Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

OBJECTIVE To assess the efficacy， safety and cost-effectiveness of tenecteplase in the treatment of acute ischemic stroke， and to provide a basis for clinical rational drug use and related decision-making. METHODS The related literature in the PubMed， the Cochrane Library， CNKI， Wanfang data and health technology assessment （HTA） databases were searched from the establishment of the database to June 30th， 2024. Systematic reviews/meta-analyses， pharmacoeconomic studies and HTA reports on tenecteplase in the treatment of acute ischemic stroke were collected. After data extraction and quality assessment， descriptive analysis of the included studies was carried out. RESULTS A total of 31 articles were included， involving 28 systematic reviews/ meta-analysis and 3 pharmacoeconomic studies. In terms of effectiveness， compared with alteplase， tenecteplase （0.25 mg/kg） could significantly increase the early neurological improvement； the 90 d excellent neurological recovery rate， 90 d good neurological recovery rate， and recanalization were not inferior to alteplase. For safety， compared with alteplase， tenecteplase did not increase the incidence of hemorrhage， symptomatic intracranial hemorrhage， 3-month mortality， or intracranial hemorrhage. In terms of cost-effectiveness， foreign research results showed that tenecteplase had economic advantages over alteplase. CONCLUSIONS Compared with alteplase， tenecteplase is effective and safe in the treatment of acute ischemic stroke， and it is cost-effective.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

Geriatric falls presenting to the emergency department (ED) are rising due to our rapidly ageing population. As part of a group of geriatric-focused emergency medicine practitioners, we describe a multidisciplinary falls prevention tool using the acronym.
Accidental Falls/prevention & control* ; Aged ; Emergency Service, Hospital ; Geriatric Assessment ; Humans

Objective:To explore the effect of functional electrical stimulation on cognition and on the expression of the brain-derived neurotrophic factor (BDNF), synaptophysin (SYN) and microtubule-associated protein 2 (MAP2) using a rat model of vascular dementia.Methods:Ninety pathogen-free male Wistar rats were randomly divided into a sham operation group, a placebo stimulation group and an electrical stimulation group. Both the placebo and electrical stimulation groups underwent bilateral occlusion of the common carotid artery to establish a model of vascular dementia. In the sham operation group the arteries were exposed without occlusion. Each group was then sub-divided into 3, 7 and 14 days subgroups with 10 rats in each subgroup. Beginning seven days after the surgery, the rats in the electrical stimulation group were given 30-minutes of stimulation every day while those in the sham operation group and the placebo stimulation group were given false electrical stimulation. After 3, 7 or 14 days the rats′ cognitive functioning was quantified using the Morris water maze test. The rats were then sacrificed and the expression of BDNF mRNA was measured using in situ hybridization. MAP2 and SYN levels were quantified immunohistochemically.Results:After 14 days the average latency in the placebo stimulation group was significantly longer than in the other groups. On the sixth day the average time in the target zone among the placebo stimulation group was significantly shorter than the other two groups′ averages. After only 3 days of simulation, the average expression of BDNF mRNA in the CA1 area of the hippocampus was significantly lower in the placebo stimulation group than among the others. After 7 days of stimulation the placebo group′s average was significantly lower than that of the sham operation group. The average expression of MAP2 had decreased significantly in the placebo stimulation group compared with the other two groups after 7 and 14 days of simulation. After 7 days the average expression of SYN in the placebo stimulation group was significantly lower than in the sham operation group, and after 14 days it was significantly lower than in the other two groups.Conclusions:Functional electrical stimulation may improve learning and memory in rats modelling vascular dementia through increasing BDNF, SYN and MAP2 expression levels.

To study the salivary cortisol level, and to analyze the correlation between salivary cortisol and peri-abortion depression in the women suffering termination of pregnancy for fetal anomaly.
 Methods: Comparing the difference in salivary cortisol level between the women with and without depression when they underwent termination of pregnancy for fetal anomaly in a prospective cohort study. Analyzing the correlation between salivary cortisol and peri-abortion depression through logistics regression analysis.
 Results: The salivary cortisol awakening response was lower in women with depression than women without depression. Based on the logistics regression analysis, the salivary cortisol awakening response showed a negative correlation with pre-abortion (OR=0.063, 95% CI 0.005 to 0.754) and post-abortion (OR=0.002, 95% CI 0.000 to 0.061) depression.
 Conclusion: Cortisol awakening response possesses a negative correlation with peri-abortion depression, and it is a predictive factor for post-abortion depression.
Depression ; Depressive Disorder ; metabolism ; Female ; Humans ; Hydrocortisone ; metabolism ; Pregnancy ; Prospective Studies ; Saliva ; metabolism

Objective To investigate the clinical value of bone metabolism biochemical marker N-MID,TP1NP and beta-CTx combined with whole body bone scintigraphy in early diagnosis of bone metastasis of tumor.Methods The concentration of the 3 markers were measured by the electrochemical luminescence analysis method in 30 cases of healthy control group and 210 cases of patients with malignant tumor,which were divided into non bone metastasis group(45 cases) and bone metastasis group(165 cases).The bone metastasis group were divided into 4 grades(0-grade Ⅲ) by Soloway classification according to whole body bone imaging.Results The levels of serum N-MID,TP1NP and beta-CTx in 165 malignant tumor patients with bone metastasis were significantly higher than in 45 malignant tumor patients with bone metastasis and in 30 healthy control group,the difference was statistically significant(P<0.05).With the increase of the number of metastatic lesions in the bone metastasis group,the serum levels of N-MID,TP1NP,and beta-CTx were increased gradually,and they were positively correlated with the progression of the disease.According to the analysis of ROC curve,the cut-off value,sensitivity and specificity in the diagnosis of tumor bone metastasis were 17.59 ng/mL,70.3％,88.9％ for serum N-MID,43.04 ng/mL,78.2％,95.6％ for TP1NP,and 0.48 ng/mL,73.9％,93.3％ for beta-CTx.Under the ROC curve(AUC) was 0.831 for serum N-MID,0.890 for TP1NP,and 0.869 for beta-CTx.The sensitivity and specificity of three bone metabolic markers in the diagnosis of bone metastasis of malignant tumor were significantly higher.Conclusion Bone metabolism biochemical markers:Serum N-MID,TP1NP and beta-CTx for diagnosis of bone metastasis of malignant tumor are sensitive,accurate and simple,which can significantly improve the efficiency of diagnosis of bone metastasis,and can be combined with whole-body bone scintigraphy in early diagnosis of bone metastasis with malignant tumor.

Objective:To explore the clinical characteristics,diagnosis,and treatments of adrenal insufficiency (AI) in the patients with acquired immune deficiency syndrome (AIDS),and to improve the clinician's understanding of the disease and provide evidences for its diagnosis and treatments.Methods:The clinical data of one patient with AIDS and AI were retrospectively analyzed and the diagnosis and treatments were summarized,and the relative literatures were reviewed.Results:The patient was clearly diagnosed as AIDS and AI after relevant examinations.The symptoms such as fatigue,nausea and vomiting of the patient were disappeared,the food intake of the patient was increased,and the electrolyte was normal after some treatments such as hormone replacement therapy (oral prednisone acetate 5.0 mg at 8:00 am.and 2.5 mg at 4:00 pm.) and symptomatic treatments.The patient died of a severe opportunistic infection when followed up for 37 d.Conclusion:The possibility of AI should be taken into account when the patients with AIDS have unexplained symptoms such as anorexia,nausea,weight loss and more characteristic manifestations such as orthostatic hypotension,hyponatremia or hyperkalemia.Early administration of glucocorticoid replacement therapy is feasible and effective.

Objective:To investigate the expression of CD56 antigen in leukemia cells of the patients with acute myeloid leukemia (AML)and its relationship with the prognosis of AML, and to clarify the role of CD5 6 antigen expression in predicting the prognosis of the AML patients.Methods:171 AML (non-M3)patients aged from 14 to 60 years old,who received a IA Regimen as the first time inducing chemotherapy were chosen.Flow cytometric analysis was used to evaluate the CD56 expression in leukemia cells.COX proportional regression analysis was used to select the prognostic factors,and bivariable analysis was used to study the relationship between the positive rate of CD56 and overall survival (OS).The CD56+ group (n=52),including CD56≥50% expression group (n=39) and CD56<50% expression group (n=13),and CD56- group (n=119)were identified by the expression of CD56 antigen.The complete remission rate (CRR), the relapse rate, the median OS, the median disease-free survival (DFS)and the survival rate of patients were compared.Results:The medium OS of the patients in CD56+ group (14.2 months)was shorter than that in CD56- group (39.4 months)(P<0.05).Moreover,the medium OS in CD56≥50% group was shorter than that in CD56<50% group (11.7 months vs 20.3 months,P<0.05).The 1-year and 2-year survival rates of the patients in CD56+ group (61.5%,46.2%)were lower than those in CD56-group (75.6%,63.9%)(P<0.05).The 1-year survival rate had no significant difference between CD56≥50%group and CD56<50% group (53.8%vs 84.6%,P>0.05),while the 2-year survival rate in CD56≥50% group was lower than that in CD56<50% group (41.0%vs 61.5%,P<0.05).There were no significant differences of the CRR between CD56+ group (76.9%)and CD56- group (68.9%)as well as CD56≥50% group (58.9%)and CD56<50% group (63.5%)(P>0.05).The relapse rate and first year relapse rate of patients in CD56+ group (64.3% and 37.5%)were significantly higher than those in CD56- group (34.3% and 17.9% )(P<0.05). However,there were no significant differences of the relapse rate and first year relapse rate between CD56≥50%group (75.0% and 42.9%)and CD56<50% group (37.5% and 16.7%)(P>0.05).The DFS in CD56+ group was shorter than that in CD56- group (P<0.05).The same DFS result was also found between CD56≥50%group and CD56<50% group (P<0.05).Conclusion:The expression of CD56 antigen in leukemia cells predicts a bad prognosis in the AML patients,and the higher expression of CD56 indicates the worse prognosis.

Objective:To comparison of three different beta blockers on murine hemangioma (EOMA cells) cells in vitro and in vivo effects.Preliminary study on the therapeutic effect of propranolol on vascular tumor in mice and possible mechanisms , provide a reference for beta blockers in the treatment of infantile hemangioma .Methods: Comparative study on the effects of three kinds of different β-receptor blockers---metoprolol, propranolol and butoxamine , on the proliferation and apoptosis of Mouse Hemangioendothelioma Endothelial cell (EOMA cells) was conducted in vitro.EOMA cells were cultured in vitro,randomly divided into different groups,propranolol and timolol were added into the medium respectively ,after 24 h intervention.MTT assay and acridine orange staining assay were conducted respectively to detect cell viability and apoptosis level .EOMA cells were transplanted into nude mice in vivo.Tumor volume growth to 100 mm3 ,animals were randomly divided into 4 groups respectively ,the control group ,metoprolol group,Bhutto Samin group and propranolol group ,drug group according to 2 mg/( kg? d) oral gavage ,control group were given an equal volume of saline ( NS ) , every two days measurement tumor volume size .Serum levels of tumor necrosis factor alpha ( TNF-α) and vascular endothelial growth factor ( VEGF ) were detected by enzyme linked immunosorbent assay ( ELISA ) in the end of the experiment.Results:For propranolol,after 24 h treatment,significant differences of cell viability and apoptosis were noted (P<0.05) at the concentration of 50 μmol/L,while continuing to increase to 800 μmol/L,the cell survival rate decreased sharply to close to 10%. Acridine orange staining at the 50 μmol/L group after 24 h revealed many apoptotic cells .For metoprolol and butoxa mine ,significant differences of cell viability and apoptosis were noted ( P<0.05 ) at the concentration of 100 μmol/L,while continuing to increase to 800μmol/L,the cell survival rate decreased sharply to close to 20%.It was significantly higher than propranolol group at the same concentration ( P<0.05 ) .It showed a similar trend in acridine orange staining .In vivo experiments showed that the end of the experiment of metoprolol , butoxamine group and propranolol drugs in mice tumor volume , respectively ( 1 642.8 ±89.3 ) , ( 1 529.3 ± 119.1) and (752.7±46.5)mm3,significantly lower than the control group of mice tumor volume of (2 023.3±123.0) mm3(P<0.001).Metoprolol,butoxamine mice and propranolol drugs group ,serum VEGF levels for (606.5±105.8 ) pg/ml,(534.3±243.2 ) pg/ml and (420.1±123.7) pg/ml, significantly lower than the PBS control group [(825.8±145.7) pg/ml,(P<0.05)],the TNF alpha result was followed by(301.3±62.3) pg/ml,(305.1±53.8) pg/ml and (288.8±59.5) pg/ml,significantly lower than the normal control group [(444±100.4) pg/ml,P<0.05].Conclusion:Three kinds of beta-blockers can effectively inhibit EOMA cells proliferation and induce apoptosis in vitro, the role of propranolol more significantly than butoxamine and metoprolol .Three kinds of beta blockers restrain the growth of the hemangioma in vivo ,in which the inhibitory effect of propranolol is stronger than the metoprolol and butoxa mine.Three kinds of beta blockers can lower the levels of VEGF and TNF-αin vivo.Indicating that propranolol on vascular tumor in mice may be one of the mechanisms of β1 and β2 receptor synergy effect and its mechanism in the treatment of hemangioma may be associated with VEGF and TNF-α.