Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.

BACKGROUND: Rifapentine is a rifamycin with unique bactericidal activity against Mycobacterium tuberculosis. It is also a potent inducer of CYP3A activity. However, the duration of rifapentine-induced hepatic enzyme activity after withdrawal is unclear. CASE REPORT: We report a case of a patient with Aspergillus meningitis treated with voriconazole after discontinuing rifapentine. Within ten days of rifapentine discontinuation, serum levels of voriconazole failed to reach the effective treatment range. CONCLUSIONS: Rifapentine is a potent inducer of hepatic microsomal enzymes. The induction of hepatic enzymes may exceed ten days after rifapentine discontinuation. Clinicians should be reminded of residual enzyme induction by rifapentine, especially when treating critically ill patients.

Insight into different host range of three planthoppers by transcriptomic and microbiomic analysis.

Brown planthopper (BPH), white-backed planthopper (WBPH) and small brown planthopper (SBPH), are the closely related rice pests that perform differentially on wheat plants. Using fecundity as a fitness measure, we found that SBPH well-adapted on wheat plants, followed by WBPH, while BPH had the worst performance. The transcriptomic responses of SBPH and BPH to wheat plants have been compared previously. To understand the different fitness mechanisms of three planthoppers, this study first investigated the transcriptomic responses of WBPH to rice and wheat plants. Genes involved in detoxification, transportation and proteasome were significantly enriched in WBPH in response to different diets. Moreover, comparative analysis demonstrated that most co-regulated genes in BPH and SBPH showed different expression changes; whereas most co-regulated genes in BPH and WBPH exhibited similar expression changes. Subsequently, this study also investigated the influences of host plants on the bacterial community of three planthoppers. The three planthoppers harboured distant diversity of bacterial communities. However, there was no dramatic change in bacterial diversity or relative abundance in planthoppers colonized on different hosts. This study illustrates generic and species-specific changes of three rice planthoppers in response to different plants, which deepen our understanding towards the host fitness for planthopper species.

Inhibition of CACNA1H can alleviate endoplasmic reticulum stress and reduce myocardial cell apoptosis caused by myocardial infarction.

OBJECTIVE: In recent years, coronary heart disease (CHD) has become a disease that cannot be ignored by residents of our country, because CHD will not only endanger people's quality of life, but also threaten their lives. Therefore, this research mainly explores the correlation between myocardial infarction (MI) with endoplasmic reticulum (ER) stress and apoptosis. MATERIALS AND METHODS: First, we constructed a model of myocardial ischemia and hypoxia (I/H) in vivo and in vitro, and examined the change of CACNA1H expression. At the same time, in order to research the role of CACNA1H, we chose CACNA1H-specific inhibitor ABT-639 to next research and detect changes in heart injury by detecting changes in creatine kinase (CK) content and lactate dehydrogenase (LDH) activity. Next, we used TUNEL staining and immunofluorescence staining to detect changes in apoptosis and ER stress, and analyzed changes in ER stress and apoptotic pathway expression by Western blotting and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: At 28 days after MI, the cardiac function of the mice was significantly reduced, the myocardial cell apoptosis rate was dramatically increased, and CACNA1H expression was dramatically increased in vivo and in vitro. In addition, we treated the model group with the ABT-639, and found that ABT-639 can partially protect myocardial function and relieve myocardial cell apoptosis. At the same time, ABT-639 may reduce H9c2 injury after I/H by reducing the degree of ER stress, because we found that the use of ABT-639 can dramatically reduce ER stress-related factors expression, and can inhibit the expression of apoptosis-related factors Caspase-3 and Caspase-9. CONCLUSIONS: The CACNA1H inhibitor ABT-639 can alleviate myocardial cell apoptosis caused by MI by reducing the ER stress response.

Functional studies of left atrium and BNP in patients with paroxysmal atrial fibrillation and the prediction of recurrence after CPVA.

OBJECTIVE: This study was aimed to observe the significance of the left atrium (LA) functional index combined with B-type natriuretic peptide (BNP) level in predicting recurrence in patients with paroxysmal atrial fibrillation (PAF) after circumferential pulmonary vein ablation (CPVA). Real-time three-dimensional echocardiography (RT-3DE) was used to observe the structural and functional changes of LA in patients with PAF after CPVA. BNP is a hemodynamic indicator of myocardial stretching increase in atrial fibrillation (AF) patients. PATIENTS AND METHODS: 243 patients with PAF who intended to undergo CPVA were selected in the study, and the following clinical data of the patients were collected. Firstly, the blood BNP levels measured before CPVA. Secondly, the measurements of routine echocardiography before CPVA. RT-3DE was used to obtain the time-volume curve of LA. Then, multivariate logistic regression analysis was used to analyze the factors affecting PAF recurrence after CPVA. Finally, we obtained the receiver operating characteristic (ROC) curve of PAF recurrence predicted by the independent risk factors. RESULTS: A total of 233 AF patients with an average age of 63.1 ± 9.3 years (range, 39-75 years; male: female =195: 38) underwent CPVA. 42 patients had AF recurrence (18.0%) during 3-6months follow-up after an operation blanking period of 3 months, BNP in the Recurrence Group was higher than that in Sinus Rhythm Group (p≤0.001). The preoperative left minimum volume index (LAVImin), left atrial volume index before contraction (LAVIpre-a) were higher in Recurrence Group than in Sinus Rhythm Group (p≤0.001). Expansion index, Diastolic emptying index (DEI), Passive emptying index (PEI), Active emptying index (AEI) were lower in the Recurrence Group than in the Sinus Rhythm Group (p≤0.001). Logistic regression analyses showed that BNP and DEI were independent predictors for PAF recurrence (OR=1.004, 95% CI: 1.01-1.07, p=0.001; OR=0.655, 95% CI: 0.57-0.75, p=0.001). The AUC of BNP, DEI and combined index for recurrence of CPVA were higher than LAVImax (p range: 0.001-0.013). CONCLUSIONS: In patients with PAF treated with CPVA, the impaired DEI of LA reservoir function and increased BNP may be useful predictors of PAF recurrence.

Association between expression of AMPK pathway and adiponectin, leptin, and vascular endothelial function in rats with coronary heart disease.

OBJECTIVE: The aim of this study was to explore the association between the expression of adenosine monophosphate-activated protein kinase (AMPK) pathway and adiponectin (APN), leptin, and vascular endothelial function in rats with coronary heart disease (CHD). MATERIALS AND METHODS: Experimental rats were divided into three groups, including: control (Col) group, CHD model (CHD) group, and CHD+AMPK activator (CHD+AICAR) group. Except those in Col group, all rats were fed with high-fat diet and intraperitoneally injected with pituitrin to establish the CHD model. The levels of serum APN, leptin, and endothelin-1 (ET-1) were determined via enzyme-linked immunosorbent assay (ELISA). The content of serum nitric oxide (NO) was detected using the nitrate reductase method. Meanwhile, the expression of AMPK pathway-related protein AMPKα in vascular endothelial tissues was detected via Western blotting (WB). Aortic vascular endothelial cells (VECs) were cultured with AICAR or ET-1 in vitro. Subsequently, the expressions of AMPK pathway and protein kinase B (AKT) pathway-related proteins were determined through co-immunoprecipitation and WB. Moreover, the expression level of NO in VECs was determined using the DAF-FM DA fluorescence probe. RESULTS: Compared with Col group, CHD group showed significantly decreased levels of serum APN and NO (p<0.05), significantly increased the levels of leptin and ET-1 (p<0.05), as well as remarkably decreased protein expression of p-AMPKα in vascular endothelial tissues (p<0.05). After injection of AMPK activator AICAR (200 mg/kg), the protein expression of p-AMPKα in CHD rats was significantly activated (p<0.05). The levels of serum APN and NO were remarkably upregulated (p<0.05), while the levels of leptin and ET-1 were significantly reduced (p<0.05). Besides, AICAR could evidently activate the activity of AMPK pathway in VECs in vitro, upregulate the protein levels of p-eNOS (Ser1177) and p-AMPKα, and promote the secretion of NO (p<0.05). In addition, AICAR remarkably inhibited ET-1-induced expression of AKT pathway (p<0.05). CONCLUSIONS: Activating the AMPK pathway may play a positive role in the normal function of VECs and exert a certain curative effect on CHD in rats.

Studying biological science does not lead to adoption of a healthy lifestyle.

AIMS: The lifestyle and physical activity (PA) habits of young people play a key role in the prevention of cardiovascular and metabolic diseases at older ages. The current generation of biological science students at university holds promise for better future medicine and medical technology. However, their physical fitness and lifestyle are often ignored. METHODS: Lifestyle, PAs and common risk factors for cardiovascular disease before, and at, university were collected from 408 students using self-completed, anonymous surveys between the academic years of 2017 and 2019 from the School of Biological Sciences, University of Reading. Statistical analysis was performed using SAS® 9.4 software. RESULTS: Among the 408 participants, 134 were male and 274 were female with a mean (SD) age of 19.6 (2.24). Approximately 19% of participants consumed alcohol beyond the safe limit of <14 units/week (112 g/week). Among them, 65% were males. Before university, 47% of students failed to meet the UK National Physical Activity Guidelines (NPAG) which increased to 56% during university with males exhibiting a steeper incline. Compared to their lifestyles before university, more students had insufficient sleep and displayed greater sedentariness during university. Moreover, 16% of students declared no engagement in PA which was greater than the value of 12% before university. Fitness perceptions worsened by 11% during university particularly for females. Statistical analysis revealed that gender, BMI and fitness perceptions were significantly correlated with PA levels. The most prevalent explanation for inadequacy in meeting NPAG was insufficient time. CONCLUSIONS: Compared to their pre-university lifestyles, biological science students at university are more likely to adopt unhealthier behaviours with less time for exercise and prolonged sedentary behaviours, which increases the risk for cardiovascular diseases. It is important to raise awareness of their fitness perceptions and to encourage health-promoting programmes at university.

Research on mechanism of PCS in damaging vascular endothelial cells and promoting formation of atherosclerosis via TLR4/TREM-1.

OBJECTIVE: The study aimed to explore the effects of p-cresyl sulfate (PCS) of damaging vascular endothelial cells and promoting the formation of atherosclerosis in mice. MATERIALS AND METHODS: The apolipoprotein E (ApoE)-/- mice were fed normally and with a high-fat diet; the ApoE-/- mice fed with high-fat diet were divided into two groups and treated with blank control and PCS, respectively. The aortic arch in each group was taken and underwent the oil red O staining, and the serum PCS content in each group was detected. The basic components of plaque were observed, including foam cells, lipid deposition, and cholesterol crystal. Moreover, human umbilical vein endothelial cells were cultured and divided into control group, PCS treatment group (PCS), PCS treatment with TLR4 overexpression group (PCS+TLR4+), and PCS treatment with TLR4 knock-out group (PCS+TLR4-). The degree of endothelial cell damage was detected using a cluster of differentiation CD42b-/CD31+ endothelial microparticles (EMPs), and expressions of Toll-like receptor 4 (TLR4), triggering receptor expressed on myeloid cells-1 (TREM-1), phosphorylated-endothelial nitric oxide synthase (p-eNOS), and tumor necrosis factor-α (TNF-α) in cells were detected via Polymerase Chain Reaction (PCR) and Western blotting. RESULTS: The serum PCS concentration in high-fat ApoE-/- mice was increased, and the aortic arch sections of ApoE-/- mice treated with PCS displayed the evident atherosclerotic plaques. Experimental results of human umbilical vein endothelial cells showed that the activity of human umbilical vein endothelial cells treated with PCS declined, the expression levels of TLR4, TREM-1, and TNF-α were increased, while that of p-eNOS was decreased. After the TLR4 knockout, the above effects of PCS were reversed. CONCLUSIONS: PCS damages vascular endothelial cells through TRL4/TREM-1, thereby accelerating the formation of atherosclerosis.

MicroRNA-218 alleviates sepsis inflammation by negatively regulating VOPP1 via JAK/STAT pathway.

OBJECTIVE: To investigate the possible role of microRNA-218 in the pathogenesis of sepsis and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-218 expression in peripheral blood mononuclear cells (PBMCs) of 53 sepsis patients and 20 healthy controls was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). MicroRNA-218 expression in Treg cells of sepsis patients and healthy controls was also detected. The binding condition of microRNA-218 to VOPP1 was confirmed by dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation (RIP) assay, respectively. Furthermore, sepsis mouse model was constructed. MicroRNA-218 mimics or inhibitor was injected into mouse tail vein, respectively. The proportion of Treg cells was compared between sepsis mice injected with microRNA-218 mimics and inhibitor. Expressions of microRNA-218 and VOPP1 in Treg cells extracted from sepsis mouse were detected. ELISA (enzyme-linked immunosorbent assay) assay was conducted to detect serum levels of inflammatory factors (TNF-α, IL-6, TGF-ß, and IL-10) in sepsis mouse. Finally, protein expressions of key genes in JAK/STAT pathway in sepsis mouse spleen were detected by Western blot. RESULTS: MicroRNA-218 expression in sepsis patients was remarkably lower than that of healthy controls, which was gradually decreased with the deteriorating symptoms. Specifically, microRNA-218 expression was the lowest in patients who died of sepsis. Downregulated microRNA-218 was seen in Treg cells extracted from advanced sepsis patients. Both dual-luciferase reporter gene assay and RIP assay suggested that microRNA-218 can bind to VOPP1. VOPP1 expression was negatively regulated by microRNA-218. In advanced sepsis mouse, administration of microRNA-218 mimics increased expressions of TNF-α and IL-6, but decreased expressions of IL-10 and TGF-ß. Western blot results indicated that microRNA-218 can inhibit the JAK/STAT pathway in sepsis mice. CONCLUSIONS: MicroRNA-218 expression in the PBMCs of sepsis patients was remarkably reduced, which inhibited sepsis development via negatively regulating VOPP1 and suppressing JAK/STAT pathway.

Obesity, weight change, and mortality in older adults with metabolic abnormalities.

BACKGROUND AND AIMS: It is expected that older adults with metabolic abnormalities may benefit from weight loss; however, data on this population are limited. Our study was to assess the effect of obesity and weight change on mortality risk in older adults with metabolic abnormalities. METHODS AND RESULTS: A total of 3649 Chinese older adults aged 60-90 years with metabolic abnormalities were included between 2000 and 2014. Weight change between two health checkup periods was calculated. During a median follow-up period of 37 months, 503 all-cause mortality and 235 cardiovascular disease mortality occurred. Death rate was the lowest in overweight participants and in the participants with weight stability. After adjustment for covariates, hazard ratios (95% confidence intervals) of overweight participants for all-cause mortality and cardiovascular mortality were 0.71 (0.59, 0.86) and 0.72 (0.55, 0.95), respectively, whereas obesity was not significantly associated with mortality risk. Furthermore, relative to weight stability, risks of mortality significantly increased with the increase in weight loss or weight gain, except small weight gain. These associations were unchanged when the participants were stratified by baseline covariates and even when several definitions of weight change were considered. CONCLUSIONS: Overweight was associated with less mortality risk, and obesity was not associated with mortality risk in older adults with metabolic abnormalities. Mortality risk increased with the increase in weight loss or weight gain, regardless of body weight levels at the baseline. These findings suggest that maintaining a stable weight may be the best choice in older adults with metabolic abnormalities.

Mutation profile and associated clinical features in Chinese patients with cytogenetically normal acute myeloid leukemia.

INTRODUCTION: Cytogenetically normal acute myeloid leukemia (CN-AML), which accounted for nearly half of total AML patients, is a highly heterogeneous subset of AML. The specific genetic profile and the ethnic features of CN-AML are worth to be studied. METHODS: Using deep sequencing technology, we detected the mutation pattern of 39 genes in 152 Chinese CN-AML patients and analyzed their clinical features. RESULTS: A total of 503 mutations of 39 genes were identified in 145 (95.4%) patients, with the median number of 3 mutations per case. Nine genes (NPM1, CEBPA, DNMT3A, GATA2, NRAS, TET2, FLT3, IDH2, and WT1) mutated in more than 10% patients. Function groups of myeloid transcription factors, activated signaling, and DNA methylation were most affected. The distribution of variant allele frequencies (VAF) of recurrent genes was different among functional groups. High mutation rates of CEBPA and GATA2 together with the low frequency of FLT3-ITD mutation seemed to be the distinct characteristics of Chinese patients. Furthermore, CEBPAbi and GATA2 were found to mutate most in M2 subtype, while NPM1 and DNMT3A mutated more in M4 and M5. The prognostic analysis identified CEBPAmo mutation as an inferior factor. FLT3-ITD, TP53, DNMT3A, CEBPAmo, and WT1 mutations were selected as high-risk markers to identify the CN-AML patients with poor prognosis. CONCLUSION: Our study provided the valuable information of ethnic genetic characteristics and the clinical relevance of Chinese CN-AML patients.

Expressions of HIF-1α and KISS-1 in patients with liver cancer and correlation analysis.

OBJECTIVE: To study the expressions of hypoxia-inducible factor-1α (HIF-1α) and tumor metastasis suppressor gene (KISS-1) in patients with liver cancer and to analyze the correlation between HIF-1α and KISS-1 and liver cancer. PATIENTS AND METHODS: 20 normal liver tissues and 30 liver cancer tissues in our hospital were selected. The expressions of HIF-1α and KISS-1 in normal liver tissues and liver cancer tissues were detected via immunofluorescence assay. The mRNA expressions of HIF-1α and KISS-1 in normal liver tissues and liver cancer tissues were detected via reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of HIF-1α and KISS-1 in normal liver tissues and liver cancer tissues were detected via Western blotting. Differences of HIF-1α and KISS-1 expressions in normal liver tissues and liver cancer tissues were analyzed using SPSS 17.0 statistical software. RESULTS: Immunofluorescence assay, RT-PCR, and Western blotting, showed that HIF-1α was highly expressed in liver cancer tissues, and its expression level was significantly higher than that in normal liver tissues. However, the expression of KISS-1 in normal liver tissues was significantly higher than that in liver cancer tissues. The results of analysis of variance showed that the differences of HIF-1α and KISS-1 expressions in normal liver tissues and liver cancer tissues were statistically significant (p<0.01). CONCLUSIONS: The abnormal expressions of HIF-1α and KISS-1 are closely related to the development and progression of liver cancer, indicating that HIF-1α and KISS-1 have important research values in liver cancer, and the expressions of HIF-1α and KISS-1 can be used as the index of deterioration degree of liver cancer, providing a new clinical basis for diagnosis and treatment.

Visceral pleural invasion impacts the prognosis of non-small cell lung cancer: A meta-analysis.

BACKGROUND: In the 7th tumor, node, metastasis (TNM) classification, T1 tumors with visceral pleural invasion (VPI) are upgraded to T2a. The objective of this study was to evaluate the prognostic impact of VPI among patients with NSCLC and to propose a method of incorporating VPI into T-status classification in future staging systems. METHODS: A systematic electronic search was conducted from each database's date of inception to October 2015. The included studies were selected according to predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining. RESULTS: A total of 22 studies, published from 2003 to 2015, were included in this meta-analysis. In the subgroup analysis, we identified that VPI was a poor prognostic factor for tumor size ≤2 cm (2.34 [95% confidence interval (CI) 1.55-3.54; P < 0.0001]), 2-3 cm (1.81 [95% CI 1.56-2.10; P < 0.0001]), 3-5 cm (1.61 [95% CI 1.38-1.87; P < 0.0001]) and 5-7 cm (1.50 [95% CI 1.24-1.82; P < 0.0001]). In addition, we also found that there were no significant differences for the following comparisons of OS: tumor size ≤2 cm with VPI versus 3-5 cm without VPI (1.04 [95% CI 0.83-1.31; P = 0.34]); 2-3 cm with VPI versus 3-5 cm without VPI (1.04 [95% CI 0.96-1.13; P = 0.30]); 3-5 cm with VPI versus 5-7 cm without VPI (0.95 [95% CI 0.78-1.17; P = 0.66]); and 5-7 cm with VPI versus T3 status (1.03 [95% CI 0.93-1.14; P = 0.57]). CONCLUSIONS: In addition to the current TNM classification recommendations, consideration should be given to classifying the T2a tumors with VPI as T2b and classifying T2b with VPI as T3 in the next edition of the TNM Classification for Lung cancer.

Evaluation of the direct nitrate reductase assay for rapid detection of extensively drug-resistant tuberculosis.

SETTING: Jiangxi, China. OBJECTIVE: To evaluate the performance of the direct nitrate reductase assay (D-NRA) for rapid, low-cost detection of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) in high-burden, resource-limited settings. METHODS: A total of 225 smear-positive sputum samples were collected from consecutive drug-resistant TB subjects. Samples were processed at the Province TB Reference Laboratory and tested for susceptibility to rifampicin (RMP), isoniazid (INH), ofloxacin (OFX), kanamycin (KM) and capreomycin (CPM) by D-NRA, using the indirect Löwenstein-Jensen proportion method (LJ-PM) as reference. RESULTS: Of the 225 smear-positive sputum samples, 214 isolates were identified as Mycobacterium tuberculosis and analysed for further comparison. The sensitivity of the D-NRA in the detection of resistance to RMP, INH, OFX, KM and CPM was respectively 95.1% (97/102), 93.1% (135/145), 97.4% (76/78), 88.9% (40/45) and 90.6% (29/32); specificity was respectively 100% (112/112), 97.1% (67/69), 100% (136/136), 98.8% (167/169) and 96.7% (176/182). The median time to culture positivity was significantly shorter for NRA than for the indirect LJ-PM (14 days vs. 70 days, P < 0.001). CONCLUSION: D-NRA showed high sensitivity and specificity in the rapid diagnosis of MDR- and XDR-TB in a high-burden, resource-limited setting.

Novel Human Three-Domain Antibody Fragments Against sTNFα as Well as tmTNFα with High Affinity Generated by the Combination of Ribosome Display and E. coli Expression System.

Human tumour necrosis factor α (hTNFα) has been proved to be a validated therapeutic target in a number of immune-mediated inflammatory diseases (IMIDs). Fully human monoclonal antibodies (mAbs) that can neutralize soluble hTNFα (sTNFα) as well as transmembrane hTNFα (tmTNFα) are more desirable hTNFα antagonists. Here, we report that novel anti-hTNFα human low-molecular-weight MAbs have been selected and identified using both sTNFα and tmTNFα as target antigens by the combination of ribosome display and E. coli expression system for the first time. As a newly born engineering small molecular antibody, three-domain antibody fragment (VH /κ) provides an alternative promising molecular principle to generate biological agents for TNFα-dependent IMIDs. In this study, a panel of novel human VH /κs (F09, F21, F49 and F409) with high affinity (10(-10) -10(-9) mol/l) to neutralize sTNFα as well as tmTNFα was generated by the combination of ribosome display and E. coli expression system. Among the four clones, F21 and F409 could reduce cytotoxicity on L929 cells induced by sTNFα as well as tmTNFα effectively, and both of them had great potential to inhibit hTNFα-mediated NF-κB activation. Soluble F21 and F409 were also able to inhibit the binding of hTNFα to TNFR1 and TNFR2. The new human antibodies described here have desirable capability to neutralize sTNFα as well as tmTNFα effectively with high affinity and reasonable stability; this may provide an alternative approach for patients who are not responding adequately to currently available anti-TNFα agents.

Cardiac autonomic neuropathy risk estimated by sudomotor function and arterial stiffness in Chinese subjects.

The SUDOSCAN test was recently developed to detect diabetic autonomic neuropathy early and screen for cardiac autonomic neuropathy (CAN) through assessment of sudomotor function. The aim of this study was to investigate the relationship of cardiac autonomic dysfunction estimated by the SUDOSCAN test with arterial stiffness. A total of 4019 subjects without diabetes or established cardiovascular disease were tested with SUDOSCAN, central systolic blood pressure (cSBP) and brachial-ankle pulse wave velocity (baPWV). Hands mean electrochemical skin conductance (ESC) measured by SUDOSCAN was 70±17 µS, feet mean ESC was 71±16 µS and the CAN risk score was 21±10%. The levels of cSBP and baPWV increased across quartiles of CAN risk score (P for trend <0.001 for all). In spearman correlation analyses, the CAN risk score was positively correlated with cSBP (r=0.391, P<0.001) and baPWV (r=0.305, P<0.001). In multivariable analyses, the values of cSBP and baPWV increased 0.17 mm Hg (P=0.002) and 2.01 cm per second (P=0.010), respectively, when CAN risk score increased 1%. The results were unchanged when stratified by glucose tolerance status. In conclusion, cardiac autonomic dysfunction estimated by sudomotor function was correlated with arterial stiffness independent of conventional factors and glucose tolerance status.

Anti-NMDA receptor encephalitis: clinical characteristics, predictors of outcome and the knowledge gap in southwest China.

BACKGROUND AND PURPOSE: The aim was to analyse the clinical profiles and outcomes of patients with anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis in China. METHODS: A retrospective study of anti-NMDAR encephalitis in China was performed between June 2011 and June 2014. The clinical characteristics and predictors of poor outcome were determined. RESULTS: A total of 51 patients with a definitive diagnosis of anti-NMDAR encephalitis were included in this study. Four of them were surgically confirmed to have a neoplasm. Thirty-two patients, amongst whom 24 were female, presented with psychiatric disorder as the initial symptom, whereas 14 patients, of whom nine were male, presented with seizure as the initial symptom (P = 0.011). Twenty-nine patients (56.86%) were initially misdiagnosed with psychosis, viral encephalitis or other diseases, and 58.8% of the patients experienced at least one type of complication. It typically took 3 weeks before these patients were admitted to our hospital and another 2 weeks before the correct diagnosis was made. Forty-one patients (80%) reached a good outcome; 10 patients (20%) had a poor outcome. Older age, extended hospital stay, memory deficits, decreased consciousness, central hypoventilation, complications and abnormal cerebrospinal fluid results were associated with poor outcome (P < 0.05). CONCLUSIONS: Female patients more frequently initially present with psychiatric disorder but male patients more frequently initially present with seizure. Patients with anti-NMDAR encephalitis in China have a lower incidence of neoplasm. Nevertheless, this study reveals several challenges in treating anti-NMDAR encephalitis in China that may contribute to poor outcome.

The histological analysis of the anterior cruciate ligament of canine after radiofrequency shrinkage.

OBJECTIVE: Radiofrequency (RF) shrinkage has been widely conducted in clinical practice and the anterior cruciate ligament (ACL) laxity is regarded as one of the indications. However, basic researches regarding the postoperative histological changes were still insufficient. The study aimed to investigate postoperative histological changes of different areas of ACL for further identifying the optimal area for RF shrinkage. MATERIALS AND METHODS: A total of 29 healthy canine (16.5 ± 2.2 kg, 4.1 ± 0.7 years) were recruited, 24 of which were randomly divided into group A and group B. The epiphyseal arrest was confirmed by X-ray examination in all animals. On one canine, an ACL's vascular perfusion model was established by the ink-perfusion method to observe the blood supply of the ACL. The mid-portion of ACL was conducted by RF in group A while the amph-portions of ACL were conducted in group B. Two legs of each canine were sub-divided into fixation group (group A1 and B1) and non-fixation group (group A2 and B2). 8 ACLs were separated from the rest 4 canine. 2 ACLs were sent for the histological examination after RF shrinkage and the rest 6 ACLs were served as blank controls. Masson staining and hematoxylin-eosin (H-E) staining were applied to observe the features of inner fibrous changes of ACL, cell count and vascular density. RESULTS: According to the Masson staining, collagenous tissues were observed in area after RF shrinkage, which was more evident among group B1 than the others. The cellar density in both group A and B was found lower at 12 weeks postoperatively than that at 6 weeks postoperatively (p < 0.05). In addition, the cellar density in B1 group was found higher than that in A1 group at both 6 and 12 weeks postoperatively (p < 0.05). The density of subsynovial vessel in B1 group was found higher than that in A1 group at 6 weeks postoperatively (p < 0.05) and the density of subsynovial vessel in both A1 and B1 groups was found lower at 12 postoperatively weeks than that at 6 weeks postoperatively (p < 0.05). In both A2 and B2 groups, all ACLs were found ruptured at 12 weeks postoperatively. CONCLUSIONS: The postoperative revascularization pattern of RF-treated ACL was permeating from the synovium to the RF-treated areas, and the best area for the RF shrinkage treatment was the amph-portions of the ACL. Moreover, the application of postoperative external fixation to restrict the movement of injured limb was necessary.

Primary intraosseous ganglioneuromatous paraganglioma of the sacrum with immunopositivity for cytokeratin.

BACKGROUND: Paragangliomas are derived from neurosecretory cells believed to be of neural crest origin. A spinal location of paraganglioma is rare and usually presents as an intradural mass. PATIENT AND METHODS: A primary intraosseous paraganglioma of sacrum is extremely unusual, and only 6 cases were reported. In this study, we report a rare case of a 44-year-old man with the complaint of low back pain and lower extremity weakness. Imaging workup, including computerized tomography (CT), and magnetic resonance imaging (MRI) presented an intraosseous sacral lesion with invasion of sacrum in the S1-S3 vertebrae, and extension to L4-L5 spinal canal. The patient underwent subtotal tumor resection, followed by radiation therapy. RESULTS: The morphological and immunohistochemical studies revealed a composite tumor of paraganglioma and ganglioneuroma components, with immunopositivity for cytokeratin. CONCLUSIONS: To the best of our knowledge, this is the first report in the literature demonstrating an intraosseous sacral paraganglioma with these 2 pathological features.

Capillarisin Exhibits Anticancer Effects by Inducing Apoptosis, Cell Cycle Arrest and Mitochondrial Membrane Potential Loss in Osteosarcoma Cancer Cells (HOS).

The aim of the present study was to assess the anticancer activity of capillarisin against human osteosarcoma (HOS) cancer cells in vitro. Cell viability after capillarisin drug treatment and evaluated by MTT assay. The extent of cell death induced by capillarisin was estimated by using lactate dehydrogenase (LDH) assay. The effect of capillarisin on cell cycle phase distribution and mitochondrial membrane potential (ΛΨm) was demonstrated via flow cytometry using propidium iodide (PI) and rhodamine-123 (Rh-123) DNA-binding fluorescent dyes respectively. Fluorescence microscopy was employed to examine the morphological changes in osteosarcoma cancer cells and presence of apoptotic bodies following capillarisin treatment. The results of this study revealed that capillarisin induced dose-dependent growth inhibition of these cancer cells after 12-h of incubation. Further, capillarisin induced significant release of LDH from these cell cultures and this LDH release was much more noticeable at higher concentrations of capillarisin. Hoechst 33258 staining revealed characteristic morphological features of apoptosis triggered by capillarisin treatment. Cell cycle analysis revealed that capillarisin induced dose-dependent G0/G1-phase cell cycle arrest. Capillarisin also trigerred a progressive and dose-dependent reduction in the mitochondrial membrane potential. In conclusion, capillarisin inhibits cancer cell growth of osteosarcoma cells by inducing apoptosis accompanied with G0/G1-phase cell cycle arrest and loss in mitochondrial membrane potential.