[Effects of P on the Uptake and Transport of Cd and As in Wheat Seedlings].

The aim of this study was to explore the effect of P on the physiological mechanism of Cd and As uptake and transport of wheat seedlings. Taking Bainong 207 as the test material, we investigated the effects of exogenous P supply and P deficiency treatment on the growth, root morphology, photosynthetic parameters, antioxidant system, ion content, and rhizome transfer coefficient of wheat seedlings under Cd and As stress using hydroponic experiments. The results showed that compared with that in the P deficiency treatment, the supply of exogenous P significantly increased the chlorophyll content of wheat seedlings under As stress, promoted the growth and development of roots, and increased biomass, whereas there were no significant effects on the growth of wheat seedlings under Cd stress. The contents of P and Cd in the root system under the condition of Cd stress were significantly increased by the supply of exogenous P, and the contents of P and Cd in the aboveground part were reduced. At the same time, the P and As content in the shoot and the transfer coefficient of As from the root to the shoot under As stress were significantly improved. Therefore, the effects of P on the poisoning of wheat Cd and As in this study showed obvious differences. Under As stress, exogenous P supply mainly promoted the growth of wheat seedlings by improving the transport of As from the root to the shoot and the CAT activity in the root system, reducing the poisoning of As in wheat. Under Cd stress, P and Cd showed a certain synergistic effect, and the toxic effect of Cd on wheat was aggravated to a certain extent after the supply of P.

Correlation between nuclear expression of heat shock protein 90 in dermis and glucocorticoid resistance in bullous dermatosis.

BACKGROUND: bullous dermatosis is a group of skin diseases that occur on the skin and mucous membrane, with blister and bulla as basic damage, mainly including pemphigus and bullous pemphigoid. Glucocorticoid (GC) is still the preferred drug for its treatment, but some patients respond poorly to GC and even develop glucocorticoid resistance (GCR). However, at present about the disease the understanding of the mechanisms for GCR is limited. OBJECTIVE: This study attempted to investigate the molecular mechanism of GCR in bullous dermatosis with heat shock proteins 90 (HSP90) and glucocorticoid receptor (GR) as molecular targets. METHODS: In this study, flow cytometry was used to measure and analyze the expression of HSP90 and GR in the lesions of patients with glucocorticoid-resistant bullosa dermatosis. Immunohistochemistry and immunofluorescence were used to observe the expression distribution and cell localization of HSP90 and GR. RESULTS: The expression of HSP90 in skin lesions of GCR group was significantly higher than that of glucocorticoid-sensitive (GCS) group, while the expression level of GR was lower than that of GCS group. In the epidermis, the expression and distribution of HSP90 were not different between the GCR group and the GCS group. And in the dermis, HSP90 and GR were more likely to be expressed in the nucleus in the GCR group. CONCLUSION: The overexpression and nuclear distribution of HSP90 may be related to the occurrence of GCR in patients with bullous dermatosis. And this correlation is more likely to occur in the dermis than in the epidermis.

Relationship of family function and pre-hospital delay among Chinese patients with recurrent ischaemic stroke and the mediation effect of stigma.

AIMS: Pre-hospital delay refers to the time span from the onset of symptoms to arrival at a hospital ≥ 3 h and is the main limitation of stroke reperfusion therapies. Family factors and stroke-related stigma may influence pre-hospital delay. However, few studies have confirmed the influence of stigma on pre-hospital delay or explored the relationships between family function, stigma, and pre-hospital delay among patients with recurrent stroke. This study aimed to explore the relationship between family function and pre-hospital delay among patients with recurrent stroke and examine the mediation role of stigma in this relationship. METHODS AND RESULTS: A cross-sectional study was performed at the neurology departments of two hospitals in Guangzhou, China between July 2021 and April 2022. A total of 115 patients with recurrent stroke completed questionnaires and were included in the analysis. Data were collected using the Short Form Family Assessment Device, the Stroke Stigma Scale, and the Stroke Knowledge Questionnaire. Spearman's correlation and a structural equation model were used for data analysis. Family function directly influenced pre-hospital delay [ß=0.27, P = 0.033, 95%CI = (0.02-0.51)] and indirectly influenced pre-hospital delay [ß=0.17, P = 0.038, 95%CI = (0.02-0.34)] through stigma. Moreover, stigma partially mediated the effect of family function on pre-hospital delay. CONCLUSION: Family function and stigma directly and indirectly influenced pre-hospital delay among patients with recurrent stroke. Future health education and interventions need to focus on strengthening and improving emotional support from family members to improve family function and reduce stigma, thereby reducing pre-hospital delay among patients with recurrent stroke.

A Decade-long Comparison of Prestroke Health Behaviors Among Hypertensive Stroke Patients in Mainland China.

ABSTRACT: BACKGROUND: Patients with hypertension are at a high risk for stroke, but a healthy lifestyle can greatly reduce the risk of stroke. However, there has been no research on the change in prestroke health behaviors in Chinese patients with hypertensive stroke over a decade. OBJECTIVES: The aims of this study were to determine whether prestroke health behaviors of patients with hypertensive stroke changed over a decade and to explore the predictors of prestroke health behaviors over a decade. METHODS: This study used data from 2 cross-sectional studies conducted in the neurology departments of 3 hospitals in Guangzhou, China. In total, 110 hypertensive stroke patients were recruited in stage I (2008-2009), and 119 hypertensive stroke patients were recruited in stage II (2018-2019). Patients' stroke knowledge was measured by the Stroke Knowledge Questionnaire. Patients' prestroke health behavior was measured by the Health Behavior Scale for Stroke Patients. RESULTS: The total score of prestroke health behaviors significantly increased over the decade (P < .001), but the scores of the subcategories of low-fat diet, low-sugar diet, and blood pressure checkups decreased over the decade (P < .05). Stroke knowledge was a significant predictor of prestroke health behaviors in stage I (P < .05). Besides stroke knowledge, sex and age were significant predictors of prestroke health behaviors in stage II (P < .05). CONCLUSIONS: Prestroke health behaviors of hypertensive stroke patients significantly improved over the decade. Moreover, prestroke health behaviors were significantly influenced by stroke-related knowledge over the decade. Healthcare providers should focus in particular on assisting patients who are male, young, and middle-aged, and lack stroke-related knowledge to improve their prestroke health behaviors, especially in terms of adherence to a low-fat/low-sugar diet and regular blood pressure checks.

Family Functioning is Associated with Post-Stroke Depression in First-Ever Stroke Survivors: A Longitudinal Study.

Background: Post-stroke depression (PSD) can aggravate the mortality and recurrence rate in stroke patients. The relationship between family functioning and PSD at different phases after a first-ever stroke is unclear. The purpose of this longitudinal study was to investigate the patterns and relationship of family functioning and PSD at acute hospitalization and 6 months post-discharge in first-ever stroke survivors. Methods: This is a longitudinal study conducted in Guangzhou, China. Family functioning and depression were measured by the Short Form Family Assessment Device (SF-FAD) and Self-Rating Depression Scale (SDS) at baseline and 6 months post-discharge. Multiple linear regression analysis was used to explore the relationship between family functioning and PSD. Results: The prevalence of PSD at acute hospitalization and 6 months post-discharge was 32.9% and 20.0%, respectively. SDS scores decreased significantly from baseline to 6 months post-discharge, while SF-FAD scores did not change significantly during this period. The Pearson correlation coefficient showed that SF-FAD scores were positively associated with SDS scores at the two time points (r 1 = 0.341, r 2 = 0.510, P < 0.05). Multiple linear regression analyses indicated that SF-FAD scores could predict PSD at baseline (unstandardized coefficient: 7.010, P < 0.05) and 6 months post-discharge (unstandardized coefficient: 9.672, P < 0.001). Conclusion: This study found that first-ever stroke survivors had good family functioning at baseline and 6 months post-discharge. The findings in this study verified that poor family functioning is positively associated with PSD at different phases post-stroke. Good family functioning is an important protective factor against PSD.

EYA2 suppresses the progression of hepatocellular carcinoma via SOCS3-mediated blockade of JAK/STAT signaling.

BACKGROUND: Somatic mutations are involved in hepatocellular carcinoma (HCC) progression, but the genetic mechanism associated to hepatocarcinogenesis remains poorly understood. We report that Eyes absent homolog 2 (EYA2) suppresses the HCC progression, while EYA2(A510E) mutation identified by exome sequencing attenuates the tumor-inhibiting effect of EYA2. METHODS: Whole-exome sequencing was performed on six pairs of human HCC primary tumors and matched adjacent tissues. Focusing on EYA2, expression level of EYA2 in human HCC samples was evaluated by quantitative real-time PCR, western blot and immunohistochemistry. Loss- and gain-of-function studies, hepatocyte-specific deletion of EYA2 (Eya2-/-) in mice and RNA sequencing analysis were used to explore the functional effect and mechanism of EYA2 on HCC cell growth and metastasis. EYA2 methylation status was evaluated using Sequenom MassARRAY and publicly available data analysis. RESULTS: A new somatic mutation p.Ala510Glu of EYA2 was identified in HCC tissues. The expression of EYA2 was down-regulated in HCC and associated with tumor size (P = 0.001), Barcelona Clinic Liver Cancer stage (P = 0.016) and tumor differentiation (P = 0.048). High level of EYA2 was correlated with a favorable prognosis in HCC patients (P = 0.003). Results from loss-of-function and gain-of-function experiments suggested that knockdown of EYA2 enhanced, while overexpression of EYA2 attenuated, the proliferation, clone formation, invasion, and migration of HCC cells in vitro. Delivery of EYA2 gene had a therapeutic effect on inhibition of orthotopic liver tumor in nude mice. However, EYA2(A510E) mutation led to protein degradation by unfolded protein response, thus weakening the inhibitory function of EYA2. Hepatocyte-specific deletion of EYA2 in mice dramatically promoted diethylnitrosamine-induced HCC development. EYA2 was also down-regulated in HCC by aberrant CpG methylation. Mechanically, EYA2 combined with DACH1 to transcriptionally regulate SOCS3 expression, thus suppressing the progression of HCC via SOCS3-mediated blockade of the JAK/STAT signaling pathway. CONCLUSIONS: In our study, we identified and validated EYA2 as a tumor suppressor gene in HCC, providing a new insight into HCC pathogenesis.

UBE2S interacting with TRIM28 in the nucleus accelerates cell cycle by ubiquitination of p27 to promote hepatocellular carcinoma development.

Genomic sequencing analysis of tumors provides potential molecular therapeutic targets for precision medicine. However, identifying a key driver gene or mutation that can be used for hepatocellular carcinoma (HCC) treatment remains difficult. Here, we performed whole-exome sequencing on genomic DNA obtained from six pairs of HCC and adjacent tissues and identified two novel somatic mutations of UBE2S (p. Gly57Ala and p. Lys63Asn). Predictions of the functional effects of the mutations showed that two amino-acid substitutions were potentially deleterious. Further, we observed that wild-type UBE2S, especially in the nucleus, was significantly higher in HCC tissues than that in adjacent tissues and closely related to the clinicopathological features of patients with HCC. Functional assays revealed that overexpression of UBE2S promoted the proliferation, invasion, metastasis, and G1/S phase transition of HCC cells in vitro, and promoted the tumor growth significantly in vivo. Mechanistically, UBE2S interacted with TRIM28 in the nucleus, both together enhanced the ubiquitination of p27 to facilitate its degradation and cell cycle progression. Most importantly, the small-molecule cephalomannine was found by a luciferase-based sensitive high-throughput screen (HTS) to inhibit UBE2S expression and significantly attenuate HCC progression in vitro and in vivo, which may represent a promising strategy for HCC therapy.

Impact of the systematic use of the volume-viscosity swallow test in patients with acute ischaemic stroke: a retrospective study.

BACKGROUND: Dysphagia is common after stroke. Patients with dysphagia have a higher risk of stroke-associated pneumonia (SAP) and poor outcomes. Early detection of dysphagia is necessary to identify and manage patients at high risk of aspiration. The aim of the study was to assess the impact of the systematic administration of the volume-viscosity swallow test (V-VST) in patients with acute ischaemic stroke. METHODS: This was a retrospective observational study that enrolled patients with acute ischaemic stroke in two consecutive time periods: pre-V-VST, when the 30-mL water-swallowing test (WST) was systematically administered, and V-VST, when all patients underwent the WST and the V-VST test was systematically administered if the patient failed the WST. RESULTS: Two hundred and 42 patients were enrolled. The mean age of the participants was 68.8 ± 10.88 years, 61.2% were male, and the median National Institutes of Health Stroke Scale score was 3 (IQR, 1-6). A total of 147 patients were enrolled during the pre-V-VST period and 95 were enrolled during the V-VST period. There was a significant difference in the occurrence of SAP (21.8% vs. 10.5%, p = 0.024) and the rate of nasogastric tube feeding (25.9% vs. 14.7%, p = 0.040) between the two groups, and no differences were found in the length of hospital stay (p = 0.277) or the total cost of hospitalization (p = 0.846). CONCLUSIONS: The V-VST was a better clinical screening tool, and it can also provide detailed suggestions regarding dietary modifications to prevent aspiration and SAP.

Zerumbone inhibits melanoma cell proliferation and migration by altering mitochondrial functions.

It has been reported that zerumbone (ZER) has marked effects on the regulation of cell proliferation and migration in multiple types of cancer, and has anti-cancer effects on various types of malignant cell. However, the effects and underlying molecular mechanisms of treatment with ZER on melanoma cells remain unclear. In the present study, the effect of treatment with ZER on the proliferation, migration and mitochondrial function of the human melanoma cell line CHL-1 was investigated. The results of the present study indicated that treatment with ZER significantly inhibited CHL-1 cell proliferation (P<0.001). Cell migration analysis further demonstrated that ZER inhibited the migration of CHL-1 cells (P<0.001). Treatment with ZER significantly increased cellular reactive oxygen species levels (P<0.001), reduced matrix membrane potential (P<0.001), decreased ATP (P<0.001) and mitochondrial DNA (P<0.001) levels, and decreased mitochondrial transcription factor A mRNA levels (P=0.002). The results of the present study suggested that the inhibition of proliferation and migration was mediated by altered mitochondrial function. In conclusion, the results of the present study suggested that ZER has chemotherapeutic effects on human melanoma cells by altering mitochondrial function.

C-arm Lipiodol CT in transcatheter arterial chemoembolization for small hepatocellular carcinoma.

AIM: To investigate the value of C-arm Lipiodol computed tomography (CT) for intra-procedural hepatocellular carcinoma (HCC) lesion detection during transcatheter arterial chemoembolization (TACE). METHODS: Forty patients (37 male, 3 female; mean age, 52.6 ± 12.5 years, age range: 25-82 years) diagnosed with HCC were enrolled in this study. All patients underwent 64-slice CT 1-2 wk before TACE. During the procedure, hepatic angiography was performed first. Following diagnostic embolization with Lipiodol injected into the hepatic artery, a C-arm CT scan was immediately conducted (C-arm Lipiodol CT). If new HCC lesions were confirmed, gelfoam particles were super-selectively injected into the tumor-nourishing blood vessel. A Lipiodol CT scan was performed 7-14 d after TACE. All images acquired from 64-slice CT, digital subtraction angiography (DSA), C-arm Lipiodol CT and Lipiodol CT were retrospectively reviewed by four radiologists and the number of detected lesions in each examination was counted, respectively. The results of Lipiodol CT were taken as the diagnostic reference. Alpha-fetoprotein values were examined both before and after TACE. This study only takes into account the lesions that were not found or were considered suspicious on 64-slice CT before TACE. RESULTS: Preprocedural 64-slice CT detected a total of 13 suspicious lesions in the 40 patients. DSA detected ten definite and four suspicious lesions. C-arm Lipiodol CT detected 71 lesions in total and Lipiodol CT confirmed 67 lesions with a diameter range of 3-12 mm. Four false-positive lesions, which were detected by C-arm Lipiodol CT, were considered to be hepatic artery-portal vein fistulas. The average alpha-fetoprotein values before and after TACE were significantly different (452.3 ± 192.6 ng/mL vs 223.8 ± 93.2 ng/mL; P = 0.039). CONCLUSION: C-arm Lipiodol CT has a higher diagnostic sensitivity for small HCC lesions. This technique may help physicians make intraprocedural decisions to provide patients with earlier treatment.

Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation.

To assess the efficacy of combining radioimmunoconjugate [(131)I] metuximab with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) treatment compared with RFA alone, a single-center randomized controlled trial was conducted on 127 patients with Barcelona Clinic Liver Cancer staging system (BCLC) classifications of 0-B stage. Patients received either RFA followed by [(131)I] metuximab (n = 62) or RFA alone (n = 65). The primary outcome was overall tumor recurrence. Statistical tests were two-sided. The one- and two-year recurrence rates in the combination group were 31.8% and 58.5%, whereas those in the RFA group were 56.3% and 70.9%, respectively. The median time to overall tumor recurrence was 17 months in the combination group and 10 months in the RFA group (P = .03). The RFA-[(131)I] metuximab treatment showed a greater antirecurrence benefit than RFA in the metuximab target (ie, CD147)-positive subpopulation (P = .007). [(131)I] metuximab may yield prevention of tumor recurrence after RFA.

[Fasudil inhibits HSC adhesion, migration and proliferation via Rho/ROCK pathway].

OBJECTIVES: To observe the effects of fasudil, a Rho/ROCK signaling pathways inhibitor, on adhesion, migration and proliferation of hepatic stellate cells (HSCs). METHODS: Cultured HSCs were divided into 5 groups. Fasudil was added to 4 groups in a concentration of 12.5, 25, 50, and 100 micromol/L, respectively. A group without fasudil added served as untreated controls. The adhesive inhibition effect of fasudil on HSCs was examined by toluidine blue colorimetric assay, the inhibition of migration of HSCs was evaluated by a modified Boyden chamber, and cell proliferation was assessed by MTT assay. The protein levels of RhoA, p-MLC (Thr18/Ser19) and alpha-SMA were assayed by Western blot. RESULTS: Fasudil inhibited HSC adhesion, proliferation and LPA-induced migration in a concentration-dependent manner; the protein expressions of alpha-SMA and p-MLC (Thr18/Ser19) were significantly decreased in the presence of fasudil. CONCLUSION: Fasudil can inhibit HSC adhesion, migration and proliferation by suppressing the cytoskeleton regulation function of Rho/ROCK signaling pathways.