ObjectiveTo investigate the value of Fried Frailty Phenotype （FFP）， liver frailty index （LFI）， and Short Physical Performance Battery （SPPB） in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital， Capital Medical University， from December 2020 to December 2021 were enrolled， and FFP， LFI， and SPPB were used to assess the state of frailty. Based on the scores of each tool， these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints （death+decompensation events）， and the Cox regression analysis， the receiver operating characteristic （ROC） curve， net reclassification index （NRI）， and integrated discrimination improvement （IDI） index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test， while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted， and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP， LFI， and SPPB was 37.2%， 22.4%， and 20.2%， respectively， with a moderate consistency between FFP and LFI/SPPB （κ=0.57， 95% confidence interval ［CI］： 0.47 — 0.67； κ=0.51， 95%CI： 0.41 — 0.62） and a relatively high consistency between LFI and SPPB （κ=0.87， 95%CI： 0.80 — 0.94）. Compared with the non-frailty group， the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints （P0.001）. After multivariate adjustment， FFP， LFI， and SPPB had a hazard ratio of 2.42（95%CI： 1.51 — 5.11）， 2.21（95%CI： 1.11 — 4.42）， and 2.21（95%CI： 1.14 — 4.30）， respectively， in predicting all-cause mortality， as well as a hazard ratio of 2.51（95%CI： 1.61 — 3.91）， 2.40（95%CI： 1.51 — 3.80）， and 2.20（95%CI： 1.39 — 3.47）， respectively， in predicting composite endpoints. Compared with Child-Pugh score， FFP had a significantly greater area under the ROC curve （AUC） in predicting all-cause mortality （0.79 vs 0.69， P=0.032） and composite endpoints （0.75 vs 0.68， P=0.044）. Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints， with an AUC of 0.81 — 0.82 and 0.77 — 0.78， respectively （P0.05）. NRI and IDI analyses further confirmed the improvement of the combined model in classification （all P0.001）. ConclusionFFP， LFI， and SPPB can independently predict adverse outcomes in patients with liver cirrhosis， among which FFP has the best predictive performance， and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.

Aim To investigate the regulatory effect of geraniol on Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion(I/R)in rats. Methods In this experiment,all the male SD rats were randomly divided into nine groups receiving the following treatments:sham operation(sham); sham operation+200 mg·kg-1 geraniol; I/R; I/R+50 mg·kg-1 geraniol; I/R+100 mg/kg geraniol; I/R+200 mg·kg-1 geraniol; edaravone; I/R+ brusatol(Nrf2 inhibitor); I/R+200mg·kg-1 geraniol+brusatol. All rats received intraperitoneal injection of geraniol for five consecutive days before MCAO and again after MCAO. During the construction of cerebral I/R injury models,the blood vessels were isolated without any suture in the sham operation and the sham operation +200 mg·kg-1 geraniol groups while the blood vessels with suture in other groups. The damage of neurological function was evaluated by the modified rating scale for neurological function. The TTC,HE and Tunel staining methods were used to determine the cerebral infarction volume,the damage of the ischemic cortex and the apoptosis of cortical cells,respectively. The oxidative stress-related parameters then were measured. The protein expressions of Nrf2 and HO-1 were detected by immunohistochemical staining and the target protein expressions of the injured cortex were detected by Western blot. Results Compared with the model group,it was found that the geraniol treatment significantly repaired neural injury,reduced cerebral infarction volume,cerebral cortex damage and cell apoptosis. Meanwhile,geraniol intervention could significantly increase the expression of Nrf2/HO-1 protein in the right-sided cortex and reduce oxidative stress level. Conclusion Geraniol can attenuate cerebral injury induced by ischemia-reperfusion in rats via activating Nrf2/HO-1 signaling pathway.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective To compare the categorical agreement between drug susceptibility testing(DST)and whole genome sequencing(WGS)for the detection of drug resistance in Mycobacterium tuberculosis(MTB),and to explore the characteristics of WGS for MTB drug resistance detection.Methods A total of 71 MTB clinical isolates retained in West China Hospital of Sichuan University from 2018 to 2020 were included in this study.The MTB strains were tested for resistance to 14 anti-tuberculosis drugs,including Isoniazid(INH),Rifampicin(RIF),Rifabutin(RFB),Ethambutol(EMB),Streptomycin(SM),Moxifloxacin(MFX),Ofloxacin(OFX),Levofloxacin(LFX),Amikacin(AMK),Kanamycin(KAN),Capreomycin(CPM),Para-aminosalicylic acid(PAS),Ethionamide(ETH)and Clofazimine(CLO),using both DST(colorimetric redox indicator meth-od)and WGS methods.Kappa test was performed to analyze the results of drug resistance detection for both methods.Results Based on DST and WGS methods to detect anti-tuberculosis drug resistance in seventy-one MTB clinical isolates,the results showed that the agreement rate of RIF,RFB,SM,MFX,OFX and LFX ex-ceeded 90.00％,and the kappa values were all greater than 0.80,with near perfect agreement;The agreement rates of INH and EMB were 84.51％and 81.69％,and Kappa values were 0.68 and 0.54,respectively,with fair agreement.No more than two drug resistant MTB strains of AMK and KAN were detected by both meth-ods,and the resistance rate was less than 3.00％.The agreement rates of CPM,ETH,PAS,and CLO ranged from 61.97％to 91.55％,and the Kappa values were less than 0.40,with slight or fair agreement.Conclusion There are differences in the ability of WGS to detect resistance to various anti-tuberculosis drugs,and it is more effective in detecting resistance to six anti-tuberculosis drugs,including RIF,RFB,SM,MFX,OFX and LFX,while there are still certain differences in detecting resistance to other anti-tuberculosis drugs compared with DST.It is necessary to further clarify the detailed resistance mechanisms of relevant anti-tu-berculosis drugs and to explore the standardization of WGS for drug resistance detection.

AIM:To study the expression of glucose transporters(GLUTs)and silent information regulators(SIRTs/sirtuins)in the liver of diabetic rats and human hepatocytes(LO2 cells)treated with high glucose.METHODS:(1)Twenty male SD rats were randomly divided into normal control(NC)group and diabetes mellitus(DM)group.The rats in DM group were given single intraperitoneal injection of streptozotocin(STZ,60 mg/kg)to establish the DM model,while the rats in NC group were intraperitoneally injected with equal volume of solvent once.Fasting blood glucose(FBG)and body mass were measured every 2 weeks.After 12 weeks of rearing,the blood and liver tissues of the rats were ob-tained after anesthesia with 1%sodium pentobarbitone,the biochemical indicators of blood were detected,and the liver in-dex was calculated.Hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining were used to observe liver histopathological changes.Lipid accumulation in liver tissues was detected by oil red O staining.The expression levels of GLUTs and SIRTs family member proteins were detected in rat liver tissues.(2)The LO2 cells were treated with different concentrations of glucose for 48 h.The viability of the cells in each group was measured by CCK-8 assay,and Western blot was used to detected the protein expression levels of GLUTs and SIRTs in the cells.RESULTS:(1)Compared with NC group,the rats in DM group were depressed,lost weight,and the FBG and liver index were significantly increased(P＜0.05).The results of HE staining showed that the hepatic sinuses were dilatated and congested near the central vein in DM rats,and mild edema and scattered infiltration of inflammatory cells were found in liver cells.The results of oil red O staining showed the red fat droplets were diffusely scattered within liver cells in DM group.The results of PAS staining showed that there were numerous diffuse light purple circular droplets in the cytoplasm of the liver cells in the central ve-nous area of the DM rats.Western blot showed that the protein levels of GLUTs were higher and the protein levels of SIRTs were lower than those in NC group(P＜0.01).(2)The results of CCK-8 assay showed that the viability of LO2 cells was increased in 50 mmol/L glucose group(P＜0.01),without significant difference in 75,100 and 125 mmol/L glucose groups(all P＞0.05),and decreased in 150,175 and 200 mmol/L glucose groups(all P＜0.01).Later,150 mmol/L glu-cose was used as the high-glucose intervention condition.Western blot showed that the protein levels of GLUTs and SIRTs in LO2 cells under high glucose intervention were consistented with the results in animal experiments.CONCLUSION:High concentration of glucose can cause liver damage in SD rats and reduce the viability of human hepatocytes(LO2 cells).It can also increase the expression of GLUTs and decrease the expression of SIRTs in rat liver tissues and LO2 cells.Therefore,GLUTs and SIRTs family members may be the target proteins of diabetes-induced liver injury.

Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.

Objective: To investigate the current status of screen exposure among preschool children in Shanghai and its association with family screen environment, so as to provide a scientific basis for family screen management. Methods: Using a convenient sampling method, a total of 349 preschool children aged 4-6 years were selected from 36 kindergarten classes in Xuhui District and Pudong New Area in Shanghai during April to June in 2023. Demographic characteristics and family screen environment were surveyed through an online questionnaire. Screen exposure of children was assessed using a diary method, with parents recording the activities over a 7day period. Multiple Logistic regression analysis was employed to identify factors influencing childrens screen content. Results: The average daily screen exposure time for children was (61.2±40.2) minutes, with an average of (12.4±17.6) minutes spent on educational screen content, 80.8% predominantly watched noneducational screen content. The percentages of time spent on educational screen content for 4yearold boys, 4yearold girls, 5yearold boys, 5yearold girls, 6yearold boys, and 6yearold girls were 20.1%, 14.7%, 21.3%, 21.9%, 20.6%, and 26.9%, respectively. Multivariate Logistic regression showed that children aged 5yearold (OR=0.49, 95%CI=0.25-0.96) and 6yearold (OR=0.45, 95%CI=0.21-0.95) were negatively associated with more noneducational screen content (P<0.05). However, occasional (OR=2.02, 95%CI=1.09-3.75) and sometimes (OR=4.50, 95%CI=1.70-11.90) using electronic devices to calm young child when crying, as well as children using electronic devices without adult supervision (OR=1.81, 95%CI=1.01-3.24) were positively associated with more noneducational screen content (P<0.05). Conclusions Preschool children in Shanghai exhibit high exposure to noneducational screen content, and family screen environment and parentchild interaction are associated with noneducational screen exposure. Strategies for family screen management should be developed to regulate childrens screen exposure behaviors, allowing electronic devices to play a positive role in their developmental process.

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.