Efficacy and safety of intrathecal dexamethasone combined with isoniazid in the treatment of tuberculous meningitis: a meta-analysis.

BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544). CONCLUSION: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. TRIAL REGISTRATION: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .

Inhibitory effect of recombinant human CXCL8(3-72)K11R/G31P on atherosclerotic plaques in a mouse model of atherosclerosis.

Context: Atherosclerosis is a chronic inflammatory disease in which the plaques were built up inside of the artery. Interleukin-8 (IL-8, CXCL8) is an inflammatory factor, known to play an important role in the development of atherosclerosis. G31P is an antagonist of the IL-8 receptor, which plays roles in vascular smooth muscle cell (VSMC) proliferation and migration. Objective: This study is to investigate the therapeutic effect of G31P on atherosclerosis through a mouse model. Materials and methods: A mouse model of atherosclerosis was generated through feeding the ApoE-/- mice with high fat diet for 12 weeks. G31P was injected subcutaneously into the mice. The levels of keratinocyte chemoattractant (KC), CXCR2, TNF-α, and IFN-γ were analyzed through ELISA. The expressions of MMP-2, MMP-9, PCNA, and Mef2a in aortic tissues were detected through RT-qPCR. In A7r5 cells, the levels of p-ERK, ROCK1, and ROCK2 were analyzed by western blot. Intracellular calcium levels were measured through Fluo-3 AM assay. Results and disccussion: G31P suppressed the abnormal lipid profile and decreased the levels of KC, MMP-2, MMP-9, PCNA, and Mef2a in a mouse model of atherosclerosis. In addition, G31P also inhibited the expressions of p-ERK, ROCK1, ROCK2, and decreased the calcium concentrations in A7r5 cells. Conclusions: These findings indicate the potential therapeutic effects of G31P in suppressing the development of atherosclerosis by antagonizing the IL-8 receptor. G31P inhibits the proliferation and migration of VSMCs through regulating the Rho-kinase, ERK, and calcium-dependent pathways.

Comparison of high flow nasal cannula with noninvasive ventilation in chronic obstructive pulmonary disease patients with hypercapnia in preventing postextubation respiratory failure: A pilot randomized controlled trial.

High flow nasal cannula (HFNC) has been shown to improve extubation outcomes in patients with hypoxemia, but the role of HFNC in weaning patients with chronic obstructive pulmonary disease (COPD) with hypercapnia from invasive ventilation is unclear. We compared the effects of HFNC to noninvasive ventilation (NIV) on postextubation vital signs and arterial blood gases (ABGs) among patients with COPD. Other outcomes included comfort scores, need for bronchoscopy, use of pulmonary medications, and chest physiotherapy. Forty-two COPD patients who had persistent hypercapnia at extubation were assigned randomly to receive HFNC (22) or NIV (20). Twenty patients in each group were enrolled for per-protocol analysis with regard to primary outcomes. Vital signs and ABGs before extubation were similar between groups. At 3 hr after extubation, pH in the NIV group was lower than HFNC group (7.42 ± 0.06 vs. 7.45 ± 0.05, p = 0.01). At 24 hr after extubation, patients' mean arterial pressure (82.97 ± 9.04 vs. 92.06 ± 11.11 mmHg, p = 0.05) and pH (7.42 ± 0.05 vs. 7.46 ± 0.03, p = 0.05) in the NIV group were lower than in the HFNC group. No significant differences were found at 48 hr after extubation. In the HFNC group, comfort scores were better (3.55 ± 2.01 vs. 5.15 ± 2.28, p = 0.02) and fewer patients needed bronchoscopy for secretion management within 48 hr after extubation (2/22 vs. 9/20, p = 0.03). HFNC is a potential alternative to NIV to wean hypercapnic COPD patients with regard to vital signs and ABGs, HFNC improved patients' comfort and secretion clearance.

Toll-like receptor 4 promotes angiogenesis in pancreatic cancer via PI3K/AKT signaling.

Deregulation of Toll-like receptor 4 (TLR4) is closely associated with the progression of various types of cancers, but its role in pancreatic carcinogenesis is unclear. This study aimed to investigate the role of TLR4 in the angiogenesis of pancreatic cancer and the underlying molecular mechanisms. The culture supernatant (conditioned medium) of PANC-1 cells after appropriate treatment was used for the treatment of HUVECs. The proliferation, migration and tube formation of HUVECs were assessed by MTT, Transwell and Matrigel, respectively. In pancreatic cancer tissues, TLR4, VEGF and CD31 were upregulated as determined by immunohistochemistry and the expression of TLR4 and VEGF was positively correlated with microvessel density as detected by CD31 staining. Activation of TLR4 signaling by LPS in PANC-1 cells resulted in increased VEGF and phosphorylation of AKT, which were abolished by TLR4 silencing with siRNA and PI3K/AKT signaling inhibitor LY294002. The conditioned medium from PANC-1 cells treated with LY294002 or transfected with TRL4 siRNA reduced the proliferation, migration and tube formation of HUVECs. In contrast, the conditioned medium from PANC-1 cells treated with LPS stimulated the proliferation, migration and tube formation of HUVECs, which was however significantly inhibited by pretreatment of PANC-1 cells with LY294002 or transfection with TRL4 siRNA. Our findings suggest TLR4 may promote angiogenesis in pancreatic cancer by activating the PI3K/AKT signaling pathway to induce VEGF expression.

A Novel Continuous Sleep State Artificial Neural Network Model Based on Multi-Feature Fusion of Polysomnographic Data.

Purpose: Sleep structure is crucial in sleep research, characterized by its dynamic nature and temporal progression. Traditional 30-second epochs falter in capturing the intricate subtleties of various micro-sleep states. This paper introduces an innovative artificial neural network model to generate continuous sleep depth value (SDV), utilizing a novel multi-feature fusion approach with EEG data, seamlessly integrating temporal consistency. Methods: The study involved 50 normal and 100 obstructive sleep apnea-hypopnea syndrome (OSAHS) participants. After segmenting the sleep data into 3-second intervals, a diverse array of 38 feature values were meticulously extracted, including power, spectrum entropy, frequency band duration and so on. The ensemble random forest model calculated the timing fitness value for all the features, from which the top 7 time-correlated features were selected to create detailed sleep sample values ranging from 0 to 1. Subsequently, an artificial neural network (ANN) model was trained to delineate sleep continuity details, unravel concealed patterns, and far surpassed the traditional 5-stage categorization (W, N1, N2, N3, and REM). Results: The SDV changes from wakeful stage (mean 0.7021, standard deviation 0.2702) to stage N3 (mean 0.0396, standard deviation 0.0969). During the arousal epochs, the SDV increases from the range (0.1 to 0.3) to the range around 0.7, and decreases below 0.3. When in the deep sleep (≤0.1), the probability of arousal of normal individuals is less than 10%, while the average arousal probability of OSA patients is close to 30%. Conclusion: A sleep continuity model is proposed based on multi-feature fusion, which generates SDV ranging from 0 to 1 (representing deep sleep to wakefulness). It can capture the nuances of the traditional five stages and subtle differences in microstates of sleep, considered as a complement or even an alternative to traditional sleep analysis.

Triptolide induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells by downregulating COX-2 and VEGF.

Triptolide (TPL) inhibits the growth and proliferation of a wide range of human cancer cells, but the underlying mechanism is largely unknown. Here, we report that TPL induces apoptosis and inhibits proliferation of PANC-1 pancreatic cancer cells by downregulating cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). Cell viability and apoptosis were measured by MTT assay and flow cytometry. Real-time PCR and Western blot were used to examine the expression of COX-2 and VEGF. The Matrigel angiogenesis and Transwell migration were employed to assess tube formation and cell migration. Pancreatic cancer mouse xenografts were established to investigate the in vivo antitumor effects of TPL. TUNEL staining and immunohistochemistry were used to detect the apoptosis rate and protein expression in tumor tissues. TPL inhibited the proliferation of pancreatic cancer cells in a time and concentration-dependent manner and decreased the expression of COX-2 and VEGF in vitro. Furthermore, medium from TPL-treated PANC-1 cells inhibited the proliferation, migration, and tube formation of HUVECs. TPL significantly reduced the growth of pancreatic cancer mouse xenografts, accompanied by an induction of apoptosis, inhibition of angiogenesis, and reduction of COX-2 and VEGF. Our data indicate that suppressing the expression of COX-2 and VEGF may be one of the molecular mechanisms by which TPL induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells.

The REM microarousal and REM duration as the potential indicator in paradoxical insomnia.

OBJECTIVE: Although paradoxical insomnia is a prevalent subtype of chronic insomnia, the etiology of it is unclear. Contrary to complaints of little or no sleep, polysomnography (PSG) findings show that paradoxical insomnia patients have near normal sleep macrostructure. The purpose of this study is to determine the changes of microstructure and explore the etiology of paradoxical insomnia. METHODS: The PSG findings of 89 paradoxical insomnia patients were compared with those of 41 gender balanced healthy controls without sleep complaints. All subjects underwent nocturnal PSG recordings. Conventional PSG measures and microarousals were quantified and statistically analyzed. Receiver operating characteristic curve and correlation analysis were used to evaluate the potential of REM sleep microarousals and REM duration as indicators of paradoxical insomnia. RESULTS: Compared with the controls, paradoxical insomnia patients had no significant differences in sleep macrostructures. Statistical analysis showed that non-rapid eye movement (NREM) microarousals revealed no significant differences between paradoxical insomnia patients and controls. Noticeably, more spontaneous microarousals appeared in rapid eye movement (REM) stage for paradoxical insomnia patients. Based on receiver operating characteristic curve (ROC), the optimal cutoff value of REM sleep microarousals could predict paradoxical insomnia. Furthermore, a positive correlation between microarousals in REM sleep and the duration of REM sleep was presented in paradoxical insomnia patients. CONCLUSIONS: The frequency of REM microarousals and the duration of REM sleep could reflect the real sleep state of paradoxical insomnia patients. That suggested PSG investigation extended to microarousal could be helpful to understand the etiology in paradoxical insomnia.

Validation of a portable monitor compared with polysomnography for screening of obstructive sleep apnea in polio survivors.

Subjective: Sleep-disordered breathing (SDB) is highly prevalent in polio survivors. Obstructive sleep apnea (OSA) is the most frequent type. Full polysomnography (PSG) is recommended for OSA diagnosis in patients with comorbidities by current practice guidelines, but it is not always accessible. The purpose of this study was to evaluate whether type 3 portable monitor (PM) or type 4 PM might be a viable alternative to PSG for the diagnosis of OSA in postpolio subjects. Methods: A total of 48 community-living polio survivors (39 men and 9 women) with an average age of 54.4 ± 5.3 years referred for the evaluation of OSA and who volunteered to participate were recruited. First, they completed the Epworth Sleepiness Scale (ESS) questionnaire and underwent pulmonary function testing and blood gas tests the day before PSG night. Then, they underwent an overnight in-laboratory PSG with a type 3 PM and type 4 PM recording simultaneously. Results: The AHI from PSG, respiratory event index (REI) from type 3 PM, and ODI3 from type 4 PM was 30.27 ± 22.51/h vs. 25.18 ± 19.11/h vs. 18.28 ± 15.13/h, respectively (P < 0.001). For AHI ≥ 5/h, the sensitivity and specificity of REI were 95.45 and 50%, respectively. For AHI ≥ 15/h, the sensitivity and specificity of REI were 87.88% and 93.33%, respectively. The Bland-Altman analysis of REI on PM vs. AHI on PSG showed a mean difference of -5.09 (95% confidence interval [CI]: -7.10, -3.08; P < 0.001) with limits of agreement ranging from -18.67 to 8.49 events/h. ROC curve analysis for patients with REI ≥ 15/h showed an area under the curve (AUC) of 0.97. For AHI ≥ 5/h, the sensitivity and specificity of ODI3 from type 4 PM were 86.36 and 75%, respectively. For patients with AHI ≥ 15/h, the sensitivity was 66.67%, and the specificity was 100%. Conclusion: Type 3 PM and Type 4 PM could be alternative ways to screen OSA for polio survivors, especially for moderate to severe OSA.

ROCK1 induces ERK nuclear translocation in PDGF-BB-stimulated migration of rat vascular smooth muscle cells.

It has been known that Rho-associated protein kinase (ROCK) signaling regulates the migration of vascular smooth muscle cells (VSMCs). However, the isoform-specific roles of ROCK and its underlying mechanism in VSMC migration are not well understood. The current study thus aimed to investigate the roles of ROCK1/2 and their relationship to the MAPK signaling pathway in platelet-derived growth factor (PDGF)-induced rat aorta VSMC migration by manipulating ROCK gene expression. The results revealed that ROCK1 small interfering ribonucleic acid (siRNA) rather than ROCK2 siRNA decreased PDGF-BB-generated VSMC migration, and upregulation of ROCK1 expression via transfection of constructed pEGFP-C1/ROCK1 plasmid further increased the migration of PDGF-BB-treated VSMCs. In PDGF-treated VSMCs, ROCK1 siRNA did not affect the phosphorylation levels of ERK and p38 in the cytoplasm, but decreased the level of ERK phosphorylation in the nucleus. These findings demonstrate that activated ROCK1 can promote VSMC migration through facilitating phosphorylation and nuclear translocation of ERK protein.

Clinical study of submucosal tunneling endoscopic resection and endoscopic submucosal dissection in the treatment of submucosal tumor originating from the muscularis propria layer of the esophagus.

Herein, we aimed to evaluate the clinical value and safety of transendoscopic submucosal tunnel tumor resection (STER) and endoscopic submucosal dissection (ESD) for the resection of esophageal submucosal intrinsic muscle tumors. We retrospectively analyzed the clinical data of 68 patients with esophageal submucosal intrinsic muscle tumors treated with STER (STER group, n = 38, March 2018 to January 2020) or ESD (ESD group, n = 30, January 2017 to January 2020) at the First People's Hospital of Lianyungang to compare the treatment efficacy, hospitalization time and costs, and postoperative complications between the 2 groups. All 68 cases were of single lesions. The mean operative duration was shorter in the STER group (53.39 ±â€…11.57 min) than in the ESD group (68.33 ±â€…18.52 min, P < .05). The postoperative hospital stay duration was significantly shorter in the STER group (5.86 ±â€…1.01 days; P < .05) than in the ESD group (8.2 ±â€…3.4 days, P < .05). The mean hospitalization cost was significantly lower in the STER group than in the ESD group (12,468.8 + 4966.8 yuan vs 17,033.3 ±â€…4547.2 yuan; P < .05). Only 1 case of intraoperative perforation occurred in ESD group. There were no other complications in both groups. The wound healed in both groups, and no residual or recurrent tumors were detected during the follow-up period. Both STER and ESD can be used for the treatment of esophageal intrinsic muscular layer (MP) tumors, and STER is safer and more efficient for lesions with a diameter <3.5 cm.

Sleep and circadian rhythm disturbances in intensive care unit (ICU)-acquired delirium: a case-control study.

OBJECTIVE: The relationships among sleep, circadian rhythm, and intensive care unit (ICU)-acquired delirium are complex and remain unclear. This study aimed to examine the pathophysiological mechanisms of sleep and circadian rhythm disturbances in patients with ICU-acquired delirium. METHODS: This study included critical adult patients aged 18 to 75 years who were treated in the ICU. Twenty-four-hour polysomnography was performed and serum melatonin and cortisol levels were measured six times during polysomnography. Receiver operating characteristic curves and binomial logistic regression were used to evaluate the potential of sleep, melatonin, and cortisol as indicators of delirium in the ICU. RESULTS: Patients with delirium (n = 24) showed less rapid eye movement (REM) sleep compared with patients without delirium (n = 24, controls). Melatonin levels were lower and cortisol levels were higher in the delirium group than in the control group. REM sleep, melatonin, and cortisol were significantly associated with delirium. The optimal cutoff values of REM sleep and mean melatonin and cortisol levels that predicted delirium were ≤1.05%, ≤422.09 pg/mL, and ≥212.14 ng/mL, respectively. CONCLUSIONS: REM sleep, and melatonin and cortisol levels are significantly associated with the risk of ICU-acquired delirium. Improved sleep and readjustment of circadian rhythmicity may be therapeutic targets of ICU-acquired delirium.

AnnexinA7 promotes epithelial-mesenchymal transition by interacting with Sorcin and contributes to aggressiveness in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and metastasis is the major cause of the high mortality of HCC. In this study, we identified that AnnexinA7 (ANXA7) and Sorcin (SRI) are overexpressed and interacting proteins in HCC tissues and cells. In vitro functional investigations revealed that the interaction between ANXA7 and SRI regulated epithelial-mesenchymal transition (EMT), and then affected migration, invasion, and proliferation in HCC cells. Furthermore overexpression/knockdown of ANXA7 was remarkably effective in promoting/inhibiting tumorigenicity and EMT in vivo. Altogether, our study unveiled a mechanism that ANXA7 promotes EMT by interacting with SRI and further contributes to the aggressiveness in HCC, which provides a novel potential therapeutic target for preventing recurrence and metastasis in HCC.

Triptolide enhances the sensitivity of pancreatic cancer PANC-1 cells to gemcitabine by inhibiting TLR4/NF-κB signaling.

BACKGROUND: This study aimed to investigate roles of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling in triptolide (TPL)-induced sensitivity of pancreatic cancer cells to gemcitabine (GEM). METHODS: In vitro, pancreatic cancer PANC-1 cells were treated with lipopolysaccharide (LPS) to activate TLR4, TLR4-siRNA, GEM alone, or GEM plus TPL. In vivo, nude mice bearing PANC-1 cell xenografts were treated with GEM, TPL, or both. Cell proliferation was detected by MTT assay and Ki-67 staining. Apoptosis was assessed by flow cytometry and TUNEL assay. A double luciferase reporter gene was used to detect NF-κB activity. RESULTS: The sensitivity of PANC-1 cells to GEM was reduced by LPS but enhanced by TLR4-siRNA. TPL inhibited expression of TLR4/NF-κB signaling components, which was reversed by LPS. The TPL+GEM group showed more apoptosis than the LPS+TPL+GEM group. Moreover, the activity of NF-κB and the expression of TLR4, p-p65 Survivin, CyclinD1 and Bcl-2 in the TPL+GEM group were lower than in the LPS+TPL+GEM group, whereas Bax expression was higher. The volume of transplanted tumors in the TPL+GEM group was lower than that in the TPL or GEM group. Phospho-p65, Survivin, CyclinD1 and Bcl-2 expression in transplanted tumors was lower in TPL+GEM group than in either single drug group. The Ki-67 staining score of the TPL+GEM group was lower and tumor cells apoptosis rate was increased when compared with TPL or GEM alone. CONCLUSIONS: TPL enhances the sensitivity of pancreatic cancer PANC-1 cells to GEM by inhibiting TLR4/NF-κB signaling.

Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients.

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori (H. pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H. pylori and ulcer healing in Chinese peptic ulcer patients. METHODS: A total of 103 subjects with H. pylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1000 mg and either clarithromycin 500 mg (OAC group, n = 58) or metronidazole 400 mg (OAM group, n = 45). All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H. pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H. pylori. Successful eradication was defined as negative results from both examination methods. RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H. pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in OAM group. Based on the intention-to-treat analysis, the eradication rate of H. pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in OAM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21) in OAM group (per-protocol analysis, P>0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%) reported adverse events (P>0.05). CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H. pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H. pylori infection in China.

Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis.

AIM: Cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasm. Helicobacter pylori (H pylori) infection is causally linked to gastric cancer. However, the expression of COX-2 in various stages of H pylori-associated gastric carcinogenesis pathway has not been elucidated. Therefore, the aim of this study was to clarify the role of H pylori induced COX-2 expression during carcinogenesis in the stomach. METHODS: Gastric biopsies from 138 subjects (30 cases of chronic superficial gastritis (CSG), 28 cases of gastric glandular atrophy (GA), 45 cases of gastric mucosal intestinal metaplasia (IM), 12 cases of moderate gastric epithelial dysplasia and 23 cases of gastric cancer) were enrolled. H pylori infection was assessed by a rapid urease test and histological examination (modified Giemsa staining). The expression of COX-1 and COX-2 in human gastric mucosa was detected by immunohistochemical staining. RESULTS: H pylori infection rate was 64.3% in GA and 69.5% in gastric cancer, which was significantly higher than that (36.7%) in CSG (P<0.05). The positive expression rates of COX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% in CSG, GA, IM, dysplasia and gastric cancer, respectively. From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa. The level of COX-2 expression in IM and dysplasia was significantly higher in H pylori-positive than in H pylori-negative subjects (P<0.01). CONCLUSION: COX-2 expression induced by H pylori infection is a relatively early event during carcinogenesis in the stomach.

[Research of 24-hour dynamic sleep monitoring and melatonin changes in patients with delirium in intensive care unit].

OBJECTIVE: To dynamic monitor and analyze the characteristic of polysomnography (PSG) and melatonin levels of delirium patients in intensive care unit (ICU). METHODS: A prospective observational study was performed from December 2013 to April 2014. The patients admitted to ICU of Affiliated Hospital of Binzhou Medical College for more than 72 hours were evaluated with confusion assessment method for the ICU (CAM-ICU), and were divided into delirium group and non-delirium group. Sleep patterns of all the patients underwent continuous PSG for up to 24 hours were evaluated. Melatonin levels were determined every 4 hours with enzyme linked immunosorbent assay (ELISA) duration sleep monitoring. RESULTS: Eighteen patients were enrolled, and 9 were delirium patients. All the patients had sleep disorders: a decrease in rapid eye movement (REM) sleep [(5.91 ± 5.26)%], an increase in the sleep fragmentations [arousal index was (15.40 ± 12.79) times/h], and the N3 sleep stage was on the lower limit of normal [(14.67 ± 11.10)%]. Compared with non-delirium group, the REM sleep was significantly decreased in delirium group [(0.10 ± 0.20)% vs. (8.83 ± 3.81)%, t=4.782, P=0.001]. Melatonin levels lost rhythm between day and night, and there was no difference in melatonin between delirium group and non-delirium group(time effect: F=1.370, P=0.287; between-group effect: F=1.646, P=0.250; interaction effect: F=1.558, P=0.247). The peak of melatonin levels of delirium group appeared on 06:00 [(137.84 ± 62.21) ng/L] and 14:00 [(148.24 ± 58.8) ng/L], the minimum value on 22:00 [(64.47 ± 26.97) ng/L]. But in non-delirium group, the peak of melatonin levels appeared on 02:00 [(63.52 ± 39.75) ng/L], the minimum value on 10:00 [(44.87 ± 11.19) ng/L]. CONCLUSIONS: ICU patients have sleep disorders, and the delirium patients have less REM stage. Normal rhythmic melatonin secretion changes of ICU patients were lost. The delirium peak of patients appears in the daytime.

CEA promoter-regulated oncolytic adenovirus-mediated Hsp70 expression in immune gene therapy for pancreatic cancer.

Gene therapy is an important means for the comprehensive treatment of pancreatic cancer. Challenges associated with gene therapy include control of vector security and effective genetic screening. In this paper, a CEA promoter-regulated oncolytic adenovirus vector was constructed. The reporter gene assay demonstrated that the viral vector was confirmed to have tumor-specific replication features. In vitro cytology studies showed that the CEA promoter regulated the proliferation of the adenovirus vector carrying the Hsp70 gene (AdCEAp-Hsp70), which significantly increased the expression levels of Hsp70 in the CEA-positive pancreatic cancer cells, resulting in an overall reduction in the survival of cancer cells. In the human pancreatic cancer Panc-1 xenograft model in immune deficient nude mice, the CEA promoter-regulated adenovirus AdCEAp-Hsp70 significantly inhibited tumor growth. In the rat pancreatic cancer DSL-6A/C1 xenograft model in rats, the viral proliferation and high expression levels of Hsp70 promoted the interstitial infiltration of CD4+, CD8+ and gamma/delta T cells into tumors, induced host secretion of the cytokines TGF-ß, INF-γ, and IL-6 and had a dual anti-tumor effects that completely inhibited the growth of pancreatic cancer. The results demonstrated that the oncolytic adenovirus under the control of CEA promoter provides additional assurances regarding the safety and efficiency of cancer gene therapy. This gene therapy model improves anti-cancer efficiency and has broad applications and developmental prospects.

[Expression of glutathione S-transferase-pi and DNA topoisomerase II alpha and their implications in colorectal carcinoma].

OBJECTIVE: To investigate the expression of GST-pi and Topo II-alpha, and their relationships with clinicopathological parameters in colorectal carcinoma. METHODS: The expression of GST-pi and Topo II-alpha were detected by avidin-biotin-peroxide complex (ABC) method in tumor specimens, matched paratumor tissues from 60 cases with colorectal carcinoma and normal colonic tissues from 15 cases. RESULTS: The expression rates of GST-pi and Topo II-alpha were 90.0% and 86.7% respectively in tumor tissues, significantly higher than those in matched paratumor tissues and normal tissues (P< 0.01). The expressions of GST-pi and Topo II-alpha were associated with cellular differentiation, Dukes stage and lymph node metastasis (all P< 0.01), but not with tumor size and histological type (all P > 0.05). The expression level of GST-pi was significantly higher in poorly differentiated tumors than that in well differentiated tumors. The expression level of Topo II-alpha in well-differentiated tumors were stronger than that in poorly differentiated tumors. CONCLUSIONS: The detection of GST-pi and Topo II-alpha expressions may be helpful to judge the malignant behavior, metastasis and prognosis in human colorectal carcinoma.

[Relationship between cyclooxygenase- 2 expression and angiogenesis in patients with gastric cancer].

OBJECTIVE: To investigate COX-2 expression in patients with gastric cancer and its relationship with angiogenesis and clinicopathologic features of gastric cancer. METHODS: COX-2 expression and CD34-stained microvessel density (MVD) were detected by immunohistochemical methods in specimens from 96 patients with gastric cancer. The correlations among COX-2 expression, MVD and clinicopathologic features were analyzed. RESULTS: The COX-2 positive rate and MVD in gastric cancer were significantly higher than those in the normal gastric mucosa (80.2% vs. 13.3%; 32.5+/- 8.3 vs. 13.1+/- 2.4, all P< 0.01). The COX-2 positive rate and MVD in the patients with stage III and IV were significantly higher (91.4% and 34.9+/- 8.7 respectively, P< 0.01), than that in the patients with stage I and II. The COX-2 positive rate and MVD in the cases with lymph node metastasis were 87.9% and (35.0+/- 8.5) respectively, higher than those in the cases without lymph node metastasis (P< 0.05). The Spearman rank correlation test showed a significant correlation between COX-2 expression and tumor MVD (r=0.311, P< 0.01). CONCLUSIONS: COX-2 plays an important role in gastric cancer angiogenesis. COX-2 and angiogenesis induced by COX-2 contribute to tumor invasion and lymph node metastasis.