Objective To screen the influencing factors associated with adverse clinical out-comes in hospitalized elderly patients with Alzheimer's disease(AD)using LASSO-Logistic regression analysis and to construct a nomogram prediction model.Methods A retrospective selection of 214 hospitalized elderly patients with AD who visited the Department of Geriatric Medicine in the hospital from February 2021 to March 2023 was conducted,and clinical data of all patients were collected.Patients were divided into adverse events group(n=53)and non-adverse events group(n=161)based on the occurrence of adverse clinical outcomes.After variable screening using LASSO regres-sion,multivariate Logistic regression analysis was performed to identify independent factors influen-cing adverse clinical outcomes in hospitalized elderly patients with AD.A Nomogram model for pre-dicting adverse clinical outcomes in these patients was established based on the results of multivariate analysis.The predictive performance,calibration,and clinical utility of the Nomogram model were evaluated using the concordance index,calibration curve,and decision curve analysis(DCA).The diagnostic performance of the Nomogram model for adverse clinical outcomes in hospitalized elderly patients with AD was assessed using the receiver operating characteristic(ROC)curve and the area under the curve(AUC).Results LASSO-Logistic regression analysis revealed that the Mini-Men-tal State Examination(MMSE)score was an independent protective factor against adverse clinical outcomes in hospitalized elderly patients with AD(P＜0.05),while the Charlson Comorbidity In-dex(CCI score),creatinine,urea,and fasting blood glucose(FBG)levels were all independent risk factors for adverse clinical outcomes in these patients(P＜0.05).The Nomogram model con-structed based on the influencing factors screened by LASSO-Logistic regression analysis showed a concordance index of 0.994(95％CI,0.958 to 1.000)for predicting adverse clinical outcomes in hospitalized elderly patients with AD.The Hosmer-Lemeshow test results indicated x2=1.909,P=0.984,suggesting good model fit.The DCA result demonstrated that the model had favorable threshold probabilities and net clinical benefits.Conclusion The Nomogram model for predicting clinical outcomes in elderly inpatients with AD constructed based on LASSO-Logistic regression anal-ysis exhibits high predictive value,and can be used to forecast the occurrence of adverse clinical outcomes in these patients.

Cognitive ability assessment and cognitive enhancement techniques play an important role in maintaining and improving human cognitive function,psychological and emotional stability,and in enhancing work efficiency.This paper begins by introducing the theory of cognitive ability,influencing factors and cognitive assessment methods before summa-rizing the latest progress in current cognitive enhancement strategies and technological paths and analyzing their prospects of applications in order to provide reference for the development and application of personnel cognitive assessment and cog-nitive enhancement technology in the future.

Objective To investigate the effect of interleukin-22(IL-22)on the activation of hepatic stellate cells(HSCs)and its mechanism.Methods The human HSC LX-2 cells were selected for the study,and the LX-2 cells induced by TGF-β1 were used to establish a model of HSC activation.LX-2 cells were treated with IL-22 at gradient concentrations,and Western blot and qRT-PCR were used to measure the expression levels of the activation markers COL1A1 and α-SMA and determine the appropriate working concentration and time of the drug.Western blot,qRT-PCR,and immunofluorescence assay were used to determine the levels of Fn14 and the markers for endoplasmic reticulum stress(ERS)and activation in activated HSCs treated by IL-22.ERS in LX-2 cells was induced by tunicamycin(TM),and Western blot and qRT-PCR were used to measure the levels of markers for ERS and activation in LX-2 cells treated by IL-22.TNF-like weak inducer of apoptosis(TWEAK)and small interfering RNA were used to upregulate and downregulate Fn14,and then the mRNA and protein expression levels of p-IRE1α,IRE1α,XBP1s,COL1A1,and α-SMA were measured.After LX-2 cells induced by TGF-β1 were treated by IL-22,TWEAK was used to upregulate Fn14,and Western blot and immunofluorescence assay were used to measure the levels of Fn14 and the markers for ERS and activation.The independent-samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the Sidak's multiple comparison test was used for further comparison between two groups.Results Compared with the TGF-β1 group,the TGF-β1+IL-22 group had significant reductions in the protein and mRNA expression levels of COL1A1 and α-SMA,with a more significant effect after treatment with 10 ng/mL IL-22 for 24 hours(all P<0.01).Compared with the TGF-β1 group,the TGF-β1+IL-22 group had significant reductions in the expression levels of Fn14,p-IRE1α,and XBP1s(all P<0.05).Compared with the TM group,the TM+IL-22 group had significant reductions in the expression levels of p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Compared with the silenced control group,the Fn14 siRNA group had significant reductions in the expression levels of p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Compared with the normal control group,the TWEAK group had significant increases in the expression levels of Fn14,p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.01).Compared with the TGFβ1+IL-22 group,the TGF-β1+IL-22+TWEAK group had significant increases in the expression levels of Fn14,p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Conclusion IL-22 negatively regulates ERS in HSCs by inhibiting Fn14,thereby inhibiting the activation of HSCs.

Objective To clarify the changes in the microRNA(miRNA)expression profile of rat alveolar lavage-fluid-derived exosomes after acute ozone exposure and analyze its potential relationship with lung injury.Methods Adult male Wistar rats were exposed to 0 ppm,0.5 ppm,and 2 ppm ozone for 6 h in a gas exposure chamber.After 24 h,the rats were anesthetized,the alveolar lavage fluid was collected,and exosomes were extracted.Differentially expressed miRNAs in exosomes were detected by miRNA-seq technology.miRDB databases were used to predict the target genes of the top 10 differentially expressed miRNAs among the groups,and Gene Ontology function enrichment and KEGG Pathway analyses were performed on the target genes.The differentially expressed miRNAs with high expression abundance and good uniformity were verified by quantitative reverse-transcription PCR(qRT-PCR).Results Compared with the findings in the 0 ppm group,there were 8 up-regulated and 55 down-regulated miRNAs in the 0.5 ppm group,and 32 up-regulated and 61 down-regulated miRNAs in the 2 ppm group.Compared with the findings in the 0.5 ppm group,90 exosomal miRNAs were up-regulated and 74 were down-regulated in the 2 ppm group.The target genes of top 10 differentially expressed miRNAs were mainly involved in regulating DNA binding,heterocyclic compound binding,and affecting transcription,and were closely related to cancer,MAPK,PIK3-AKT,TNF,ErbB,mitophagy,and FoxO signaling pathways.The qRT-PCR showed that the sequencing result were basically reliable.Conclusions Acute ozone exposure can lead to changes in the expression profile of exosomal miRNA in the alveolar lavage fluid of rats.Differentially expressed miRNAs may be involved in pathological processes,such as lung tissue inflammation and lung injury,caused by ozone exposure.

Dendrobii officinalis, with a definite effect of nourishing Yin and clearing heat, has been a folk habit for drinking after being mixed with water. Because its superfine powder has the advantages of high dissolution and convenient drinking, we observed the effect of D. officinalis superfine powder on metabolic hypertension model rats and its possible mechanism in this experiment, which can be used as a reference for its clinical application for hypertension. The overeating greasy-induced metabolic hypertension model was established with high-fat, high-sugar and high-purine diet. These rats were orally administered with 400 mg·kg~(-1) and 200 mg·kg~(-1) of D. officinalis superfine powder for 20 consecutive weeks. During this period, blood pressure, blood lipid, blood glucose, insulin and other related indexes of glucose and lipid metabolism were monitored; the levels of lipopolysaccharide(LPS), C-reactive protein(CRP), interleukin 6(IL-6) and other inflammatory mediators were measured; the levels of nitric oxide(NO) and endothelin-1(ET-1) were detected, and the histomorphological and ultrastructural changes of aorta were observed. In addition, the expression of LPS/TLR4 pathway-related molecules in aorta was determined. The results showed that long-term administration of D. officinalis superfine powder significantly reduced the levels of systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial pressure(MBP) in metabolic hypertension model rats, decreased the levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-c), glucose(Glu), and insulin(INS) levels in blood, increased the contents of high density lipoprotein cholesterol(HDL-c),decreased the LPS, CRP, IL-6 and ET-1 levels in blood and increased NO content. Furthermore, it improved the abnormality of aortic histomorphology and endothelial ultrastructure, and inhibited the protein expression of TLR4, myeloid differentiation factor(MyD88), IL-6, interleukin-1 β(IL-1β), and tumor necrosis factor-α(TNF-α) as well as mRNA expression of TNF-α and IL-1β in aorta. In conclusion, D. officinalis superfine powder may improve the abnormal function and structure of blood vessels by inhibiting the activation of LPS/TLR4 pathway, thus playing a role against metabolic hypertension.
Animals ; Dendrobium/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Hyperphagia ; Hypertension/drug therapy* ; Interleukin-6 ; Powders ; Rats ; Tumor Necrosis Factor-alpha

OBJECTIVE: To investigate the mechanism of Chinese medicine Buyang Huanwu decoction (BYHWD) promoting neurogenesis and angiogenesis in ischemic stroke rats. METHODS: Male SD rats were randomly divided into sham operation group, model group, BYHWD group, antagonist group and antagonist control group with 14 rats in each. Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery for 90 min with intraluminal filament and reperfusion for 14 d in all groups except sham operation group. BYHWD (13 g/kg) was administrated by gastrogavage in BYHWD group, antagonist group and antagonist control group at 24 h after modeling respectively, and BrdU (50 mg/kg) was injected intraperitoneally in all groups once a day for 14 consecutive days. miR-199a-5p antagomir or NC (10 nmol) was injected into the lateral ventricle at d5 after ischemia in antagonist and antagonist control groups, respectively. The neurological deficits were evaluated by the modified neurological severity score (mNSS) and the corner test, and the infract volume was measured by toluidine blue staining. Neurogenesis and angiogenesis were detected by immunofluorescence double labeling method. The expression level of miR-199a-5p was tested by real-time RT-PCR, and the protein expressions of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were determined by Western blotting. RESULTS: BYHWD treatment significantly promoted the recovery of neurological function ( CONCLUSIONS Buyang Huanwu decoction promotes neurogenesis and angiogenesis in rats with cerebral ischemia, which may be related to increased protein expression of VEGF and BDNF through upregulating miR-199a-5p.
Animals ; Brain Ischemia/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Ischemic Stroke/drug therapy* ; Male ; MicroRNAs/genetics* ; Neurogenesis/drug effects* ; Rats ; Rats, Sprague-Dawley ; Up-Regulation/drug effects* ; Vascular Endothelial Growth Factor A/genetics*

Objectives:To observe the clinical features and factorsrelated to treatment decision for hospitalizedpatients with mitral regurgitation (MR). Methods:A total of 3 450 consecutivepatients with transthoracic echocardiography (TTE) confirmed moderate to severe MR admitted in our hospital from 2014-01-01 to 2015-12-31 were enrolled. Base on therapeutic method, the patients were divided into 2 groups:Surgery group, n=1 845 and Medication group, n=1 605. The baseline data including TTE results were collected, clinical features were compared between 2 groups and factors related to treatment decision were analyzed. Results:Mean age of this patient cohort was (54.8±13.8) years including 26.99% (931/3 450) patients aged ≥65 years. The most common etiology was primary MR, 324 (9.39%) patients were asymptomatic at admission and decreased left ventricular ejection fraction (LVEF) was evidenced in 55.28% (1 907) patients. Total in-hospital mortality was 0.75% (26). Compared with Medication group, the patients in Surgery group were younger ([52.65±12.01] years vs [57.39±15.25] years), prevalence of severe MR (56.69% vs 26.79%) and primary MR (89.49% vs 39.00%), as well as LVEF value ([61.62±9.20] % vs [48.00±17.53] %) were higher (all P＜0.001).Logistic regression analysis indicated that age (OR=0.561, 95% CI 0.503-0.627), MR etiology (OR=3.062, 95% CI 2.565-3.654), MR grade (OR=0.103, 95% CI 0.085-0.126) and LVEF (OR=2.478, 95% CI 2.147-2.860) were the determinants for treatmentdecision making in hospitalized patients with moderate to severe MR. Conclusions:In this patient cohort, there are considerable proportion of aged patients with moderate to severe MR. Primary MRis the major etiology. 46.52% patients received conservative therpay instead of surgery, older age,secondary MR, moderate MR and decreased LVEF are the major reasons for choosing conservative therapy in this patient cohort.

OBJECTIVEShellfish are recognized as important vehicles of norovirus-associated gastroenteritis. The present study aimed to monitor norovirus contamination in oysters along the farm-to-fork continuum in Guangxi, a major oyster production area in Southwestern China.

METHODSOyster samples were collected monthly from farms, markets, and restaurants, from January to December 2016. Norovirus was detected and quantified by one-step reverse transcription-droplet digital polymerase chain reaction (RT-ddPCR).

RESULTSA total of 480 oyster samples were collected and tested for norovirus genogroups I and II. Norovirus was detected in 20.7% of samples, with genogroup II predominating. No significant difference was observed in norovirus prevalence among different sampling sites. The norovirus levels varied widely, with a geometric mean of 19,300 copies/g in digestive glands. Both norovirus prevalence and viral loads showed obvious seasonality, with a strong winter bias.

CONCLUSIONThis study provides a systematic analysis of norovirus contamination 'from the farm to the fork' in Guangxi. RT-ddPCR can be a useful tool for detection and quantification of low amounts of norovirus in the presence of inhibitors found particularly in foodstuffs. This approach will contribute to the development of strategies for controlling and reducing the risk of human illness resulting from shellfish consumption.

Objective To explore the role of the PI3K/Akt signaling pathway in the calvarial osteolysis induced by TCP wear particles in mice model.Methods Thirty-six male ICR mice were randomly divided into a sham group (n=12),TCP group (n=12)and a LY294002-treated group (n=12).A murine calvarial model of osteolysis was established through implanting 30 mg of TCP particles onto the surface of bilateral parietal bones following the removal of the periosteum.On the second postoperative day,LY294002 (5 mg·kg-1)was locally injected to the calvarium under the periosteum three times a week;mice in the sham group received local injection of normal saline (N.S.)in the calvarium,and the injection time was consistent with that of LY294002.Two weeks later,the calvaria and periostea were obtained after the mice were executed.The calvarial osteolysis,bone mineral density (BMD)and bone mineral content(BMC)were analyzed using Micro-CT,Hematoxylin-Eosin (HE)staining was conducted to observe the inflammatrory response and formation of osteoclasts.Real-time PCR was applied to detect the mRNA level of tartrate-resistant acid phosphatase (TRAP),the marker of osteoclasts formation,cathepsin K (CstK),receptor activator for nuclear factor-κB kigand (RANKL)and c-Fos.The release of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6)and IL-1β were measured using enzyme-linked immumsorbent assay (ELISA).Results Micro-CT and histological analysis indicated that LY294002,the specific inhibitor of PI3K,significantly prevented TCP wear particles-induced osteolysis and osteoclastogenesis,and increased BMD and BMC in the calvaria of mice.Real-time PCR data revealed LY294002 significantly suppressed the increase in mRNA level of osteoclastogenic genes such as TRAP,CstK,RANKL and c-Fos in the calvaria of TCP wear particles-implanted group.ELISA assay showed that TCP wear particles-induced release of TNF-α,IL-1β and IL-6 was significantly inhibited by LY294002 treatment.Furthermore,LY294002 significantly attenuated TCP wear particles-triggered activation of Akt,and down-regulated the level of p-AktSer473 and p-AktThr308.Conclusion PI3K/Akt signaling pathway contributes to TCP wear particle-induced osteolysis,and can be developed as a new therapeutic target for the prevention and treatment of bone destruction diseases caused by wear debris.

Objective To discuss the clinical efficacy of internal fixation with miniature steel plate and kirschner pins in treatment for metacarpal neck fracture.Methods A total of 142 patients with cervix metacarpal fracture in our hospital from January 2015 to December 2016 were divided into the control group(n =71) and the observation group(n =71) randomly.The patients in control group were treated with internal fixation with kirschner pins,and the patients in observation group were treated by internal fixation with miniature steel plate.The operative time,postoperative healing time,postoperative pain,metacarpophalangeal joint function and complications were compared between the two groups.Results The operation time of observation group was (38.4 ± 3.8) minutes,the fracture healing time was (3.1 ± 1.4)weeks,the excellent and good rate of TAM was 97.2％ after operation,the excellent and good rate of FAFS was 98.6％ after operation,all these indexes were significantly better than those in the control group with statistical significance (P ＜ 0.05).Conclusion Internal fixation with miniature steel plate in the treatment of cervix metacarpal fracture has the advantages of exact clinical effect,short operative time,quick fracture healing and good recovery of joint function.