Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Objective To investigate expression levels and clinical significance of annexin A2 and S100 calcium binding protein A10 (S100A10) in cerebrospinal fluid of patients with secondary intracranial infection after craniocerebral surgery. Methods A total of 120 patients with secondary intracranial infection after craniocerebral surgery were selected as test group, while 120 patients with no infection after craniocerebral surgery in the same period were selected as control group. The levels of Annexin A2 and S100A10 in cerebrospinal fluid were detected by enzyme-linked immunosorbent assay(ELISA). Pearson correlation analysis was applied to analyze the correlations of Annexin A2 and S100A10 with clinical indicators. Logistic regression analysis was applied to analyze the influencing factors of secondary intracranial infection after craniocerebral surgery. Receiver operator characteristic (ROC) curve was applied to analyze the predictive value of Annexin A2 and S100A10 levels for the occurrence of secondary intracranial infection after craniocerebral surgery. Results The proportions of diabetes and cerebrospinal fluid leakages, blood l actate dehydrogenase (LDH), cerebrospinal fluid Annexin A2 and S100A10 levels in the test group were higher than those in the control group (P < 0.05). Annexin A2 in cerebrospinal fluid of patients with intracranial infection was positively correlated with S100A10, LDH, and S100A10 level was positively correlated with LDH (P < 0.05). Multivariate Logistic regression analysis showed that diabetes, cerebrospinal fluid leakage, blood LDH, Annexin A2 and S100A10 in cerebrospinal fluid were independent influencing factors for secondary intracranial infection after craniocerebral surgery (P < 0.05). ROC results showed that the AUCs of Annexin A2 level or S100A10 level alone in cerebrospinal fluid and their combined prediction for secondary intracranial infection after craniocerebral surgery was 0.788, 0.768 and 0.865 respectively, the AUC of combined prediction was larger than that of the single prediction (P < 0.05). Conclusion The expression levels of Annexin A2 and S100A10 are increased in cerebrospinal fluid of patients with secondary intracranial infection after craniocerebral surgery, which are independent influencing factors for secondary intracranial infection after craniocerebral surgery. Their combination has higher predictive value for secondary intracranial infection after craniocerebral surgery.

Objective    To investigate the surgical strategies and clinical efficacy of transmitral septal myectomy in the treatment of recurrent left ventricular outflow tract obstruction (LVOTO) after alcohol septal ablation. Methods    The clinical data of patients with recurrent LVOTO after alcohol septal ablation from July 2020 to July 2021 in the Department of Cardiac Surgery, Guangdong Provincial People's Hospital were retrospectively analyzed. Patients were preoperatively evaluated by echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, 3D modeling and printing technology. A personalized surgical strategy was preoperatively developed according to multimodality imaging assessment, while visual exploration was performed on the digital model and simulated surgical resection was performed on the printed model. Results     Two female patients were enrolled, aged 62 years and 64 years, respectively. Totally endoscopic transmitral extended myectomy was successfully performed on both patients with aortic cross-clamping time of 96 min and 85 min, respectively. LVOTO was relieved immediately (subaortic peak pressure gradient decreased from 100 mm Hg to 4 mm Hg and from 84 mm Hg to 6 mm Hg, respectively) and the mitral regurgitation significantly improved after the procedure. No patient had complete atrioventricular block or required permanent pacemaker implantation. The patients were discharged uneventfully without postoperative complications. Conclusion    Personalized totally endoscopic transmitral extended myectomy combined with multimodality imaging assessment and 3D modeling and printing has an acceptable clinical effect in patients with recurrent LVOTO after alcohol septal ablation. The procedure can precisely resect the hypertrophic septal myocardium while avoiding serious complications such as septal perforation or complete atrioventricular block.

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective:To investigate the value of brainstem auditory evoked potential (BAEPs) combined with cochlear electrogram (ECochG) monitoring in the protection of auditory function during microvascular decompression (MVD) for patients with facial spasm (HFS).Methods:Clinical data of 908 patients with HFS who received MVD treatment in our hospital from January 2018 to December 2020 were retrospectively analyzed. The patients were divided into BAEPs group ( n=309), ECochG group ( n=301) and BAEPs+ECochG group ( n=298) according to the different methods of auditory nerve function monitoring. Waveform extraction rate, mean extraction time, amplitude, latency, intraoperative warning effect of 3 monitoring methods, as well as hearing status immediately after surgery and during follow-up were compared in patents from the 3 groups. Results:(1) The overall waveform extraction rate in ECochG group and BAEPs+ECochG group was significantly higher than that in BAEPs group, and the average waveform extraction time in ECochG group and BAEPs+ECochG group was significantly shorter than that in BAEPs group ( P<0.05). The amplitude of compound action potential (CAP) wave in ECochG group was significantly higher than that of V wave in BAEPs group, and the latency of CAP wave was also significantly earlier than that of V wave ( P< 0.05). (2) A total of 48 patients of the 288 patients in the BAEPs group showed warning signs; a total of 73 of the 292 patients in the ECochG group showed warning signs; and a total of 65 of the 292 patients in the BAEPs+ECochG group showed warning signs. (3) There was significant difference in hearing grading (American Association of Otolaryngology Head and Neck Surgery [AAO-HNS] grading) among the 3 groups immediately after surgery ( H=18.041, P=0.000), and the average rank suggested that the hearing of patients in the BAEPs+ECochG group was superior to the other two groups. All patients were followed up for an average of 15 months (ranged 3-24 months); there was still a significant difference in AAO-HNS grading among the 3 groups ( H=29.625, P=0.000), and the hearing of patients in the BAEPs+ECochG group was still superior to the other two groups. Conclusion:The combined application of ECochG and BAEPs monitoring can reflect the changes of intraoperative hearing impairment comprehensively, accurately and timely, which is of great significance for the protection of auditory function in HFS patients during MVD.

Objective To investigate the characteristics of pulmonary function and pathological changes in rats with acute lung injury (ALI) and provide experimental basis for further study on the mechanism of ALI.Methods Twenty five male SD rats were randomly divided into the control group (n =5) and acute lung injury (ALI) group (n =20).Lipopolysaccharide (LPS) (4.5 mg/kg) were injected into the ALI group rats to establish the ALI rat model.The rats in control group were given 150 μl isotonic saline.At 12,24,48,and 72 hours after injury,lung function of the rats were tested by Buxco small animal lung function test system,including the dynamic lung compliance (Cdyn),forced vital capacity (FVC),functional residual gas (FRC),quasi static compliance (Cchord),100th millisecond expiratory volume (FEV100),and airway resistance (RI).In addition,the bronchoalveolar lavage fluid (BALF) was collected for detection of protein level and tumor necrosis factor (TNF-alpha)concentration.At the same time,the changes of lung tissues were recorded,and the pathological changes were observed by HE staining.Results Compared with the control group,Cdyn,FVC,FRC,and FEV100 in ALI group were significantly decreased at each time point after injury (P ＜0.05 or ＜0.01),while the airway resistance (R1) in ALI group was significantly increased at 24 and 48 hours after injury (P ＜ 0.01).There was no significant difference in quasi static compliance (Cchord) between two groups (P ＞ 0.05).The protein level and TNF-alpha concentration of BALF in ALI group were increased significantly (P ＜0.05 or ＜0.01) 12-72 hours after injury (P ＜ 0.01).Compared with the control group,the whole lung was dark red in ALI group 12 hours after injury,and the most serious bleeding occurred in the pulmonary hilum area with single or multiple hemorrhagic foci of different sizes.Multiple punctate and focal bleeding of different sizes were seen on the lung surface,which were radially distributed around the pulmonary hilum.The color of lung tissue was gradually restored to normal at 72 hours after injury.Under the light microscope,pulmonary interstitial edema,inflammatory cell infiltration,pulmonary vascular congestion and focal pulmonary hemorrhage were observed 12 h after injury,showing typical ALl pathological changes.The pathological changes were the most significant at 24 hours and reduced obviously at 72 hours.Conclusions A single intratracheal injection of LPS can induce typical ALI pathological changes.There is a similar trend between the pulmonary function indexes,lung pathology characteristics,and the protein level of BALF and proinflammatory cytokine level,suggesting that the pulmonary function test parameters can provide reference for evaluation of ALI.