Neuro-11: a new questionnaire for the assessment of somatic symptom disorder in general hospitals.

Background: Somatic symptom disorder (SSD) commonly presents in general hospital settings, posing challenges for healthcare professionals lacking specialised psychiatric training. The Neuro-11 Neurosis Scale (Neuro-11) offers promise in screening and evaluating psychosomatic symptoms, comprising 11 concise items across three dimensions: somatic symptoms, negative emotions and adverse events. Prior research has validated the scale's reliability, validity and theoretical framework in somatoform disorders, indicating its potential as a valuable tool for SSD screening in general hospitals. Aims: This study aimed to establish the reliability, validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD. Through this comparative analysis, we aimed to validate the effectiveness and precision of the Neuro-11, enhancing its utility in clinical settings. Methods: Between November 2020 and December 2021, data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People's Hospital in China for various physical discomforts. The patients completed multiple questionnaires, including the Neuro-11, Short Form 36 Health Survey, Patient Health Questionnaire 15 items, Hamilton Anxiety Scale and Hamilton Depression Scale. Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD. Results: The Neuro-11 demonstrated strong content reliability and structural consistency, correlating significantly with internationally recognised and widely used questionnaires. Despite its brevity, the Neuro-11 exhibited significant correlations with other questionnaires. A test-retest analysis yielded a correlation coefficient of 1.00, Spearman-Brown coefficient of 0.64 and Cronbach's α coefficient of 0.72, indicating robust content reliability and internal consistency. Confirmatory factor analysis confirmed the validity of the three-dimensional structure (p<0.001, comparative fit index=0.94, Tucker-Lewis index=0.92, root mean square error of approximation=0.06, standardised root mean square residual=0.04). The threshold of the Neuro-11 is set at 10 points based on the maximum Youden's index from the receiver operating characteristic curve analysis. In terms of diagnostic efficacy, the Neuro-11 has an area under the curve of 0.67. Conclusions: (1) The Neuro-11 demonstrates robust associations with standard questionnaires, supporting its validity. It is applicable in general hospital settings, assessing somatic symptoms, negative emotions and adverse events. (2) The Neuro-11 exhibits strong content reliability and validity, accurately capturing the intended constructs. The three-dimensional structure demonstrates robust construct validity. (3) The threshold of the Neuro-11 is set at 10 points.

Cytochrome P450 metabolism studies of [6]-gingerol, [8]-gingerol, and [10]-gingerol by liver microsomes of humans and different species combined with expressed CYP enzymes.

Gingerols, mainly [6]-gingerol (6G), [8]-gingerol (8G), and [10]-gingerol (10G), are the functional and specific pungent phytochemicals in ginger. However, poor oral bioavailability limits their applications owing to extensive metabolism. The present study aims to characterize the cytochrome P450 (CYP) metabolic characteristics of 6G, 8G, and 10G by using pooled human liver microsomes (HLM), different animal liver microsomes, and the expressed CYP enzymes. It is shown that NADPH-dependent oxidation and hydrogenation metabolisms of gingerols are the main metabolic types in HLM. With the increase of the carbon chain, the polarity of gingerols decreases and the formation of hydrogenated metabolites is more efficient (CLint: 1.41 µL min-1 mg-1 for 6G, 7.79 µL min-1 mg-1 for 8G and 14.11 µL min-1 mg-1 for 10G), indicating that the phase I metabolism of gingerols by HLM varied with the chemical structure of the substrate. The phase I metabolism of gingerols revealed considerable species variations, and compared to HLM, novel metabolites such as (3S,5S)-gingerdiols and demethylated metabolites are generated in some animal liver microsomes. The primary enzymes involved in the oxidized and demethylated metabolism of these gingerols are CYP1A2 and CYP2C19, but their affinities for gingerols are not the same. CYP2D6 and CYP2B6 contributed significantly to the formation of (3R,5S)-[8]-gingerdiol and (3R,5S)-[10]-gingerdiol, respectively; however, the enzyme responsible for the production of (3R,5S)-[6]-gingerediol is yet to be identified. Some metabolites in microsomes cannot be detected by the 12 investigated CYP enzymes, which may be related to the combined effects of multiple enzymes in microsomes, the different affinity of mixed liver microsomes and CYP enzymes, gene polymorphisms, etc. Overall, this work provides a deeper knowledge of the influence of CYP metabolism on the gingerols, as well as the mode of action and the possibility for drug-herbal interactions.

Effects of Peripheral Neural Blocks in Laparoscopic Sleeve Gastrectomy: a Pilot Study on Cognitive Functions in Severe Obese Patients.

BACKGROUND: In addition to the analgesic effect, peripheral neural blocks also prevent cognitive impairment and peripheral inflammation induced by surgery. However, it is unknown if there is collateral impact on cognitive improvement after bariatric surgery. METHODS: In this pilot study, 75 patients with severe obesity for selective laparoscopic sleeve gastrectomy (LSG) were recruited and randomized into three groups (1:1:1) as general anesthesia (GA) group, transverse abdominis plane block (TAPB) group, and quadratus lumborum block (QLB) group. Bilateral TAPB or QLB was performed (0.33% ropivacaine with dexmedetomidine 1 µg/kg) before the standardized general anesthesia. Cognitive test battery was completed before LSG and in 1-month and 3-month follow-up. The levels of peripheral inflammatory cytokines were determined at equivalent time points. RESULTS: Patients with LSG exhibited massive cognitive improvement in postoperative 3 month without or with TAPB or QLB (Ptime < 0.001). Compared to GA, QLB significantly strengthened performance in MoCA (ß = 0.56, 95%CI: 0.08, 1.05). IL-6, IL-8, and high-sensitivity CRP significantly verified among three groups. Changes in IL-6 within postoperative 3 months were negatively correlated with MMSE and MoCA, and positively correlated with AVLT-DR for QLB group. Similar correlation was found in the GA group for changes in IL-6 and AVLT-IR. CONCLUSION: Laparoscopic sleeve gastrectomy ideally improved memory and attention as early as postoperative 1 month. QLB promoted cognitive improvement in MoCA, which was negatively correlated with changes in IL-6. More precise trials are needed to determine the overall effect of peripheral neural block on cognition following bariatric surgery.

Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule.

Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used for the treatment of osteoporosis. However, it significantly elevates levels of serum estrogens. Here we aimed to assess the dominant contributors of sulfotransferase (SULT) enzymes to the sulfation of estrogens and identify the effective inhibitors of this pathway in XLGB. First, estrone, 17ß-estradiol, and estriol underwent sulfation in human liver S9 extracts. Phenotyping reactions and enzyme kinetics assays revealed that SULT1A1, 1A2, 1A3, 1C4, 1E1, and 2A1 all participated in estrogen sulfation, with SULT1E1 and 1A1 as the most important contributors. The incubation system for these two active enzymes were optimized with Tris-HCl buffer, DL-Dithiothreitol (DTT), MgCl2, adenosine 3'-phosphate 5'-phosphosulfate (PAPS), protein concentration, and incubation time. Then, 29 compounds in XLGB were selected to investigate their inhibitory effects and mechanisms against SULT1E1 and 1A1 through kinetic modelling. Moreover, in silico molecular docking was used to validate the obtained results. And finally, the prenylated flavonoids (isobavachin, neobavaisoflavone, etc.) from Psoralea corylifolia L., prenylated flavanols (icariside II) from Epimedium brevicornu Maxim., tanshinones (dihydrotanshinone, tanshinone II-A,) from Salvia miltiorrhiza Bge., and others (corylifol A, corylin) were identified as the most potent inhibitors of estrogen sulfation. Taken together, these findings provide insights into the understanding regioselectivity of estrogen sulfation and identify the effective components of XLGB responsible for the promotion of estrogen levels.

Dual-targeted repetitive transcranial magnetic stimulation modulates brain functional network connectivity to improve cognition in mild cognitive impairment patients.

Background: Mild cognitive impairment (MCI) is a condition between normal aging and dementia; nearly 10-15% of MCI patients develop dementia annually. There are no effective interventions for MCI progression. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has attempted to improve the overall cognitive function of MCI patients. However, it does not affect episodic memory improvement. Methods: In this study, we engaged 15 clinically diagnosed MCI patients and normal controls to explore the effect of dual-targeted rTMS on progressing cognitive function, particularly episodic memory in MCI patients. Resting-state EEG recordings and neuropsychological assessments were conducted before and after the intervention. EEG features were extracted using an adaptive algorithm to calculate functional connectivity alterations in relevant brain regions and the mechanisms of altered brain functional networks in response to dual-target rTMS. Results: The study revealed that the functional brain connectivity between the right posterior cingulate gyrus (PCC) and the right dorsal caudate nucleus (DC) was significantly reduced in MCI patients compared to normal controls (p < 0.001). Dual-target rTMS increased the strength of the reduced functional connectivity (p < 0.001), which was related to cognitive enhancement (p < 0.05). Conclusion: This study provides a new stimulation protocol for rTMS intervention. Improving the functional connectivity of the right PCC to the right DC is a possible mechanism by which rTMS improves overall cognitive and memory function in MCI patients.

The postoperative cognitive dysfunction induced by central inflammation with possible involvement of the gut-brain axis.

BACKGROUND: Postoperative cognitive dysfunction is widely recognized as severe postoperative central nervous dysfunction and has a significant impact on the 'patient's physical and mental health. METHODS: Postoperative models of tibial fracture in aged rats were established, including the control group, model group, CCL11 protein injection group, and saline injection group. Morris water maze test was used to detect the behavioral characteristics of rats. Enzyme-Linked Immunosorbent Assay was used or determine the content of CCL11 and CXCL10. Immunofluorescence staining was used to detect the distribution of CD14+CD163+macrophages in colon tissues and CD11b+CCR3+microglia cells in hippocampal tissues. Western blot analyzed NOX1 and STAT3 expression in hippocampus tissues. RESULTS: Water maze test results confirmed severe cognitive impairment in CCL11 rats. The content of CCL11 and CXCL10 in the CCL11 group was much higher than that of the model group. The distribution of macrophage and microglia cells in the CCL11 model group was greater than that in the model group and the saline group. The expression of NOX1 and STAT3 in the CCL11 group was higher compared with the model group. CONCLUSION: Abnormal macrophage function and excessive CCL11 secretion were observed in the rats with lower limb fractures after surgery. Postoperative central inflammation in rats with lower limb fracture induced postoperative cognitive dysfunction through the gut-brain axis molecular mechanism.

Prognostic Nutritional Index and Neutrophil/Lymphocyte Ratio Can Serve as Independent Predictors of the Prognosis of Hepatocellular Carcinoma Patients Receiving Targeted Therapy.

Objective: The prognostic nutritional index (PNI) is an immunonutritional indicator, and the neutrophil/lymphocyte ratio (NLR) reflects the inflammatory status. This research intends to determine the implications of NLR and PNI in evaluating the outcome of hepatocellular carcinoma (HCC) patients undergoing targeted therapy (TT). Methods: We retrospectively analyzed 83 patients' records with sorafenib treatment for advanced HCC in the Second Affiliated Hospital of Anhui Medical University. Patient records comprised general data and blood routines. The PNI and NLR values were calculated using the serum albumin levels (ALB), neutrophil (NEU) count, and lymphocyte (LY) count. The optimal thresholds of the PNI and NLR for predicting HCC patients' outcomes were calculated by X-tile. Patients were further assigned to low- and high-groups of PNI and NLR according to their thresholds. By using the Cox proportional hazards regression models, univariate and multivariate analyses were conducted to identify risk factors influencing the patient's prognosis. Results: The participants were assigned to the corresponding low-PNI (≤42.9; n = 10) and high-PNI (>42.9; n = 73) groups, as well as low-NLR (≤2.4; n = 64) and high-NLR (>2.4; n = 19) groups based on the critical values of PNI (42.9) and NLR (2.4) obtained through the X-tile calculation. A higher overall survival (OS) rate was observed in the high-PNI group and low-NLR group, than in the low-PNI group and high-NLR group, respectively. The disease control rate showed no evident difference between the groups. The PNI and NLR were of high reliability in predicting the OS of patients. Cox multivariate analysis identified the independence of the PNI and NLR as prognostic factors for patients receiving TT for advanced HCC. Conclusions: The pretreatment PNI and NLR levels have great prognostic implications for advanced HCC patients receiving TT. A higher PNI and a lower NLR suggest a higher postoperative survival rate.

Optimising fluid requirements after initial resuscitation: A pilot study evaluating mini-fluid challenge and passive leg raising test in patients with predicted severe acute pancreatitis.

BACKGROUND: The goals and approaches to fluid therapy vary through different stages of resuscitation. This pilot study was designed to test the safety and feasibility of a fluid therapy protocol for the second or optimisation stage of resuscitation in patients with predicted severe acute pancreatitis (SAP). METHODS: Spontaneously breathing patients with predicted SAP were admitted after initial resuscitation and studied over a 24-h period in a tertiary hospital ward. Objective clinical assessment (OCA; heart rate, mean arterial pressure, urine output, and haematocrit) was done at 0, 4, 8, 12, 18-20, and 24 h. All patients had mini-fluid challenge (MFC; 250 ml intravenous normal saline within 10 min) at 0 h and repeated at 4 and 8 h if OCA score ≥2. Patients who were fluid responsive (>10% change in stroke volume after MFC) received 5-10 ml/kg/h, otherwise 1-3 ml/kg/h until the next time point. Passive leg raising test (PLRT) was done at each time point and compared with OCA for assessing volume status and predicting fluid responsiveness. RESULTS: This fluid therapy protocol based on OCA, MFC, and PLRT and designed for the second stage of resuscitation was safe and feasible in spontaneously breathing predicted SAP patients. The PLRT was superior to OCA (at 0 and 8 h) for predicting fluid responsiveness and guiding fluid therapy. CONCLUSIONS: This pilot study found that a protocol for intravenous fluid therapy specifically for the second stage of resuscitation in patients with predicted SAP was safe, feasible, and warrants further investigation.

Vitamin D and Pancreatitis: A Narrative Review of Current Evidence.

Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.

Extracellular histones cause intestinal epithelium injury and disrupt its barrier function in vitro and in vivo.

Extracellular histones are cytotoxic to various cells and have been extensively proven a vital mediator of multiple organ injuries. However, the effect of extracellular histones on the intestine remains largely unknown. This study aimed to clarify the effect of extracellular histones on the intestine. IEC-6, a cell line of rat small intestinal epithelial crypt, and C57BL/6 or ICR mice were treated with histones. The IEC-6 cells treated with histones from 20 µg/mL to 200 µg/mL for 0-24 h displayed a decline of cell viability and an increase of cell death in a concentration- and time-dependent manner. Moreover, histones (100 µg/mL) induced IEC-6 apoptosis through activating caspase 3 and necroptosis through up-regulation of receptor-interacting serine/threonine protein kinase 1 and 3 (RIPK1 and RIPK3), phosphorylated mixed-lineage kinase domain-like protein (p-MLKL) along with the decrease of caspase-8. Histones treatment disturbed zonular occludens 1 (ZO-1) expression and increased permeability of IEC-6 cell monolayer. In vivo, histones 50 mg/kg injection caused mice intestinal edema, loss apex of villus, epithelial lifting down the sides of the villi, and increased neutrophil infiltration. Elevation of serum intestinal fatty acid binding protein (I-FABP), d-lactate, or Diamine oxidase (DAO) and loss of tight junction protein, ZO-1, at 3 h and 6 h after histones injection strongly indicated severe intestinal epithelium injury, which led to increased permeability of the intestine. In conclusion, extracellular histones cause intestinal epithelial damage via direct cytotoxicity. Consequently, intestinal epithelial tight junction and barrier integrity are disrupted, which may play pivotal roles in diverse diseases.

The postoperative cognitive dysfunction induced by central inflammation with possible involvement of the gut-brain axis

Abstract Background: Postoperative cognitive dysfunction is widely recognized as severe postoperative central nervous dysfunction and has a significant impact on the 'patient's physical and mental health. Methods: Postoperative models of tibial fracture in aged rats were established, including the control group, model group, CCL11 protein injection group, and saline injection group. Morris water maze test was used to detect the behavioral characteristics of rats. Enzyme-Linked Immunosorbent Assay was used or determine the content of CCL11 and CXCL10. Immunofluorescence staining was used to detect the distribution of CD14+CD163+macro-phages in colon tissues and CD11b+CCR3+microglia cells in hippocampal tissues. Western blot analyzed NOX1 and STAT3 expression in hippocampus tissues. Results: Water maze test results confirmed severe cognitive impairment in CCL11 rats. The content of CCL11 and CXCL10 in the CCL11 group was much higher than that of the model group. The distribution of macrophage and microglia cells in the CCL11 model group was greater than that in the model group and the saline group. The expression of NOX1 and STAT3 in the CCL11 group was higher compared with the model group. Conclusion: Abnormal macrophage function and excessive CCL11 secretion were observed in the rats with lower limb fractures after surgery. Postoperative central inflammation in rats with lower limb fracture induced postoperative cognitive dysfunction through the gut-brain axis molecular mechanism.

Use of intravenous lidocaine for dose reduction of propofol in paediatric colonoscopy patients: a randomised placebo-controlled study.

BACKGROUND: Propofol, a widely used sedative in endoscopic procedures, sometimes causes cardiopulmonary complications. Intravenous lidocaine can diminish visceral pain and decrease the dose of propofol. The purpose of this study was to assess the efficacy and safety of intravenous lidocaine in reducing propofol dosage during paediatric colonoscopy. METHODS: Forty children who underwent colonoscopy were divided into two groups. Lidocaine hydrochloride (1.5 mg/kg induction and 2 mg/kg/h maintenance) was given intravenously to the lidocaine group, and the same amount of saline was given to the control group after they received lidocaine induction. Propofol initial plasma concentration of 5 µg/mL was targeted, and the procedure was performed after the bispectral index value reached 55. The primary outcome was propofol requirement. RESULTS: The propofol requirement in the lidocaine group was decreased by 35.5% (128.6 ± 30.4 mg vs. 199.4 ± 57.6 mg; p < 0.001; 95%CI: - 100.60, - 41.02). The incidence of involuntary body movements was significantly lower in the lidocaine group (p = 0.028; OR = 0.17; 95%CI: 0.03, 0.92). The awakening time (p < 0.001; 95%CI: - 7.67, - 5.13) and recovery times (p < 0.001; 95%CI: - 7.45, - 4.35) were significantly lower in the lidocaine group. Pain was significantly less at 30 min and 60 min after the procedure in the lidocaine group (0 [0-4] vs. 3 [0-5], p < 0. 001; 0 [0-2] vs. 1 [0-3], p = 0.001). There was no difference in the incidence of bradycardia, hypotension, or hypoxia between the two groups. CONCLUSIONS: For colonoscopy procedures in paediatric patients, intravenous lidocaine reduces the amount of propofol needed, provides better sedation and postprocedural pain management, as well as a reduction in recovery time. TRIAL REGISTRATION: The trial was registered on November 6, 2020 at China Clinical Trials Registration Center ( www.chictr.org.cn ) ref.: ChiCTR 2,000,039,706.

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials.

Background: Mild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. It has a high risk of progression in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with MCI and AD. Although previous meta-analyses included studies carried on patients with MCI and AD, few studies have analyzed patients with MCI independently. This meta-analysis aimed to evaluate the effects and safety of rTMS on cognition function in patients with MCI and factors that may influence such effects. Methods: Data used in this study were searched and screened from different databases, including PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Database, and China BioMedical Literature Database (SinoMed). The retrieved studies were carefully reviewed, data were extracted, and the quality of data was assessed. Results: A total of 12 studies involving 329 patients with MCI were included in the present meta-analysis. The analyses results revealed that rTMS improved cognitive function [standardized mean difference (SMD) = 0.83, 95% confidence interval (CI) = 0.44-1.22, p = 0.0009] and memory function (SMD = 0.73, 95% CI = 0.48-0.97, p < 0.00001) in the MCI + rTMS active group when compared to the sham stimulation group. The showed that: (1) cognitive improvement was more pronounced under high-frequency rTMS stimulation of multiple sites, such as the bilateral dorsolateral prefrontal cortex and (2) more than 10 rTMS stimulation sessions produced higher improvement on cognition function in patients with MCI. Conclusions: This study shows that rTMS can improve cognitive function in patients with MCI, especially when applied at high frequency, multi-site, and for a prolonged period. However, further studies are required to validate these findings and explore more effective stimulation protocols and targets. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/], identifier: CRD 42021238708.

Alleviation of acute pancreatitis-associated lung injury by inhibiting the p38 mitogen-activated protein kinase pathway in pulmonary microvascular endothelial cells.

BACKGROUND: Previous reports have suggested that the p38 mitogen-activated protein kinase signaling pathway is involved in the development of severe acute pancreatitis (SAP)-related acute lung injury (ALI). Inhibition of p38 by SB203580 blocked the inflammatory responses in SAP-ALI. However, the precise mechanism associated with p38 is unclear, particularly in pulmonary microvascular endothelial cell (PMVEC) injury. AIM: To determine its role in the tumor necrosis factor-alpha (TNF-α)-induced inflammation and apoptosis of PMVECs in vitro. We then conducted in vivo experiments to confirm the effect of SB203580-mediated p38 inhibition on SAP-ALI. METHODS: In vitro, PMVEC were transfected with mitogen-activated protein kinase kinase 6 (Glu), which constitutively activates p38, and then stimulated with TNF-α. Flow cytometry and western blotting were performed to detect the cell apoptosis and inflammatory cytokine levels, respectively. In vivo, SAP-ALI was induced by 5% sodium taurocholate and three different doses of SB203580 (2.5, 5.0 or 10.0 mg/kg) were intraperitoneally injected prior to SAP induction. SAP-ALI was assessed by performing pulmonary histopathology assays, measuring myeloperoxidase activity, conducting arterial blood gas analyses and measuring TNF-α, interleukin (IL)-1ß and IL-6 levels. Lung microvascular permeability was measured by determining bronchoalveolar lavage fluid protein concentration, Evans blue extravasation and ultrastructural changes in PMVECs. The apoptotic death of pulmonary cells was confirmed by performing a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis and examining the Bcl2, Bax, Bim and cle-caspase3 levels. The proteins levels of P-p38, NFκB, IκB, P-signal transducer and activator of transcription-3, nuclear factor erythroid 2-related factor 2, HO-1 and Myd88 were detected in the lungs to further evaluate the potential mechanism underlying the protective effect of SB203580. RESULTS: In vitro, mitogen-activated protein kinase (Glu) transfection resulted in higher apoptotic rates and cytokine (IL-1ß and IL-6) levels in TNF-α-treated PMVECs. In vivo, SB2035080 attenuated lung histopathological injury, decreased inflammatory activity (TNF-α, IL-1ß, IL-6 and myeloperoxidase) and preserved pulmonary function. Furthermore, SB203580 significantly reversed changes in the bronchoalveolar lavage fluid protein concentration, Evans blue accumulation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell numbers, apoptosis-related proteins (cle-caspase3, Bim and Bax) and endothelial microstructure. Moreover, SB203580 significantly reduced the pulmonary P-p38, NFκB, P-signal transducer and activator of transcription-3 and Myd88 levels but increased the IκB and HO-1 levels. CONCLUSION: p38 inhibition may protect against SAP-ALI by alleviating inflammation and the apoptotic death of PMVECs.

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis.

BACKGROUND: Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. METHODS: The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. RESULTS: Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. CONCLUSION: Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

Single-Molecule Level Rare Events Revealed by Dynamic Surface-Enhanced Raman Spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) is a powerful tool to monitor various interfacial behaviors providing molecular level information with high spatial and temporal resolutions. However, it is a challenge to obtain SERS spectra with high quality for analytes having a weak binding affinity with plasmonic nanostructures due to the short dwell time of the analyte on the surface. Here, we employed dynamic SERS, an acquisition method consisting of the rapid acquisition of a series of consecutive SERS spectra, to study the adsorption/desorption behavior of R6G on Ag surfaces. We demonstrated that the signal-noise ratio of SERS spectra of mobile molecules can be improved by dynamic SERS even when the acquisition time cannot catch up with the diffusion time of the molecule. More interestingly, we captured the neutral R6G0 state (spectroscopically different from the dominated positive R6G+ state) of R6G at the single-molecule level, which is a rare molecule event hardly detectable by traditional SERS. Dynamic SERS provides near real-time molecular vibrational information with an improved signal-noise ratio, which opens a new avenue to capture metastable or rare molecule events for the comprehensive understanding of interfacial processes related to catalysis and life science.

The clinical significance of serum adipocytokines level in patients with lung cancer.

BACKGROUND: Adipocytokines were known to play a relevant role in metabolism, inflammation responses and carcinogenesis of several malignancies. Our aims were to detect the expression of serum adipocytokines, explore their potential diagnostic ability and relationship with clinicopathological characteristics of lung cancer. METHODS: Adipocytokines, insulin-like growth factor binding protein 1 (IGFBP-1), resistin, tumor necrosis factors (TNFα), TNF RI and TNF RII, vascular endothelial growth factor (VEGF), leptin, interleukin (IL)-6 and IL-10, chemerin, brain-derived neurotrophic factor (BDNF), plasminogen activator inhibitor-1 (PAI-1) were assessed in 49 untreated lung cancer patients and 20 healthy controls. The protein chip was used to detect the serum levels of adipocytokines. RESULTS: Lung cancer patients exhibited significantly elevated serum IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 levels compared to controls (P<0.05) and most of these adipocytokines revealed a modest discriminative ability for the diagnosis of lung cancer, while BDNF were lower in patients (P<0.05). TNF RI was associated with distant metastasis of lung cancer, while there was no relation between other adipocytokines and the patient clinicopathological features. CONCLUSIONS: These results suggest that cytokines IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 may be involved in the development and progression of lung cancer, and TNF RI may be involved in distant metastasis of lung cancer. Additionally, IGFBP-1, TNF RI, VEGF and TNF RII probably represent potentially useful biomarkers for the diagnosis of lung cancer.

Risk Analysis of Prostate Cancer Treatments in Promoting Metabolic Syndrome Development and the Influence of Increased Metabolic Syndrome on Prostate Cancer Therapeutic Outcome.

In clinical practice, few prostate cancer (PCa) patients are associated with metabolic syndrome (MetS), while few others acquire MetS during treatment. Whether the treatment of PCa increases the occurrence of MetS remains to be confirmed. This study reviewed the changes in MetS patients before and after PCa treatment to evaluate the effects of various treatment methods on MetS. We analyzed data of 1162 PCa patients, whether or not diagnosed with MetS, and changes in MetS patients after PCa treatment. Data of lower urinary tract symptoms, C-reactive protein (CRP), platelet distribution width (PDW), prostate-specific antigen (PSA), Gleason score, clinical stage, treatment methods, and progressive incidents were evaluated using logistic regression according to MetS diagnosis. The results showed significant differences in the prevalence of MetS before (17.38%) and after (23.67%) PCa treatment (P < 0.001). Bad diet, living habits, and prostate cancer treatment were considered as risk factors for MetS (OR = 1.731, 95%CI 1.367-2.193, P < 0.001). Radical prostatectomy (RP), androgen deprivation therapy including surgical castration and medical castration, iodine-125 seed brachytherapy (125I limited), and chemotherapy were independent risk factors of MetS. The MetS incidence rates after treatment in ADT+125I limited+chemotherapy compared to RP+TURP+EBRT were statistically significant at the corresponding risk grade (all P < 0.001). After treatment, the occurrence rates of progressive incidences were higher in MetS-PCa patients compared to non-MetS-PCa patients (all P < 0.001). So, the findings suggested that among PCa patients, multiple factors contribute to the occurrence of MetS, and PCa treatment is one among them. ADT+125I limited+chemotherapy may be the most influential treatment for MetS.

Novel Locus for Paroxysmal Kinesigenic Dyskinesia Mapped to Chromosome 3q28-29.

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent and brief attacks of dystonia or chorea precipitated by sudden movements. It can be sporadic or familial. Proline-Rich Transmembrane Protein 2 (PRRT2) has been shown to be a common causative gene of PKD. However, less than 50% of patients with primary PKD harbor mutations in PRRT2. The aim of this study is to use eight families with PKD to identify the pathogenic PRRT2 mutations, or possible novel genetic cause of PKD phenotypes. After extensive clinical investigation, direct sequencing and mutation analysis of PRRT2 were performed on patients from eight PKD families. A genome-wide STR and SNP based linkage analysis was performed in one large family that is negative for pathogenic PRRT2 mutations. Using additional polymorphic markers, we identified a novel gene locus on chromosome 3q in this PRRT2-mutation-negative PKD family. The LOD score for the region between markers D3S1314 and D3S1256 is 3.02 and we proposed to designate this locus as Episodic Kinesigenic Dyskinesia (EKD3). Further studies are needed to identify the causative gene within this locus.