Zanubrutinib plus cytarabine in patients with refractory/relapsed primary central nervous system lymphoma.

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare subtype of aggressive extranodal non-Hodgkin lymphoma. Currently, there is no standard of care for the treatment of refractory or relapsed PCNSL (r/r PCNSL). We conducted a prospective single-arm phase II study to evaluate zanubrutinib plus cytarabine for r/r PCNSL. METHODS: Using Simon's two-stage design, we analyzed 34 patients who received high-dose cytarabine (3.0 g/m2 once daily) for 2 days and zanubrutinib (160 mg twice daily) for 21 days each cycle for up to 6 cycles. The study was registered at www.chictr.org.cn as #ChiCTR2000039229. RESULTS: The median follow-up was 19 months. The overall response rate was 64.7% (95% confidence interval (CI), 47.9% to 78.5%) with a complete remission or unconfirmed complete remission rate of 47.1% (16/34) and a partial remission rate of 17.6% (6/34). The median progression-free survival was 4.5 months (95% CI, 1.5 to 9.4) and the median OS was 18 months (95%CI, 9.5 to not estimable). The median duration of the response was 9 months (95%CI, 3.2 to not estimable). The most common treatment-emergent adverse events were thrombocytopenia (55.9%). No treatment-related death occurred. CONCLUSION: Zanubrutinib and cytarabine showed efficacy in r/r PCNSL with an acceptable safety profile.

A prospective cohort study of methotrexate plus idarubicin in newly diagnosed primary CNS lymphoma.

PURPOSE: High-dose methotrexate (HD-MTX)-based chemotherapy regimen is the first-line option for primary central nervous system lymphoma (PCNSL). This prospective cohort study aimed to evaluate the efficacy and adverse effects of HD-MTX plus idarubicin (IDA) in patients with newly diagnosed immunocompetent PCNSL. METHODS: We recruited newly diagnosed PCNSL patients from January 2017 to August 2020. Patients were assigned into two groups: HD-MTX monotherapy and HD-MTX plus IDA (HD-MTX/IDA). In the HD-MTX monotherapy group, patients were treated with MTX 8 g/m2 alone on day 1, while the HD-MTX/IDA group received MTX 8 g/m2 on day 1 and IDA 10 mg/m2 on day 2. Treatments were repeated every 3 weeks for 8 cycles except for progression and/or unacceptable toxicity. RESULTS: We recruited 61 PCNSL patients, including 36 in the HD-MTX and 25 in the HD-MTX/IDA group. The CR rate was 68% in the HD-MTX/IDA group and 72.22% of patients in the HD-MTX monotherapy group (p = 0.7221), while the overall response rate was 72% vs. 77.78% (p = 0.6063). Median PFS in HD-MTX/IDA group and HD-MTX monotherapy group were 15.6 months and 18.5 months, respectively (p = 0.6374). Median OS was not reached in both groups. There were no significant differences in adverse effects between the two groups. CONCLUSIONS: The combination of IDA with HD-MTX showed no obvious therapeutic advantage over HD-MTX monotherapy in newly diagnosed patients with PCNSL. HD-MTX dose of 8 g/m2 monotherapy can still provide better therapeutic benefits in patients with acceptable adverse effects. Future studies could explore HD-MTX in combination with other chemotherapeutic agents in the first-line treatment of PCNSL.

The role of ABCB1 polymorphism as a prognostic marker for primary central nervous system lymphoma.

To investigate the possible role of functional single nucleotide polymorphism (SNP) in circadian genes as prognostic markers of primary central nervous system lymphoma (PCNSL). We conducted a prospective study using data from Huashan Hospital 2006-2015 and followed up 91 PCNSL patients until June 30, 2016. The survival of patients with different prognostic factors was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression. During a long-term follow-up (6-110 months), overall survival (OS) was 32 months (95% CI, 13.3-91.1) and progression-free survival (PFS) was 23 months (95% CI, 9.0-41.0) for the entire cohort. Age (P = 0.046, P = 0.001) and performance status (PS) score (P = 0.013, P = 0.003) showed differences in OS and PFS. ABCB1 rs1045642 variant showed significant difference in PFS between patients with CC genotype and those with CT/TT genotypes (P = 0.020). In multivariate analysis, age (HR = 2.3; 95% CI, 1.2-4.2, P = 0.008), PS (HR = 2.4; 95% CI, 1.3-4.4, P = 0.007), and ABCB1 rs1045642 (HR = 1.9; 95% CI, 1.0-3.3, P = 0.036) were the independent risk factors for PFS. In our results, the most important prognostic factors associated with higher risk of progression were ABCB1 rs1045642 CC genotype, PS > 2, and older age.

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells.

BACKGROUND/AIMS: Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. METHODS: We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. RESULTS: Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. CONCLUSION: Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells.

[Correlation between Expression of Peripheral IL-17 Protein and Aggression of Bipolar Mania].

OBJECTIVE: To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania. METHODS: Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA. RESULTS: The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05). CONCLUSION: Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.

The efficacy of plasma biomarkers in early diagnosis of Alzheimer's disease.

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) is imperative for the prevention of disease progression and the development of effective treatments. OBJECTIVE: Clinically, AD diagnosis has been based on adherence to clinical criteria. It has recently been proposed that diagnostic criteria should also incorporate biomarker findings. However, the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins, needs further research. The current study aimed to investigate the capabilities of the following plasma proteins in the diagnosis of AD and amnesia mild cognitive impairment (aMCI): peripheral interleukin (IL) 10, IL-6, amyloid-ß (Aß) 40, Aß42, phosphorylated tau 181, and total tau. METHODS: In addition to 122 normal control (NC) group, 97 AD patients and 54 aMCI patients were recruited for this study. An enzyme-linked immunosorbent assay was used to analyze the concentration of the following blood plasma biomarkers: IL-10, IL-6, Aß40, Aß42, phosphorylated tau 181, and total tau. RESULTS: A one-way analysis of variance (one-factor analysis of variance) of Aß40 and IL-10 levels revealed a statistically significant difference between the three groups (p < 0.001 and p = 0.020). Using Aß40 ≥ 42.70 pg/ml as the cut-off point, the sensitivity of the ability of Aß40 to discriminate between AD and NC groups was 80.0%, and specificity was 69.6%. CONCLUSIONS: The plasma Aß40 biomarker was able to distinguish between AD and NC groups. However, the plasma biomarkers in the present research were not able to distinguish between aMCI and NC groups.

Designing hard carbon microsphere structure via halogenation amination and oxidative polymerization reactions for sodium ion insertion mechanism investigation.

Hard carbon as a negative electrode material for sodium-ion batteries (SIBs) has great commercial potential and has been widely studied. The sodium-ion intercalation in graphite domains and the filling of closed pores in the low voltage platform region still remain a subject of controversy. We have successfully constructed hard carbon materials with a pseudo-graphitic structure by using polymerizable p-phenylenediamine and dichloromethane as carbon sources. This was achieved by a halogenated amination reaction and oxidative polymerization. It was found that the capacity of hard carbon materials mainly originates from intercalation into graphite domains. The study found that the prepared hard carbon could store 339.33 mAh g-1 of sodium in a reversible way at a current density of 25 mA g-1, and it had an initial coulomb efficiency of 80.23%. It even maintained a reversible sodium storage capacity of 125.53 mAh g-1 at a high current density of 12.8 A g-1. Based on the analysis of hard carbon structure and electrochemical performance, it was shown that the materials conform with an "adsorption-intercalation" mechanism for sodium storage.

Effects of memantine on clinical ratings, fluorodeoxyglucose positron emission tomography measurements, and cerebrospinal fluid assays in patients with moderate to severe Alzheimer dementia: a 24-week, randomized, clinical trial.

Most experts consider that memantine has a symptomatic treatment, but clinical trials have not yet provided compelling evidence to support a disease-modifying effect. We investigate the effects of memantine on clinical ratings; fluorodeoxyglucose positron emission tomography (FDG-PET) measurements, which can monitor disease-modifying effect; and cerebrospinal fluid (CSF) assays in patients with moderate to severe probable Alzheimer disease (AD) dementia. Twenty-two patients completed a 24-week, double-blind, placebo-controlled, randomized clinical trial of memantine, titrated up to 10 mg twice per day using the Severe Impairment Battery, AD Assessment Scale-Cognitive subscale, Mini-Mental State Examination, FDG-PET measurements of the regional cerebral metabolic rate for glucose (CMRgl), and CSF amyloid ß (Aß) and tau assays. An automated brain mapping algorithm and predefined regions of interest were each used to analyze treatment-related regional CMRgl effects. In comparison with the placebo group, the memantine treatment group had significantly less cognitive decline on the Severe Impairment Battery and significantly less CMRgl declines in regions preferentially affected by AD. There were no significant treatment effects on CSF Aß1₋42, CSF Aß1₋40, total tau, or phosphor-tau levels or ratios. This relatively small and brief randomized clinical trial suggests an association between memantine's clinical benefit and its effects on FDG-PET measurements in AD-affected brain regions. Larger and longer studies are needed to confirm these findings, extend them to earlier clinical and preclinical stages of AD, and help determine the extent to which FDG-PET should be qualified for use as a reasonably likely surrogate end point in the evaluation of putative AD-modifying treatments.

Prognostic impact of peripheral natural killer cells in primary central nervous system lymphoma.

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma with a poor prognosis. We aimed to evaluate the prognostic impact of circulating NK cells in PCNSL. Materials and methods: Patients diagnosed with PCNSL who were treated at our institution between December 2018 and December 2019 were retrospectively screened. Patient variables including age, sex, Karnofsky performance status, diagnostic methods, location of lesions, lactate dehydrogenase, cerebrospinal fluids (CSF), and vitreous fluids involvement or not were documented. NK cell count and NK cell proportion (NK cell count/lymphocyte count) in the peripheral blood were evaluated by flow cytometry. Some patients underwent two consecutive NK cell tests before and three weeks after chemotherapy (before the next chemotherapy). The fold change in NK cell proportion and NK cell counts were calculated. CD56-positive NK cells in tumor tissue were assessed by immunohistochemistry. NK cell cytotoxicity assay was performed using flow cytometry. Results: A total of 161 patients with PCNSL were included in this study. The median NK cell count of all NK cell tests was 197.73/µL (range 13.11-1889.90 cells/µL). The median proportion of NK cells was 14.11% (range 1.68-45.15%) for all. Responders had a higher median NK cell count (p<0.0001) and NK cell proportion (p<0.0001) than non-responders. Furthermore, Responders had a higher median fold change in NK cell proportion than non-responders (p=0.019) or patients in complete remission/partial remission (p<0.0001). A higher median fold change in NK cell count was observed in responders than in non-responders (p=0.0224) or patients in complete remission/partial remission (p=0.0002). For newly diagnosed PCNSL, patients with a high NK cell count (>165 cells/µL) appeared to have a longer median overall survival than those with a low NK cell count (p=0.0054). A high fold change in the proportion of NK cells (>0.1957; p=0.0367) or NK cell count (>0.1045; p=0.0356) was associated with longer progression-free survival. Circulating NK cells from newly-diagnosed PCNSL demonstrated an impaired cytotoxicity capacity compared to those from patients with PCNSL in complete remission or healthy donors. Conclusion: Our study indicated that circulating NK cells had some impact on the outcome of PCNSL.

Specific KIR-HLA genotypes predict outcomes in refractory or relapsed primary central nervous system lymphoma.

INTRODUCTION: An effective salvage regimen for the reinduction of remission is lacking for refractory or relapsed primary central nervous system lymphoma (r/r PCNSL). This study aimed to evaluate the efficacy and safety of cytarabine plus temozolomide in treating r/r PCNSL and to explore the associated prognostic factors. METHODS: A single-center retrospective cohort study was conducted to assess the efficacy and safety of cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping was performed on peripheral blood samples. RESULTS: Thirty PCNSL patients receiving an AT regimen (cytarabine 3 g/m2 for 2 days combined with temozolomide 150 mg/m2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25-79 years). A total of 43.4% of patients (13/30) achieved an overall response within a median follow-up of 16 months (95% confidence interval [CI]: 11-23 months). The median PFS and OS of the cohort were 1.5 months (95% CI: 1-4 months) and 19.5 months (95% CI: 11 months to not calculable), respectively. Patients harboring KIR3DL1/HLA-B genotypes predicting low affinity had a higher response rate (p = 0.042) and longer median PFS (3 months) than those with KIR3DL1/HLA-B genotypes predicting high affinity (1 month) (p = 0.0047). Cox regression analysis indicated that KIR/HLA-B genotypes were independently associated with PFS (p = 0.043). However, KIR/HLA-B genotypes had no impact on the OS of the cohort. The toxicity of AT treatment was mild and manageable. CONCLUSION: The AT regimen was well tolerated, and patients with specific KIR-HLA genotypes may benefit from this regimen.

Radiotherapy or chemotherapy: a real-world study of the first-time relapsed and refractory primary central nervous system lymphoma.

Background: Primary central nervous system lymphoma (PCNSL) is an uncommon variant of non-Hodgkin lymphoma (NHL) with high aggressiveness and poor prognosis. Although complete remission (CR) could be achieved with therapy, some patients remain refractory or recurrently with a worse response to salvage treatment and poor prognosis. No consensus on rescue therapy has been established currently. This study is aimed to evaluate the efficacy of radiotherapy or chemotherapy in first-time relapsed or refractory progressed PCNSL (R/R PCNSL) and analysis the prognostic factors, to explore differences between relapsed and refractory PCNSL. Methods: Totally 105 R/R PCNSL patients from Huashan Hospital between 1 January 2016 and 31 December 2020 were enrolled, underwent salvage radiotherapy or chemotherapy and received response assessments after each course. PFS1 was defined as the time from diagnosis to the first time of recurrence or refractory progression. Statistical analysis was performed with SPSS version 26.0. Results: Response and survival were analyzed over a 17.5months (median) follow-up. Compared to relapsed PCNSL (n = 42), refractory PCNSL (n = 63) had a shorter median PFS1 related to deep lesions. 82.4% of cases were discovered as the second relapse or progression. ORR and PFS were both higher in relapsed PCNSL than those in refractory PCNSL. ORR of radiotherapy in both relapsed and refractory PCNSL was higher than that of chemotherapy. Elevated CSF protein and ocular involvement were related to PFS and OS after recurrence respectively in relapsed PCNSL. Age ≥ 60y was unfavorable to OS-R (OS after recurrence or progression) in refractory PCNSL. Conclusions: Our results indicate that relapsed PCNSL responds well to inducing and salvage therapy and has a better prognosis compared to refractory PCNSL. Radiotherapy is effective for PCNSL after the first relapse or progression. Age, CSF protein level, and ocular involvement could be potential factors to predict prognosis.

Cerebrospinal fluid metabolic markers predict prognosis behavior of primary central nervous system lymphoma with high-dose methotrexate-based chemotherapeutic treatment.

Background: Primary central nervous system lymphoma (PCNSL) is a highly aggressive non-Hodgkin's B-cell lymphoma which normally treated by high-dose methotrexate (HD-MTX)-based chemotherapy. However, such treatment cannot always guarantee a good prognosis (GP) outcome while suffering several side effects. Thus, biomarkers or biomarker-based models that can predict PCNSL patient prognosis would be beneficial. Methods: We first collected 48 patients with PCNSL and applied HPLC-MS/MS-based metabolomic analysis on such retrospective PCNSL patient samples. We then selected the highly dysregulated metabolites to build a logical regression model that can distinguish the survival time length by a scoring standard. Finally, we validated the logical regression model on a 33-patient prospective PCNSL cohort. Results: Six metabolic features were selected from the cerebrospinal fluid (CSF) that can form a logical regression model to distinguish the patients with relatively GP (Z score ≤0.06) from the discovery cohort. We applied the metabolic marker-based model to a prospective recruited PCNSL patient cohort for further validation, and the model preformed nicely on such a validation cohort (AUC = 0.745). Conclusions: We developed a logical regression model based on metabolic markers in CSF that can effectively predict PCNSL patient prognosis before the HD-MTX-based chemotherapy treatments.

High-throughput quantitation of amino acids and acylcarnitine in cerebrospinal fluid: identification of PCNSL biomarkers and potential metabolic messengers.

Background: Due to the poor prognosis and rising occurrence, there is a crucial need to improve the diagnosis of Primary Central Nervous System Lymphoma (PCNSL), which is a rare type of non-Hodgkin's lymphoma. This study utilized targeted metabolomics of cerebrospinal fluid (CSF) to identify biomarker panels for the improved diagnosis or differential diagnosis of primary central nervous system lymphoma (PCNSL). Methods: In this study, a cohort of 68 individuals, including patients with primary central nervous system lymphoma (PCNSL), non-malignant disease controls, and patients with other brain tumors, was recruited. Their cerebrospinal fluid samples were analyzed using the Ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) technique for targeted metabolomics analysis. Multivariate statistical analysis and logistic regression modeling were employed to identify biomarkers for both diagnosis (Dx) and differential diagnosis (Diff) purposes. The Dx and Diff models were further validated using a separate cohort of 34 subjects through logistic regression modeling. Results: A targeted analysis of 45 metabolites was conducted using UHPLC-MS/MS on cerebrospinal fluid (CSF) samples from a cohort of 68 individuals, including PCNSL patients, non-malignant disease controls, and patients with other brain tumors. Five metabolic features were identified as biomarkers for PCNSL diagnosis, while nine metabolic features were found to be biomarkers for differential diagnosis. Logistic regression modeling was employed to validate the Dx and Diff models using an independent cohort of 34 subjects. The logistic model demonstrated excellent performance, with an AUC of 0.83 for PCNSL vs. non-malignant disease controls and 0.86 for PCNSL vs. other brain tumor patients. Conclusion: Our study has successfully developed two logistic regression models utilizing metabolic markers in cerebrospinal fluid (CSF) for the diagnosis and differential diagnosis of PCNSL. These models provide valuable insights and hold promise for the future development of a non-invasive and reliable diagnostic tool for PCNSL.

Pemetrexed Plus Lenalidomide for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Prospective Single-Arm Phase II Study.

The prognosis of relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) is dismal, and there are limited treatment options for these patients. This was a prospective single-arm phase II study of combined pemetrexed and lenalidomide for salvage treatment of R/R PCNSL. Patients with R/R PCNSL (n = 38) who had undergone two or more different therapeutic regimens and experienced disease progression or recurrence were enrolled. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patients were followed up for a median of 18 (range, 1-36) months. ORR was 68.4%, with median PFS and OS of 6 and 18 months, respectively. Adverse events (AEs) included myelosuppression, fatigue, nausea, fever, infection, cardiac disease, and thrombogenesis. Commonly observed grade ≥ 3 AEs included neutropenia (5.3%), leukopenia (2.6%), thrombocytopenia (7.9%), and infection (2.6%). Elevated lactate dehydrogenase (LDH) levels (χ2 = 13.25; P = 0.0003) and bulky disease (P = 0.032; χ2 = 4.580) were associated with short PFS. Elevated serum LDH level (P = 0.011; χ2 = 6.560), abnormal lymphoma cells in the cerebrospinal fluid (CSF) [P = 0.011; χ2 = 6.445], and multiple lesions (P = 0.036; χ2 = 4.404) were significantly associated with poorer OS. Abnormal lymphoma cells in the CSF were an independent predictor of poor prognosis on multivariate analysis (P = 0.034; hazard ratio (HR) = 2.836; 95% confidence interval, 1.082-7.434). Our results indicate that pemetrexed plus lenalidomide is effective for heavily treated R/R PCNSL, with moderate toxicity. Trial registration: #ChiCTR1900028070.

Improvement of outcomes of an escalated high-dose methotrexate-based regimen for patients with newly diagnosed primary central nervous system lymphoma: a real-world cohort study.

PURPOSE: High-dose methotrexate (HD-MTX)-based chemotherapy regimen is the first-line treatment of primary central nervous system lymphoma (PCNSL). At present, doses of MTX in the range of 3.5-8 g/m2 are frequently used. However, the optimal dose of methotrexate for PCNSL remains controversial. The purpose of this real-world study was to compare the efficacy and toxicity of HD-MTX in patients with untreated PCNSL. METHODS: Immunocompetent adults with newly diagnosed PCNSL between January 2015 and December 2018 were investigated and followed up to June 2019. All patients' initial treatments were based on HD-MTX chemotherapy regimens. RESULTS: A total of 73 patients were reviewed. For patients who received HD-MTX at 8 g/m2 vs.3.5 g/m2, the complete response (CR) rates were 68.29% vs 43.75% (p = 0.03), and the median PFS times were 17.7 months vs 9.05 months (HR=0.455, 95% CI 0.239-0.865, p=0.016). There was no significant difference in OS between the two groups. Serious adverse effects were uncommon and clinically manageable. CONCLUSION: There is a correlation of treatment response and clinical outcomes between the dosage of MTX in initial induction therapy in newly diagnosed PCNSL. MTX dose of 8 g/m2 provided a higher CR rate and PFS benefits with acceptable adverse effects.

Intermediation of perceived stress between early trauma and plasma M/P ratio levels in obsessive-compulsive disorder patients.

OBJECTIVES: This study is to find the correlation among BDNF metabolism, early trauma, and current stress status of OCD patients. As well as to study the BDNF metabolism-stress related pathological mechanism in OCD development. METHODS: A total of 140 participants were recruited in this study, including 64 drug-naïve OCD patients (OCDs) and 76 healthy controls (HCs). The clinical data of the subjects were measured using YBOCS, CTQ, and PSS. The plasma mBDNF and proBDNF values were measured by ELISA while the M/P ratio was calculated. RESULTS: The mBDNF, proBDNF plasma levels, and M/P ratio of unmedicated OCD individuals decreased evidently comparing with HCs. Also, positive associations were found between PSS and CTQ and between CTQ and M/P ratio. The negative correlation included proBDNF and PSS as well as proBDNF and CTQ. Intermediary analysis generated by SPSS has showed that the perceived stress played a complete mediating role between early trauma and plasma M/P ratio levels, and the mediating effect was 0.043 in non-medication OCD patients. CONCLUSIONS: Findings from this study suggested that early trauma experience and stress state work together in regulating BDNF metabolism level in OCD patients. The nucleus accumbens and reward loop are also pivotal in the pathogenesis of OCD.

Effects of the combination of second-generation antipsychotics on serum concentrations of aripiprazole and dehydroaripiprazole in Chinese patients with schizophrenia.

BACKGROUND: Aripiprazole (ARI) is often prescribed alone or in combination with other second-generation antipsychotics (SGAs) to treat patients with schizophrenia. However, this may increase the potential clinical significance of drug-drug interactions. Therapeutic drug monitoring (TDM) is an important and fundamental tool both when administering ARI alone and in combination with other SGAs to monitor ARI pharmacokinetics, adjust the dosage and thereby achieve more effective and safer treatment. AIMS: This study retrospectively investigated the effects of four SGA comedications (clozapine, risperidone, quetiapine (QTP) and olanzapine) and other potential factors (sex, age and ARI dose) on the serum concentrations of ARI and dehydroaripiprazole (DARI) in Chinese patients with schizophrenia using TDM data. METHODS: High-performance liquid chromatography was used to test the serum concentrations of ARI, DARI and ARI+DARI. In addition, steady-state dose-adjusted serum concentrations (ie, concentration-to-dose ratios, C:D ratios) of ARI, DARI and ARI+DARI; sex; age; ARI dose and SGA comedication dose between 299 inpatients with schizophrenia who received ARI or SGA comedication were all collected and analysed. Spearman's correlation and multiple linear regression analysis were used to evaluate bivariate associations between ARI dose and serum ARI and DARI concentrations and describe the effect of independent variables on serum ARI and DARI concentrations, respectively. RESULTS: There were significant differences in the C:D ratios of ARI (χ2=-3.21, p=0.001) and ARI+DARI (χ2=-2.50, p=0.01) between the ARI and SGA groups, as well as in the C:D ratios of ARI (χ2=-3.59, p<0.001) and ARI+DARI (χ2=-3.10, p=0.002) between the female patients in the two groups. Of the four SGAs, only QTP had significant effects on the C:D ratios of ARI (Z=-4.12, p<0.001) and ARI+DARI (Z=-3.62, p<0.001) when compared with the ARI group in the whole sample and on the C:D ratios of ARI, DARI and ARI+DARI (Z=-3.96, p<0.001; Z=-2.22, p=0.03; Z=-3.75, p<0.001, respectively) in women when compared with their counterparts in the ARI group. CONCLUSION: Comedication with SGAs resulted in lower C:D ratios of ARI and ARI+DARI compared with ARI monotherapy, and comedication with QTP resulted in lower C:D ratios of ARI and ARI+DARI than ARI monotherapy. Despite this statistical significance of our findings, whether the presently observed effect has clinical significance requires exploration by further research. TDM and dosage regulation of ARI should be performed in Chinese inpatients with schizophrenia who are receiving SGA comedication (especially QTP) to maintain a safe and effective dose-adjusted serum concentration of ARI and DARI.

A Preliminary Investigation on Plasma Cell Adhesion Molecules Levels by Protein Microarray Technology in Major Depressive Disorder.

Objectives: Major depressive disorder (MDD) is a serious mental disorder, and there is a great difficulty to diagnose and treat. Hitherto, relatively few studies have explored the correlation between the levels of plasma cell adhesion molecules and MDD. Methods: Thirty outpatients with acute episodes of MDD in Shanghai Mental Health Center and 34 healthy volunteers from the community were recruited as subjects. Protein microarray technology was applied to compared the differences in plasma levels of 17 kinds of adhesion molecular proteins between the two groups. Meanwhile, the diagnostic value of different proteins in depression was discussed by using the receiver operating characteristic curve. Results: The levels of Carcinoembryonic Antigen Related Cell Adhesion Molecule-1(CEACAM-1) and Neural Cell Adhesion Molecule (NrCAM) in MDD patients were significantly higher than those in healthy controls (P < 0.05). The area under ROC curve of CEACAM-1 combined with NrCAM was 0.723, with the sensitivity 0.800 and the specificity 0.676. Conclusion: The plasma levels of CEACAM-1 and NrCAM were significantly up-regulated in MDD, and their combined application was of potential diagnostic value, deserving to expand the sample size for further verification.

High Level of IL-10 in Cerebrospinal Fluid is Specific for Diagnosis of Primary Central Nervous System Lymphoma.

PURPOSE: The pathological diagnosis of primary central nervous system lymphoma (PCNSL) by stereotactic brain biopsy and craniotomy is not often applicable due to the high cost and associated complications. In recent years, some biomarkers in cerebrospinal fluid (CSF), including interleukin 10 (IL-10), microRNAs, CXC chemokine ligand 13 (CXCL13), have been reported to be associated with PCNSL. However, this conclusion was controversial. Therefore, this study was to test whether Th17 cell-related cytokines could be used to distinguish PCNSL from other brain tumors. PATIENTS AND METHODS: Th17 cell-related cytokines in CSF were measured in 108 patients with intracranial tumors, which included 66 PCNSL patients and 42 patients with other types of brain tumors. A receiver-operating characteristic (ROC) curve was utilized to analyze the diagnostic value of the cytokines based on the area under the curve (AUC). RESULTS: The CSF IL-10 level and IL-10/IL-6 ratios were significantly higher in PCNSL than in the other brain tumors (58.2 pg/mL VS 1.5 pg/mL, p=0.001; 24.3 VS 0.6, p=0.001). When the cutoff level of IL-10 was set at 8.3 pg/mL, its sensitivity and specificity for diagnosing PCNSL were 59.0% and 98%, respectively. The CSF IL-10 levels over 5pg/mL (+LR 12.3) were of significant value for the diagnosis of PCNSL. These parameters are highly valuable in PCNSL diagnosis, but their sensitivity is less valuable. The sensitivity of IL-4 and IL-17A, the ratio of mature lymphocytes and the monocytes/macrophages ratio in CSF were relatively high. In combination, the sensitivity increased by 15% and the specificity remained above 85%. The best combination was IL-10 and IL-17A, whose sensitivity was 70% and specificity was 96%. CONCLUSION: The CSF level of IL-10 is a useful diagnostic biomarker in patients with PCNSL. The CSF levels of IL-4, IL-17A, mature lymphocytes and monocytes/macrophages can be used to increase the diagnostic value of CSF IL-10 level and IL-10/IL-6 ratio.

Curative effect of methotrexate combined with teniposide in the treatment of primary central nervous system lymphoma.

The present study aimed to investigate the curative effect of high-dose methotrexate (HD-MTX) combined with teniposide (Vm26) vs. HD-MTX alone in the treatment of primary central nervous system lymphoma (PCNSL), in order to provide data for assisting decisions associated with clinical treatment. Data from 56 patients with PCNSL admitted in Shanghai Huashan Hospital (Shanghai, China) from January 2009 to December 2014 were included into the present study. Clinical data, curative effects and prognosis of patients in these two groups were retrospectively analyzed using SPSS 20 statistical software. In the HD-MTX+Vm26 group, 12 patients (42.85%) achieved complete remission (CR) and 10 patients (35.71%) achieved partial remission (PR), while in the HD-MTX group 7 patients (25%) achieved CR and 11 patients (39.29%) achieved PR (P=0.158). The median progression-free survival (PFS) time was 22 months in the HD-MTX+Vm26 group and 12 months in the HD-MTX group (P=0.019). The median overall survival time was 57 months in the HD-MTX+Vm26 group, and 28 months in the HD-MTX group (P=0.013). Compared with HD-MTX alone, the combined treatment of HD-MTX+Vm26 had an improved curative effect in the treatment of PCNSL, effectively controlled tumor progression in patients, prolonged survival time and improved prognosis. Age was an independent prognostic factor in patients with PCNSL. Patients with an age of ≤60 years exhibited longer PFS compared with patients with an age of >60 years.