Radiographical Evaluation of Tumor Immunosuppressive Microenvironment and Treatment Outcomes in Gastric Cancer: A Retrospective, Multicohort Study.

BACKGROUND: The tumor immunosuppressive microenvironment can influence treatment response and outcomes. A previously validated immunosuppression scoring system (ISS) assesses multiple immune checkpoints in gastric cancer (GC) using tissue-based assays. We aimed to develop a radiological signature for non-invasive assessment of ISS and treatment outcomes. METHODS: A total of 642 patients with resectable GC from three centers were divided into four cohorts. Radiomic features were extracted from portal venous-phase CT images of GC. A radiomic signature for predicting ISS (RISS) was constructed using the least absolute shrinkage and selection operator (LASSO) regression method. Moreover, we investigated the value of the RISS in predicting survival and chemotherapy response. RESULTS: The RISS, which consisted of 10 selected features, showed good discrimination of immunosuppressive status in three independent cohorts (area under the curve = 0.840, 0.809, and 0.843, respectively). Multivariate analysis revealed that the RISS was an independent prognostic factor for both disease-free survival (DFS) and overall survival (OS) in all cohorts (all p < 0.05). Further analysis revealed that stage II and III GC patients with low RISS exhibited a favorable response to adjuvant chemotherapy (OS: hazard ratio [HR] 0.407, 95% confidence interval [CI] 0.284-0.584); DFS: HR 0.395, 95% CI 0.275-0.568). Furthermore, the RISS could predict prognosis and select stage II and III GC patients who could benefit from adjuvant chemotherapy independent of microsatellite instability status and Epstein-Barr virus status. CONCLUSION: The new, non-invasive radiomic signature could effectively predict the immunosuppressive status and prognosis of GC. Moreover, the RISS could help identify stage II and III GC patients most likely to benefit from adjuvant chemotherapy and avoid overtreatment.

[Transcriptome analysis of rhizome of Polygonatum cyrtonema and identification of candidate genes involved in biosynthetic pathway of steroidal saponin].

To enrich the transcriptome data in rhizome of Polygonatum cyrtonema seedlings, identify candidate functional genes involved in steroidal saponin biosynthesis and provide genetic resources for the research on anabolism pathway and regulatory mechanism of active components in P. cyrtonema, Illumina platform was applied to perform transcriptomic sequencing of rhizome of P. cyrtonema, followed by a series of bioinformatics analysis on RNA-seq data, including de novo assembly, annotation, classification and metabolic pathway analysis of the assembled unigene. Meanwhile, a deep analysis on the steroidal saponin biosynthesis in secondary metabolism pathway was performed. The results showed a total of 126 546 unigene were obtained by de novo transcriptome assembly, of which 47 226 were annotated. Of these, 16 499 unigene were mapped to 132 specific pathways, of which 2 768 were identified to be involved in 22 secondary metabolic pathways. One hundred and thirteen unigene were identified from the transcriptome database, which encoded 27 metabolic enzymes associated with steroidal saponin biosynthesis and shared similarity with 45 functional genes in Arabidopsis thaliana. In conclusion, a series of candidate functional genes, which might be involved in steroidal saponin biosynthesis, were selected from the transcriptome database of P. cyrtonema rhizome. Further investigation of these candidate genes will provide insight into their actual functions in the steroidal saponin biosynthetic pathway in P. cyrtonema. In addition, this study also provide abunant reference data for transcriptome characterization of P. cyrtonema and has important significance for functional genomics of P. cyrtonema.

Suicide attempt and suicidal ideation and their associations with demographic and clinical correlates and quality of life in Chinese schizophrenia patients.

OBJECTIVES: This study aimed to examine the prevalence and correlates of lifetime suicide attempts and current suicidal ideation in community-dwelling schizophrenia patients in China. METHOD: A sample of 540 schizophrenia patients was randomly selected in Beijing, China. All subjects were interviewed using standardized assessment instruments and their basic socio-demographic and clinical data including history of suicide attempts were collected. RESULTS: The prevalence of lifetime suicide attempts and the point prevalence of suicidal ideation were 12.0%, and 21.1%, respectively. In multiple logistic regression analyses, the presence of lifetime suicide attempt was independently associated with rural residence, having major medical conditions and better social functioning, while higher likelihood of current suicidal ideation was associated with past suicide attempt, the severity of overall psychopathology and depressive symptoms and lower psychological quality of life (QOL). CONCLUSION: Among Chinese outpatients with schizophrenia, increased current symptoms and poorer QOL were correlated with current suicidal ideation, while demographic factors and indicators of greater social support were mostly correlated with lifetime suicide attempts. This study may help to identify important subgroups of patients with schizophrenia at particularly high risk of suicidal behavior.

Quality of life in community-dwelling patients with schizophrenia in China.

The aim of this study was to assess Chinese schizophrenia patients' quality of life (QOL) and identify its demographic and clinical correlates. A random sample of 540 community-dwelling schizophrenia patients was interviewed using standardized assessment instruments. The patients' basic sociodemographic and clinical data and QOL were collected. Compared with the general population, patients had significantly lower scores in the physical and psychological QOL domains. Multivariate analyses showed that better social support independently predicted higher QOL in all domains, whereas more severe positive symptoms predicted worse psychological and environmental domains. Overall psychopathology predicted both worse physical and psychological domains; depressive symptoms and being married predicted worse physical and social QOL, respectively. Our results suggest that therapeutic and psychosocial interventions alleviating positive and depressive symptoms and improving poor social support and marriage-related problems in Chinese patients with schizophrenia might be of considerable benefit in improving their QOL.

Predictors of relapse in Chinese schizophrenia patients: a prospective, multi-center study.

OBJECTIVE: Relapse prevention is the main goal of maintenance treatment in schizophrenia. This study aimed to determine the rate and the socio-demographic and clinical predictors of relapse in Chinese schizophrenia patients following treatment of the acute phase of the illness. METHODS: In a multi-center, randomized, controlled, longitudinal study, 404 patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to either the maintenance (i.e., initial optimal therapeutic doses continued throughout the study) or the dose-reduction group (i.e., initial optimal therapeutic doses continued for 4 or 26 weeks followed by a 50% dose reduction that was maintained until the end of the study). Participants were interviewed at entry using standardized assessment instruments, and followed up for 12-26 months. RESULTS: In univariate analyses, relapse was significantly associated with the membership of the dose-reduction group, poor medication adherence, and having a diagnosis of the paranoid type of schizophrenia. In Cox proportional-hazards regression analysis the membership of the dose-reduction group, poorer medication adherence, more severe drug-induced side effects and prominent paranoid symptoms independently predicted a higher risk of relapse. CONCLUSION: The study confirmed the importance of maintenance medication in preventing relapse in Chinese schizophrenia patients underscoring the risk of relapse associated with lack of treatment adherence, severe side effects and the patients' paranoid attitude. Socio-demographic characteristics were not associated with relapse in Chinese schizophrenia patients. Potential residual confounding caused by unmeasured variables should be fully considered in future studies.

Sex differences in patients with schizophrenia: A prospective, multi-center study.

This study aimed to determine sex differences in socio-demographic and clinical characteristics of Chinese schizophrenia patients. In a multi-center, randomized, controlled, longitudinal study, 404 clinically stable patients with schizophrenia were randomly assigned to a maintenance group (optimal therapeutic doses continued throughout the study), a 26-week group (optimal therapeutic doses continued for 26 weeks, followed by a 50% dose reduction maintained until the end of the study), or a 4-week group (optimal therapeutic doses continued for 4 weeks, followed by a 50% dose reduction maintained until the end of the study). Participants were interviewed regularly using standardized assessment instruments, and followed up for 12-26 months. In the univariate analyses, the following factors were significantly associated with the male sex: not married, smoking, younger age, earlier age at onset, higher body mass index (BMI) at baseline, and more severe negative and hostility-excitement symptoms at baseline. The following factors were independently associated with the male sex in the multivariate analyses: not being married, smoking, a higher BMI at baseline, less deterioration in disorganized thoughts (4-week group) and positive symptoms (26-week group) and less increase in BMI in all three treatment groups over the study period. The majority of the sex differences in schizophrenia patients in this study are in accordance with results of previous studies worldwide suggesting that sex differences seen in schizophrenia are not dependent on cultural differences between geographically separate patients.

Gender differences in sociodemographic and clinical characteristic and the quality of life of Chinese schizophrenia patients.

OBJECTIVE: The aim of the present study was to determine the sociodemographic and clinical correlates of the gender of Chinese schizophrenia outpatients and their impact on patients quality of life (QOL). METHODS: Two hundred and fifty-five clinically stable schizophrenia outpatients were randomly selected in Hong Kong. Counterparts matched according to gender, age, age at onset, and length of illness were recruited in Beijing, China. All of the subjects at both sites were interviewed by the same investigator using standardized assessment instruments. RESULTS: The combined Beijing-Hong Kong sample contained 251 male and 254 female patients. On univariate analysis more male patients were employed, they had a significantly higher monthly income, and took higher doses of antipsychotic drugs. No difference was found, however, in any of the QOL domains between the genders. On multivariate analysis being employed, taking a higher dose of antipsychotic drugs, having more severe extrapyramidal side-effects, and a higher score on the physical domain of QOL were independently associated with male gender. CONCLUSION: Female gender is independently associated with lower scores on the physical aspects of QOL, but there is no difference between the genders in the psychological, social and environmental aspects.

Cigarette smoking in patients with schizophrenia in China: prospective, multicentre study.

OBJECTIVE: The aim of the present study was to explore the rate of cigarette smoking and its sociodemographic and clinical characteristics in Chinese schizophrenia patients. METHODS: In a multicentre, randomized, controlled, longitudinal study, 374 clinically stable patients with schizophrenia were interviewed at entry using standardized assessment instruments, and followed up for 1-2 years. RESULTS: The rate of cigarette smoking was 13.9% in the whole sample, and 26.2% in men and 3.5% in women. On univariate analysis, male sex, unemployment, alcohol consumption, older age, older age at onset, longer duration of illness, more frequent admissions, more severe hostility-excitement at entry and less deterioration in hostility-excitement over the study period were significantly associated with cigarette smoking. On multivariate analysis, male sex, unemployment, alcohol consumption, more frequent admissions, less severe positive and negative symptoms at entry, smaller decline in negative symptoms and more deterioration in disorganized thoughts over the study period were independently associated with cigarette smoking. CONCLUSION: The rate of cigarette smoking in Chinese schizophrenia patients is considerably lower than most figures reported in the Western literature.

The metastasis of hepatocarcinoma can be inhibited by T lymphocytes reconstitution in nude mice model.

BACKGROUND/AIMS: The metastasis of hepatic carcinoma is correlated with the body's immune status. T lymphocytes play a big part role in tumor immune. The aim of the present study is to investigate the inhibition effects of metastatsis in nude mice bearing hepatic carcinoma after T lymphocytes reconstitution. METHODOLOGY: An immune reconstitution model was established in nude mice. Then, 42 nude mice were distributed into 4 groups for T lymphocytes reconstitution. The lymph nodes of each group were obtained to investigate the tumor metastasis. And the secretion of cytokines and the apoptosis of tumor cells in each group were also detected. RESULTS: The ratio of CD3, CD4, CD8, CD4/CD8 in reconstituted groups were higher than controlled groups. The average time of tumor formation in Balb/c nu/nu mice was 7.7 +/- 0.6 days and in Balb/c mice was 11.5 +/- 1.3 days. After active T lymphocytes reconstitution, the extent lymph nodes metastasis in reconstitution groups was lower than control groups (p < 0.05), but proximal metastasis has no significant difference. The level of serum IL-10 in nude mice after immune reconstitution was significantly lower and VEGF was significantly higher than that of the control group (p < 0.05). Apoptosis of the hepatic carcinoma cells was increased significantly after immune reconstitution (p < 0.05). CONCLUSIONS: The metastasis of hepatic carcinoma can be inhibited by reconstitution of actived T lymphocytes in nude mice, which indicated that tumor metastasis can be affected by the immune status in host body.

Prevalence and correlates of insomnia and its impact on quality of life in Chinese schizophrenia patients.

STUDY OBJECTIVES: This study aimed to determine the prevalence and the sociodemographic and clinical correlates of insomnia in Chinese schizophrenia outpatients and its impact on patients' quality of life (QOL). DESIGN: Two hundred fifty-five clinically stable schizophrenia outpatients were randomly selected in Hong Kong and their counterparts matched according to sex, age, age at onset, and length of illness were recruited in Beijing, China. All subjects at both sites were interviewed by the same investigator using standardized assessment instruments. SETTING: Hong Kong and Beijing, China. PATIENTS OR PARTICIPANTS: Clinically stable schizophrenia outpatients. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In the combined Beijing-Hong Kong sample the frequency of at least one type of insomnia over the previous 12 months was 36.0%; the rates of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA) were 21.2%, 23.6%, and 11.9%, respectively. Poor sleep was significantly associated with advanced age, older age at onset, fewer psychiatric admissions, severity of positive symptoms, anxiety, extrapyramidal symptoms (EPS) and depressive symptoms, less frequent use of atypical antipsychotic medications (AP), and more frequent use of benzodiazepines (BZD) and hypnotics. Poor sleepers had significantly poorer QOL in all domains than patients without insomnia. After controlling for the potential confounding effects of sociodemographic and clinical factors, a significant difference remained between the 2 groups with regard to the physical QOL domain. A multiple logistic regression analysis found that advanced age, fewer psychiatric admissions, severity of depressive symptoms and use of hypnotics were significant contributors to poor sleep. CONCLUSION: Insomnia is independently associated with poor QOL. More attention should be paid in clinical practice to the high rate of insomnia in Chinese schizophrenia patients.

Fungal polysaccharide similar with host Dendrobium officinale polysaccharide: Preparation, structure characteristics and biological activities.

Based on the concept of endophytic fungus, if endophytic fungus can produce the same or similar product as the host plant, which will get rid of the restrictions of farmland, seasonal and pest, the active product could be sustainably obtained. In this study, an endophytic fungus polysaccharide FP showing the similar structure with the host Dendrobium officinale polysaccharide (DOP) was sustainably and cost-effectively obtained under preferred reaction conditions with different C/N ratio. The FP with high yield up to 2.77 ±â€¯0.51 g/L showed same monosaccharide composition with DOP as well as some host-plant-associated polysaccharides in published literatures. The main chain of FP was composed by →3,6)-ß-L-Man-(1→, α-D-Glc-(1→, →4)-α-D-Glc-(1→, →3,6)-ß-D-Gal-(1→, and →6)-ß-D-Gal-(1→, while the side chain was α-D-Glc-(1→. Meanwhile, FP was confirmed as a safe polysaccharide with good antioxidant, antiglycation and immunomodulatory activities. Furthermore, TLR2 and TLR4 were confirmed as the membrane receptors of FP on RAW264.7 cells.

Socio-demographic and clinical correlates of lifetime suicide attempts and their impact on quality of life in Chinese schizophrenia patients.

This study determines the socio-demographic and clinical correlates of suicide attempts in Chinese schizophrenia outpatients and their impact on patients' quality of life (QOL). Two hundred and fifty-five clinically stable schizophrenia outpatients were randomly selected in Hong Kong (HK) and their counterparts matched according to sex, age, age at onset and length of illness were recruited in Beijing (BJ). All subjects at both sites were interviewed by the same investigator using standardized assessment instruments. Basic socio-demographic and clinical data and history of suicide attempts were collected. The lifetime prevalence of suicide attempts was 26.7% in the whole sample and 20% and 33.6% in the HK and BJ samples, respectively. Patients with a history of suicide attempts were less likely to receive depot antipsychotic (AP) medication, more likely to receive clozapine, benzodiazepines (BZD) and higher doses of APs; were younger at onset, had more hospitalizations; had more severe positive, depressive, anxiety and extrapyramidal (EPS) symptoms; were poorer QOL in the physical, psychological, social and environmental domains; and were more likely to be BJ residents. In multiple logistic regression analysis, early age at onset, poor physical QOL, use of clozapine and BZDs, and study site (HK vs BJ) were significant contributors to lifetime suicide attempts. Significant difference was found between matched samples in HK and BJ with respect to suicide attempts. HK is a cosmopolitan city with a Western social structure and mental health system, whereas in BJ more traditional Chinese cultural values predominate, with a mental health policy radically different from that of HK. These differences suggest that socio-cultural factors play a significant role in determining suicide attempts in schizophrenia.

[The level of transgelin related to the function of dendritic cells pulsed with liver cancer].

OBJECTIVE: To explore the relationships between the expression of transgelin in dendritic cells (DCs) pulsed with hepatocellular carcinoma lysates and the functions of the DCs. METHODS: DCs derived from healthy human white blood cells were divided into 3 groups: one was pulsed with high metastatic potential hepatocellular carcinoma cell line (MHCC97H) lysates, one with lysates of a low metastatic potential cell line (MHCC97L), and one un-pulsed DCs served as the control. The morphology of the DCs was observed by confocal microscopy and scanning electron microscopy. The phenotypes of the DCs were detected by flowcytometric analysis. The mixed leucocyte reaction (MLR) test and IL-12 secretion of DCs in the supernatants of MLR were employed to determine the functions of the DCs; the expression of transgelin was detected by Western blot. RESULTS: There were no morphological changes in the different DCs, but the levels of HLA-DR, CD80, CD83, CD86, MLR and IL-12 and transgelin were significantly higher in the two pulsed groups than those in the control group (P less than 0.01). In MHCC97H pulsed DCs, their CD80, CD83, CD86, and the expression of transgelin were also higher than those in the control group (P less than 0.05). The expression of transgelin was significantly higher in the MHCC97H pulsed group than in the MHCC97L loaded group, but CD80, CD83, CD86 and the level of IL-12 were all lower in the MHCC97H loaded DC group in comparison with those in the MHCC97 pulsed group (P less than 0.05). CONCLUSION: The expression of transgelin in DCs pulsed with HCC lysates is related to the functions of the DCs.

Plasma S-100B protein in Chinese patients with schizophrenia: comparison with healthy controls and effect of antipsychotics treatment.

PURPOSE: To examine the possibility that structural damage to the brain may play a role in the pathogenesis of schizophrenia by measuring the level of plasma S-100B, a calcium-binding protein found predominantly in the cytosol of glial cells. METHOD: Fifty-seven Chinese psychiatric inpatients who met DSM-IV diagnosis of schizophrenia and 60 healthy controls were enrolled in the study. Patients were assessed with the Positive and Negative Symptoms Scale (PANSS) at admission and at 12 weeks after treatment. Plasma samples were collected from patients and controls and S-100B protein was assayed using ELISA. RESULTS: (1) 29 of 57 patients (50.9%) showed increased S-100B level compared to the mean level of 60 healthy controls (p<0.005) vs. only 1 of 60 (1.67%) controls. The S-100B levels of unmedicated (0.119+/-0.059microg/L) and medicated patients (0.117+/-.0.057microg/L) were significantly higher than controls (0.067+/-0.022microg/L, both p<0.001), and S-100B levels of unmedicated patients were higher than those of medicated patients (p=0.024); (2) at admission, S-100B level was positively correlated with total score of PANSS (r=0.269, p=0.043), especially with negative subscore of PANSS (r=0.306, p=0.021), but the correlation was no longer present after patients were treated by anti-psychotic agents. CONCLUSION: The S-100B levels of patients with schizophrenia are significantly higher than that of healthy controls, and the S-100B level is associated with severity of psychopathology, particularly negative symptoms, indicating that patients with schizophrenia may suffer structural damage to central nervous system. The concentration of S-100B may also be associated with treatment progress.

Clinical and social determinants of psychotropic drug prescription for schizophrenia outpatients in China.

To date, few studies have investigated prescription patterns of psychotropic drugs in Chinese patients with schizophrenia in general and outpatients in particular. This study examined the role that socio-demographic and clinical factors play in determining psychotropic drug prescriptions for schizophrenia outpatients in China. Two hundred and fifty-five and 250 clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ) respectively, using standardized assessment instruments. Prescriptions of psychotropic drugs for all 505 subjects were collected at the time of the assessment. The relationship between antipsychotic drug prescription patterns and a host of socio-demographic and clinical variables was analyzed and compared between the two study sites. Prescription patterns were quite different for the two ethnically homogenous and clinically very similar samples. In multiple logistic regression analyses, the use of depot antipsychotics (DA) and site (HK vs BJ) both significantly predicted antipsychotic polypharmacy (APP), while symptoms of anxiety, use of clozapine and APP and site predicted use of DA. Age, number of hospitalizations, site, and use of DA predicted use of clozapine. No significant differences were found between the quality of life domains of patients with respect to APP, DA, and clozapine. A complex web of economic and clinical factors and health policies plays an important role in determining psychotropic drug prescription practices for Chinese outpatients with schizophrenia.

[Relation between changes of dendritic cell function and down-regulation of beta-centractin in hepatocellular carcinoma].

OBJECTIVE: To investigate the relation between the changes of dendritic cell (DC) function and down-regulation of beta-centractin in hepatocellular carcinoma. METHODS: DC derived from peripheral blood were cultured and then pulsed by lysates from hepatocarcinoma cells (HCC) with high, low, or none metastatic potential of the lines HCCLM6, MHCC97L, and Hep3B, and from normal human liver cell of the line Chang liver. DC not pulsed were used as control group. Three days later scanning electron microscopy and inverted microscopy were used to observe the morphology of the DC. Flow cytometry was used to observe the phenotype. The protein expression of beta-centractin was detected by Western blotting and immunocytochemistry. RESULTS: Scanning electron microscopy and inverted microscopy showed no change in the morphology of the DC pulsed by different antigens. The expression levels of HLA-DR, CD80, CD83, and CD86 of the 4 pulsed groups were all significantly higher than that of the un-pulsed group (all P < 0.05). The expression of CD86 of the DC + LM6 group was significantly lower than those of the DC + Chang, DC + Hep3B, and DC + 97L groups (all P < 0.05). The mixed lymphocyte reaction (MLR) levels of the 4 pulsed groups were all significantly higher than that of the control group (all P < 0.05). The MLR level of the DC + LM6 group was significantly lower than those of the DC + Chang, DC + Hep3B, and DC + 97L groups (all P < 0.05). Western blotting showed that beta-centractin was not expressed in the control DC and was expressed in the 3 pulsed DC groups, and the beta-centractin expression levels of the DC + Chang, DC + Hep3B, and DC + 97L groups were all higher than that of the DC + LM6 group. The results of immunocytochemistry were similar to that of Western blotting. CONCLUSION: The down-regulation of beta-centractin in the DC pulsed with high metastatic potential HVV cell lysates is associated DC dysfunction and may be one of the mechanisms of HCC immune escape.

[A preliminary study of the killing function in vitro by T lymphocytes activated by dendritic cells loaded with exosomes secreted by hepatic cancer cell lines with high or low metastatic potentials].

OBJECTIVE: To study the tumor cell killing function of T lymphocytes stimulated by dendritic cells (DC) and to analyze the differences of protein contents of exosomes in each type of cell. METHODS: The exosomes of hepatic cell lines with high (P group) or low (F group) metastatic potentials were isolated by a process of four-step centrifugation and the collected exosomes were observed under an electron microscope (EM). The tumor cell killing experiment was performed by adding T lymphocytes activated by DC loaded with exosomes from corresponding P and F group cells and was studied using 3H-TdR experiments. The proteomic analysis was performed by surface-enhanced laser desorption/ ionization time of flight mass spectrometry (SELDI-TOF-MS ) on the exosomes of P and F group cells. RESULTS: The density distribution and content of exosomes in the P group were not equal to those in the F group observed by EM. The CD80, CD86, MHC-I and MHC-II in the P group were 64.27+5.00, 44.89+10.11, 84.35+19.89 and 59.03+19.37, and those in the F group were 71.53+4.85, 50.01+9.50, 80.68+29.87 and 58.86+21.11, respectively (P>0.05, compared with the control group). The counts per minute value in the P group was 528.40+179.06 and 78.80+24.44 in the F group after being loaded with exosomes (P<0.01, compared with the control group). There were significant differences between the proteins in the exosomes of hepatic cancer cell lines with high or low metastatic potentials. CONCLUSION: Exosomes have potential values of application in immunotherapy and in biotherapy for recurrences and metastases of hepatic carcinomas.

Serum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia.

Schizophrenic outpatients (n=102) whose condition had stabilized with clozapine (CLZ) therapy and were being maintained on CLZ were followed for 1 year. Clinical status and concentrations of serum clozapine (CLZ) and its metabolite norclozapine (NCLZ) were evaluated periodically or when relapse occurred. Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization. Thirty-three patients relapsed and 69 did not. Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses (CLZ: 162 ng/ml vs. 237 ng/ml, p<0.001; CLZ+NCLZ: 225 ng/ml vs. 301 ng/ml, p<0.001). When all subjects were pooled together, a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale (BPRS) from baseline and serum levels of CLZ alone (r=0.404, p<0.001) and the sum of CLZ and NCLZ (r=0.364, p<0.001). Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73% and a specificity of 80%. The threshold value represented about a 40% lower serum CLZ level than concentration achieved in acute treatment. Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria. These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60% of the acute-phase level during long-term maintenance treatment of schizophrenia.

[The relationship between lymphangiogenesis and lymphatic metastasis in murine hepatic carcinoma of high and low metastatic potentialities].

OBJECTIVES: To study the relationship between lymphangiogenesis and lymphatic metastasis in mice bearing hepatic carcinoma and analyze the mechanism of the lymphatic metastasis. METHODS: Hepatic carcinoma cell lines of high and low potentialities of lymphatic metastasis were injected into the footpads of Balb/c mice. Their metastases to lymph nodes were examined. The tumor tissues of each group were stained with 5'-nucleotidase-ALP to observe the lymphoangiogenesis. The total RNA of high and low metastatic potential cell lines were extracted for metastasis gene DNA array. The vascular endothelial cell growth factor C (VEGF-C) and VEGF-D of each cell line were detected using semi-quantitative RT-PCR and were further quantatively analyzed using real time PCR. RESULTS: The para-common iliac a. and renal hilar lymph nodes metastases of the high metastatic potential cells were significantly higher than in the controls (P>0.05). The quantity of lymphatic vessels in the high metastasis group was significantly larger than that of the control group (P<0.05). The expressions of CD44, E-cadherin, HER2/neu, H-Ras and VEGF-C in the high metastasis group were higher than those in the low metastasis group shown by the cDNA micro array experiment but the expressions of nm23A, nm23-E4, p16ink4a, CD61 were lower. The VEGF-C expression was higher and the VEGF-D was lower in the high metastasis group compared to those of the low metastasis group shown by semi-quantitative RT-PCR. The secretion of VEGF-D was significantly lower and the ratio of VEGF-C/VEGF-D was significantly higher in the high metastasis group than the low metastasis group (P<0.05). CONCLUSIONS: The lymphatic metastasis of hepatic carcinoma is related to lymphoangiogenesis. The changes of VEGF-C and VEGF-D expressions might be a cause influencing the lymphoangiogenesis. VEGF-C/VEGF-D might be an effective parameter in affecting lymphatic metastases.