Effectiveness of traditional Chinese medicine in treating gastrointestinal dysfunction in patients with acute stroke: a systematic review and meta-analysis of 16 randomized controlled trials.

BACKGROUND: Gastrointestinal dysfunction is one of the complications after stroke. If it is not treated in time, it will affect the rehabilitation process after stroke and reduce the quality of life of patients. In this study, we conducted a systematic review and meta-analysis of the reports on the treatment of gastrointestinal dysfunction after stroke with traditional Chinese medicine (TCM) in recent years to provide evidence for clinical diagnosis and treatment. METHODS: The clinical randomized controlled trials (RCTs) published in Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases from January 2010 to August 2021 were searched. After screening the qualified literatures, literature quality evaluation was performed. The software Stata 16.0 was used to analyze and compare the outcome indicators of TCM and conventional western medicine treatment, and the utility of TCM in the treatment of gastrointestinal disorders after stroke was comprehensively evaluated. RESULTS: A total of 16 studies were finally selected including a total of 1,589. Meta-analysis showed that TCM treatment of gastrointestinal disorders after stroke was more effective than conventional western medicine treatment [odds ratio (OR) =3.94; 95% confidence interval (CI): 2.63 to 5.89; P=0.000]. It was also shown that TCM can reduce the recovery time of bowel sounds and is superior to conventional western medicine [standard mean difference (SMD) =-1.92; 95% CI: -2.51 to -1.34; P=0.000]; reduce defecation and flatulence recovery time (SMD =-2.51; 95% CI: -3.41 to -1.61; P=0.000); increase gastrin level (SMD =0.80; 95% CI: 0.35 to 1.25; P=0.001); increase motilin level (SMD =2.27; 95% CI: 1.55 to 3.00; P=0.000); increase serum albumin level (SMD =0.72; 95% CI: 0.54 to 0.90; P=0.000); increase transferrin levels (SMD =1.11; 95% CI: 0.86 to 1.36; P=0.000); and it can increase serum prealbumin levels (SMD =1.50; 95% CI: 0.78 to 2.22; P=0.000). DISCUSSION: The use of TCM in the treatment of gastrointestinal dysfunction after stroke can effectively reduce symptoms, shorten the recovery time of bowel sounds, the first defecation and flatulence time, promote gastric motility and gastrointestinal hormone secretion, and improve the nutritional status of patients.

Circ_0134944 inhibits osteogenesis through miR-127-5p/PDX1/SPHK1 pathway.

INTRODUCTION: Osteoporosis, a common skeletal disorder mainly affecting postmenopausal women, is characterized by the imbalance between osteogenesis and osteoclastogenesis. Circ_0134944 has been recently found to be upregulated in postmenopausal osteoporosis (PMOP) patients. However, its role in osteogenesis remains unknown. Here we aimed to explore the role of circ_0134944 in osteogenesis and reveal the underlying mechanism. METHODS: qRT-PCR was used to determine the expression of circ_0134944, miR-127-5p, PDX1 and SPHK1 in the blood mononuclear cells (BMCs) of PMOP patients. Bone marrow mesenchymal stem cells (BMSCs) were used as the cellular model. Western blotting and qRT-PCR were used to determine the expression of osteogenesis-related genes (Runx2, OPN, OCN). ALP and Alizarin Red S staining were performed to evaluate osteogenic differentiation. The interactions between circ_0134944 and miR-127-5p, miR-127-5p and PDX1, PDX1 and SPHK1 were determined by dual-luciferase reporter and ChIP assay. RESULTS: Circ_0134944, PDX1 and SPHK1 were upregulated while miR-127-5p was downregulated in PMOP patients. Enhanced expression of circ_0134944 suppressed osteogenesis, which was then reversed by miR-127-5p overexpression. The binding between circ_0134944 and miR-127-5p, PDX1 and miR-127-5p were confirmed by dual-luciferase reporter assay. Moreover, PDX1 was enriched in the promoter region of SPHK1, and SPHK1 overexpression prevented the promotion of osteogenesis induced by miR-127-5p overexpression. CONCLUSIONS: Taken together, these results demonstrate that circ_0134944 inhibit osteogenesis via miR-127-5p/PDX1/SPHK1 axis. Thus, the present study offered evidence that circ_0134944/miR-127-5p/PDX1/SPHK1 axis could be a potential therapeutic target for PMOP.

ALDH3B1 Is an Independent Prognostic Biomarker of Lung Adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer-related death, and adenocarcinoma is the most common type of lung cancer. Although emerging evidence implicates the role of several aldehyde dehydrogenases in cancer progression, the expression and clinical significance of aldehyde dehydrogenase 3B1 in lung adenocarcinoma has never been studied. MATERIALS: In our study, the expression of aldehyde dehydrogenase 3B1 in 250 cases of lung adenocarcinoma was detected with immunohistochemistry, and the patients were further divided into subgroups with different aldehyde dehydrogenase 3B1 expression. Using real-time polymerase chain reaction, we investigated the aldehyde dehydrogenase 3B1 messenger RNA in 20 lung adenocarcinoma and paired normal lung tissues. With the χ2 test, we evaluated the clinical significance of aldehyde dehydrogenase 3B1 by analyzing its correlation with the clinicopathological factors. Propensity score matching was performed to balance the baseline of cohort. With univariate and multivariate analyses, we screened the prognostic factors of lung adenocarcinoma and identified the independent prognostic factors before and after the propensity score matching. RESULTS: Aldehyde dehydrogenase 3B1 expression was significantly associated with the sex and age of patients, tumor size, and histological grade. High expression of aldehyde dehydrogenase 3B1 predicted the poor prognosis (P = .003). Moreover, male patients (P = .020), large tumor size (P = .009), advanced T stage (P = .001), positive lymphatic invasion (P < .001), and advanced tumor-node-metastasis stage (P < .001) were all the prognostic factors for unfavorable outcome. Aldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma, indicating the poor prognosis. In addition, after balancing the baseline characteristics by propensity score matching, we also demonstrated that aldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma (P = .007). CONCLUSIONS: Aldehyde dehydrogenase 3B1 was an independent prognostic biomarker of lung adenocarcinoma, indicating the unfavorable prognosis. Postoperative detection of aldehyde dehydrogenase 3B1 would help stratify the high-risk patients with lung adenocarcinoma and guide individual treatment.

Decreased miR-218-5p Levels as a Serum Biomarker in Bone Metastasis of Prostate Cancer.

BACKGROUND: miR-218-5p is an extensively studied microRNA (miRNA) in prostate cancer (PCa). However, the clinical significance and biological role of miR-218-5p in bone metastasis of PCa remain unclear. MATERIALS AND METHODS: miR-218-5p expression was evaluated in 38 bone metastatic and 115 non-bone metastatic PCa tissues and serum samples. Clinical correlation of miR-218-5p expression with clinicopathological characteristics was analyzed. The biological roles of miR-218-5p in bone metastasis of PCa were investigated in vitro by invasion and migration assays. Bioinformatics analysis, real-time polymerase chain reaction, western blot, and luciferase reporter assay were applied to discern and examine the relationship between miR-218-5p and its potential targets. RESULTS: miR-218-5p expression was reduced in bone metastatic PCa tissue and serum samples, which positively correlated with poor clinicopathological characteristics and bone metastasis-free survival in PCa patients. Upregulating miR-218-5p repressed PCa cell invasion and migration. Furthermore, miR-218-5p inhibited NF-κB signaling via simultaneously targeting TRAF1, TRAF2, and TRAF5, which suppressed the invasion and migration abilities of PCa cells. ROC curve analysis of miR-218-5p in the serum of PCa patients exhibited an area under the curve of 0.86 (95% confidence interval 0.80-0.92, p < 0.001). CONCLUSION: Our findings indicate that miR-218-5p might represent a novel serum biomarker for bone metastasis of PCa.

Energy stress-induced lncRNA HAND2-AS1 represses HIF1α-mediated energy metabolism and inhibits osteosarcoma progression.

During recent years, long noncoding RNAs (lncRNAs) have been recognized as key regulators in the development and progression of human cancers, however, their roles in osteosarcoma metabolism are still not well understood. The present study aims to investigate the expression profiles and potential modulation of specific lncRNA(s) in osteosarcoma metabolism. The high-throughput Hiseq sequencing was performed to screen for abnormally expressed lncRNAs in osteosarcoma cells cultured under glucose starvation condition, and lncRNA HAND2-AS1 was eventually identified as one that was significantly up-regulated when compared with normal cultured cells. Mechanistic investigations indicated that knockdown of HAND2-AS1 abrogated the energy stress-induced effect on cell apoptosis and proliferation, and promoted osteosarcoma progression. Moreover, knockdown of HAND2-AS1 promoted glucose uptake, lactate production, and the expression level of a serious of enzymes that involved in energy metabolism. Subsequently, RNA pull-down and RNA immuneprecipitation revealed that, upon energy stress, HAND2-AS1 regulated osteosarcoma metabolism through sequestering FBP1 from binding to HIF1α, thereby releasing HIF1α expression and promoting the protein level. Taken together, our integrated approach reveals a regulatory mechanism by lncRNA HAND2-AS1 to control energy metabolism and tumor development in osteosarcoma. Thus, HAND2-AS1 may be a potential biomarker and therapeutic target for the repression of osteosarcoma metabolism.

MiR-103 alleviates autophagy and apoptosis by regulating SOX2 in LPS-injured PC12 cells and SCI rats.

OBJECTIVES: Recent studies revealed that microRNAs (miRNAs) may play crucial roles in the responses and pathologic processes of spinal cord injury (SCI). This study aimed to investigate the effect and the molecular basis of miR-103 on LPS-induced injuries in PC12 cells in vitro and SCI rats in vivo. MATERIALS AND METHODS: PC12 cells were exposed to LPS to induce cell injuries to mimic the in vitro model of SCI. The expression of miR-103 and SOX2 in PC12 cells were altered by transient transfections. Cell viability and apoptotic cell rate were measured by CCK-8 assay and flow cytometry assay. Furthermore, Western blot analysis was performed to detect the expression levels of apoptosis- and autophagy- related proteins, MAPK/ERK pathway- and JAK/STAT pathway-related proteins. In addition, we also assessed the effect of miR-103 agomir on SCI rats. RESULTS: LPS exposure induced cell injuries in PC12 cells. miR-103 overexpression significantly increased cell viability, reduced cell apoptosis and autophagy, and opposite results were observed in miR-103 inhibition. miR-103 attenuated LPS-induced injuries by indirect upregulation of SOX2. SOX2 overexpression protected PC12 cells against LPS-induced injuries, while SOX2 inhibition expedited LPS-induced cell injuries. Furthermore, miR-103 overexpression inhibited MAPK/ERK pathway and JAK/STAT pathway through upregulation of SOX2. We also found that miR-103 agomir inhibited cell apoptosis and autophagy in SCI rats. CONCLUSION: This study demonstrates that miR-103 may represent a protective effect against cell apoptosis and autophagy in LPS-injured PC12 cells and SCI rats by upregulation of SOX2 expression.

Genetic and clonal dissection of osteosarcoma progression and lung metastasis.

Osteosarcoma is a primary malignant bone tumor that has a high potential to metastasize to lungs. Little is known about the mechanisms underlying the dissemination of OS cancer cells to lungs. We performed whole exome sequencing of 13 OS primary tumors, with matched lung metastases and normal tissues. Phylogenetic analyses revealed that lung metastatic tumors often harbor clones that are nonexistent or rare in the matched primary OS tumors. Spatially and temporally separated lung metastases were from parallel seeding events with a polyphyletic pattern. Loss of TP53 or RB1 is among the early events during OS tumorigenesis, while loss of PTEN is involved at the later stages associated with lung metastases. Finally, KEAP1 was identified as a novel biomarker for increased metastatic risk. Patients whose primary tumors harbored KEAP1 amplification have significantly poorer lung-metastasis free survival. This finding was validated in two independent datasets. Further, in vitro experiments exhibited that KEAP1 depletion suppressed the invasion of OS cells. Our findings uncover the patterns of clonal evolution during OS progression and highlight KEAP1 as a novel candidate associated with the risk of lung metastasis in OS patients.

[Comparative study of decompression and non-decompression surgeries in treatment of thoracolumbar fractures with intraspinal occupying and without neurological symptoms].

Objective: To investigate the effectiveness of posterior non-decompression surgery in the treatment of thoracolumbar fractures without neurological symptoms by comparing with the conventional posterior decompression surgery. Methods: Between October 2008 and October 2015, a total of 97 patients with thoracolumbar fractures with intraspinal occupying 1/3-1/2 and without neurological symptoms were divided into the decompression surgery group (51 cases) and the non-decompression surgery group (46 cases). There was no significant difference in gender, age, cause of injury, injury segment, the thoracolumbar injury severity score (TLICS), combined injury, disease duration, and preoperative relative anterior vertebral height, kyphosis Cobb angle, intraspinal occupying percentage, visual analogue scale (VAS), Oswestry disability index (ODI), and Japanese Orthopaedic Association (JOA) score between 2 groups ( P>0.05). The operation time, intraoperative blood loss volume, postoperative drainage, bed rest time, hospitalization time, and relative anterior vertebral height, kyphosis Cobb angle, intraspinal occupying percentage, and VAS score, ODI, JOA score at preoperative and postoperative 3 days and 1 year were recorded and compared. Results: The operation time, intraoperative blood loss volume, and postoperative drainage in non-decompression surgery group were significantly less than those in decompression surgery group ( P<0.05). There was no significant difference in the postoperative bed rest time and hospitalization time between 2 groups ( P>0.05). In decompression surgery group, 4 cases had cerebrospinal fluid leakage and healed after conservative treatment. All incisions healed by first intention, and no nerve injury or infection of incision occurred. All patients were followed up 10-18 months (mean, 11.7 months). The recovery of vertebral body height was satisfactory in 2 groups, without secondary kyphosis and secondary nerve symptoms. The imaging indexes and effectiveness scores of 2 groups at 3 days and 1 year after operation were significantly improved when compared with preoperative ones ( P<0.05). The intraspinal occupying percentage, VAS score, and ODI at 1 year after operation were significantly lower than those at 3 days after operation in 2 groups ( P<0.05), and JOA score at 1 year after operation was significantly higher than that at 3 days after operation ( P<0.05). Relative anterior vertebral height at 1 year after operation was significantly higher than that at 3 days after operation in non-decompression surgery group ( P<0.05); and there was no significant difference in decompression surgery group ( P>0.05). At 3 days, the intraspinal occupying percentage and JOA score in non-decompression surgery group were higher than those in decompression surgery group ( P<0.05), and VAS score and ODI at 3 days in non-decompression surgery group were lower than those in decompression surgery group ( P<0.05). No significant difference was found in the other indexes between 2 groups at 3 days and 1 year after operation ( P>0.05). Conclusion: Compared with the posterior decompression surgery, posterior non-decompression surgery has the advantages of less bleeding, less trauma, less postoperative pain, and so on. It is an ideal choice for the treatment of thoracolumbar fractures with intraspinal occupying 1/3-1/2 and without neurological symptoms under the condition of strict indication of operation.

FTY-720P Suppresses Osteoclast Formation by Regulating Expression of Interleukin-6 (IL-6), Interleukin-4 (IL-4), and Matrix Metalloproteinase 2 (MMP-2).

BACKGROUND Osteoclast formation is closely related to the immune system. FTY720, a new immunosuppressive agent, has some functions in immune regulation. Its main active ingredients become FTY-720P in vivo by phosphorylation modification. The objective of this study was to determine the effects of FTY-720 with various concentrations on osteoclasts in vitro. MATERIAL AND METHODS RAW264.7 cells and bone marrow-derived mononuclear phagocytes (BMMs) were treated with RANKL to obtain osteoclasts in vitro. To investigate the role of FTY-720 in osteoclast formation, trap enzyme staining was performed and the number of osteoclasts was counted. Bone slices were stained with methylene blue, we counted the number of lacunae after bone slices were placed into dishes together with osteoclasts, and we observed the effect and function of FTY-720 in osteoclasts induced by RAW264.7 cells and BMMs. Then, we used a protein array kit to explore the effects of FTY-720P on osteoclasts. RESULTS The results of enzyme trap staining and F-actin staining experiments show that, with the increasing concentration of FTY-720P, the number of osteoclast induced by RAW264.7 cells and BMMs gradually decreased (P<0.05), especially when the FTY-720P concentration reached 1000 ng/ml, and the number of osteoclasts formed was the lowest (P<0.05). With bone lacuna toluidine blue staining, the results also show that, with the increasing concentration of FTY-720P, the number of bone lacuna gradually decreased (P<0.05), and the number of lacunae is lowest when the concentration reached 800 ng/ml. Finally, protein array results showed that IL-4, IL-6, IL-12, MMP-2, VEGF-C, GFR, basic FGF, MIP-2, and insulin proteins were regulated after FTY-720P treatment. CONCLUSIONS FTY-720P can suppress osteoclast formation and function, and FTY-720P induces a series of cytokine changes.

Quality-control method for the determination of biological activity of engineered calcineurin subunit B.

The aim of this study was to establish a quality-control method for calcineurin subunit B (CNB) biological activity determinations. CNB enhances the p-nitrophenylphosphate (pNPP) dephosphorylating activity of calcineurin subunit A Δ316 mutant (CNAΔ316). A series of CNB concentrations were fitted to a four-parameter equation to calculate the corresponding pNPP maximum dephosphorylation rates. Values were calculated based on biological activity references using a parallel line method. The method was then validated for accuracy, precision, linearity, linear range, sensitivity, specificity, and robustness. The recovery results were greater than 98%. Intra-plate precision was 6.7%, with inter-plate precision of 10.8%. The coefficient of determination was greater than 0.98. The linear range was 0.05-50 µg mL(-1), with sensitivity of 50 µg mL(-1). Tested cytokines did not induce CNAΔ316 dephosphorylation of pNPP. The chosen CNAΔ316 concentration range did not affect activity determinations.

Qing-Yi decoction in participants with severe acute pancreatitis: a randomized controlled trial.

BACKGROUND: Qing-Yi Decoction (QYD) has been used for severe acute pancreatitis (SAP) patients in China for many years. There were two kinds of QYD: Num 1. QYD (QYD1) which is used in the acute response stage of SAP and Num 2. QYD (QYD2) which is used in the second stage of SAP. This study aims to evaluate the therapeutic efficacy of QYD in participants with SAP. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, participants aged 18-70 years within the first 7 days after acute onset of typical abdominal pain (the definition of SAP was according to the 2007 Guidelines for Management of Severe Acute Pancreatitis in China) were selected. The disease severity was determined by the Ranson, Acute Physiology and Chronic Health Evaluation II, and Balthazar CT scores. The test group received Western medicine and Chinese medicine (Num.1 QYD and Num.2 QYD), while the control group received Western medicine and placebo. The primary end-points were length of hospital stay, total hospitalization expenses, operation rate, and mortality. The secondary end-points were organ complications (i.e., heart failure, respiratory failure, acute renal failure, and hepatic failure), duration of paralytic ileus, infection, intensive care unit stay, and respirator use. RESULTS: From March 2008 to July 2010, a total of 300 participants with severe acute pancreatitis were assessed for eligibility in West China Hospital, and 100 were eligible for randomized allocation. Eighty-five participants (46 in the test group; 39 in the control group) were included in the statistical analyses. The two groups were similar in their baseline clinical characteristics (age, sex, and etiology) and disease severity. After the interventions, there were no differences between the two groups for length of hospital stay (P = 0.323), total hospitalization expenses (P = 0.252), operation rate (P = 0.231), mortality (P = 0.462), organ complications (P > 0.05), intensive care unit stay (P = 0.209), and respirator use (P > 0.05). However, the duration [median (interquartile range)] of paralytic ileus, i.e., 4 (2-6) days vs. 6 (4-8) days (P = 0.014) and rate of infection, i.e., (13.0 % vs. 35.9 %) (P = 0.013) differed significantly. CONCLUSIONS: QYD could restore gastrointestinal motility to normal and reduce the infection rates in the SAP patients who completed a full course of QYD treatment according to per protocol analysis.

Paxilitaxel induces apoptosis accompanied by protective autophagy in osteosarcoma cells through hypoxia-inducible factor-1α pathway.

Paxilitaxel, a drug used in cancer chemoprevention and treatment, has shown promising anti­cancer effects against a broad spectrum of tumors. However, the effect of paxilitaxel on osteoblasts has remained to be elucidated. The aim of the present study was to investigate the anti­tumor effect of paxilitaxel on human osteosarcoma cancer cells, the underlying molecular mechanism as well as drug resistance involved. The results showed that paxilitaxel not only induced apoptosis via the mitochondrial pathway but also induced autophagy, which partially inhibited cell apoptosis. The present study also demonstrated that paxilitaxel induced autophagy through the hypoxia­inducible factor (HIF)­1α pathway. Moreover, paxilitaxel­induced apoptosis decreased following incubation with with the autophagy inducer rapamycin. By contrast, co­treatment with the HIF­1α inhibitor YC­1 or autophagy inhibitor 3­methyladenine significantly blocked autophagy and augmented the anti­tumor effects of paxilitaxel. Therefore, the results of the present study suggested that the combination of paxilitaxel with an autophagy inhibitor or a HIF­1α inhibitor may be an effective and potent strategy for improved chemotherapy of osteosarcoma in the future.

[Assessing splenic vein complications in patients with acute pancreatitis using color Doppler ultrasound and contrast enhanced ultrasound].

OBJECTIVE: To evaluate the diagnostic value of color Doppler flow imaging (CDFI) and contrast enhanced ultrasonography (CEUS) for splenic vein complications (SVCs). METHODS: 144 inpatients (86 male, 58 female) with acute pancreatitis from Jan 2012 to Apr 2013 were recruited for this study. The participants had a mean age of (44.3 +/- 11.9) years. All participants were examined using CDFI, CEUS and contrast enhanced computer tomography (CECT) (less than 72 h interval between examinations). The CECT results were regarded as a golden standard, which were compared with the results of CDFI and CEU. The Medcalc 12.7.1.0 was used for drawing ROC curves and calculating AUC. RESULTS: The CECT confirmed 17 cases of SVCs; whereas, the CEUS identified 12 cases and the CDFI identified 4 cases of SVCs. The difference between the results of CDFI and CEUS was significant (Z = 2.233, P < 0.05). Higher levels of sensitivity (58.82%), specificity (98.43%), accuracy (93.75%), positive likelihood ratio (37.46), and negative likelihood ratio (0. 42) were found using CEUS for diagnosing SVCs, compared with those of using CDFI (sensitivity = 17.65%, specificity = 99.21%, accuracy = 89.58%, positive likelihood ratio = 22.34,negative likelihood ratio = 0.83). The area of AUC were 0.618 and 0.853 for CDFI and CEUS, respectively. CONCLUSION: CEUS is a better imaging method for diagnosing SVCs in patients with acute pancreatitis.

Short-term continuous high-volume hemofiltration on clinical outcomes of severe acute pancreatitis.

OBJECTIVES: This study aimed to conduct a single-center prospective trial of short-term continuous high-volume hemofiltration (HVHF) in patients with predicted severe acute pancreatitis (SAP). METHODS: Patients with acute pancreatitis with Acute Physiology and Chronic Health Evaluation II scores of greater than 15 on admission between January 2008 and December 2010 were allocated to receive either optimal standard therapy or 72 hours of continuous HVHF on an alternate basis, beginning as soon as possible after admission. Biomarkers and clinical outcomes were compared between the 2 groups. RESULTS: A total of 61 patients received either conventional therapy (n = 29) or HVHF (n = 32). High-volume hemofiltration treatment was associated with a significant reduction in the incidence of renal failure (P = 0.013), infected pancreatic necrosis (P = 0.048), length of hospitalization (P = 0.005), mortality (P = 0.033), as well as duration of renal (P < 0.001), respiratory (P = 0.002), and hepatic failure (P = 0.001). Acute Physiology and Chronic Health Evaluation II score and C-reactive protein and interleukin 6 levels were significantly reduced after the start of HVHF on days 1, 3, and 7 (all, P < 0.05). CONCLUSIONS: This study suggests that short-term HVHF may reduce local and systemic complications and mortality in patients with SAP with Acute Physiology and Chronic Health Evaluation score of greater than 15.

The role of organ failure and infection in necrotizing pancreatitis: a prospective study.

OBJECTIVE: To clarify the roles of organ failure and infection in the outcome of necrotizing pancreatitis. BACKGROUND: Results of previous cohort studies that focused on the roles of infection and organ failure in acute pancreatitis are controversial. METHODS: In this study, we collected the medical records of 447 patients with necrotizing pancreatitis from January 2009 to June 2012. Data associated with organ failure and infection were analyzed. RESULTS: The overall mortality rate was 13% (58/447). Intervention was performed in 223 of 447 patients. Among these 223 patients, 134 were confirmed to be with infected necrosis by a positive culture. The mortality rate was 15% (13/89) in the sterile necrosis group and 18% (24/134) in the infected necrosis group (P = 0.52). A multivariate analysis of death predictors indicated that bacteremia (odds ratio [OR] = 2.76, 95% confidence interval [CI], 1.23-5.46, P < 0.001), age (OR = 1.07, 95% CI, 1.03-1.11, P < 0.001), American Society of Anesthesiologists class (OR = 3.56, 95% CI, 1.65-7.18, P = 0.001), persistent organ failure in the first week (OR = 16.72, 95% CI, 7.04-32.56, P < 0.001), and pancreatic necrosis (OR = 1.73, 95% CI, 1.14-2.98, P = 0.008) were significant factors. CONCLUSIONS: Among patients with necrotizing pancreatitis, the effects of organ failure on mortality are more critical than those of infection. Bacteremia, age, American Society of Anesthesiologists class, persistent organ failure in the first week, and pancreatic necrosis were identified as the predictors of mortality.

Human leukocyte antigen-DR expression on peripheral monocytes may be an early marker for secondary infection in severe acute pancreatitis.

BACKGROUND/AIMS: To investigate whether the human leukocyte antigen-DR (HLA-DR) expression on peripheral monocytes can be utilized as a precursor to a secondary infection of severe acute pancreatitis (SAP). METHODOLOGY: Patients diagnosed with SAP who were admitted into West China Hospital within 48 h after symptom onset from July 1, 2010 to December 31, 2010 (n = 40) were included. HLD-DR expression on peripheral monocytes on the 1st, 3rd, 5th and 7th day of hospitalization was detected with flow cytometry analysis to determine whether a prediction could be made in regards to development of a secondary infection. RESULTS: There were 11 patients with secondary infection complications, 4 of which died during hospitalization. On the 1st, 3rd, 5th and 7th day, HLA-DR expression on monocytes in the infected patients was lower than those in the noninfected patients (P < 0.05). There was no statistical significance in the serum CRP and APACHE II between the groups on the first day (P > 0.05). Upon initial admission HLA-DR expression showed a negative correlation with longer-term admission APACHE II (r = -0.790, P = 0.000) and serum CRP (r = -0.642, P = 0.000). The area under the ROC curve (AUC) was 0.837 (95%CI: 0.685-0.989, P = 0.001) for admission HLA-DR, 0.809 (95% CI: 0.667-0.951; P = 0.003) for APACHE II score and 0.781 for serum CRP (95% CI: 0.627-0.934; P = 0.007) to predict secondary infection. The cut-off value of prediction of secondary infection was 35.8% in HLA-DR expression with a sensitivity of 81.8% and a specificity of 82.8%, 10.5 in APACHE II on admission with a sensitivity of 90.9% and a specificity of 48.3%, 155 mg/L in serum CRP on admission with a sensitivity of 90.9% and a specificity of 44.8%. CONCLUSIONS: The HLA-DR expression on monocytes may be an ideal marker for an early prediction of secondary infection in SAP.

Can contrast-enhanced ultrasound evaluate the severity of acute pancreatitis?

OBJECTIVES: To investigate the ability of contrast-enhanced ultrasound (CEUS) in the assessment of acute pancreatitis (AP), as well as its diagnostic accuracy in the evaluation of the severity of pancreatitis. METHODS: A prospective double-blind study was carried out in 33 AP patients from May 2007 to January 2008. Each patient underwent both CEUS and contrast-enhanced computed tomography (CECT) with the time interval between two examinations less than 72 h. Using CECT as gold standard, the ability of CEUS to diagnose pancreatic necrosis as well as peripancreatic effusion and/or complications, and its diagnostic value in the evaluation of the severity of pancreatitis, were investigated. Balthazar's grading system was used to measure CT and ultrasound severity indices (CTSI and USSI), and the correlation between CTSI and USSI was tested by Spearman's rank correlation coefficient. RESULTS: A strong correlation between CTSI and USSI was found (r = 0.92, P < 0.01).The sensitivity, specificity, accuracy, positive and negative predictive value of CEUS in the diagnosis of pancreatic parenchyma necrosis were 90, 95, 94, 90 and 95%, in the diagnosis of peripancreatic effusion and/or complications were 83, 100, 93, 100 and 91%, and in the diagnosis of severe pancreatitis were 97, 67, 94, 97 and 67%, respectively. CONCLUSIONS: CEUS has shown to be of clinical value in the assessment of pancreatic necrosis as well as peripancreatic complications in AP and has a high diagnostic accuracy in the evaluation of the severity of pancreatitis. Further studies are needed to add it to the diagnostic algorithm for acute pancreatitis.

Treatment of functional constipation with the Yun-chang capsule: a double-blind, randomized, placebo-controlled, dose-escalation trial.

BACKGROUND AND AIM: Functional constipation is a common functional bowel disorder for which there is no reliable medical treatment. This study was designed to determine the therapeutic efficacy and safety of the Yun-chang capsule, a Chinese herbal formula, in the treatment of patients with functional constipation. METHODS: In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with functional constipation received 70 mg of Yun-chang capsule plus 35 mg placebo (group A), 105 mg of Yun-chang capsule (group B), or 105 mg placebo (group C), three times daily for 2 weeks. The primary end-points were the changes in main symptom score and cumulative symptom score 2 weeks after the treatment. The secondary end-points were adverse events. RESULTS: A total of 140 patients were recruited and 132 met the inclusion criteria; 44 patients constituted each of the three treatment groups. Compared with patients in group C, patients in groups A and B had significant improvement in the main symptom score, cumulative symptom score, the change from baseline of the main symptom score, and the change from baseline of the cumulative symptom score at week 1 and week 2. The scores showed slight superiority of group B over group A at week 1 and week 2, although these differences were not statistically significant. There were no differences in adverse events. CONCLUSIONS: The Yun-chang capsule is efficacious and safe for the treatment of patients with functional constipation. Larger and longer-term trials are required to fully assess the benefits and safety of this treatment for functional constipation.

[Protective effects of emodin on intestinal lesion in rat model with acute necrotizing pancreatitis].

OBJECTIVE: To explore the protective effects and mechanism of Emodin on intestinal lesion in the rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty SD rats were randomly divided into 3 groups: sham-operated (SO) group, ANP group and Emodin-treated group. ANP was induced by retro-pumping 3.5% sodium cholate to pancreaticobiliary duct. 5.5 hours after modeling, phenol red, which was employed to measure intestinal transit, was injected to duodenum. 0.5 hour later, rats were sacrificed to collect intestine for the results of intestinal transit and other tests of intestine. Furthermore, intestinal tissue (HE staining) was observed by light microscope, and the activity of nuclear factor-kappa B (NF-kappaB) in intestine was detected by immunohistochemical method. The content of intestinal tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was detected with the method of enzyme-labeled immunosorbent assay (ELISA). RESULTS: Compared with SO group, there was significantly decrease of intestinal transit in ANG group (P < 0.05). Furthermore, intestinal transit in Emodin-treated group significantly increased when compared with ANP group (P < 0.05). NF-kappaB p65 positive rate of intestinal cell nuclei, content of intestinal TNF-alpha and IL-1beta in ANP group were obviously higher than those in SO group (P < 0.05). After the treatment of Emodin, NF-kappaB p65 positive rate of intestinal cell nuclei, content of TNF-alpha and IL-1beta were decreased (P < 0.05). Moreover, there was a negative correlation between intestinal transit and content of TNF-alpha, IL-1beta, with correlation coefficients--0.83, -0.76, respectively (P < 0.05). CONCLUSION: Emodin could increase intestinal transit, suppress the activity of NF-kappaB in intestine, decrease the content of intestinal TNF-alpha and IL-1beta, and attenuate the pathological damage of intestine.

[Yunchang Capsule in treatment of functional constipation: a randomized, double-blinded controlled, multicenter trial].

BACKGROUND: Although there are some Chinese herbal medicines in treatment of constipation, but no multi-center randomized controlled trials have been carried out to prove their effectiveness. OBJECTIVE: To evaluate the safety and efficacy of Yunchang Capsule in treatment of functional constipation with deficiency of both qi and yin and internal accumulation of poisonous pathogenic factors syndrome, and to explore the clinical dosage. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized, double-blinded controlled, multicenter trial was conducted. A total of 240 patients with functional constipation from West China Hospital of Sichuan University, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, the First Affiliated Hospital of Tianjing University of Traditional Chinese Medicine and Fujian Academy of Traditional Chinese Medicine were randomly divided into three groups: low dose group (80 cases), high dose group (80 cases) and control group (80 cases). Patients in the low dose group were treated with two pills (0.35 g/pill) of Yunchang Capsule and one pill of Yunchang Capsule simulant for three times daily; patients in the high dose group were treated with three pills (0.35 g/pill) of Yunchang Capsule for three times daily; and patients in the control group were treated with three pills (0.35 g/pill) of Biantong Capsule for three times daily. The therapeutic course was 14 days. MAIN OUTCOME MEASURES: Clinical symptoms, syndromes, and adverse effects were observed before and after the treatment, and blood, urine and stool tests, hepatorenal function and electrocardiogram were also examined. RESULTS: Two cases were excluded, eleven cases were lost to follow-up, and there were 234 patients entered to intention-to-treat (ITT) analysis. After the treatment, the therapeutic effects were calculated by full analysis set (FAS) and per-protocol population set (PPS) analysis respectively. The effects on functional constipation in FAS showed the response rates in the low dose, high dose and control groups were 86.25% (69/80), 82.90% (63/76), and 70.52% (55/78) respectively, and PPS analysis showed the response rates were 85.71% (66/77), 83.56% (61/73), and 70.13% (54/77) respectively. There were no significant differences among the three groups (P>0.05). The effects on traditional Chinese medicine syndrome in FAS showed the response rates in the low dose, high dose and control groups were 78.75% (63/80), 69.74% (53/76), and 67.95% (53/78) respectively, and PPS analysis showed the response rates were 77.92% (60/77), 69.87%(51/73), and 67.53% (52/77) respectively. There were also no significant differences among the three groups (P>0.05). No severe adverse events were observed. CONCLUSION: Both low dose and high dose of Yunchang Capsule are effective and safe in treatment of functional constipation with deficiency of both qi and yin and internal accumulation of poisonous pathogenic factors syndrome.