Health economics study of paliperidone palmitate in the treatment of schizophrenia: a 12-month cohort study.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05). CONCLUSION: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

Primary duodenal papilla lymphoma producing obstructive jaundice: a case report.

BACKGROUND: Obstructive jaundice caused by primary duodenal lymphoma is a rare disease. CASE PRESENTATION: We reported a 59-year-old man who underwent endoscopic ultrasonography for obstructive jaundice and found a duodenal papilla tumor. Light microscopy revealed a non-Hodgkin's lymphoma. Immunohistochemical staining showed that the tumor was aggressive B-cell lymphoma. We carried out molecular targeted therapy combined with CHOP regimen chemotherapy. CONCLUSION: Surgery plays an important role in resolving obstructive jaundice when accurate histological diagnosis cannot be made. After diagnosis, chemotherapy should play a central role in treatment.

Diagnosis and management of primary hepatic pregnancy: literature review of 31 cases.

PURPOSE: To summarize the appropriate diagnostic methods and therapeutic options for primary hepatic pregnancy (PHP). METHODS: Literature searches were performed in Pubmed, Web of Science, Cochrane Library and Embase databases (1956-2017), using the following search terms: primary hepatic pregnancy, hepatic pregnancy, liver pregnancy, hepatic ectopic pregnancy and intrahepatic pregnancy. Further literature was confirmed through cross-referencing. RESULTS: Thirty-one cases were reviewed and collected. The site mostly described in literatures is the right lobe of liver (93.5%). Main symptoms of PHP included abdominal pain (77.4%), amenorrhea (45.2%), acuteperitonism (32.3%), shock (25.8%) and vomit (16.1%). Majority of patients (83.9%) were treated by laparotomy. Less-invasive approaches (16.1%) such as laparoscopy or combination of postoperative injection of methotrexate were used less frequently. The outcome was acceptable at the end of the follow-up period in ten cases (1-72 months) and the recovery rate was 96.7%. One patient died and other complications were noted in three patients during the postoperative period. CONCLUSIONS: The clinical diagnosis of PHP can be settled up by comprehensive analysis of serum HCG levels, ultrasound and imaging. The analysis should be assessed carefully before therapeutic procedure. Invasive methods should be preferential. Less-invasive approaches can be selected when the patients have stable hemodynamics and non-acute abdomen.

A comprehensive comparison and analysis of soil screening values derived and used in China and the UK.

China and the UK use different risk-based approaches to derive soil screening or guideline values (SSVs; SGVs) for contaminants. Here we compare the approaches and the derived values for 6 illustrative contaminants. China's SSVs are derived using an approach developed in the US as follows: for carcinogens, acceptable level of risk (ACR) is set at 10-6 and the SSVs calculated as 10-6 divided by the soil exposure and toxicity data; for non-carcinogens, the hazard quotient is 1 and the SSV is calculated as 1 divided by the soil exposure and toxicity data. The UK's SGVs are calculated by the CLEA model, for which the Average Daily Exposure (ADE) from soil sources by a specific exposure route equals the health criteria values (HCVs) for that route, whether for carcinogens or a non-carcinogens. The UK's CLEA model is also used here to derive SSVs with Chinese input parameters. China's SSVs, the UK's SGVs and values for Chinese conditions derived using the UK approach were as follows (mg/kg): As, <1, 35, 20; Cd, 20, 18, 11; Cr (VI), <1, 14, 29; benzene, 1, 1, 2; toluene, 1200, 3005, 3800; ethyl-benzene, 7, 930, 1200. By comparing the differences in toxicity assessment and risk characterization, exposure assessment and parameter types in the methodologies to obtain SSVs in China and the UK, and by combining the CLEA model with Chinese parameterisation, these comparisons highlight that the difference in toxicity assessment and risk characterization methods of carcinogens results in the biggest difference in SSVs between the 2 countries. However, for non-carcinogenic substances, the difference of SSVs calculation method and SSVs is small. The difference in SSVs for carcinogenic substances is also related to the route of exposure. For volatile organic compounds, the presence of indoor respiratory exposure pathways greatly reduces the differences caused by toxicity assessment and risk characterization methods. For non-volatile substances such as heavy metals, the effects of toxicity assessment and risk characterization methods are significant. The SSV of As obtained by the CLEA model with Chinese parameters is closer to the background value of soil in China. In the management of non-volatile contaminated sites such as heavy metals in China, the CLEA model can be used for risk assessment and calculation of site specific SSVs. In the future, China can use the UK method to strengthen its toxicity assessment and risk characterization methods for carcinogenic substances, to reduce the uncertainty in the risk assessment of contaminated sites and improve the scientific management of contaminated sites.

Oncogenicity of lncRNA FOXD2-AS1 and its molecular mechanisms in human cancers.

OBJECTIVES: Long non-coding RNAs (lncRNAs) are a group of noncoding RNAs with length larger than 200 nucleotides. LncRNAs have limited or no protein-coding capacity because of lack of obvious open reading frame. An increasing number of researches have shown that lncRNAs participate in the complex regulation network of cancer and play an important role in tumourigenesis and progression such as proliferation, migration and invasion. LncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1), located on chromosome 1p33 and with a transcript length of 2527 nucleotides, is a novel cancer-related lncRNA. FOXD2-AS1 was recently found to exhibit aberrant expression in various malignancies, including gastric, lung, bladder, colorectal, nasopharyngeal, esophageal, hepatocellular, thyroid and skin cancer, and its deregulation might be related to survival and prognosis of cancer patients. Pertinent to clinical practice, FOXD2-AS1 might act as a feasible biomarker or therapeutic target in human cancers. In this paper, we made a summary on the current findings concerning the biological functions and molecular mechanisms of FOXD2-AS1 in tumor progression. MATERIALS AND METHODS: In this paper, we summarized and figured out recent studies about the expression and molecular biological mechanisms of FOXD2-AS1 in tumor progression. Existing relevant studies were obtained through a systematic search from PubMed, Embase, BioMedNet, GEO database and Cochrane Library. RESULTS: FOXD2-AS1 was a valuable tumor-associated lncRNA. Its expression level was up-regulation in various malignancies, including gastric, lung, bladder, colorectal, nasopharyngeal, esophageal, hepatocellular, thyroid and skin cancer. In addition, the aberrant expressions of FOXD2-AS1 have shown to contribute to proliferation, migration and invasion of cancer cells, and its deregulation is related to carcinogensis, overall survival, disease free survival, prognosis and tumor progression. CONCLUSIONS: LncRNA FOXD2-AS1 is an oncogene and probably represents a feasible biomarker or therapeutic target in human cancers.

LncRNA HOXA-AS2 and its molecular mechanisms in human cancer.

Long non-coding RNAs (lncRNAs), a novel class of noncoding RNAs, are commonly defined as RNA molecules more than 200 nucleotides in length. Emerging research indicated that lncRNA played a vital role in human tumorigenesis and progression by serving as tumor oncogenes or suppressors. LncRNA has been shown to get involved in participate various biological processes, such as cell growth, anti-apoptosis, migration and invasion. LncRNA HOXA cluster antisense RNA2 (HOXA-AS2) is a novel cancer-related lncRNA. It was recently found to exhibit aberrant expression in a variety of malignancies, including breast cancer, gastric cancer, gallbladder carcinoma, hepatocellular carcinoma and pancreatic cancer. The oncogenicity of lncRNA HOXA-AS2 mainly inhibits or promotes the expression of related genes through direct or indirect pathways, suggesting that HOXA-AS2 likely represents a feasible biomarker or therapeutic target in human cancers. In this review, we summarize current evidences concerning the biological functions and mechanisms of HOXA-AS2 during tumor development.

Psychotomimetic effects of different doses of MK-801 and the underlying mechanisms in a selective memory impairment model.

Although N-methyl-d-aspartate receptor antagonists-induced hypoglutamate rodent models are the most well-established models for preclinical studies of schizophrenia-related deficits, they also evoke a wide spectrum of psychotomimetic side effects. It is significant to increase the specificity of hypoglutamate rodent models. In this study, the recognition memory was evaluated in rats by object recognition test (ORT), sensorimotor gating was evaluated by prepulse inhibition of the startle reflex (PPI), and locomotor activity was measured using open field test. High-performance liquid chromatography was used to measure neurotransmitters content in the medial prefrontal cortex (mPFC) and thalamus (THA). Total Akt and phospho-Akt protein was measured by Western blots. Results showed that 0.3mg/kg of MK-801 was most effective in inducing locomotion. 0.3mg/kg of MK-801 was most effective in decreasing PPI. 0.03mg/kg of MK-801 was most effective in decreasing object memory while not affecting exploration manners in the training session. 0.03mg/kg of MK-801 significantly increased HVA and Glu content in the mPFC. 0.1mg/kg of MK-801 significantly decreased GABA content in the THA. 0.03mg/kg of MK-801 significantly decreased Akt phosphorylation in the mPFC, which was related to the ORT index. In conclusion, a dose of 0.03mg/kg MK-801 can establish a "pure" memory impairment model without contaminations of sensorimotor gating and locomotor activity. MK-801-induced cognitive deficits is associated with increased DA metabolites and glutamate content in the mPFC and decreased GABA content in the THA as well as decrease in Akt phosphorylation in the mPFC.

Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings.

UNLABELLED: Among individuals diagnosed with schizophrenia, approximately 20%-33% are recognized as treatment-resistant schizophrenia (TRS) patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophrenia may be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL) brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs. CONTROL: To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level) on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1) 69 patient-specific connectivity (PCN); 2) 102 shared connectivity (SCN); and 3) 457 unshared connectivity (UCN). While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS.

Promoter variant rs2301228 on the neural cell adhesion molecule 1 gene confers risk of schizophrenia in Han Chinese.

BACKGROUND: Schizophrenia is recognized as a disorder of the brain and neuronal connectivity. The neural cell adhesion molecule 1 (NCAM1) gene plays a crucial role in regulating neuronal connectivity. METHODS: We conducted a two-stage association analysis on 17 NCAM1 SNPs in two independent Han Chinese schizophrenia case-control cohorts (discovery sample from Hunan Province: 986 patients and 1040 normal controls; replication sample from Yunnan Province: 564 cases and 547 healthy controls). Allele, genotype and haplotype frequencies were compared between case and control samples. Transcription factor binding site prediction and luciferase reporter assays were employed to assess the potential function of promoter SNPs. We detected developmental changes at the transcriptional level of NCAM1 during neuron differentiation in Macaca mulatta neural progenitor cells (NPC). Serum levels of NCAM1 were measured in 72 cases and 88 controls. RESULTS: A promoter variant, rs2301228, was found to be associated with schizophrenia at the allelic level and was validated in a replication cohort. Luciferase reporter assays demonstrated that risk allele rs2301228-A significantly down-regulated NCAM1 gene transcription compared to the G-allele. Concordantly, schizophrenia patients had a significantly lower level of serum NCAM1 compared to healthy donors. During the NPC neuronal differentiation, NCAM1 mRNA was significantly increased, suggesting a critical role of this gene in neural development. CONCLUSIONS: Our results provide direct evidence for NCAM1 as a susceptibility gene for schizophrenia, which offers support to a neurodevelopmental model and neuronal connectivity hypothesis in the onset of schizophrenia.

White matter microstructural abnormalities in patients with late-onset schizophrenia identified by a voxel-based diffusion tensor imaging.

Reduced fractional anisotropy (FA) has been previously found in diffusion tensor imaging (DTI) studies of white matter in schizophrenic patients. However, there are no reports in the literature that address FA alterations in late-onset schizophrenia (LOS). The current study measured FA in whole white matter and subsequently analyzed its association with psychotic symptoms in LOS. DTI was carried out in 20 patients with LOS and 17 age-, gender- and education-matched healthy subjects. Fractional anisotropy in different areas of white matter was compared between groups using a voxelwise analysis after inter-subject registration to standard Montreal Neurological Institute (MNI) space. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functions were measured using the Wisconsin Card Sorting Test (WCST), the Digit Span Test, and the Trail-making Test. Significant reduction in FA was found in the left parietal lobe and right posterior cingulum in LOS patients compared with healthy subjects. Significant deficits in cognitive functions were observed in LOS. No significant correlation was found between FA value and PANSS scores, cognitive test scores, age, or antipsychotic medication dosages in LOS patients. Our study suggests that abnormalities in white matter integrity may contribute to the pathophysiology of LOS. However, these microstructural abnormalities provided no evidence for the emergence of psychotic symptoms in LOS.