Prevalence and genotype/subtype distribution of Enterocytozoon bieneusi and Blastocystis in donkeys in Shanxi Province, north China.

Enterocytozoon bieneusi and Blastocystis may cause diarrhea in humans and various animals. However, little information is available regarding the prevalence and genetic diversity of E. bieneusi and Blastocystis in donkeys. To fill this gap, we molecularly assessed E. bieneusi and Blastocystis in fecal samples from donkeys (n = 815) in Shanxi Province, north China. The overall prevalence of E. bieneusi and Blastocystis in donkeys was 8.1% and 0.2%, respectively. Region and age were risk factors associated with E. bieneusi infection in donkeys. Three internal transcribed spacer (ITS) genotypes of E. bieneusi were identified in the current study, including two previously described genotypes (D and Henan-IV) and one novel genotype (named SXD1). Of which, genotype D was found to be the most prevalent. Phylogenetic analysis demonstrated that the three genotypes belonged to group 1, implying a potential of zoonotic transmission. Multilocus sequence typing showed that 19, 15, 13, and 22 types were identified at the loci MS1, MS3, MS4, and MS7, respectively, forming six multilocus genotypes (MLGs) distributed in the genotype D. One Blastocystis subtype (ST33) was identified, which has previously been reported only in horses. This is the first molecular-based description of E. bieneusi and Blastocystis infections in donkeys in Shanxi Province, north China, contributing to a better understanding of transmission dynamics and molecular epidemiological characteristics of the two intestinal protozoa.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Neurological soft signs precede the onset of schizophrenia: a study of individuals with schizotypy, ultra-high-risk individuals, and first-onset schizophrenia.

Neurological soft signs (NSS) are one of the biomarkers for schizophrenia spectrum disorders. However, a few studies have examined the prevalence of NSS across the schizophrenia spectrum. The present study adopted a quasi-longitudinal study design and examined the prevalence of NSS and their associations with clinical and behavioural manifestations in participants in different stages of the illness. The abridged version of the Cambridge Neurological Inventory was administered to 39 patients with the first-episode schizophrenia, 39 individuals with ultra-high risk (UHR) for psychosis, 39 individuals with schizotypy, and 39 healthy controls. Patients with the first-episode schizophrenia had a higher prevalence of NSS in motor coordination than healthy controls as well as individuals with UHR and schizotypy. Individuals with UHR exhibited a higher prevalence of sensory integration items than individuals with schizotypy and healthy controls. Discriminant analysis classified the membership of the individuals correctly across the spectrum with an accuracy of up to 60.9%. In particular, NSS could discriminate individuals with UHR from healthy controls at up to 85.9% accuracy. These findings suggest that NSS are robust biomarkers to detect and discriminate individuals in different stages of the schizophrenia spectrum from healthy controls.

mRNA 5-methylcytosine in Eimeria tenella oocysts: An abundant post-transcriptional modification associated with broad-ranging biological processes.

Eimeria tenella is the major causative agent of chicken coccidiosis. 5-Methylcytosine (m5C) is a type of RNA chemical modifications reported to regulate diverse biological processes. However, the distribution and biological functions of m5C in E. tenella mRNAs are yet to be known. Herein, we report transcriptome-wide profiling of mRNA m5C in E. tenella by employing m5C RNA immunoprecipitation followed by a deep-sequencing approach (m5C-RIP-seq). Our data showed that m5C peaks were distributed across the whole mRNA body. Compared with unsporulated oocysts, there were 2813 hypermethylated and 1850 hypomethylated m5C peaks in sporulated oocysts. Generally, a positive correlation between m5C modification and gene expression levels was observed. The mRNA sequencing (RNA-seq) and m5C-RIP-seq data were consistent with the results of the quantitative reverse transcription PCR (RT-qPCR) and methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), respectively. Gene Ontology (GO) and pathway enrichment analysis predicated diverse biological functions and pathways, including microtubule motor activity, helicase activity, cGMP-PKG signaling pathway, aminoacyl-tRNA biosynthesis, glycolysis/gluconeogenesis, and spliceosome. Meanwhile, stage-specific gene expression signatures of m5C-related regulators were observed. Altogether, our findings reveal the transcriptional significance of m5C modification in E. tenella oocysts, providing resources and clues for further in-depth research.

Associations between cytokine levels and cognitive function among individuals at clinical high risk for psychosis.

OBJECTIVE: To explore the intricate interplay among cytokines, cognitive functioning, and conversion to psychosis in individuals at clinical high-risk (CHR) for psychosis. METHOD: We initially enrolled 385 individuals at CHR and 95 healthy controls (HCs). Subsequently, 102 participants at CHR completed the 1-year follow-up assessments, and 47 participants transitioned to psychosis. We assessed the levels of interleukins (IL-1ß, IL-2, IL-6, IL-8, IL-10), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). We comprehensively evaluated cognitive performance across six domains, including speed of processing (SP), attention/vigilance (AV), working memory (WM), verbal learning (VeL), visual learning (ViL), and reasoning and problem-solving (RPS). RESULTS: Higher baseline cognitive domain scores were associated with elevated GM-CSF and reduced VEGF levels. In the follow-up analysis, significant time effects were observed for IL-1ß and IL-2. We also observed significant interaction effects between specific cognitive domains (AV, WM, VeL, and OCS) and levels of cytokine (GM-CSF, IL-1ß, IL-6, and TNF-α). Changes in WM were negatively correlated with changes in TNF-α levels and positively correlated with changes in VEGF levels. Variations in VeL were inversely correlated with changes in GM-CSF and IL-10 levels, whereas changes in RPS were positively associated with changes in GM-CSF and IL-8 levels. CONCLUSIONS: Our results revealed intricate associations among cytokine levels, cognitive performance, and psychosis progression.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Symptom Dimensions and Cognitive Impairments in Individuals at Clinical High Risk for Psychosis.

OBJECTIVE: Understanding the intricate relationship between symptom dimensions, clusters, and cognitive impairments is crucial for early detection and intervention in individuals at clinical high-risk(CHR) for psychosis. This study delves into this complex interplay within a CHR sample and aims to predict the conversion to psychosis. METHODS: A comprehensive cognitive assessment was performed among 744 CHR individuals. The study included a three-year follow-up period to assess conversion to psychosis. Symptom profiles were determined using the Structured Interview for Prodromal Syndromes. By applying factor analysis, symptom dimensions were categorized as dominant negative symptoms(NS), positive symptoms-stressful(PS-S), and positive symptoms-odd(PS-O). The factor scores were used to define three dominant symptom groups. Latent class analysis(LCA) and factor mixture model(FMM) were employed to identify discrete clusters based on symptom patterns. The three-class solution was chosen for the LCA and FMM analysis. RESULTS: Individuals in the dominant NS group exhibited significantly higher conversion rates to psychosis than those in the other groups. Specific cognitive variables, including performance in the Brief Visuospatial Memory Test-Revised(Odd ratio, OR=0.702, p=0.001) and Neuropsychological Assessment Battery mazes(OR=0.776, p=0.024), significantly predicted conversion to psychosis. Notably, cognitive impairments associated with NS and PS-S affected different cognitive domains. LCA- and FMM-Cluster 1, characterized by severe NS and PS-O, exhibited more impairments in cognitive domains than other clusters. No significant difference in the conversion rate was observed among LCA and FMM clusters. CONCLUSIONS: These findings highlight the importance of NS in the development of psychosis and suggest specific cognitive domains that are affected by symptom dimensions.

Childhood maltreatment profile in a clinical population in China: a further analysis with existing data of an epidemiologic survey.

To determine the lifetime prevalence and diverse profiles of types of childhood maltreatment (CM) in a high-risk clinical sample using standardized assessment tools (Child Trauma Questionnaire, CTQ) in China, Shanghai, 2090 subjects were sampled from the Shanghai Mental Health Centre. Personality disorder (PD) was assessed using the Personality Diagnostic Questionnaire (PDQ-4+) and subjects were interviewed using the Structured Clinical Interview (SCID-II). CTQ was used to assess CM in five domains (emotional abuse, EA; physical abuse, PA; sexual abuse, SA; emotional neglect, EN; and physical neglect, PN). The prevalence estimate of EA in the sample is 22.2%, followed by 17.8% of PA, and 12.5% of SA. The prevalence estimate was more frequent in PN (65.0%) and in EN (34.0%) than in childhood abuse (EA, PA and SA). It seems that males reported more PA and females reported more SA, the older subjects reported more neglect and the younger subjects reported more abuse. There was a higher prevalence of EA and SA in borderline PD patients (44.4%, 22.5%), PA in antisocial PD patients (38.9%). Multi-PD patients reported more forms of CM in childhood. Additionally, factor analysis of CTQ items confirmed factorial validity by identifying a five-factor structure that explained 50% of the total variance. These findings support the view that prevalence of CM was commonly experienced in clinical population during their childhood, especially for subjects with PDs. Factorial validity in PN needs to be further improved, and can in part be culturally explained.

Seroprevalence of Toxoplasma gondii infection in sheep and cattle in Shanxi Province, North China.

Toxoplasmosis is a worldwide zoonotic disease caused by infection with the intracellular protozoan parasite Toxoplasma gondii, posing significant economic losses to the livestock industry. As a major livestock province, little is known of the prevalence of T. gondii infection in sheep and cattle in Shanxi Province, North China. In this study, a total of 1962 blood samples from cattle (n = 978) and sheep (n = 984), collected from 11 administrative cities in Shanxi Province, were examined for antibodies against T. gondii by using the indirect enzyme linked immunosorbent assay (ELISA) kits commercially available. The results showed that antibodies to T. gondii were detected in 306 of the 978 cattle serum samples (31.29%, 95% CI 28.38-34.19), ranging from 12.64% to 60.00% among the different cities. The overall seroprevalence of T. gondii in sheep was 17.78% (175/984, 95% CI 15.40-20.17), ranging from 2.22% to 41.11% among the different administrative cities. The T. gondii seroprevalence was associated with the management mode and geographical location. This is the first report of T. gondii seroprevalence in cattle and sheep in Shanxi Province, North China, which provides baseline data to plan future control strategies for T. gondii infection in this province.

Prevalence and Multilocus Genotyping of Giardia duodenalis in Donkeys in Shanxi Province, North China.

Giardia duodenalis is a ubiquitous flagellated protozoan, causing significant economic losses to animal husbandry and posing threats to public health. China ranks the world's sixth largest major producer of donkeys, rearing approximately 2.6 million donkeys in 2019, but limited investigation of G. duodenalis prevalence has been conducted in the past, and it is yet to be known whether donkeys in Shanxi Province are infected with G. duodenalis. In the present study, a total of 815 fecal samples collected from donkeys in representative regions of Shanxi Province, North China, were examined for G. duodenalis using nested PCR. Then, the assemblages and multilocus genotypes (MLGs) were examined based on three established loci: namely, ß-giardin (bg), triosephosphate isomerase (tpi), and glutamate dehydrogenase (gdh). The overall prevalence of G. duodenalis in donkeys in Shanxi Province was 16.81% (137/815). The region was identified as the main risk factor for the observed difference in G. duodenalis prevalence in donkeys among the three study areas (χ2 = 21.611, p < 0.001). Assemblages A, E, and B were identified, with the latter as the predominant assemblage. Three MLGs (MLG-novel-1 to 3) were formed based on sequence variation among the three loci. The present study reveals the presence of G. duodenalis in donkeys in Shanxi Province, North China, for the first time, which not only enriches the data on the distribution of G. duodenalis in donkeys in China but also provides useful baseline data for planning control strategies against G. duodenalis infection in the sampled areas.

[The preparation and kinetic study on enzymatically-controlled drug release of isotretinoin/amylose inclusion complex].

The inclusion complex of isotretinoin was prepared by sealed-control temperature method and amylose was used as carrier. The formation of inclusion complex was confirmed by powder X-ray diffraction and DSC. The equation of enzymatically-controlled drug release was established by kinetic theory, and the release characteristic of drug was confirmed by using the kinetic equation. The results show that the drug release was attributed to first order reaction without alpha-amylase. However, with alpha-amylase, the drug release was an acceleration process by the effect of both dissociation and enzymatic hydrolysis simultaneously. The research indicates that drug release from the inclusion complex was modulated by the addition of alpha-amylase.

Imbalance Model of Heart Rate Variability and Pulse Wave Velocity in Psychotic and Nonpsychotic Disorders.

OBJECTIVES: Patients with psychiatric disorders have an increased risk of cardiovascular pathologies. A bidirectional feedback model between the brain and heart exists widely in both psychotic and nonpsychotic disorders. The aim of this study was to compare heart rate variability (HRV) and pulse wave velocity (PWV) functions between patients with psychotic and nonpsychotic disorders and to investigate whether subgroups defined by HRV and PWV features improve the transdiagnostic psychopathology of psychiatric classification. METHODS: In total, 3448 consecutive patients who visited psychiatric or psychological health services with psychotic (N = 1839) and nonpsychotic disorders (N = 1609) and were drug-free for at least 2 weeks were selected. HRV and PWV indicators were measured via finger photoplethysmography during a 5-minute period of rest. Canonical variates were generated through HRV and PWV indicators by canonical correlation analysis (CCA). RESULTS: All HRV indicators but none of the PWV indicators were significantly reduced in the psychotic group relative to those in the nonpsychotic group. After adjusting for age, gender, and body mass index, many indices of HRV were significantly reduced in the psychotic group compared with those in the nonpsychotic group. CCA analysis revealed 2 subgroups defined by distinct and relatively homogeneous patterns along HRV and PWV dimensions and comprising 19.0% (subgroup 1, n = 655) and 80.9% (subgroup 2, n = 2781) of the sample, each with distinctive features of HRV and PWV functions. CONCLUSIONS: HRV functions are significantly impaired among psychiatric patients, especially in those with psychosis. Our results highlight important subgroups of psychiatric patients that have distinct features of HRV and PWV which transcend current diagnostic boundaries.

Heterogenous Subtypes of Late-Life Depression and Their Cognitive Patterns: A Latent Class Analysis.

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptom profiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group. Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences. Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with the membership in the "pessimistic" group. Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance.

Attenuated and delayed niacin skin flushing in schizophrenia and affective disorders: A potential clinical auxiliary diagnostic marker.

AIM: Schizophrenia and affective disorders all show high heterogeneity in clinical manifestations. A lack of objective biomarkers has long been a challenge in the clinical diagnosis of these diseases. In this study, we aimed to investigate the performance of niacin skin flushing in schizophrenia and affective disorders and determine its clinical potential as an auxiliary diagnostic marker. METHODS: In this case-control study, niacin skin-flushing tests were conducted in 613 patients (including 307 schizophrenia patients, 179 bipolar disorder patients, and 127 unipolar depression patients) and 148 healthy controls (HCs) with a modified method. Differences in niacin skin-flushing responses were compared with adjustment for gender, BMI, age, nicotine dependence, alcohol consumption and educational status. A diagnostic model was established based on a bivariate cut-off. RESULTS: Schizophrenia and affective disorders showed similar performance of niacin bluntness, characterized by attenuated flushing extent and reduced flushing rate. An innovative bivariate cut-off was established according to these two features, by which we could identify -patients with either schizophrenia or affective disorders from HCs with a sensitivity of 55.28%, a specificity of 83.56% and a positive predictive value of 93.66%. CONCLUSIONS: The niacin-induced skin flushing was prevalently blunted in patients with schizophrenia or affective disorders, indicating a promising potential as an auxiliary diagnostic marker in risk prediction and clinical management of these disorders. Additionally, the niacin-blunted subgroup implies a common biological basis in the investigated disorders, which provokes new thoughts in elucidating the pathological mechanisms.

[Experimental study on sensory gating in generalized anxiety and obsessive compulsive disorders].

OBJECTIVE: To observe the characteristics of sensory gating P50 in generalized anxiety disorder (GAD) and in obsessive compulsive disorder (OCD) patients. METHODS: Auditory evoked potentials P50 were recorded in 41 GAD patients, 69 OCD patients and in 58 normal controls by the conditioning/testing paradigm presented with auditory double clicks stimuli, using American Nicolet Bravo instrument. RESULTS: (1) No significant differences was found in latencies of S1-P50 and S2-P50 among these three groups (P > 0.05). (2) Significant differences were found in indices of S1-P50 amplitudes (NC: 6 +/- 3, GAD: 3 +/- 2, OCD: 5 +/- 3, P < 0.01), S2-P50 amplitudes (NC: 2 +/- 1, GAD: 4 +/- 1, OCD: 2 +/- 1, P < 0.01), S2/S1, S1-S2 and 100(1-S2/S1). (3) Compared with NC, GAD and OCD patients showed a decreased S1-P50 amplitude and OCD patients also showed an increased S2-P50 amplitude. (4) P50 inhibition significantly decreased in GAD and OCD patients. The values of S2/S1 ratio were 39% +/- 22% in NC, 50% +/- 29% in GAD and 88% +/- 42% in OCD (P < 0.01). (5) Both S1-S2 and 100 (1-S2/S1) decreased in GAD and OCD patients (NC: 3 +/- 2, 61 +/- 22; OCD: 1 +/- 1, 15 +/- 22; GAD: 3 +/- 3, 50 +/- 29. P < 0.01). (6) Compared with GAD, OCD patients showed a lower S2/S1 ratio (P < 0.01) and a higher value of S1-S2 (P < 0.01) and 100 (1-S2/S1) (P < 0.01). CONCLUSION: The anxiety disorder patients has sensory gating deficits. The inhibition deficit can be measured by auditory evoked potential P50. And S2/S1 ratio, S1-S2 and 100(1-S2/S1) may be biological markers of GAD and OCD patients.

MiRNA-506 presents multiple tumor suppressor activities by targeting EZH2 in nasopharyngeal carcinoma.

OBJECTIVE: MiR-506 has been reported to be associated with multiple malignancies, but its roles in nasopharyngeal cancer (NPC) are not fully understood. Our objective is to demonstrate its effects on NPC and the underlying mechanisms. METHODS: Totally fifteen pairs of NPC and adjacent non-tumorous tissues were collected for the detection of miR-506 and enhancer of zeste homolog 2 (EZH2) expression. Dual luciferase reporter assay was employed for verifying the relationship between miR-506 and EZH2. The flow cytometry and MTT assays were employed to explore the effects of miR-506 and EZH2 on the cell apoptosis and proliferation, respectively. Wound closure and transwell assays were used to evaluate the cell migration and invasion abilities. Western blotting or RT-qPCR assays were applied to detect the alterations of miR-506, EZH2 and epithelial-mesenchymal transition (EMT)-related markers. Morphological changes of cells with EMT were assessed by light microscopy. RESULTS: MiR-506 was significantly decreased and EZH2 was obviously increased in NPC tissues. Overexpression of miR-506 decreased the EZH2 level, promoted apoptosis, inhibited proliferation, invasion and migration of NPC cells. Accordingly, miR-506 overexpression attenuated EMT process of NPC cells as demonstrated by the alterations of EMT-related markers and the morphological changes. In addition, the luciferase assay proved that miR-506 directly targeted EZH2. Furthermore, the overexpression of EZH2 reversed the tumor-suppressive effects induced by miR-506 mimics. CONCLUSION: MiR-506 acted as a tumor suppressor to promote apoptosis and inhibit invasion and migration via directly targeting EZH2. MiR-506 can be a candidate target for gene therapy against NPC.

Class I hysterectomy in stage Ia2-Ib1 cervical cancer.

INTRODUCTION: During the last 3 decades, the standard treatment for stage Ia2-Ib1 cervical cancer has been Piver-Rutledge class II or III radical hysterectomy. However, this surgery is associated with a high rate of urologic morbidity. AIM: To determine the efficacy of class I radical hysterectomy compared with class III radical hysterectomy in terms of morbidity, overall survival, and patterns of relapse in patients with Ia2-Ib1 cervical cancer undergoing primary surgery. MATERIAL AND METHODS: A total of 101 patients with stage Ia2-Ib1 cervical cancer < 2 cm were randomized to class I and class III hysterectomy groups. Clinical, pathologic, and follow-up data were prospectively collected. Univariate analysis was carried out. Of the total patients, 45 were randomized to class I surgery and 56 to class III surgery. No significant differences were observed in terms of pathologic findings or adjuvant treatment (p > 0.05). The morbidity rates were higher after class III surgery. RESULTS: The difference in recurrence rate between the class I and class III groups was not statistically significant (p > 0.05). The 5-year overall survival rate was 93% and 91%, respectively (p > 0.05). There were no significant differences in terms of recurrence rate or overall survival among patients with stage Ia2-Ib1 cervical cancer < 2 cm who underwent class I or radical (class III) hysterectomy. Morbidity was proportional to the extent of radicality. CONCLUSIONS: These data confirm the need for reducing surgical radicality in the treatment of patients with early cervical cancer, by tailoring the extent of resection according to the extent of disease.

Effectiveness of Traditional Chinese Medicineas as an Adjunct Therapy for Refractory Schizophrenia: A Systematic Review and Meta Analysis.

Although recent studies focused on traditional Chinese medicine (TCM) for the treatment of refractory schizophrenia have reported that it may be beneficial, there is still lack of convincing evidence and critical meta-analytic work regarding its effectiveness as an adjunctive therapy. Therefore, we performed a meta-analysis to investigate the effectiveness of TCM in combination with antipsychotics for refractory schizophrenia. Fourteen articles involving 1725 patients published as of December 2016 were included which compared antipsychotic therapies to either TCM alone, or TCM as an adjunctive therapy. TCM was observed to have beneficial effects on aspects of the Positive and Negative Syndrome Scale (PANSS) including total score changes and negative score changes, as well as clinical effects estimated with PANSS or the Brief Psychiatric Rating Scale (BPRS). The changes in extrapyramidal side effects (RSESE) scores from baseline to the end of the treatment period were similar in two groups of related trials. TCM was also reported to mitigate some anti-psychotic related side-effects and overall, TCM adjuvant therapy was generally safe and well tolerated. While, the results indicated the potential utility of TCM as an alternative adjunctive therapeutic for refractory schizophrenia treatment, there remains a need for further high-quality studies.

In vitro and in vivo evaluation of hypothermia on pharmacokinetics and pharmacodynamics of nimodipine in rabbits.

Objective To investigate the effect of hypothermia on the pharmacokinetics and pharmacodynamics of nimodipine in rabbits using in vivo and in vitro methods. Methods Five healthy New Zealand rabbits received a single dose of nimodipine (0.5 mg/kg) intravenously under normothermic and hypothermic conditions. Doppler ultrasound was used to monitor cerebral blood flow, vascular resistance, and heart rate. In vitro evaluations of protein binding, hepatocyte uptake and intrinsic clearance of liver microsomes at different temperatures were also conducted. Results Plasma concentrations of nimodipine were significantly higher in hypothermia than in normothermia. Nimodipine improved cerebral blood flow under both conditions, but had a longer effective duration during the hypothermic period. Low temperature decreased the intrinsic clearance of liver microsomes, with no change in protein binding or hepatocyte uptake of nimodipine. Conclusion Nimodipine is eliminated at a slower rate during hypothermia than during normothermia, mainly due to the decreased activity of cytochrome P450 enzymes. This results in elevated system exposure with little enhancement in pharmacological effect.