Rotor syndrome is an autosomal recessive disorder of bilirubin metabolism， and it is difficult to diagnose and differentiate due to its extreme rarity and a lack of specific clinical manifestations. In recent years， the development of genetic testing technology has enabled the early diagnosis of atypical patients. Literature search shows that only 19 cases with detailed clinical and genetic data have been reported. This article reports a case of a pregnant woman with an increase in direct bilirubin during pregnancy who was diagnosed with Rotor syndrome based on a bi-allelic mutation in the SLCO1B1 and SLCO1B3 genes and delivered successfully at last， and a retrospective analysis was performed for related articles， in order to facilitate the early accurate diagnosis of patients with Rotor syndrome and guide medications from the perspective of genetic mechanisms.

Depressed mood and sleep problems are prevalent among elderly people and tend to form a vicious cycle that seriously affects their quality of life and physical health. However， most of the existing studies rely on cross-sectional design， limiting the ability to clarify their predictive relationship and causal direction. ObjectiveTo explore the longitudinal association between nighttime sleep duration and depressed mood among the elderly in China over a 10-year period， providing scientific evidence for developing sleep-related interventions and depression prevention strategies tailored to the elderly. MethodsBased on nationally representative data from the China Health and Retirement Longitudinal Study （CHARLS） between 2011 and 2020， a sample of 5 954 elderly peolpe who had completed the baseline survey and at least one follow-up survey in 2011 was selected. Depressed mood was assessed using the 10-item Centre for Epidemiological Studies Depression Scale （CESD-10）. Basic information including nighttime sleep duration， was collected through a self-designed questionnaire. Cross-lagged path analysis （CLPA） model was employed to analyze the bidirectional relationship between nighttime sleep duration and depressed mood among the ederly. ResultsThe nighttime sleep duration in elderly people showed a negative correlation with CESD-10 scores at both baseline and the last follow-up （r=-0.299， -0.247， P<0.01）. The results of the CLPA model showed that the baseline CESD-10 scores negatively predicted nighttime sleep duration at the last follow-up （β=-0.100， P<0.01）， while baseline nighttime sleep duration also predicted CESD-10 scores at the last follow-up （β=-0.041， P<0.01）. ConclusionDepressed mood in elderly people exhibits a longitudinal association with nighttime sleep duration， demonstrating a bidirectional negative predictive relationship between the two factors.

Objective:To analyze the role of interleukin-33(IL-33)in the occurrence and development of glioma and its related mechanism by bioinformatics technology,and to validate it through histopathological experiments,and to discuss the possibility of IL-33 as an auxiliary marker for the diagnosis and treatment of brain glioma.Methods:The glioblastoma multiforme/lower grade glioma(GBMLGG)case data were downloaded from the UCSC XENA database,including data of 689 glioma samples,5 paracancerous samples,and 1 152 normal brain tissue samples;Mann-Whitney U test was used to analyze the difference in the expression of IL-33 mRNA between the GBMLGG samples and the normal brain tissues;according to the expression level of IL-33 in GBMLGG tissue,the tumor samples were divided into IL-33 low expression group and IL-33 high expression group;the Human Protein Atlas(HPA)was used to validate the difference in the protein expression of IL-33 in the GBMLGG samples;the R language DESeq2(v.1.36.0)package was used to screen the differentially expressed genes(DEGs)in the GBMLGG tumor case samples;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were used to perform pathway analysis on the DEGs;Gene Set Enrichment Analysis(GSEA)was used to discuss the pathways significantly enriched by IL-33 in the GBMLGG tissues;GSVA package was used to analyze the immune infiltration in the GBMLGG samples;survival package and survminer package were used to analyze the effect of IL-33 expression level on the survival of the patients in different clinical subgroups of GBMLGG;univariate and multivariate Cox proportional hazards regression models were used to analyze the relationship between IL-33 expression and the clinicopathological characteristics of the GBMLGG patients;the GBMLGG and control tissue samples were collected;immunohistochemical staining was used to detect the expression levels of IL-33 and its receptor suppression of tumorigenicity 2(ST2)in the GBMLGG and normal brain tissue samples.Results:The expression levels of IL-33 mRNA and protein in the GBMLGG tissues were significantly increased compared with those in normal brain tissues;there were 634 DEGs in total between the IL-33 low and high expression groups,including 283 up-regulated DEGs and 351 down-regulated DEGs;the GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the DEGs were associated with biological behaviors such as activation of the classical pathway of complement,immunoglobulin complex formation,and mediated immunoglobulin receptor binding;in the course of GBMLGG development,high expression of IL-33 could degrade valine,leucine,and isoleucine,induce limonene and pinene degradation,promote propanoate metabolism,and simultaneously activate the Leishmania infection pathway,NOD-like receptor signaling pathway,and allograft rejection pathway;the infiltration levels of dendritic cell(DC)and mast cell in the IL-33 high expression group were higher than those in IL-33 low expression group;the infiltration levels of eosinophil,helper T cell,and central memory T cell(Tcm)were lower than those in IL-33 low expression group;the expression level of IL-33 was positively correlated with the infiltration of γδT cell(Tgd),helperT cell,macrophage,eosinophil,Tcm,and effector memory T cell(Tem)(P＜0.05);it was negatively correlated with the infiltration levels of DC,natural killer cell(NK),CD8+T cell,and CD56bright NK cell(P＜0.05).There were no significant differences in the overall survival(OS),disease-specific survival(DSS),and disease-free interval(DFI)of the GBMLGG patients between IL-33 high expression group and IL-33 low expression group(P＞0.05);the clinical subgroup analysis results showed that the expression level of IL-33 in oligodendrocytoma tissues was lower than those in astrocytoma and oligoastrocytoma tissues,and the expression level of IL-33 in glioblastoma tissues was higher than that in oligodendroglioma tissues.World Health Organization(WHO)stage and age were risk factors affecting the prognosis of the GBMLGG patients,and IDH mutation and primary treatment effect were protective factors affecting the prognosis;The immunohistochemical staining results showed that compared with normal brain tissues,the expression levels of IL-33 and its receptor ST2 proteins in the malignant glioma tissues were significantly increased(P＜0.05),and their expression levels were positively correlated in both normal brain tissues and malignant glioma tissues(P＜0.05).Conclusion:The expression level of IL-33 in the glioma tissue is significantly increased,and high expression of IL-33 may be a potential factor for poor prognosis in the glioma patients.

OBJECTIVE: To investigate the expression and possible regulatory mechanism of miR-34a in the lung tissue of neonatal rat model of bronchopulmonary dysplasia (BPD) induced by hyperoxia. METHODS: In the study, 80 newborn SD rats were randomly divided into hyperoxia group (FiO₂=60%) and air group (FiO₂=21%) within 2 hours after birth, 40 rats per group. Lung tissue samples of the SD rats in each group were extracted on the 1st, 7th, 14th and 21st days after birth, and the pathological changes of lung tissue were observed under light microscope after HE staining. The number of radial alveolar counts (RAC) and the mean alveolar diameter (MAD) and the thickness of alveolar septal thickness (AST) were measured to evaluate the development of alveoli. Real-time fluorescence quantitative PCR was used to detect the expression of miR-34a, angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) in lung tissue of rats in hyperoxia group and air group at different time points. Enzyme-linked immunosorbent assay (ELISA) was used to detect the proteins expression of Ang-1 and Tie-2 in the lung tissues of the two groups at different time points. RESULTS: The weight of rats in the hyperoxia group on the 7th, 14th and 21st days after birth was significantly lower than that in the air group (P all < 0.05). With the prolongation of oxygen exposure, the number of alveoli decreased, the volume increased, the structure simplified, the alveolar cavity enlarged obviously and the alveolar septum thickened in the hyperoxia group. On the 7th, 14th and 21st days after birth, the RAC in the hyperoxia group was significantly lower than that in the air group (P all < 0.05). Compared with the air group, MAD and AST increased significantly on the 7th, 14th and 21st days after birth in the hyperoxia group, and the difference was statistically significant (P all < 0.05). The expression level of miR-34a in lung tissue of hyperoxia group was significantly higher than that of air group on the 7th, 14th and 21st days after birth, and the difference was statistically significant (P all < 0.05). Compared with the air group at the same time point, the expression levels of Ang-1 and Tie-2 mRNA and protein in the hyperoxia group were lower than those in the air group on the 14th and 21st days after birth (P all < 0.05). CONCLUSION The new BPD model of newborn SD rats can be successfully established by continuous exposure to 60% hyperoxia. The expression of miR-34a was up-regulated in the lung tissue of the new BPD model of neonatal rats. MiR-34a may play an important role in the occurrence and development of BPD by regulating Ang-1/Tie-2 signal pathway.
Animals ; MicroRNAs/metabolism* ; Bronchopulmonary Dysplasia/genetics* ; Hyperoxia/metabolism* ; Rats, Sprague-Dawley ; Animals, Newborn ; Rats ; Angiopoietin-1/genetics* ; Disease Models, Animal ; Receptor, TIE-2/genetics* ; Lung/pathology* ; Male

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

Objective To evaluate the anticoagulation efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in patients with high-risk atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI). Methods A computer-based search was conducted on PubMed, EMbase, The Cochrane Library, CNKI, SinoMed, and VIP databases to identify studies on the application of NOACs and VKAs in high-risk AF patients after TAVI. The search period was from database inception to January 2023. The quality of the included studies was assessed using the Cochrane risk assessment tool and the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4 software. Results A total of 7 studies involving 24 592 patients were included. The meta-analysis results showed that compared to patients using VKAs, those treated with NOACs had a significantly lower risk of all-cause mortality [RR=0.74, 95%CI (0.58, 0.94), P=0.01]. Subgroup analysis indicated that when the follow-up period was less than 1 year, there was no significant difference in all-cause mortality between the NOAC and VKA groups [RR=0.57, 95%CI (0.17, 1.88), P=0.35]; however, when the follow-up period was ≥1 year, the VKA group had a higher all-cause mortality rate than the NOAC group, with a statistically significant difference [RR=0.73, 95%CI (0.57, 0.95), P=0.02]. No significant differences were found between the two groups regarding early stroke [RR=0.50, 95%CI (0.19, 1.28), P=0.15], stroke during follow-up [RR=1.04, 95%CI (0.88, 1.22), P=0.64], bleeding [RR=0.94, 95%CI (0.73, 1.21), P=0.61], major or life-threatening bleeding [RR=0.80, 95%CI (0.49, 1.31), P=0.38], or acute kidney injury [RR=0.51, 95%CI (0.16, 1.59), P=0.24]. Conclusion Compared to VKAs, the use of NOACs in patients with high-risk AF undergoing TAVI may reduce the risk of all-cause mortality, especially during long-term anticoagulation therapy, potentially offering greater benefits. However, further evidence from randomized controlled trials is needed to confirm these findings.

OBJECTIVE To explore the prognostic significance of the prognostic nutrition index(PNI)in patients with hypopharyngeal cancer undergoing surgical treatment.METHODS Clinical and pathological data of 117 patients with hypopharyngeal carcinoma who underwent surgical treatment at the center of Otolaryngology Head and Neck Surgery of Beijing Friendship Hospital,Capital Medical University from May 2014 to June 2022 were collected.The prognostic significance of hematological indicators such as PNI and neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and systemic immune inflammation index(SⅡ)were investigated.The time-dependent receiver operating characteristic(tROC)curves were used to analyze the sensitivity and specificity of various hematological indicators and to determine their optimal cutoffvalues.The Kaplan-Meier method was used to plot the postoperative survival curve,and the Cox regression model was used to analyze the correlation between PNI and overall survival(OS)and disease-free survival(DFS).RESULTS 117 patients were enrolled in this cohort,of which 109 were clinically classified as advanced stage(Ⅲ-Ⅳ).63 cases underwent surgery to preserve laryngeal function.The 5-year OS is 46.07％.According to the analysis of the tROC curve,the optimal cutoffvalue for PNI is 46.75.PNI is correlated with tumor T staging,NLR,PLR,and SⅡ.Kaplan Meier univariate analysis showed that PNI was significantly correlated with OS and DFS(P<0.05).In addition,tumor N-stage,postoperative complications,adverse pathological prognostic factors,NLR,PLR,and SⅡ were all significantly correlated with OS(P<0.05).Tumor N-stage,laryngeal preservation,postoperative complications,NLR,and SⅡ were significantly correlated with DFS(P<0.05).The Cox multivariate analysis results indicated that PNI,tumor N-stage,and postoperative complications were independent factors affecting OS and DFS.CONCLUSION Preoperative PNI,tumor N-stage,and postoperative complications are independent risk factors for OS and DFS in patients with hypopharyngeal carcinoma.PNI,as a prognostic indicator for predicting hypopharyngeal cancer patients,is superior to other hematological indicators.

Objective To investigate the effect of progressive muscle relaxation training intervention strategy in relieving fatigue of elderly patients with primary hepatocellular carcinoma(HCC)after receiving transcatheter arterial chemoembolization(T ACE),and to analyze its influencing factors.Methods Using convenience sampling method,a total of 150 elderly patients with HCC,who received TACE at a certain grade Ⅲ-A hospital at Peking of China from May 2021 to March 2023,were selected as the subjects of research.The patients were randomly divided into the study group and the control group,and progressive muscle relaxation training intervention strategy and conventional postoperative fatigue care method were employed respectively.The preoperative fatigue status and the postoperative fatigue recovery status were compared between the two groups,and the influencing factors were analyzed.Results In both groups,the postoperative one-day fatigue score was the highest,which was gradually decreased thereafter.The average recovery time of fatigue in the control group was 9.84 days,which in the study group was 6.16 days,the difference between the two groups was statistically significant(P=0.013).The body mass index(BMI),Child-Pugh classification,and preoperative grip strength index had an effect on the postoperative fatigue recovery time after intervention.A BMI of β=-0.953 and a preoperative grip strength index of β=-0.185 were negatively correlated with the postoperative fatigue recovery time after intervention,while a Child-Pugh classification of β=2.177 was positively correlated with the postoperative fatigue recovery time after intervention.Conclusion Progressive muscle relaxation training intervention strategy is helpful for shortening the postoperative fatigue recovery time in elderly patients with HCC after receiving TACE,and it is worth of promotion in clinical practice.The patient's nutrition and physical status such as BMI,hepatic reserve function and grip strength index,are the factors influencing the effectiveness of progressive muscle relaxation training intervention strategy.

BACKGROUND:Oxidative stress is one of the main causes of osteoporosis,and reducing the level of oxidative stress with increasing antioxidant defense is an important research direction for the treatment of osteoporosis.Studies have confirmed that astragaloside IV has anti-osteoporosis effects,but its mechanism of action is not clear.OBJECTIVE:To investigate the osteogenic effect of astragaloside IV in MC3T3-E1 cells under oxidative stress conditions.METHODS:MC3T3-E1 cells were randomly divided into four groups:the control group was cultured in a complete medium;the model group was cultured in the complete medium containing hydrogen peroxide which was replaced with another complete medium after 24 hours of intervention;the astragaloside IV group was cultured with the complete medium containing hydrogen peroxide and astragaloside IV which was replaced with another complete medium containing astragaloside IV after 24 hours of intervention;and the inhibitor group was cultured in the complete medium containing hydrogen peroxide,astragaloside IV,and extracellular signal-regulated kinases(ERK)inhibitor which was replaced with complete medium containing hydrogen peroxide,astragaloside IV,and ERK inhibitor after 24 hours of intervention.After 48 hours of intervention with hydrogen peroxide,malondialdehyde content was detected to evaluate the mitigating effect of astragaloside IV on the oxidative stress in MC3T3-E1 cells.Osteogenic induction was performed after 48 hours of intervention with hydrogen peroxide,and the osteogenic and mineralizing ability of MC3T3-E1 cells was verified by alkaline phosphatase staining and alizarin red staining;the expression of osteogenesis-related genes was detected by RT-qPCR;and the expression of osteogenesis-related proteins and ERK/AMP-activated protein kinase(AMPK)signaling pathway proteins was detected by western blot.RESULTS AND CONCLUSION:The intracellular alkaline phosphatase content and mineralized nodule formation were less in the model group than in the control group(P<0.05),and were more in the astragaloside IV group than in the model group(P<0.05).Compared with the control group,intracellular malondialdehyde content increased in the model group(P<0.05),mRNA and protein expression of osteocalcin,RUNX2,and type Ⅰ collagen decreased(P<0.05),and AMPK mRNA and p-AMPK protein expressions were elevated(P<0.05);compared with the model group,intracellular malondialdehyde content in the astragaloside IV group decreased(P<0.05),the mRNA and protein expressions of osteocalcin,RUNX2,and type Ⅰ collagen were elevated(P<0.05),the mRNA expressions of ERK1/2 and AMPK were elevated(P<0.05),and the protein expressions of p-AMPK and p-ERK1/2 were elevated(P<0.05).Additionally,ERK inhibitors partially inhibited the above effects of astragaloside IV.To conclude,astragaloside IV can promote osteogenic differentiation of MC3T3-E1 cells by activating the ERK/AMPK pathway.

Objectives:To investigate the relationship between QRS duration and its changes during hospitalization and long-term all-cause mortality in patients with chronic heart failure.Methods:A total of 3 580 patients who attended three tertiary hospitals in Shanxi Province(First Hospital of Shanxi Medical University,Shanxi Cardiovascular Hospital,Shanxi Bethune Hospital)and were diagnosed with chronic heart failure from March 2014 to November 2021,were enrolled in this study.QRS duration at admission and discharge were collected,and the changes in QRS duration during hospitalization(ΔQRS)and the ΔQRS ratio(ΔQRS/admission QRS duration×100% )were calculated.Patients were divided into three group according to tertiles of ΔQRS:the group with decreasing QRS duration(n=1 364),the group with stable QRS duration(n=1 248),and the group with progressing QRS duration(n=968).Telephone follow-up was conducted at months 1,3,6,12,and every 6 months thereafter after discharge till May 1,2023,long-term all-cause mortality was the primary endpoint.Survival curves were plotted using the Kaplan-Meier method,and comparisons between groups were made using the log-rank method.Cox proportional risk regression model was used for prognostic analysis,and restricted cubic spline curves were calculated to evaluate QRS duration-related variables during hospitalization and the risk of long-term all-cause mortality in patients with chronic heart failure.Results:The median follow-up was 71(56,92)months,and all-cause mortality occurred in 502(14.0% )patients.Long-term all-cause mortality was lower in the group with decreasing QRS duration and the group with stable QRS duration compared with the progressing QRS duration group(13.9% vs.10.7% vs.18.6%,χ2=28.607,P<0.001).Multifactorial Cox regression analysis showed that admission QRS duration(HR=1.005,95% CI:1.002-1.009,P=0.003)and higher ΔQRS ratio during hospitalization(HR=2.071,95% CI:1.247-3.440,P=0.005)were independent influencing factors of long-term all-cause mortality in chronic heart failure patients.Restricted cubic spline curves showed that when the admission QRS duration was>96.36 ms,the longer the QRS duration,the higher the risk of all-cause mortality;when the admission QRS duration fluctuated from 89.32-96.36 ms,the QRS duration was a protective factor for long-term all-cause mortality in patients with chronic heart failure;and when the ΔQRS ratio during hospitalization was≥3.40%,higher ΔQRS ratio was linked with increased risk of all-cause mortality.Conclusions:QRS duration and ΔQRS ratio during hospitalization are independent predictors of long-term all-cause mortality in patients with chronic heart failure.Admission QRS duration>96.36 ms and ΔQRS ratio during hospitalization≥3.40% are associated with increased risk of long-term all-cause mortality in patients with chronic heart failure.