Objective To study the effect of Lishukang capsule on learning and memory impairment in mice with high altitude hypoxia based on Keap1/Nrf2/HO-1 signal pathway. Methods Sixty male Balb/C mice were randomly divided into normal control group, hypoxia model group, Rhodiola capsule group (400 mg/kg), low, medium and high dose groups of Lishukang capsule (400、 600、 800 mg/kg), with 10 mice in each group. The normal control group was fed at the local altitude (1 500 m) after 7 days of intragastric administration in each group, and the rest groups were fed at the low pressure and hypoxia animal experimental cabin to simulate the altitude of 7500 m for hypoxia for 3 days. During this period, the normal control group and the hypoxia model group were given normal saline once a day, and 1 hour after the last administration, the eight arm maze was used to test the spatial memory ability of mice under simulated high altitude hypoxia; HE staining was used to observe the morphological changes of hippocampus in mice; Western blot was used to detect the changes of protein content of Keap1/Nrf2/HO-1 signal pathway and apoptosis related protein in hippocampus of mice. Results Compared with the normal control group, the spatial memory ability of mice in the hypoxia model group was significantly impaired (P<0.01); HE staining showed that hippocampal neurons in mice were seriously injured; the content of brain tissue Keap1 protein and apoptosis related protein Bax and Caspase-3 increased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 decreased （P<0.01）. Compared with the hypoxia model group, the error rate of mice in the high dose group of Lishukang capsule in the eight arm maze behavior experiment was significantly reduced (P<0.05, P<0.01); HE staining showed that the neurons were arranged orderly and the cell morphology was good; the content of Keap1 protein and apoptosis related protein Bax and Caspase-3 decreased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 increased（P<0.01）. Conclusion High altitude hypoxia can lead to oxidative stress injury in mice and induce the expression of apoptosis related genes, thus aggravating the cognitive dysfunction of mice; Lishukang capsule can effectively improve the learning and memory impairment in mice caused by hypoxia, and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signal pathway and reducing apoptosis.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

Objective To predict the invasion degree of subsolid nodule(SSN)lung adenocarcinoma using a combined model incorporating artificial intelligence(AI)quantitative parameters and imaging signs,and to validate the predictive efficacy of this model.Methods A total of 281 SSN lung adenocarcinoma CT images in 243 patients were retrospectively collected and randomly divided into training set(224 cases)and validation set(57 cases)in an 8∶2 ratio,with atypical adenomatous hyperplasia(A AH)+adenocarcinoma in situ(AIS)+minimally invasive adenocarcinoma(MIA)(191 cases)as the non-invasive adenocarcinoma(I AC)group and I AC(90 cases)as the IAC group.Multivariate logistic regression analysis was performed based on the AI quantitative parameters and CT signs in the training set to obtain independent predictors of IAC.A combined model and nomogram were then constructed and validated.The diagnostic efficacy and clinical applicability of the model were evaluated by the receiver operating characteristic(ROC)curve,calibration curve,and clinical decision curve analysis(DCA).Results Multivariate logistic regression analysis of the training set showed nodule type,spicule sign,vascular abnormality,long diameter＞11.5 mm,median CT value＞—426.25 HU,and mass＞391.5 mg were independent predictors of IAC(P＜0.05).The area under the curve(AUC)of the training set model,based on these independent predictive factors,was 0.915[95％confidence interval(CI)0.875-0.954],and the AUC of the validation set model was 0.903(95％CI 0.824-0.982),indicating both the training set and validation set models had high efficacy in distinguishing IAC.The nomogram model,which quantified these independent factors,demonstrated enhanced predictive power for IAC.The calibration curve indicated good fit of the prediction model,and the clinical DCA showed the model had good clinical applicability.Conclusion The model combining AI quantitative parameters and imaging signs has a higher ability to predict the risk of IAC,compared to a single indicator.It helps clinicians in determining the appropriate surgical timing,formulating surgical methods,and reducing overtreatment.

Objective To predict the invasion degree of subsolid nodule(SSN)lung adenocarcinoma using a combined model incorporating artificial intelligence(AI)quantitative parameters and imaging signs,and to validate the predictive efficacy of this model.Methods A total of 281 SSN lung adenocarcinoma CT images in 243 patients were retrospectively collected and randomly divided into training set(224 cases)and validation set(57 cases)in an 8∶2 ratio,with atypical adenomatous hyperplasia(A AH)+adenocarcinoma in situ(AIS)+minimally invasive adenocarcinoma(MIA)(191 cases)as the non-invasive adenocarcinoma(I AC)group and I AC(90 cases)as the IAC group.Multivariate logistic regression analysis was performed based on the AI quantitative parameters and CT signs in the training set to obtain independent predictors of IAC.A combined model and nomogram were then constructed and validated.The diagnostic efficacy and clinical applicability of the model were evaluated by the receiver operating characteristic(ROC)curve,calibration curve,and clinical decision curve analysis(DCA).Results Multivariate logistic regression analysis of the training set showed nodule type,spicule sign,vascular abnormality,long diameter＞11.5 mm,median CT value＞—426.25 HU,and mass＞391.5 mg were independent predictors of IAC(P＜0.05).The area under the curve(AUC)of the training set model,based on these independent predictive factors,was 0.915[95％confidence interval(CI)0.875-0.954],and the AUC of the validation set model was 0.903(95％CI 0.824-0.982),indicating both the training set and validation set models had high efficacy in distinguishing IAC.The nomogram model,which quantified these independent factors,demonstrated enhanced predictive power for IAC.The calibration curve indicated good fit of the prediction model,and the clinical DCA showed the model had good clinical applicability.Conclusion The model combining AI quantitative parameters and imaging signs has a higher ability to predict the risk of IAC,compared to a single indicator.It helps clinicians in determining the appropriate surgical timing,formulating surgical methods,and reducing overtreatment.

BACKGROUND:Previous studies found that the proliferative scar-specific long non-coding RNA lncRNA HSFAS is a novel biomarker that can be used in the diagnosis of hypertrophic scar,but how it functions in hypertrophic scar is not clear. OBJECTIVE:To investigate the role and mechanism of lncRNA HSFAS in hypertrophic scar.METHODS:Fresh scar tissue and surrounding normal skin tissue samples from three patients with hypertrophic scar were collected,and tissue immunofluorescence was used to detect the expression of lncRNA HSFAS in frozen sections of two skin tissues. Primary fibroblasts were isolated from proliferative scarred skin tissue and normal skin tissue and cultured by enzyme digestion method. Quantitative real-time PCR was used to detect the mRNA expression of lncRNA HSFAS in cells. The proteins bound to lncRNA HSFAS were detected by RNA pull-down combined mass spectrometry. GO and KEGG were used to analyze the main functions and pathways of lncRNA HSFAS involved in hypertrophic scar progression. The targeted binding of lncRNA HSFAS to proteins was determined by catRAPID and RPISeq website analysis. RESULTS AND CONCLUSION:Compared with normal skin tissue and fibroblasts from normal skin tissue,the expression of lncRNA HSFAS in human hypertrophic scar tissue and primary fibroblasts from hypertrophic scar tissue was significantly increased (P<0.05). There were 510 proteins clearly bound to lncRNA HSFAS by RNA pull-down combined mass spectrometry. The results of GO and KEGG analyses showed that these proteins were mainly involved in RNA splicing and processing,chromosome synthesis and separation,and cell cycle. Among them,the proteins involved in RNA splicing and processing included scaffold attachment factor B2 and DICER1,and the binding fraction with lncRNA HSFAS was higher. The results of bioinformatics analysis showed that lncRNA HSFAS was bound to scaffold attachment factor B2 and DICER1 proteins. To conclude,lncRNA HSFAS may affect gene expression by interacting with scaffold attachment factor B2 and DICER1 proteins to regulate RNA splicing and processing modification,thus promoting the occurrence and development of hypertrophic scar.

A 67-year-old female patient with erythrodermic psoriasis showed no significant improvement in rash after 2 weeks of treatments with acitretin, ebastine, etc., with the psoriasis area and severity index (PASI) score of 72 points (the highest value). Secukinumab 300 mg once a week was given by subcutaneous injection, which was changed to 300 mg once a month after 5 weeks of medication. After 5 weeks of treatment(medication 5 times), the patient′s PASI improvement rate was 75%, but the patient developed alopecia areata and her eyebrows fall off. After 6 months of treatment, the PASI improvement rate was 100%, but the patient developed alopecia totalis and her eyebrows completely disappeared. During the 9-month follow-up, the patient did not stop taking medication or received hair loss treatment. No psoriasis rash recurred and her hair loss was not improved.

Objective To evaluate the brain injury in children with congenital diaphragmatic hernia(CDH)after surgery through examination methods such as amplitude-integrated electroencephalogram(aEEG),regional cerebral oxygen saturation(rSO2)and neonatal behavioral neurological assessment(NBNA),so as to clarify their diagnostic value.Methods A total of 83 full-term CDH children admitted to our hospital were retrospectively enrolled as the research subjects.According to the brain damage syndrome(BDS)diagnostic criteria,they were divided into brain injury group(n=36)and control group(n=47).We compared the general data of the neonates in the two groups,as well as the modified aEEG scores and rSO2 at admission,14 days after birth,and 28 days after birth.We compared the NBNA scores at 28 days after birth.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of the three tools for brain injury.Results The modified aEEG scores of the children in the brain injury group at each time point were lower than those in the control group.The rSO2 of the children in the brain injury group was lower than that in the control group at 14 days and 28 days after birth and recovered slowly.The NBNA scores also indicated that the neurodevelopment of the children in the brain injury group was significantly lower than that in the control group.The ROC curve showed that the areas under the curve of combined diagnosis exhibited the best diagnostic efficacy compared with rSO2 used alone at 28 days after birth,aEEG at 28 days after birth,and NBNA scores(the area under the curve:0.968 vs.0.701 vs.0.685 vs.0.870;sensitivity:92.0％ vs.53.7％ vs.87.8％ vs.95.1％;specificity:97.0％ vs.86.1％ vs.50.0％ vs.72.2％).Conclusion The combined application of the modified aEEG score,rSO2,and NBNA has high sensitivity and specificity in the diagnosis of brain injury in children with CDH;therefore,it is worthy of clinical promotion and application.

Objective To evaluate the brain injury in children with congenital diaphragmatic hernia(CDH)after surgery through examination methods such as amplitude-integrated electroencephalogram(aEEG),regional cerebral oxygen saturation(rSO2)and neonatal behavioral neurological assessment(NBNA),so as to clarify their diagnostic value.Methods A total of 83 full-term CDH children admitted to our hospital were retrospectively enrolled as the research subjects.According to the brain damage syndrome(BDS)diagnostic criteria,they were divided into brain injury group(n=36)and control group(n=47).We compared the general data of the neonates in the two groups,as well as the modified aEEG scores and rSO2 at admission,14 days after birth,and 28 days after birth.We compared the NBNA scores at 28 days after birth.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of the three tools for brain injury.Results The modified aEEG scores of the children in the brain injury group at each time point were lower than those in the control group.The rSO2 of the children in the brain injury group was lower than that in the control group at 14 days and 28 days after birth and recovered slowly.The NBNA scores also indicated that the neurodevelopment of the children in the brain injury group was significantly lower than that in the control group.The ROC curve showed that the areas under the curve of combined diagnosis exhibited the best diagnostic efficacy compared with rSO2 used alone at 28 days after birth,aEEG at 28 days after birth,and NBNA scores(the area under the curve:0.968 vs.0.701 vs.0.685 vs.0.870;sensitivity:92.0％ vs.53.7％ vs.87.8％ vs.95.1％;specificity:97.0％ vs.86.1％ vs.50.0％ vs.72.2％).Conclusion The combined application of the modified aEEG score,rSO2,and NBNA has high sensitivity and specificity in the diagnosis of brain injury in children with CDH;therefore,it is worthy of clinical promotion and application.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*