A voxel-level resting-state fMRI study on patients with alcohol use disorders based on a power spectrum slope analysis method.

Background: Earlier neuroimaging investigations showed that abnormal brain activity in patients with alcohol use disorder (AUD) was frequency dependent. However, there is lacking of a comprehensive method to capture the amplitude of multi-frequency bands directly. Here, we used a new method, the power spectrum slope (PSS) to explore abnormal spontaneous activity of brain in patients with AUD. Methods: Thirty-three AUD patients and 29 healthy controls (HCs) enrolled in this study. The coefficient b and the power-law slope b' were calculated and compared between two groups. We also used the receiver operating characteristic (ROC) curve to examine the ability of the PSS analysis to distinguish between AUD and HCs. We next examined the correlation between PSS difference in the brain areas and the severity of alcohol dependence. Results: Thirty AUD patients and 26 HCs were retained after head motion correction. The two metrics of PSS values increased in the left precentral gyrus in AUD patients. The area under the curve values of PSS differences in the specific brain area were respectively 0.836 and 0.844, with sensitivities of 86.7% and 83.3% and specificities of 73.1% and 76.9%. The Michigan Alcoholism Screening Test (MAST) and Alcohol drinking scale (ADS) scores were not significantly correlated with the PSS values in the specific brain area. Conclusion: As a novel method, the PSS can well detect abnormal local brain activity in the AUD patients and may offer new insights for future fMRI studies.

Machine learning-based prediction of in-hospital mortality in patients with pneumonic chronic obstructive pulmonary disease exacerbations.

OBJECTIVE: While linear regression and LASSO models have been established for predicting in-hospital mortality, there is currently no validated clinical prediction algorithm to predict in-hospital mortality for patients with chronic obstructive pulmonary disease (COPD) exacerbations using machine learning. Thus, we will evaluate the BAP-65 and CURB-65, and construct a novel prediction model using the random forest (RF) technique. METHODS: A dataset of 1,418 patients with COPD exacerbations was collected. Age, gender, mental status, vital signs, and laboratory results were all taken into account for predictors. The categorical outcome variable was hospital-based mortality of people over 65 years. The dataset was divided randomly into a training dataset (70%) and a testing dataset (30%). We trained three prediction models, BAP-65, CURB-65, and the RF model, estimated the area under the receiver operating characteristic curve (AUROC) for the entire dataset. We also conducted a comparison of the AUROC values using the Delong test. RESULTS: A total of 658 individuals with COPD acute exacerbations were enrolled. Our analysis using the receiver operating characteristic curve demonstrated that the RF model exhibited excellent performance, with an AUROC of 0.80 (95% confidence interval: 0.75-0.84). In comparison, the BAP-65 prediction model yielded an AUROC of 0.72 (0.68-0.75), while the CURB-65 prediction model achieved an AUROC of 0.69 (0.67-0.73). CONCLUSIONS: The RF model demonstrated superior predictive capabilities than the BAP-65 and CURB-65 models in predicting in-hospital mortality. The results further highlighted significant factors for predicting in-hospital mortality, including blood eosinophil count, systolic blood pressure, and prior history of asthma.

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway.

OBJECTIVE: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. METHODS: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). CONCLUSION: EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

Alterations of brain activity in patients with alcohol use disorder: a resting-state fMRI study.

BACKGROUND: Alcohol use disorder (AUD) has a negative impact on one's health and wastes a lot of societal resources since it damages one's brain tissue. Yet the knowledge of the neural mechanisms underlying alcohol addiction still remains limited. This study aims to investigate the neural mechanisms underlying alcohol addiction by using voxel-wise binarized degree centrality (DC), weighted DC and functional connectivity (FC) methods to analyze brain network activity in individuals with AUD. METHODS: Thirty-three AUD patients and 29 healthy controls (HC) participated in this study. Binarized and weighted DC approach coupled with a second seed-based FC algorithm was used to assess the abnormal intrinsic hub features in AUD. We also examined the correlation between changes in functional network nodes and the severity of alcohol dependence. RESULTS: Thirty AUD patients and 26 HC were retained after head motion correction. The spatial distribution maps of the binarized DC and weighted DC for the AUD and HC groups were roughly similar. In comparison to HC, the AUD group had decreased binarized DC and decreased weighted DC in the left precentral gyrus (PreCG) and the left inferior parietal lobule (IPL). Significantly different brain regions in the DC analysis were defined as seed points in the FC analysis. Compared with HC, changes in FC within the right inferior temporal gyrus (ITG), right middle temporal gyrus (MTG), left dorsolateral superior frontal gyrus (SFGdor), bilateral IPL, left precuneus (PCUN), left lingual gyrus (LING), right cerebellum_crus1/ITG/inferior occipital gyrus (IOG) and right superior parietal gyrus (SPG) were observed. The correlation analysis revealed that FC of right MTG-right PreCG was negatively correlated with MAST scores, and FC of right IPL-left IPL was positively correlated with ADS scores. CONCLUSIONS: Alcohol use disorder is associated with aberrant regional activities in multiple brain areas. Binarized DC, weighted DC and FC analyses may be useful biological indicators for the detection of regional brain activities in patients with AUD. Intergroup differences in FC have also been observed in AUD patients, and these variations were connected to the severity of the symptoms. The AUD patients with lower FC value of the right IPL - left IPL has a lighter dependence on alcohol. This difference in symptom severity may be a compensation for cognitive impairment, indicating a difference in pathological pathways. Future AUD research will now have a fresh path thanks to these discoveries.

Association of intraoperative hypotension and postoperative acute kidney injury after adrenalectomy for pheochromocytoma: a retrospective cohort analysis.

BACKGROUND: Perioperative acute kidney injury (AKI) has been one of the leading causes of morbidity and mortality for surgical patients. Pheochromocytoma is a rare, catecholamine-secreting neuroendocrine neoplasm characterized by typical long-term hypertension that needs surgical resection. Our objective was to determine whether intraoperative mean arterial pressures (MAPs) less than 65 mmHg are associated with postoperative AKI after elective adrenalectomy in patients with pheochromocytoma. METHODS: We performed a retrospective review of patients undergoing adrenalectomy for pheochromocytoma between 1991 and 2019 at Peking Union Medical College Hospital, Beijing, China. Two intraoperative phases, before and after tumor resection, were recognized based on distinctly different hemodynamic characteristics. The authors evaluated the association between AKI and each blood pressure exposure in these two phases. The association between the time spent under different absolute and relative MAP thresholds and AKI was then evaluated adjusting for potential confounding variables. RESULTS: We enrolled 560 cases with 48 patients who developed AKI postoperatively. The baseline and intraoperative characteristics were similar in both groups. Though time-weighted average MAP was not associated with postoperative AKI during the whole operation (OR 1.38; 95% CI, 0.95-2.00; P = 0.087) and before tumor resection phase (OR 0.83; 95% CI, 0.65-1.05; P = 0.12), both time-weighted MAP and time-weighted percentage changes from baseline were strongly associated with postoperative AKI after tumor resection, with OR 3.50, 95% CI (2.25, 5.46) and 2.03, 95% CI (1.56, 2.66) in the univariable logistic analysis respectively, and with OR 2.36, 95% CI (1.46, 3.80) and 1.63, 95% CI (1.23, 2.17) after adjusting sex, surgical type (open vs. laparoscopic) and estimated blood loss in the multiple logistic analysis. At any thresholds of MAP less than 85, 80, 75, 70, and 65 mmHg, prolonged exposure was associated with increased odds of AKI. CONCLUSIONS: We found a significant association between hypotension and postoperative AKI in patients with pheochromocytoma undergoing adrenalectomy in the period after tumor resection. Optimizing hemodynamics, especially blood pressure after the adrenal vessel ligation and tumor is resected, is crucial for the prevention of postoperative AKI in patient with pheochromocytoma, which could be different from general populations.

Efficacy of continuous intravenous remimazolam versus midazolam in the extraction of impacted wisdom teeth: protocol of a randomised controlled trial.

INTRODUCTION: Benzodiazepines such as midazolam are widely used to moderately sedate patients during impacted wisdom tooth extraction to reduce anxiety in outpatient surgery. This present protocol was designed to determine whether continuous intravenous remimazolam, a new ultrashort-acting benzodiazepine, produces superior postoperative recovery quality to that of midazolam in patients undergoing extraction of impacted wisdom teeth. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial conducted at Peking Union Medical College Hospital, Beijing Anzhen Hospital and Beijing Shijitan Hospital in China. Approximately 150 participants undergoing extraction of impacted mandibular wisdom teeth will be randomly allocated to two groups (remimazolam and midazolam). The participants will be administered standard interventions to ensure they achieve a sedation level of III on the Ramsay sedation scale during the treatment. Preoperative and anaesthesia management and surgical techniques will be standardised for all participants. The primary outcome is recovery time for complete alertness and the secondary outcomes are anterograde amnesia during and after surgery, and interruption during operation for poor compliance or safety concerns. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Review Committee of Peking Union Medical College Hospital (approval number: ZS-3142), Beijing Anzhen Hospital (approval number: KS2022082) and Beijing Shijitan Hospital (approval number: 2023-4). TRIAL REGISTRATION NUMBER: NCT05350085.

Dechlorination of 2,4-dichlorophenol by Fe/Ni nanoparticles: the pathway and the effect of pH and the Ni mass ratio.

ABSTRACTThe dechlorination of 2,4-dichlorophenol (2,4-DCP) by a nanoscale Fe/Ni material was investigated at room temperature. 2,4-DCP can be removed more quickly by an Fe/Ni material with 2% Ni. Fe/Ni exhibited excellent adsorption and reduction efficiency toward 2,4-DCP in an aqueous solution over a wide range of pH values. The removal rate of 2,4-DCP exceeded 95% in 60 min in the pH range of 3.0-9.0, and more than 75% was dechlorinated to phenol (CA). The degradation pathway of 2,4-DCP was confirmed based on analysis of the intermediate and end products. A portion of 2,4-DCP was first dechlorinated with a chlorine atom to produce 2-chlorophenol and 4-chlorophenol, and then dechlorination was performed sequentially to form CA. The other portion of 2,4-DCP was dechlorinated to remove two chlorine atoms simultaneously to generate CA. The investigations are essential to the application of iron-based remediation technology.

Case Report: Takotsubo Syndrome Induced by Severe Anaphylactic Reaction During Anesthesia Induction and Subsequent High-Dose Epinephrine Resuscitation.

Takotsubo syndrome (TTS) is a type of non-ischemic cardiomyopathy characterized by an acute reversible left ventricular dysfunction with typical apical ballooning, usually with subsequent complete recovery. Early diagnosis and prompt treatment are of great essence. Herein, we described a case of TTS of a patient who was scheduled initially for laparoscopic endometrial cancer staging. The 69-year-old woman presented with cardiogenic shock induced by the severe anaphylactic reaction to the antibiotics during anesthesia induction. Cardiopulmonary resuscitation (CPR) was implemented while several boluses of 1 mg epinephrine were injected. After the return of spontaneous circulation, a large number of orange peel-like rash appeared on the head, face, neck, and trunk of the patient. Transesophageal echocardiography (TEE) revealed diffused decreased left ventricular systolic function. Therefore, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pump (IABP) were applied in the intensive care unit. Biomarkers like cardiac troponin I (cTnI) subsequently decreased with improved cardiac insufficiency. Finally, the patient was discharged in good condition. This case demonstrated that TTS could be secondary to severe anaphylactic shock and exogenous catecholamines. With the consideration of the reversible condition and predictable recovery of TTS, early vigilance and advanced life support devices should be necessary.

Assessing Empathy in Anesthesia Residents with the Chinese Version of the Consultation and Relational Empathy: A Pilot Standardized Patient Program.

Objectives To validate the reliability of the Chinese version of the Consultation and Relational Empathy (CARE) in physician-standardized patient (SP) encounter. We also tried to examine the agreement between video-based ratings and in-room ratings, as well as the agreement between the faculty ratings and SP ratings. Methods The CARE was translated into Chinese. Forty-eight anesthesia residents were recruited to make preoperative interview in SP-counter. Performance of each resident was graded by in-room raters, video raters and SP raters. Consistency between different raters was examined. Results The Chinese-CARE measure demonstrated high scale reliability with a Cronbach's alpha value of 0.95 and high consistency in the in-room ratings in intraclass correlation (coefficient=0.888,P<0.001). Despite a good consistency in intraclass correlation, video ratings were significantly higher than in-room ratings (39.6±7.1vs. 24.0±10.0,P<0.001), and Wilcoxon signed-rank test indicated that the pass/fail rate was significantly higher based on video ratings than based on in-room ratings (45/48vs. 22/48, P<0.001). SP ratings had a moderate consistency with in-room faculty ratings (coefficient=0.568,P<0.001), and there was no significant difference between the pass/fail rates based on the in-room ratings and SP ratings (22/48vs. 28/48, P=0.12). Conclusions The Chinese-CARE measure is reliable in the assessment of empathy during preoperative anesthesia interview. In-room and video ratings are not equivalent, while SP may provide a feasible alternative for the faculty rater in the assessment of communication skills with an appropriate measure.

The nature and reported incidence of suspected perioperative allergic reactions: A cross-sectional survey.

STUDY OBJECTIVE: Perioperative allergic reactions (POHs) are common and can lead to severe intraoperative instability and even mortality. In contrast to the situation in developed countries, where databases of perioperative anaphylaxis are well documented and analyzed, relevant data are lacking in China. Therefore, we aimed to conduct a national survey to explore the characteristics of perioperative allergic reactions, as well as the knowledge and attitudes toward management and reporting among anesthesiologists. DESIGN: Cross-sectional survey. SETTING: Anesthesia department. PATIENTS: A nationally representative sample comprising anesthesiologists from 12 province-level regions was selected. MEASUREMENTS: A 20-item questionnaire was designed and validated using the Delphi method. Survey distribution was performed between June 2019 and January 2020 by the Chinese Society of Anesthesiology (CSA), which is the official academic society of Chinese anesthesiologists. Responses were compiled and analyzed. MAIN RESULTS: We received responses from 4389 anesthesiologists across China. The estimated rate of suspected POH was 2/1000 patients (0.2%). On average, an anesthesiologist encountered 2.1 suspected POH cases per year. Neuromuscular blocking agents (NMBAs) were perceived as the most common causative agents, followed by antibiotics and succinylated gelatin. The rates of referral and allergy consultations were very low. Institutional support, including protocol development, cognitive aids, and tool kits, was not ideal. Additionally, the management of POH varied substantially. Most anesthesiologists believed that reporting and documenting POH was necessary. CONCLUSIONS: Our survey revealed that POH is commonly encountered by Chinese anesthesiologists, but few patients are referred to allergy specialists or clinics for further investigation. A standardized recommendation based on research and data derived from Chinese patients is required.

Identifying the Gap Between Novices and Experts in Fiberoptic Scope Control.

BACKGROUND: Fiberoptic intubation (FOI) is key in managing difficult airways. Good scope control increases efficiency and patient safety. Understanding the gap between novices and experts in scope control would help medical educators develop a feedback-based teaching approach for novices. We designed and used a checklist for evaluating the gap in fiberoptic scope control between novices and experts. METHODS: Twelve first-year anesthesiology residents (novice group) attended a lecture, followed by hands-on practice with a fiberoptic scope on a manikin. Five staff anesthesiologists (expert group) only did the hands-on practice. After practice, each participant was video-recorded while conducting an FOI on the manikin. Two senior anesthesiologists developed and used a 7-item checklist to assess the FOIs. Checklist scores and total times for FOIs were compared between groups using the Mann-Whitney U test. Internal consistency of the checklist items, interrater reliability, and the relationship between checklist score and total time for FOI were assessed with Cronbach alpha, Cohen kappa, and the Pearson correlation coefficient, respectively. RESULTS: Experts had higher checklist scores than novices (P = .0016). The item with the lowest success rate for novices (50%) was keeping the scope straight. Novices spent more time on the FOI than experts (P = .0005). Cronbach alpha, Cohen kappa, and the Pearson correlation coefficient were 0.8699, 0.75, and -0.9454, respectively. CONCLUSIONS: Our checklist was used to detect differences in fiberoptic scope control skills between novices and experts. With a video-based assessment method, it can be used to develop a feedback-based teaching method for fiberoptic scope control.

Screening for the action mechanisms of Fe and Ni in the reduction of Cr(VI) by Fe/Ni nanoparticles.

Zero-valent iron (ZVI), Fe2+ and H2 are possible electron donors in the reduction of Cr(VI) by nanoscale ZVI (n-ZVI). However, it is often ambiguous about the roles of these electron donors in the reductive removal of Cr(VI) from groundwater and wastewater. This study investigated the action mechanisms of Fe and Ni in Cr(VI) reduction by Fe/Ni nanoparticles (n-Fe/Ni). Among the three possible reduction mechanisms of ZVI, direct electron transfer from ZVI and its corrosion product, Fe2+, were confirmed to be responsible for the reduction removal of Cr(VI). H2, another product of ZVI corrosion, was found incapable of reducing Cr(VI). In addition, the secondary metal Ni in n-Fe/Ni was found to facilitate the direct electron transfer from ZVI owing to its ability to inhibit the passivation of ZVI and to enhance the production of Fe2+ due to the formation of FeNi galvanic cells. The results of characterizations on n-Fe/Ni before and after the reaction with Cr(VI) demonstrated that Cr(VI) was reduced to Cr(III), which existed as FeCr2O4 precipitates on the surface of n-Fe/Ni, resulting in effective sequestration of Cr(VI). These findings are important for understanding the main mechanisms of bimetallic nanoparticles or nanomaterials for reductive immobilization of Cr(VI), and may guide further ZVI-based technology development for remediation of contaminated water or soil with redox-active contaminants.

A new insight into the main mechanism of 2,4-dichlorophenol dechlorination by Fe/Ni nanoparticles.

Three possible dechlorination mechanisms of chloroorganics by nanoscale zero-valent iron (n-ZVI) have been proposed and widely accepted, however, the main mechanism is still controversial and not verified by experimental results. In this study, 2,4-dichlorophenol (2,4-DCP) was selected as the target pollutant and the experiments were carried out for the screening of the main mechanism of 2,4-DCP dechlorination by n-ZVI and Fe/Ni nanoparticles (n-Fe/Ni). The results indicated that >95% of 2,4-DCP could be dechlorinated to phenol by n-Fe/Ni within 120 min, while 2,4-DCP could hardly be dechlorinated by n-ZVI particles. The active hydrogen atom (H*) that transformed from H2 under the catalysis of Ni was responsible for >90% of 2,4-DCP dechlorination by n-Fe/Ni and <10% of the dechlorination was attributed to the direct electron transfer from ZVI. Fe2+ was not able to dechlorinate 2,4-DCP. Correspondently, Ni in n-Fe/Ni mainly acted as a catalyst, while the acceleration of electron transfer from ZVI by Ni had a positive effect on 2,4-DCP dechlorination. The investigations on the relative importance of these three mechanisms are essential to iron-based remediation technology.

α-Asarone Alleviated Chronic Constriction Injury-Induced Neuropathic Pain Through Inhibition of Spinal Endoplasmic Reticulum Stress in an Liver X Receptor-Dependent Manner.

BACKGROUND: Neuropathic pain is an intractable and complex disease. Recent studies have shown a close relationship between endoplasmic reticulum (ER) stress and neuropathic pain. Here, we investigated the effect of α-asarone, an ER stress inhibitor, on chronic constriction injury (CCI)-induced neuropathic pain. METHODS: Two parts were included in this study. In part 1, rats were assigned to 7 groups: the sham group, the sham + α-asarone 20 mg/kg group, the CCI group, the CCI + vehicle group, the CCI + α-asarone 5 mg/kg group, the CCI + α-asarone 10 mg/kg group, and the CCI + α-asarone 20 mg/kg group. After surgery, the rats were treated with α-asarone or normal saline daily. Pain thresholds were measured, and samples of the L3-6 spinal cord were taken for western blotting and immunofluorescence on day 7. In part 2, rats were intrathecally implanted with PE-10 tubes and divided into 4 groups: the CCI + α-asarone 20 mg/kg group, the CCI + α-asarone 20 mg/kg + vehicle group, the CCI + α-asarone 20 mg/kg + SR9243 group, and the CCI group. Five rats in each group were separated for behavioral tests 1 hour after intrathecal injection. The rest of them were killed for western blotting on day 7. RESULTS: In this study, CCI surgery significantly induced mechanical allodynia and thermal hyperalgesia. CCI surgery significantly induced activation of ER stress (PERK-eIF2α, IRE1α, CHOP, and XBP-1s) in rats. However, treatment with 20 mg/kg of α-asarone significantly alleviated CCI-induced activation of ER stress. Behavioral results showed that daily treatment with 20 mg/kg of α-asarone significantly alleviated CCI-induced nociceptive behaviors, on day 7 (mechanical allodynia, P = .016, 95% confidence interval, 0.645-5.811; thermal hyperalgesia, P = .012, 95% confidence interval, 0.860-6.507). Furthermore, α-asarone induced upregulated expression of liver X receptor ß (LXRß) and downstream proteins in the spinal cord. The LXR antagonist SR9243 completely inhibited the anti-ER stress and antinociceptive effects of α-asarone in rats. CONCLUSIONS: α-Asarone relieved CCI-induced neuropathic pain in an LXR-dependent manner. α-Asarone may be a potential agent for treatment of neuropathic pain.

Hemodynamic Changes in Patients Undergoing Pericardiectomy.

OBJECTIVE: To observe the hemodynamic changes in patients undergoing pericardiectomy at different operational stages. METHODS: Totally 16 consecutive patients receiving radical pericardiectomy were enrolled in this observational study. Hemodynamic variables were monitored continuously by pulse-indicated continuous cardiac output(PiCCO)system. Totally,three sets of intraoperative hemodynamic parameters were obtained at three different stages of pericardiectomy. RESULTS: During the pericardiectomy,the cardiac index[CI,(1.9±0.6),(2.7±0.6),(3.0±0.5)L·min(-1)·m(-2);P<0.05]and stroke volume index[SI,(22.5±8.7),(29.9±8.5),(30.1±8.5)dyn·s·cm(-5)·m(2);P<0.05]showed significant improvement,whereas central venous pressure[CVP,(17.1±5.0),(13.3±3.9),(12.3±3.0)mmHg;P<0.05]decreased significantly. Global end-diastolic volume index[GEDVi,(533±156),(580±153),(559±144)ml·m(-2);P<0.05]increased and stroke volume variation[SVV,(15.6±6.1)%,(10.8±4.2)%,(9.4±5.4)%;P<0.05]decreased intra-operatively. The majority of the above-mentioned hemodynamic improvements occurred after the resection of pericardium over the left ventricular outflow tract(LVOT). CONCLUSIONS: PiCCO system can serve as a reliable,less invasive hemodynamic monitoring method during pericardiectomy. Resection of the pericardium over the LVOT is the most important step of the pericardiectomy.

[Overexpression of p-Stat3 and Mcl-1, and their correlation with differentiation and apoptotic resistance in esophageal squamous cell carcinoma].

OBJECTIVE: To detect the expression of phosphorylated-signal transducer and activator of transcription 3 (p-Stat3) and myeloid leukemia-1 (Mcl-1) as well as their correlation, and to investigate the functional role of Stat3 and Mcl-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: Stat3 activity in ESCC cells was inhibited with JAK/Stat3 inhibitors (AG490 or JSI-124). Specific siRNA was used to inhibit the Stat3 expression. Cell apoptosis was detected by flow cytometry. Expression of Mcl-1 protein was determined by Western blotting. Expression of phospho-Stat3 (Tyr705) and myeloid leukemia-1 (Mcl-1) proteins in ESCC tissues was detected by tissue microarray and immunohistochemistry. The relationship between p-Stat3 or Mcl-1 aberrant expression and clinicopatholohical features of ESCC was analyzed. The correlation of their expression was also analyzed. RESULTS: Suppression of the Stat3 signaling activation in ESCC cells led to marked apoptosis, and dramatic reduction of Mcl-1 protein. The positive rate of phospho-Stat3 (Tyr705) expression was 45.0% in 50/111 of the ESCC tissue samples. The lower the degree of tumor differentiation, the higher the positive rate of phospho-Stat3 (Tyr705), showing a significant difference (P = 0.018). The positive rate of Mcl-1 protein expression was 72.1% (80/111), and the lower the degree of tumor differentiation was, the higher there was the positive rate of Mcl-1, with a significant difference (P = 0.026). There was a positive correlation between the expressions of p-Stat3 and Mcl-1 proteins (P = 0.012). CONCLUSIONS: In a subset of ESCC tissues, p-Stat3 (Tyr705) and Mcl-1 are overexpressed and positively correlated with each other, and both are correlated with tumor differentiation. Persistent activation of Stat3 contributes to apoptotic resistance in ESCC cells, and may be at least partly mediated through upregulation of Mcl-1.

Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells.

BACKGROUND & AIMS: Aberrant activation of the signal transducer and activator of transcription (Stat)3 and overexpression of polo-like kinase (PLK)1 each have been associated with cancer pathogenesis. The mechanisms and significance of dysregulation of Stat3 and PLK1 in carcinogenesis and cancer progression are unclear. We investigated the relationship between Stat3 and PLK1 and the effects of their dysregulation in esophageal squamous cell carcinoma (ESCC) cells. METHODS: We used immunoblot, quantitative reverse-transcription polymerase chain reaction, immunochemistry, chromatin immunoprecipitation, mobility shift, and reporter assays to investigate the relationship between Stat3 and PLK1. We used colony formation, fluorescence-activated cell sorting, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and xenograft tumor assays to determine the effects of increased activation of Stat3 and PLK1 in proliferation and survival of ESCC cells. RESULTS: Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3. PLK1 then potentiated the expression of Stat3; ß-catenin was involved in PLK1-dependent transcriptional activation of Stat3. This mutual regulation between Stat3 and PLK1 was required for proliferation of esophageal cancer cells and resistance to apoptosis in culture and as tumor xenografts in mice. Furthermore, phosphorylation of Stat3 and overexpression of PLK1 were correlated in a subset of ESCC. CONCLUSIONS: Stat3 and PLK1 control each other's transcription in a positive feedback loop that contributes to the development of ESCC. Increased activity of Stat3 and overexpression of PLK1 promote survival and proliferation of ESCC cells in culture and in mice.

[B cell activated co-receptor].

B cell activated co-receptor plays important roles in linkage of innate and acquired humoral immune responses. CD21 molecule in the co-receptor complex is a receptor for C3dg and CD19 molecule enhances BCR signal transduction. CD21 also expresses on the surface of follicular dendritic cells, which mediates the long-term maintenance of antigens and is indispensable for maintaining the memory of B cells. B cell activated co-receptor also has an effect on the negative selection of B cells reactive to autoantigens.