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.

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.

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.

Transient Electrochemical Surface-Enhanced Raman Spectroscopy: A Millisecond Time-Resolved Study of an Electrochemical Redox Process.

The pursuit of techniques with a high time resolution together with molecular signature information at the electrochemical interfaces has never stopped in order to explicitly monitor and understand the dynamic electrochemical processes. Here, we developed a transient electrochemical surface-enhanced Raman spectroscopy (TEC-SERS) to monitor the structural evolution of surface species at a time resolution that equals the transient electrochemical methods (e.g., cyclic voltammetry and chronoamperometry), so that the Raman signal with the molecular signature information and the electrochemical current signal can be precisely correlated. The technique was employed to study the redox process of nile blue on Ag surfaces. We revealed an interesting two-rate constant process and a peculiar increase of the absolute intensity during the reduction of nile blue on the Ag surface, which both related to the dissociation of nile blue aggregates and the follow-up reduction. Therefore, we were able to uncover the processes that are impossible to observe by conventional steady state SERS methods. The ability to provide a time resolution shorter than the charging time of the double layer capacitance with molecular fingerprint information has unprecedented significance for investigation of both reversible and irreversible electrochemical processes.

Systemic lidocaine versus erector spinae plane block for improving quality of recovery after laparoscopic cholecystectomy: A randomized controlled trial.

STUDY OBJECTIVE: To compare intravenous lidocaine, ultrasound-guided erector spinae plane block (ESPB), and placebo on the quality of recovery and analgesia after laparoscopic cholecystectomy. DESIGN: A prospective, triple-arm, double-blind, randomized, placebo-controlled non-inferiority trial. SETTING: A single tertiary academic medical center. PATIENTS: 126 adults aged 18-65 years undergoing elective laparoscopic cholecystectomy. INTERVENTIONS: Patients were randomly allocated to one of three groups: intravenous lidocaine infusion (1.5 mg/kg bolus followed by 2 mg/kg/h) plus bilateral ESPB with saline (25 mL per side); bilateral ESPB with 0.25% ropivacaine (25 ml per side) plus placebo infusion; or bilateral ESPB with saline (25 ml per side) plus placebo infusion. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. The non-inferiority of lidocaine versus ESPB was assessed with a margin of -6 points and 97.5% confidence interval (CI). Secondary outcomes included 24-h area under the curve (AUC) for pain scores, morphine consumption, and adverse events. MAIN RESULTS: 124 patients completed the study. Median (IQR) 24-h QoR-15 scores were 123 (117-127) for lidocaine, 124 (119-126) for ESPB, and 112 (108-117) for placebo. Lidocaine was non-inferior to ESPB (median difference  -1, 97.5% CI: -4 to ∞). Both lidocaine (median difference 9, 95% CI: 6-12, P < 0.001) and ESPB (median difference 10, 95% CI: 7-13, P < 0.001) were superior to placebo. AUC for pain scores and morphine use were lower with lidocaine and ESPB versus placebo (P < 0.001 for all), with no significant differences between lidocaine and ESPB. One ESPB patient reported a transient metallic taste; no other block-related complications occurred. CONCLUSIONS: For patients undergoing laparoscopic cholecystectomy, intravenous lidocaine provides a non-inferior quality of recovery compared to ESPB without requiring specialized regional anesthesia procedures. Lidocaine may offer a practical and accessible alternative within multimodal analgesia pathways.

Chemotherapy-induced prospective memory impairment in patients with breast cancer.

OBJECTIVE: This study aimed to investigate the event-based prospective memory (EBPM) and time-based prospective memory (TBPM) in chemotherapy-induced cognitive impairment in patients with breast cancer. METHODS: Forty patients with breast cancer who underwent adjuvant chemotherapy and 40 age-matched and education-matched healthy women were administered with a battery of neuropsychological tests including EBPM and TBPM tasks. RESULTS: A significant difference between breast cancer patients and controls was found in the scores on the mini-mental state examination (t = -11.684, p < 0.01), verbal fluency test (t = -7.939, p < 0.01), and digit span (t = -2.538, p < 0.05). Compared with healthy controls, breast cancer patients exhibited a poorer performance on EBPM (t = -7.096, p < 0.01) but not on TBPM (t = -1.921, p > 0.05). CONCLUSIONS: Our results suggest that breast cancer patients who had undergone adjuvant chemotherapy show deficits in EBPM but not in TBPM.

The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats.

BACKGROUND: While lipid emulsion may reverse the systemic toxicity of bupivacaine, the pharmacokinetics and tissue distribution of bupivacaine after lipid emulsion infusion are not clear. In this study, we assessed the influence of lipid emulsion administration on the pharmacokinetics and tissue distribution of bupivacaine. METHODS: Rats in the lipid group were administered IV bupivacaine at the rate of 2 mg·kg(-1)·min(-1) for 4 minutes, and then were treated with an infusion of 30% lipid emulsion at the rate of 3 mL·kg(-1)·min(-1) for 5 minutes; saline was substituted in the control group (n = 6 for pharmacokinetics). We then randomly assigned 100 rats into the lipid group and control group (n = 50 for distribution). The toxicity model and treatment were the same as the pharmacokinetic portion. Plasma and tissues including brain, heart, liver, spleen, lung, kidney, omentum, and muscle were collected. The plasma concentration and tissue content of bupivacaine were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the pharmacokinetics of bupivacaine. RESULTS: All data are shown as mean ± SD. After treatment with the lipid emulsion, t1/2ß of bupivacaine in the lipid group was significantly shorter (110 ± 25 minutes vs 199 ± 38 minutes, P = 0.001), the clearance was higher (14 ± 4 mL·mg(-1)·kg(-1) vs 9 ± 4 mL·mg(-1)·kg(-1), P = 0.038), and the t1/2α was longer than that of the control group (4 ± 1 minutes vs 2 ± 1 minutes, P = 0.014); the K12 in the lipid group was less than that of the control group (0.13 ± 0.04 vs 0.32 ± 0.13, P = 0.011). In the lipid group, the bupivacaine content in heart, brain, lung, kidney, and spleen was lower than that in the control group, but higher in the liver at 20, 30, and 45 minutes. CONCLUSION: The lipid sink phenomenon was observed in this study. The use of a lipid emulsion accelerated the elimination of bupivacaine.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cerebral schistosomiasis japonica without gastrointestinal system involvement.

BACKGROUND: Schistosoma japonicum is the most widespread schistosoma in the world. Although gastrointestinal system involvement with S japonicum appears to be considerably common, cerebral schistosomiasis is not frequent. Cerebral schistosomiasis japonica intestinal and hepatosplenic involvement is more rare. We collected 2 cases of cerebral schistosomiasis identified by pathological diagnosis, lacking extracranial involvement. In addition, one of them had multiple lesions, which was also rare. CASE DESCRIPTION: Two male patients came from Dongting Lake region, Hunan province, one of the oldest and most severe endemic areas of China. Their clinical symptoms varied, such as headache, dizziness, seizures, and others. Studies in blood were normal except for eosinophilia. Computed tomography of brains showed hyperdense areas, and MRI showed isointense signal on T1-weighted images, hyperintense signal on T2-weighted images, and heterogeneous enhancement. The definitive diagnosis was cerebral schistosomiasis japonium by biopsy. Standard use of praziquantel and corticosteroid drugs was applied, and the prognosis was good. CONCLUSION: Cerebral schistosomiasis japonica without intestinal and hepatosplenic involvement is exactly rare and easily ignored. The diagnosis sometimes is difficult. Laboratory and imaging examinations are helpful but not specific. Although operation can give the definitive diagnosis, it is not imperative. The administration of praziquantel and corticosteroid drugs in early stages is good for prognosis.