Synergistic action of Hedyotis diffusa Willd and Andrographis paniculata in Nasopharyngeal Carcinoma: Downregulating AKT1 and upregulating VEGFA to curb tumorigenesis.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) remains a challenging cancer to treat. This study investigates the molecular mechanisms of Hedyotis diffusa Willd (HDW) combined with Andrographis paniculata (AP) in treating NPC. METHODS: Key compounds and target genes in HDW and AP were analyzed using network pharmacology. Protein-protein interaction (PPI) networks were constructed with STRING and visualized using Cytoscape. MCODE identified critical clusters, while DAVID facilitated GO and KEGG analyses. In vivo and in vitro experiments evaluated HDW-AP effects on NPC, including tumor volume, weight, Ki-67 expression, cell apoptosis, migration, invasion, cell cycle distribution, and DNA damage. RESULTS: The database identified 495 NPC-related genes and 26 compounds in the HDW-AP pair, targeting 165 genes. Fifty-eight potential therapeutic genes were found, leading to 18 key targets. KEGG analysis revealed a significant impact on 78 pathways, especially cancer pathways. Both in vivo and in vitro tests showed HDW-AP inhibited NPC cell proliferation, migration, invasion, and induced apoptosis. Mechanistically, this was achieved through AKT1 downregulation and VEGFA upregulation. CONCLUSION: The combination of HDW and AP targets 16 key genes to impede the development of NPC, primarily by modulating AKT1 and VEGFA pathways.

Visuospatial ability and attention as risk factors for suicidal ideation in middle-aged and elderly schizophrenia patients: a cross-sectional study.

BACKGROUND: Schizophrenia patients have a high risk of suicide, and their cognition function is impaired with increasing age. The association between neurocognitive and suicidality in schizophrenia patients are heterogeneous. We aimed to explore the relationship between neurocognitive function and suicidal ideation in schizophrenia patients across age groups. METHODS: A total of 587 patients with schizophrenia were enrolled in this study. The schizophrenia patients were divided into young group (aged 18-44) and middle-aged and elderly group (aged 45-70). The schizophrenia patients were divided into suicidal ideation group and non-suicidal ideation group according to the evaluation results of the Beck Scale for Suicide Ideation. Insomnia symptoms were measured by the Insomnia Severity Index (ISI). Psychotic symptoms were measured by the Positive and Negative Syndrome Scale (PANSS), and cognitive function was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: There was a negative correlation between the age and attention scores of RBANS (P = 0.018). The young schizophrenia patients had higher risk of suicidality than middle-aged and elderly schizophrenia patients (P = 0.001). In the logistic regression analysis, the scores of ISI and positive symptoms scores of PANSS were associated with suicidal ideation among young schizophrenia patients (All P < 0.05). Age, BMI, the scores of ISI, general symptoms scores of PANSS, visuospatial scores of RBANS and attention scores of RBANS were associated with suicidal ideation in middle-aged and elderly schizophrenia patients (All P < 0.05). CONCLUSIONS: High visuospatial scores of RBANS and attention scores of RBANS were risk factors for suicidal ideation in middle-aged and elderly schizophrenia patients.

Overexpressed RBPMS-AS1 increased cell radiosensitivity by sponging miR-19a-3p in lung cancer cell lines (A549 and SK-MES-1) via regulating PTEN/AKT axis.

PURPOSE: This paper intended to study RBPMS-AS1 in lung cancer (LC) radiosensitivity. MATERIALS AND METHODS: LC cells were transfected with RBPMS-AS1 overexpression plasmid and miR-19a-3p mimic and treated with radiation. PTEN, AKT, p-AKT, RBPMS-AS1, and miR-19a-3p expressions were detected via Western blot and qRT-PCR. The localization of RBPMS-AS1 in cells was determined through fluorescence in situ hybridization assay. The targeting relationships of RBPMS-AS1 and miR-19a-3p/miR-19a-3p and PTEN were determined through RIP and dual luciferase reporter analysis. Cell survival, viability, and apoptosis were assessed through colony formation, CCK-8, and flow-cytometry assays. RESULTS: RBPMS-AS1 was downregulated in LC and mainly distributed in cytoplasm. RBPMS-AS1 targeted miR-19a-3p in LC cells. Radiation suppressed LC cell survival, viability, and induced apoptosis, as overexpressed RBPMS-AS1 performed the similar effects and enhanced those effects induced by radiation. MiR-19a-3p mimic reversed the effect of overexpressed RBPMS-AS1 on enhancing radiation-induced LC cell apoptosis. MiR-19a-3p targeted PTEN and miR-19a-3p mimic reversed the effect of overexpressed RBPMS-AS1 on PTEN and phosphorylation of AKT in LC cells. CONCLUSION: Overexpressed RBPMS-AS1 sponged miR-19a-3p to increase cell radiosensitivity in LC via regulating PTEN/AKT axis.

Risk factors, clinical correlates, and social functions of Chinese schizophrenia patients with drug-induced parkinsonism: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study.

Background: Drug-induced parkinsonism (DIP) is the most prevalent neurological side effect of antipsychotics in the Chinese population. Early prevention, recognition, and treatment of DIP are important for the improvement of treatment outcomes and medication adherence of schizophrenia patients. However, the risk factors of DIP and the impact on the clinical syndromes of schizophrenia remain unknown. Aim: The goal of this study was to explore the risk factors, clinical correlates, and social functions of DIP in Chinese schizophrenia patients. Methods: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study of the Chinese schizophrenia population with a baseline assessment was conducted from the year 2012 to 2018. Participants were recruited from four mental health centers in Shanghai and totaled 969 subjects. Sociodemographic data, drug treatment, and clinical variables were compared between the DIP group and the non-DIP group. Variables that correlated with the induction of DIP, and with p≤ 0.1, were included in the binary logistic model for analyzing the risk factors of DIP. First generation antipsychotics (FGA)/second generation antipsychotics (SGA) model and high and low/medium D2 receptor antipsychotics were analyzed respectively to control the bias of co-linearity. All risk factors derived from the a forementioned models and clinical variables with p≤ 0.1 were included in the multivariate analysis of clinical correlates and social function of DIP patients. The Positive and Negative Syndrome Scale (PANSS) model and the personal and social performance (PSP) model were analyzed separately to control for co-linearity bias. Results: Age (OR = 1.03, p< 0.001), high D2 receptor antagonist antipsychotic dose (OR = 1.08, p = 0.032), and valproate dose (OR = 1.01, p = 0.001) were the risk factors of DIP. FGA doses were not a significant contributor to the induction of DIP. Psychiatric symptoms, including more severe negative symptoms (OR = 1.09, p< 0.001), lower cognition status (OR = 1.08, p = 0.033), and lower excited symptoms (OR = 0.91, p = 0.002), were significantly correlated with DIP induction. Social dysfunction, including reduction in socially useful activities (OR = 1.27, p = 0.004), lower self-care capabilities (OR = 1.53, p< 0.001), and milder disturbing and aggressive behavior (OR = 0.65, p< 0.001), were significantly correlated with induction of DIP. Valproate dose was significantly correlated with social dysfunction (OR = 1.01, p = 0.001) and psychiatric symptoms (OR = 1.01, p = 0.004) of DIP patients. Age may be a profound factor that affects not only the induction of DIP but also the severity of psychiatric symptoms (OR = 1.02, p< 0.001) and social functions (OR = 1.02, p< 0.001) of schizophrenia patients with DIP. Conclusion: Age, high D2 receptor antagonist antipsychotic dose, and valproate dose are risk factors for DIP, and DIP is significantly correlated with psychiatric symptoms and social performance of Chinese schizophrenia patients. The rational application or discontinuation of valproate is necessary. Old age is related to psychotic symptoms and social adaption in Chinese schizophrenic patients, and early intervention and treatment of DIP can improve the prognosis and social performance of schizophrenia patients. Clinical Trial Registration: Identifier: NCT02640911.

Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC.

Non-small cell lung cancer (NSCLC), a commonly diagnosed lung cancer, is characterized by a high incidence of metastatic spread to the brain, which adversely impacts prognosis. The present study aimed to assess the value of combined dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the treatment outcomes of whole-brain radiotherapy (WBRT) and gefitinib in brain metastases from non-small cell lung cancer (NSCLC) from the perspectives of response rate and short- and long-term efficacy. These results suggested that the indicators measured by DCE-MRI combined with DWI can be used as key imaging-derived markers that predicted the efficacy of WBRT combined with gefitinib in NSCLC patients with brain metastases. Specifically, patients with higher ΔADCmid and ΔADCpost values showed better treatment outcomes. ROC curve analysis indicated ADCpost, ΔADCpost, ΔADCpost (%), and tumor regression rate as the best predictors of efficacy of WBRT combined with gefitinib in these patients. The short-term and long-term effects noted were also significant. Taken together, the findings of this study reveal that tumor regression rate, ADCpost, ΔADCpost, and ΔADCpost (%) can be used as important imaging indicators that predict the therapeutic effect of WBRT combined with gefitinib in NSCLC patients with brain metastases.

Weighted Gene Coexpression Network Analysis Identifies Cysteine-Rich Intestinal Protein 1 (CRIP1) as a Prognostic Gene Associated with Relapse in Patients with Acute Myeloid Leukemia.

BACKGROUND Acute myeloid leukemia (AML) is associated with a high relapse rate and poor prognosis. This study aimed to use weighted gene coexpression network analysis (WGCNA) of gene coexpression networks to identify candidate prognostic biomarker genes in patients with AML and to investigate the expression of these genes in the human U937 cell line in vitro. MATERIAL AND METHODS RNA-seq data were retrieved from the Cancer Genome Atlas (TCGA) and included bone marrow samples and survival data of patients with AML (N=151), patients who did not relapse after treatment (N=119), and patients with relapse (N=40). Differentially expressed genes were identified, WGCNA was used to detect functional modules, and survival analysis was performed. The Cell Counting Kit-8 (CCK-8) assay investigated the proliferation of U937 cells transfected with short hairpin RNAs (shRNAs), shCRIP1, shHIST1H1C, and shHIST1H1E. RNA-seq analysis identified gene expression following CRIP1 knockdown. RESULTS Eighty-two genes were associated with both relapse and prognosis in patients with AML. There were two prognosis-related gene modules in the coexpression network. In the coexpression network, the histone cluster 1 H1 family member gene, HIST1H1C had the maximum relapse fold change, HIST1H1E had the lowest survival p-value, and the cysteine-rich intestinal protein 1 (CRIP1) gene had the most edge numbers and was significantly associated with poor prognosis (P=0.0165786). RNA-seq data showed that there was a significant difference in gene expression after CRIP1 knockdown in U937 cells. CONCLUSIONS WGCNA of gene coexpression networks identified CRIP1 as a potential prognostic biomarker gene in patients with AML.

Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is an immune system meditated disease, especially T cells. It disturbed many people around the world and hard to therapy. Paeonia lactiflora Pall has been used as a medicine in china for thousands of years. Recent studies found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases. In this study, we researched the effects and possible mechanisms of total glucosides of paeony (TGP) on animal psoriasis. AIM OF THE STUDY: To study the therapeutic effects and mechanisms of TGP in 5% propranolol cream-induced psoriasis in guinea pigs and Imiquimod (IMQ) cream-induced psoriasis in mice. MATERIALS AND METHODS: The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice. Ear thickness was accessed, and pathology injury was observed by H&E staining. The levels of serum IL-1ß, IL-6, IL-12, IL-17, IL-23, TNF-α, and IFN-γ, skin IL-17A, IL-22 and orphan nuclear receptor (RORγt) mRNA expression, proliferating cell nuclear antigen (PCNA), total or phosphorylated signal transducers and activators of transcription (STAT1, STAT3) were determined by enzyme linked immunosorbent assays (ELISAs), real time PCR, immunohistochemical staining, and western blotting, respectively. RESULTS: Compared with model group, TGP treatment decreased the ear thickness, improved pathology of psoriasis, alleviated IMQ-induced keratinocyte proliferation, reduced the inflammatory cytokine, and downregulated IL-17A, IL-22, and RORγt mRNA in mice. Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice. CONCLUSIONS: TGP alleviates the symptoms of psoriasis-like guinea pigs and mice, and the possible mechanism may relate to inhibit T helper 17 (TH17) cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.

Up-regulation of microRNA-497 inhibits the proliferation, migration and invasion but increases the apoptosis of multiple myeloma cells through the MAPK/ERK signaling pathway by targeting Raf-1.

Multiple myeloma (MM) is a cancer that occurs in plasma cells, which fall under the category of white blood cells that are in charge of antibody production. According to previous studies, microRNA-497 (miR-497) functions as a tumor suppressor in several types of cancer, including gastric cancer and colorectal cancer. Therefore, the present study aims to investigate the effects of miR-497 on cellular function of human MM cells through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by targeting Raf-1. The differentially expressed genes and miRs in MM, and the relationship between the miR and gene were verified. It was found that Raf-1 was a target gene of miR-497. The data obtained from MM tissues showed increased Raf-1 level and decreased miR-497 level. MM cells were treated with mimic, inhibitor and siRNA in order to evaluate the role of miR-497, Raf-1 and MAPK/ERK in MM. The expression pattern of miR-497, Raf-1, ERK1/2, survivin, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) as well as the extent of ERK1/2 phosphorylation were determined. Retored miR-497 and si-Raf-1 resulted in increases in the Bax expression and cell apoptosis and decreases in the expressions of Raf-1, MEK-2, survivin, Bcl-2, along with the extent of ERK1/2 phosphorylation. In addition, the biological function evaluations of MM cells revealed that miR-497 mimic or si-Raf-1 led to suppression in cell proliferation, invasion and migration. In conclusion, our results have demonstrated that miR-497 targets Raf-1 in order to inhibit the progression of MM by blocking the MAPK/ERK signaling pathway.

Effects of biochar application on the abundance and community composition of denitrifying bacteria in a reclaimed soil from coal mining subsidence area.

As a new soil amendment, biochar has become an environmentally friendly material. The application of biochar is one of the most promising management practice to improve soil quality. Using a reclaimed soil from a coal mine subsidence area, the plat soil cultivation experiment in this study investigated the effects of biochar application at varying rates on soil properties, the abundance and composition of soil denitrifier communities. Biochar application significantly increased the crop yield which might be associated with the increased level of cation exchange capacity (CEC), total nitrogen (N), ammonium-N, available phosphorus (P) and potassium (K) in soil. In combination with N fertilizer, the abundance of both nirK and nirS genes significantly increased only at biochar application rate of 4% compared with the nil-biochar treatment. Biochar application significantly increased the community diversity of nirK gene, while not for nirS gene. Redundancy analysis showed that the level of nitrate-N (NO3--N), available P, and pH in soil significantly affected community structure of nirK gene, while the nirS community composition was only affected by soil NO3--N level. Our results indicate that biochar application to the reclaimed soil in coal mine subsidence area could influence the abundance and diversity of soil denitrifiers and improve soil nutrients thus crop yield.

[Total hip arthroplasty for degeneration of infected hip: a report of 7 cases].

OBJECTIVE: To evaluate indications and clinical results of total hip arthroplasties for degenerative hips with history of infection. METHODS: Seven cases of degenerative hip with history of infection underwent primary total hip arthroplasties, which involved 5 males and 2 females, with an average age of 45.8 years (range, 30 to 65 years). The quiescent period of infection were more than 10 years in all hips. According to Kim classification, 3 cases were of type I, and 4 of type II. The method to exclude active infection at the site of degenerative hips preoperatively was combination of physical examination, erythrocyte sedimentation rate and C-reactive protein level. The lateral incision was adopted in all cases, and all prosthesis were cementless. The clinical results of affected hips were assessed according to Harris hip score. RESULTS: The follow-up was performed with the mean duration of 33.5 months (range, 21 to 44 months). No recurrence of infection, damage of nerve function or deep vein thrombosis of lower extremities occurred in all cases. The mean Harris hip scores improved from 44.5 points preoperatively to 84 points at the latest follow-up. No aseptic loosening of prosthesis or periprosthetic osteolysis were found at the latest follow-up. CONCLUSION: Total hip arthroplasties has good short term results for degenerative hips with history of infection. It is important to select indicated cases and rule out the possibility of active infection.