The subcortical visual pathway is generally thought to be involved in dangerous information processing, such as fear processing and defensive behavior. A recent study, published in Human Brain Mapping, shows a new function of the subcortical pathway involved in the fast processing of non-emotional object perception. Rapid object processing is a critical function of visual system. Topological perception theory proposes that the initial perception of objects begins with the extraction of topological property (TP). However, the mechanism of rapid TP processing remains unclear. The researchers investigated the subcortical mechanism of TP processing with transcranial magnetic stimulation (TMS). They find that a subcortical magnocellular pathway is responsible for the early processing of TP, and this subcortical processing of TP accelerates object recognition. Based on their findings, we propose a novel training approach called subcortical magnocellular pathway training (SMPT), aimed at improving the efficiency of the subcortical M pathway to restore visual and attentional functions in disorders associated with subcortical pathway dysfunction.

Objective In this study,inbred BALB/c mice infected with the pneumonia virus of mice(PVM)were used to establish an animal model of viral pneumonia,and the changes in the pro-inflammatory alarmin molecule,high mobility group box 1 protein(HMGB1),during PVM infection were observed,as well as the in vivo intervention effects of the HMGB1 inhibitor,glycyrrhizic acid(GA),on PVM-induced lung injury.Methods Three-week-old female BALB/c mice were randomly divided into three groups,each consisting of 6 mice.One group,uninfected by PVM,served as the control group(Control).The other two groups were inoculated intranasally with PVM at a dose of 1×104 50％tissue culture infective dose(TCID50)/25 μL,and subsequently treated with GA saline solution(GA group)or plain saline solution(normal saline,NS group)via gavage for 15 consecutive days.During this period,changes in body weight and appearance were monitored in each group.At the end of the experiment,lung tissue samples were collected from all groups.The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry.The expression levels of HMGB1 and its Toll-like receptor 4(TLR-4),advanced glycosylation end-product-specific receptor(AGER),and inflammatory cytokines such as interleukin(IL)-1β,IL-2,and tumor necrosis factor-α(TNF-α)in lung tissues of mice were measured using real time fluorescence quantitative PCR.Results Compared with the Control group,the NS group showed a significant weight loss after 6 days(P＜0.05).Histopathological tests revealed pronounced inflammatory lesions in their lungs.Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm,and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1,IL-1β,and IL-2 were significantly upregulated(P＜0.05).In the GA group,there was no significant change in the clinical symptoms or body weight.However,compared with the NS group,the pathological damages of lung tissues in the GA group were significantly reduced,and the expression levels of HMGB1,IL-1 β,IL-2,and interferon-γ(IFN-γ)in lung tissues were also significantly decreased(P＜0.05),although the expression level of AGER was significantly increased(P＜0.05).Conclusion PVM infection can cause significant inflammatory pathological lung damages in mice,and GA can effectively alleviate the damages.Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.

Objective: To translate the English version of the non-alcoholic fatty liver disease quality of life scale (CLDQ-NAFLD) into the Chinese version in order to test its reliability and validity. Methods: The English version of the CLDQ-NAFLD was translated according to the cross-cultural research tool debugging and validation guidelines to form the Chinese version of the CLDQ-NAFLD. A questionnaire survey was conducted on 515 NAFLD cases in a tertiary hospital in Hangzhou from September 2021 to April 2022 to evaluate the reliability and validity of the scale. Results: The Chinese version of the CLDQ-NAFLD contained six domains with a total of thirty-six items (X2/DF=3.105, RMSEA=0.064, TLI=0.905, CFI=0.912, and IFI=0.913). I-CVI, S-CVI/UA, and S-CVI/Ave was 0.83 to 1.00, 0.86 and 0.98, respectively. The 12-item Short-Form Health Survey (SF-12) was used as the calibration standard, and the correlation validity of the calibration standard was 0.704 (P<0.001). The Cronbach's alpha coefficient of the total scale and each dimension of the scale was 0.964 and 0.807-0.956, respectively. The test-retest reliability was 0.839. Conclusion: The Chinese version of the CLDQ-NAFLD has good reliability and validity. Thus, it can be used to evaluate the quality of life for NAFLD patients with a Chinese cultural background.
Humans ; Reproducibility of Results ; Quality of Life ; Non-alcoholic Fatty Liver Disease ; Surveys and Questionnaires ; Asian People ; China ; Psychometrics

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC₅₀ value of 6.35 μmol·L^-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.
China/epidemiology* ; Humans ; Male ; PTEN Phosphohydrolase/genetics* ; Prognosis ; Prostatic Neoplasms ; Retrospective Studies

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

BACKGROUND: Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs. METHODS: In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs. RESULTS: There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment. CONCLUSIONS Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.
Aged ; Antihypertensive Agents/therapeutic use* ; Blood Pressure ; China ; Drugs, Generic/therapeutic use* ; Humans ; Male ; Prospective Studies

Objective:To explore the potential targets and related mechanism involved in the paclitaxel resistance to ovarian cancer. Method:Ovarian cancer A2780 cells and A2780 paclitaxel-resistant cells （A2780/T） were treated by 2， 4， 8， 16， 32， 64， 128， 256 μmol·L^-1 paclitaxel （PTX） for 24 h or 48 h respectively in vitro. The proliferation rate of A2780 cells and A2780/T cells treated with paclitaxel was determined by methyl thiazolyl tetrazolium （MTT） colorimetric method assay. A2780 and A2780/T cells were analyzed by LC-MS/MS Label-Free quantitative proteomics to identify and screen differentially expressed proteins in the two groups of cells. Gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway analysis were used to determine the potential biomarkers of paclitaxel resistance in ovarian cancer. Conventionally cultured A2780 cells were used as a control group， and A2780/T cells were treated with 0， 1， 4 μmol·L^-1 PTX. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot methods were used to detect and verify the mRNA and protein expression levels of potential target transforming growth factor-β-activated kinase 1 binding protein 1 （TAB1） and its downstream related molecules transforming growth factor-β-activated kinase （TAK1） and p38. Result:After PTX treatment for 24 h and 48 h， the cell viability of A2780 and A2780/T cells decreased. The inhibitory rate of PTX on A2780 cells was significantly higher than that of A2780/T cells. In A2780 cells， the IC₅₀ of PTX treatment for 48 h was 0.002 μmol·L^-1， while in A2780/T cells， the IC₅₀ of PTX was greater than the maximum concentration of 128 μmol·L^-1， indicating that A2780/T cells were resistant to PTX compared with A2780 cells. 441 differentially expressed proteins and 421 special differentially expressed proteins between A2780/T and A2780 cells were screened by label-free quantitative proteomic analysis. GO function enrichment analysis showed that the binding proteins accounted for the majority （80%） among the differentially expressed proteins. According to the results of KEGG pathway analysis and expression site analysis， TAB1 might be a potential biomarker in paclitaxel-resistant ovarian cancer. Compared with A2780 cells， mRNA and protein expression levels of TAB1 in A2780/T cells were significantly reduced （P<0.01）. mRNA expression of TAK1 and p38 that interacted with TAB1 were also significantly reduced （P<0.05， P<0.01）， while there was no significant change in protein expression. Conclusion:TAB1 may be a potential biomarker of paclitaxel resistance to ovarian cancer ， and its mechanism may be related to the TAB1/TAK1/p38 MAPK pathway.

Lysophosphatidic acid (LPA), a bioactive lipid medium, plays an important role in the development and progression of ovarian cancer. Doxorubicin hydrochloride (DOX) is a first-line drug in the ovarian cancer clinical therapy, while the effect and molecular mechanism of LPA in the ovarian cancer with DOX treatment is still unclear. This study intended to explore the effect and molecular mechanism of LPA in ovarian cancer treated with DOX. SKOV3 and OVCAR-3 cells of human ovarian cancer and Chinese hamster ovary cells were treated with control, LPA (lOp-mol/L), DOX (2jjLmol/L) and LPA (10jJLmol/L) + DOX (2p,mol/L) respectively for 24 hours. The morphological changes of SKOV3 cells were observed under optical microscope and transmission electron microscope. Results showed that LPA reduced cell death and the degree of chromatin aggregation in SKOV3 cells treated with DOX; RT-qPCR showed that LPA treatment could down-regulate the mRNA levels of caspase-3 in DOX-treated SKOV3 cells (P<0. 05); Western blot showed that LPA treatment could reduce caspase-3 and cleaved caspase-3 levels treated with DOX in SKOV3, OVCAR-3 and CHO cells (P<0. 05); Flow cytometry using Annexin V/PI double staining showed that LPA could down-regulate apoptosis in SKOV3 cells treated with DOX (P<0. 05); DCFH-DA method was used to detect intracellular levels of reactive oxygen species (ROS) in SKOV3 cells. It was found that LPA reduced the intracellular ROS level treated with DOX (P<0. 05). Our preliminarily study showed the effect of LPA in the apoptosis of ovarian cancer treated with DOX, which may provide a reference for the drug therapy of ovarian cancer targeting LPA.