female students than in male students(Ps＜0.05).The scores of dissociative anxiety factor and depression were higher in middle school students than in primary school students(Ps＜0.05).Conclusion:During the COVID-19 epidemic,middle school students quarantined in hotels are more likely to have anxiety and depression symptoms than primary school students,and female students are more likely to have anxiety symptoms than male students.

Objective To evaluate the predictive value of serum carbohydrate antigen 50(CA50),tumor specific growth factor(TSGF),and tissue polypeptide antigen(TPA)levels for sensitivity to radiochemotherapy in patients with middle-and advanced-stage breast cancer using a nomogram model.Methods Eighty-two patients with middle-and advanced-stage breast cancer were selected as the study sub-jects.All patients received paclitaxel chemotherapy combined with radiotherapy and were divided into sensitive(n= 57)and insensitive(n= 25)groups according to the Response Evaluation Criteria in Solid Tumors.The general information of the patients,serum expression of CA50,TSGF,and TPA,and their differences before and after treatment were recorded.A nomogram model was constructed,and cali-bration curves,receiver operating characteristic(ROC)curves,and decision curves were used to evaluate the predictive power and clinical utility of the nomogram model.Results Significant differences were observed in tumor diameter,vascular invasion,TNM stage,lymph node metastasis,and degree of differentiation between the two groups(P＜0.05).Compared to those in the sensitive group,the serum expression of CA50,TSGF,and TPA after treatment was higher,and the difference in CA50,TSGF,and TPA was smaller in the insensitive group(P＜0.05).Three predictive variables were identified in the LASSO regression:differences in CA50,TSGF,and TPA.The logistic regression results showed that differences in CA50,TSGF,and TPA influenced sensitivity to radiochemotherapy in middle-and advanced-stage breast cancer(P＜0.05).A nomogram model was constructed using differences in CA50,TSGF,and TPA.Calibration,ROC,and decision curves showed the model's good predictive accuracy and clinical utility.Conclusion Serum expression of CA50,TSGF,and TPA is high in patients with middle-and advanced-stage breast cancer who are insensitive to radiochemotherapy,and differences in CA50,TSGF,and TPA affect their sensitivity to radiochemotherapy.The nomogram model had good predictive value and clinical utility.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*