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β-transducin repeat-containing E3 ubiquitin protein ligase (β-TrCP) serves as the substrate recognition subunit for the Skp1-Cullin1-F-box protein E3 ubiquitin ligase, which recognizes the double phosphorylated DSG (X)2+nS destruction motif in various substrates that are essential for numerous aspects of tumorigenesis and regulates several important signaling pathways. However, the biological significance of β-TrCP in glioma progression remains largely unknown. A previous study by the authors demonstrated that the levels of β-TrCP protein expression in brain glioma tissues were significantly lower compared with non-tumorous tissues and that higher grades of gliomas exhibited lower levels of β-TrCP expression in comparison with lower glioma grades. In addition, low β-TrCP expression was associated with poor prognosis in patients with glioma. Subsequently, the present study aimed to investigate the effect of β-TrCP on migratory, invasive and proliferative abilities of glioma cells. β-TrCP plasmids were transfected into cultured U251 and U87 glioma cells, and changes in migration, invasion and proliferation were analyzed using wound healing, Transwell and EdU assays. It was identified that the overexpression of β-TrCP inhibited migration, invasion and proliferation in glioma cells. In summary, these results indicate that β-TrCP may serve a protective role against the progression of glioma by suppressing cell migration, invasion and proliferation. The potential mechanism of β-TrCP I glioma cells requires additional investigation. [ABSTRACT FROM AUTHOR]

Vesicoureteral reflux (VUR) is one of the most common ureteric complications after kidney transplantation that might cause symptomatic infections which deteriorate graft function. Surgical reimplantation has been the standard treatment; recently, endoscopic injection has been an alternative approach. We report our endoscopic treatment results and analyze the long-term outcome, even in patients with less optimal graft function. A total of 16 patients and 19 symptomatic VUR were diagnosed at mean time of 88.3 months after their transplantation. The distribution of VUR grade was 1, 2, 8, 6, and 2 for grade I to V, respectively, with a mean VUR grade of 3.26 according to their voiding cystourethrogram images. Endoscopic Deflux injections were performed by a single urologist via rigid cystoscope with a beveled needle system. They were followed monthly thereafter. The average number of admissions due to symptomatic urinary tract infection was 2.68/person, and the mean creatinine level before endoscopic treatment was 1.63 mg/dL. The amount of Deflux injection was 0.7 to 1.2 mL per affected ureter; the mean creatinine level after endoscopic treatment was 1.41 mg/dL. The eGFR remained stationary in both eGFR > 60 and eGFR < 60 mL/min groups with a clinical success rate of 75% in both groups. Endoscopic dextranomer-hyaluronic acid injection is a safe and feasible treatment option for VUR after kidney transplantation. Our data showed its efficacy in recipients whose eGFR is less than 60 mL/min. • VUR may occur early or late after kidney transplantation and can deteriorate graft function or cause urosepsis. • Endoscopic injection of Deflux for VUR following kidney transplant is safe and feasible with an overall success rate of 75%. • In recipients with inferior graft function (eGFR <60 mL/min), endoscopic injection remains effective. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Submucosal tunneling endoscopic resection (STER) has become a potential option for the endoscopic treatment of a selected group of patients with submucosal tumors (SMTs) originating from the muscularis propria layer in the upper gastrointestinal tract. The aim of this retrospective study was to analyze the incidence and management of STER-related complications.Patients and Methods: From January 2011 to August 2013, 290 patients with upper gastrointestinal SMTs treated by STER were included in the study. Clinicopathological characteristics and complication data were collected and analyzed retrospectively.Results: Mucosal injury occurred in three cases (1.0 %) and major bleeding occurred in five cases (1.7 %). The gas-related complications were very common; however, only nine cases of major pneumothorax (> 30 % lung collapse) needed therapeutic intervention (3.1 %). Thoracic effusion occurred in 49 patients, 11 of whom had low grade fever or segmental atelectasis that required thoracentesis and drainage (3.8 %). Thus, although the overall incidence of complications was 23.4 % (68/290), only 10.0 % of procedures (29/290) required intervention for complications. Based on the statistical analysis, irregular shape, tumor in the deep muscularis propria layer, long procedure time, and air insufflation were risk factors of STER-related major complications.Conclusion: Although the incidence of STER-related complications was relatively high, most of these complications were minor and did not require therapeutic intervention. STER is a safe technique for the treatment of upper gastrointestinal SMTs. [ABSTRACT FROM AUTHOR]

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Background: Endoscopic full-thickness resection (EFTR) is a minimally invasive method for en bloc resection of gastrointestinal (GI) lesions originating from the muscularis propria layer. Successful closure of the wall defect is a critical step.Objective: The aim of this study was to evaluate the feasibility and efficacy of a novel and simplified endoscopic grasp-and-loop (GAL) closure method using an endo-loop assisted with grasping forceps for defect closure.Methods: From January 2015 to March 2016, 13 patients with submucosal tumors (SMTs) originating from the muscularis propria (MP) layer underwent EFTR and were enrolled in this study. After successful tumor resection, an endo-loop was anchored onto the circumferential margin of the gastric defect with grasping forceps assistance and tightened gently. Patient characteristics, tumor size, en bloc resection, and postoperative complications were evaluated.Results: Of the 13 lesions in the stomach, two were located in the greater curvature of the mid-upper body, 11 were located in the fundus. The endoscopic GAL closure method was successfully performed after EFTR in all the 13 patients without laparoscopic assistance. The mean procedure time was 43.5 min (range 20-80 min), while the GAL closure procedure took a mean of 9.4 min (range 3-18 min). The mean resected lesion size was 1.5 cm (range 0.5-3.5 cm). Pathological diagnoses of these lesions were 11 gastrointestinal stromal tumors (GISTs) and two leiomyomas. No major adverse events occurred during or after the procedure. All the patients were discharged after a mean time of 2.4 days (range 1-4 days). No residual lesion or tumor recurrence was found during the follow-up period (median, 5 months; range, 1-15 months).Conclusions: The endoscopic GAL closure method is feasible, effective, and safe for closing the gastric defect after EFTR in patients. [ABSTRACT FROM AUTHOR]

Background and aims Peroral endoscopic myotomy (POEM) is now an established treatment for esophageal achalasia. The standard protocol ensures a smooth operation in most patients, but technical challenges and failures exist and little is known about the incidence, causes, and impact of aborted procedures. Here, using a large patient cohort, we attempted to answer these questions. Methods All patients admitted for planned POEM between August 2010 and July 2015 underwent chart review. Aborted POEM was defined as the inability to finish the procedure after submucosal injection. The cause of the failure, clinical course, management, and follow-up data were analyzed. Results Thirteen of the 1693 POEMs (0.77 %) were aborted. Out of the 13 failures, 12 (92.3 %) were due to severe submucosal fibrosis, which precluded tunneling, and one (7.7 %) was due to atrial fibrillation related to the electric current of the endoscopic knife. Submucosal fibrosis, prior Heller myotomy, and age ( ≥ 60 years) were related to technical failure, while a disease duration of ≥ 6 years, sigmoid esophagus, mucosal edema, and prior interventions were risk factors for the presence of fibrotic changes. In turn, fibrosis was correlated with a prolonged operation, longer hospital stay, more mucosal injuries, and more major perioperative adverse events. Finally, the yearly frequency of aborted POEMs decreased after the second year as operators became more experienced. Conclusions Aborted POEM is a rare event and is largely due to the presence of submucosal fibrosis, which not only causes increased procedural difficulties, but also gives rise to major adverse events. [ABSTRACT FROM AUTHOR]

Background. We performed this meta-analysis to investigate the efficacy of probiotics on prevention of infection-related complications following colorectal resection. Method. PubMed, EMBASE, Cochrane Library, and the Web of Science were searched up to January 2016. According to the results, only randomized controlled trials that compared the efficacy of probiotics on patients with colorectal resection were included for meta-analysis. Results. Nine studies including a total of 1146 patients met the criteria (556 received multistrain probiotic bacteria, 590 with non-multistrain probiotic bacteria). The combination of multistrain probiotics was beneficial in the reduction of total infections (OR = 0.30, 95%CI: 0.15–0.61, p=0.0009), including surgical site infections (SSI) (OR = 0.48, 95%CI: 0.25–0.89, p=0.02) and nonsurgical site infections (NSSI) (OR = 0.36, 95%CI: 0.23–0.56, p<0.00001). However, there was no significant reduction in total infections (OR = 0.74, 95%CI: 0.50–1.09, p=0.13) or SSI (OR = 0.77, 95%CI: 0.52–1.12, p=0.17) with the application of non-multistrains of probiotics. Conclusion. Combinations of multistrain probiotic bacteria showed promise in preventing the incidence of infections following colorectal surgery. However, the efficacy of one or two strains of probiotics remains undetermined. [ABSTRACT FROM AUTHOR]

The present study was undertaken to investigate whether hederacochiside C (HSC) possesses antischistosomal effects and anti-inflammatory response activities inSchistosoma japonicum-infected mice. Different concentrations of HSC were administrated to the mice infected by schistosomula or adult worm by intravenous injection twice a day for five consecutive days. The total worm burden, female worm burden, and the egg burden in liver of mice treated with 400 mg/kg HSC were fewer than those in non-treated ones. Murine immune responses following HSC treatment were investigated using enzyme-linked immunosorbent assays (ELISA). Our results indicated that 200 mg/kg HSC could reduce the expression of IgG, tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-17 in comparison to infected group, exhibiting best immunomodulatory effects. In addition, scanning electron microscopical examination revealed that male worms treated with HSC lost their normal surface architecture since its surface showed extensive swelling, erosion, and peeling in tegumental regions. Remarkable amelioration was noticed in histopathological investigations, and 200 mg/kg HSC treatment could reduce the size of granulomatous inflammatory infiltrations in the liver which was reflected in nearly normalization of liver architecture. These results suggested that HSC had potential antischistosomal activity and provided a basis for subsequent experimental. [ABSTRACT FROM PUBLISHER]

Background: Anterior cervical discectomy and fusion (ACDF) is widely used in the treatment of cervical degenerative disease; however, the variation of cervical sagittal alignment changes after ACDF has been rarely explored. The purpose of this study is to determine the relationship between changes of cervical sagittal alignment after ACDF and spino-pelvic sagittal alignment under Roussouly classification.Methods: A cohort of 133 Chinese cervical spondylotic patients who received ACDF from 2011 to 2012 was recruited. All patients were categorized with Roussouly Classification. Lateral X-ray images of global spine were obtained, and preoperative and postoperative parameters were measured and analyzed, including C2-C7 angles (C2-C7), C0-C7 angles (C0-C7), external auditory meatus (EAM) tilt, sacral slope (SS), thoracic kyphosis (TK), lumbar lordosis (LL), spinal sacral angles (SSA), Superior adjacent inter-vertebral angle (SAIV), inferior adjacent inter-vertebral angle (IAIV) and et al. The Wilcoxon signed-rank test was used for intragroup comparisons preoperatively and at postoperative 48 months.Results: Among the parameters, C2-C7 and C0-C7 showed significant increase, while EAM TK, and IAIV decreased significantly. In type I, EAM and TK decreased significantly, however SS showed a significant increase; in type II, TK showed a significant decrease, but SSA showed a significant increase; in type III, a significant increase of C0-C7 was observed with a significant decrease in EAM, nevertheless, LL, SS and SSA showed significant decreases; and in type IV, C2-C7 showed a significant increase and EAM decreased significantly. The percentage of lordotic alignment in cervical spine increased, which was presenting in type I, III and IV. Nevertheless, the amount of patients with straight cervical alignment increased in type II.Conclusion: The backward movement of head occurs is the compensatory mechanism in cervical sagittal alignment modifications after ACDF. The compensatory alteration of spino-pelvic sagittal alignment varied in different Roussouly type. [ABSTRACT FROM AUTHOR]

Resveratrol is a small polyphenol that has been intensively studied in a wide spectrum of therapeutic fields. More recently, resveratrol has been demonstrated to exert its antitumor activity in numerous tumor models. The present study reported that resveratrol exhibited a marked anti-proliferative effect on human esophageal squamous cell carcinoma (ESCC) cells by inducing cell cycle G0/G1 phase arrest and cell death, which was associated with a decrease in the expression levels of cyclin D1 and an increase in cleaved PARP/cleaved caspase-3 expression levels. The mechanisms underlying the antitumor potency of resveratrol were principally attributed to the downregulation of epidermal growth factor receptor (EGFR) signaling. The western blotting results showed that exposure of ESCC cells to resveratrol inhibited EGF-induced EGFR activation in addition to decreasing the total protein levels of EGFR and membrane/nuclear localization. In summary, the results suggested that resveratrol, or an associated analog, may have a role in the management of human ESCC. [ABSTRACT FROM AUTHOR]

A heme-dependent peroxidase (HDP) catalyzes the ortho-hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in the presence of hydrogen peroxide. L-DOPA can be used for the treatment of Parkinson's disease. In this work, to improve the catalytic efficiency, the heme-dependent peroxidase has been genetically modified with an elastin-like polypeptide (ELP). bicinchoninic acid (BCA) assay demonstrated that HDP-ELP has a higher solubility in aqueous solutions than HDP. Circular dichroism (CD) spectra showed that HDP-ELP has a higher stability than HDP. Enzyme kinetics has been investigated over a range of substrate concentrations. It has been demonstrated that HDP-ELP exhibited a catalytic efficiency 2.4 times that of HDP. [ABSTRACT FROM AUTHOR]

Objective Endoscopic variceal sclerotherapy (EVS) is usually carried out at weekly intervals in patients with esophageal variceal bleeding (EVB). However, some patients receive sclerotherapy at irregular intervals. In this study we aimed to elucidate the reasons and risk factors for irregular-interval sclerotherapy in patients with EVB, and to evaluate the safety and efficacy of interrupted irregular intervals in these patients. Methods Medical records of patients who were admitted to the Chinese PLA General Hospital from December 2013 to June 2015 for EVS were retrospectively analyzed. EVS sessions were scheduled to be repeated at regular weekly intervals. However, some of these patients received at least one treatment session at irregular intervals (mainly <7 days). This irregular-interval group was further divided into those whose treatment was rescheduled for emergency and elective reasons. Results Irregular treatment intervals were mainly caused by early rebleeding, initial emergency treatment, and holidays. However, there were no differences in the rates of complication and variceal eradication between patients treated at weekly and irregular intervals. Multivariate logistic regression analysis identified ascites ( P = 0.0009), variceal erosion ( P = 0.0003), and maximum injected volume of sclerosing agent per session ( P = 0.0008) to be associated with emergency irregular-interval treatment. Only age differed between the elective irregular-treatment and weekly treatment groups. Conclusions Early rebleeding, initial emergency treatment, and treatment over holidays may necessitate irregular sclerotherapy intervals in patients with EVB. Moreover, ascites, variceal erosion, and maximum injected volume of sclerosing agent per session are risk factors for emergency sclerotherapy, whereas elective adjustments to treatment schedules as a result of holidays do not affect the outcomes of patients undergoing EVS for EVB. [ABSTRACT FROM AUTHOR]

Aim: This study assessed the efficacy and safety of tigecycline in children with life-threatening infections.Methods: We retrospectively reviewed the clinical records of patients treated with tigecycline from June 2012 to May 2014 in a Chinese tertiary centre.Results: The study comprised 24 patients (14 male) with a median age of four years (range, 50 days-12 years). The most frequently isolated microorganism, most common isolation site and type of infection were Acinetobacter baumannii, tracheal aspirate fluid and ventilator-associated pneumonia, respectively. Tigecycline was administered at a loading dose of 1.5 or 2.0 mg/kg and 1.0 mg/kg every 12 hours after that. The average duration of treatment was 11.6 ± 5.8 days. The clinical response and microbiological eradication rate were 37.5% and 29.2%, respectively. Six of the patients we studied (25.0%) died, and three of these deaths were considered to be infection related. Adverse drug reactions were identified in four patients (16.7%) during the treatment, including abnormal liver function, prolonged prothrombin time and diarrhoea.Conclusion: Our findings suggest that tigecycline may be an option for children with severe infections. However, more prospective, controlled trials are required to objectively evaluate the efficacy and safety of tigecycline in children. [ABSTRACT FROM AUTHOR]

Objective: This multicenter, randomized, placebo-controlled study evaluated the efficacy and side effects of parecoxib during patient-controlled epidural analgesia (PCEA) after abdominal hysterectomy. Methods: A total of 240 patients who were scheduled for elective abdominal hysterectomy under combined spinal-epidural anesthesia received PCEA plus postoperative intravenous parecoxib 40 mg or saline every 12 h for 48 h after an initial preoperative dose of parecoxib 40 mg or saline. An epidural loading dose of a mixture of 6 mL of 0.25% ropivacaine and 2 mg morphine was administered 30 min before the end of surgery, and PCEA was initiated using 1.25 mg/mL ropivacaine and 0.05 mg/mL morphine with a 2-mL/h background infusion and 2-mL bolus with a 15-min lockout. The primary end point of this study was the quantification of the PCEA-sparing effect of parecoxib. Results: Demographic data were similar between the two groups. Patients in the parecoxib group received significantly fewer self-administrated boluses (0 (0, 3) vs. 7 (2, 15), P < 0.001) and less epidural morphine (5.01 ± 0.44 vs. 5.95 ± 1.29 mg, P < 0.001) but experienced greater pain relief compared with the control group (P < 0.001). Patient global satisfaction was higher in the parecoxib group than the control group (P < 0.001). Length of hospitalization (9.50 ± 2.1, 95% CI 9.12~9.88 vs. 10.41 ± 2.6, 95% CI 9.95~10.87, P = 0.003) and postoperative vomiting (17% vs. 29%, P < 0.05) were also reduced in the parecoxib group. There were no serious adverse effects in either group. Conclusion: Our data suggest that adjunctive parecoxib during PCEA following abdominal hysterectomy is safe and efficacious in reducing pain, requirements of epidural analgesics, and side effects. Trial Registration: ClinicalTrials.gov () [ABSTRACT FROM AUTHOR]

Purpose: Calcific discitis is a self-limiting process most commonly seen in the cervical spine of children. Rare literature exists regarding the natural history and management of this condition in adults, especially when it presents as a giant thoracic disc herniation into the spinal canal. Giant herniations in the thoracic spine are typically surgically removed to reduce the chance of permanent neurologic deficit from spinal cord compression. However, when associated with calcific discitis, they may undergo spontaneous regression with the need for surgery obviated.Methods: Medical records and radiographic studies of two adult patients with calcific discitis and myelopathy due to spinal cord compression by giant thoracic disc herniations were retrospectively reviewed. Search of the literature on calcific discitis in adults and spontaneous regression of calcified thoracic disc herniations was separately performed.Results: Both patients were young male adults presenting with back pain and early signs of myelopathy. With restriction of activities and oral NSAIDs, their symptoms were relieved within 3 months. Four adult cases of calcific discitis (characteristic central calcification confined within the nucleus pulposus) and three instances of spontaneous regression of small- to medium-sized thoracic calcified disc herniations were identified from the literature.Conclusions: The demonstration of spontaneous resorption of giant calcified thoracic disc herniations in two adult patients with calcific discitis supplements the existing literature and provides the first evidence that giant calcified thoracic disc herniations may still undergo spontaneous remission and a "wait and watch" strategy may be justified at least in the initial management of these patients, even with the presence of mild myelopathy. [ABSTRACT FROM AUTHOR]

An optimal therapeutics to manage opioid withdrawal syndrome is desired for opioid addiction treatment. Down-regulation of endogenous endomorphin-2 (EM2) level in the central nervous system after continuous morphine exposure was observed, which suggested that increase of EM2 could be an alternative novel method for opioid dependence. As a short peptide, the short half-life of EM2 limits its clinical usage through conventional administration. In the present study, we engineered an EM2 gene using a signal peptide of mouse growth factor for an out-secretory expression of EM2 and an adenovirus as a vector, which ultimately sustained the release of EM-2. After administration of the adenovirus in central nervous system, a sustained increase of EM2 level in the cerebral spinal fluid (CSF) was observed along with a reduction of morphine withdrawal syndrome. These findings suggest that the engineered EM2 gene delivered to the central nervous system could be a novel therapeutics for withdrawal syndrome in opioid dependent subjects. [ABSTRACT FROM AUTHOR]

Background: Vincristine, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and there are currently no effective drugs to prevent or treat this side effect. Previous studies have shown that methylcobalamin has potential analgesic effect in diabetic and chronic compression of dorsal root ganglion model; however, whether methylcobalamin has effect on vincristine-induced painful peripheral neuropathy is still unknown. Results: We found that vincristine-induced mechanical allodynia and thermal hyperalgesia, accompanied by a significant loss of intraepidermal nerve fibers in the plantar hind paw skin and an increase in the incidence of atypical mitochondria in the sciatic nerve. Moreover, in the spinal dorsal horn, the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the protein expression of p-p65 as well as tumor necrosis factor α was increased, whereas the protein expression of IL-10 was decreased following vincristine treatment. Furthermore, intraperitoneal injection of methylcobalamin could dose dependently attenuate vincristine-induced mechanical allodynia and thermal hyperalgesia, which was associated with intraepidermal nerve fibers rescue, and atypical mitochondria prevalence decrease in the sciatic nerve. Moreover, methylcobalamin inhibited the activation of NADPH oxidase and the downstream NF-κB pathway. Production of tumor necrosis factor α was also decreased and production of IL-10 was increased in the spinal dorsal horn following methylcobalamin treatment. Intrathecal injection of Phorbol-12-Myristate-13-Acetate, a NADPH oxidase activator, could completely block the analgesic effect of methylcobalamin. Conclusions: Methylcobalamin attenuated vincrinstine-induced neuropathic pain, which was accompanied by inhibition of intraepidermal nerve fibers loss and mitochondria impairment. Inhibiting the activation of NADPH oxidase and the downstream NF-κB pathway, resulting in the rebalancing of proinflammatory and anti-inflammatory cytokines in the spinal dorsal horn might also be involved. These findings might provide potential target for preventing vincristine-induced neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Submucosal tunneling endoscopic resection (STER) can be adequately adopted as an effective treatment for submucosal tumors (SMTs) originating from the muscularis propria (MP) layer at the esophagus and cardia. However, it has been seldom used for gastric SMTs. Our purpose was to evaluate the clinical impact of STER for gastric SMTs arising from the MP layer.Methods: Thirty-two patients with gastric SMTs from the MP layer were retrospectively included. The main outcome measurements were complete resection rate, adverse events, local recurrence, and distant metastases during follow-up.Results: Of the 32 lesions, 12 were located in the gastric corpus close to the cardia, 3 in the gastric fundus close to the cardia, 6 in the lesser curvature of the gastric corpus, and 11 in the greater curvature of the gastric antrum. STER was successfully performed in all patients with en bloc resection of tumors. The mean tumor size was 2.3 cm (range 1.0-5.0 cm). The complete resection rate was 100%. The operation time ranged from 25 to 125 min (mean 51.8 min). All complications related to STER were successfully managed with conservative treatments. Local recurrence or distant metastasis did not occur during a follow-up period of 6-32 months.Conclusion: STER is a safe and effective therapeutic strategy for eligible gastric SMTs originating from the MP layer. Submucosal tunneling in the stomach may be more challenging than that in the esophagus, but does not increase procedure-related adverse events or prevent successful STER for eligible gastric SMTs. [ABSTRACT FROM AUTHOR]

Objective: The optimal surgical treatment for multilevel cervical spondylotic myelopathy (MCSM) remains controversial. This study compared the outcomes of three surgical approaches for MSCM treatment, focusing on the efficacy and safety of a combined approach. Methods: This retrospective study included 153 consecutive MCSM patients (100 men, 53 women; mean age ± standard deviation, 55.7 ± 9.4 years) undergoing operations involving ≥3 intervertebral segments. The patients were divided into three groups according to surgical approach: anterior (n = 19), posterior (n = 76), and combined (n = 58). We assessed demographic variables, perioperative parameters, and clinical outcomes ≥12 months after surgery (20.5 ± 7.6 months), including Japanese Orthopaedic Association (JOA) score, improvement, recovery rate, and complications. Results: The anterior group had the most favorable preoperative conditions, including the highest preoperative JOA score (12.95 ± 1.86, p = 0.046). In contrast, the combined group had the highest occupancy ratio (48.0% ± 11.6%, p = 0.002). All groups showed significant neurological improvement at final follow-ups, with JOA recovery rates of 59.7%, 54.6%, and 68.9% in the anterior, posterior, and combined groups, respectively (p = 0.163). After multivariable adjustments, the groups did not have significantly different clinical outcomes (postoperative JOA score, p = 0.424; improvement, p = 0.424; recovery rate, p = 0.080). Further, subgroup analyses of patients with occupancy ratios ≥50% showed similar functional outcomes following the posterior and combined approaches. Overall complication rates did not differ significantly among the three approaches (p = 0.600). Occupancy ratios did not have a significant negative influence on postoperative recovery following the posterior approach. Conclusions: If applied appropriately, all three approaches are effective for treating MCSM. All three approaches had equivalent neurological outcomes, even in subgroups with high occupancy ratios. Further investigations of surgical approaches to MCSM are needed, particularly prospective multicenter studies with long-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To explore the relationship between cervical spine and the global spine alignment and to postulate the hypotheses that a lordotic alignment of cervical spine is not the only standard to identify asymptomatic subjects, and the degenerative modification of cervical curves depends primarily on their spinal-pelvic alignment. Methods: A cohort of 120 cases of Chinese asymptomatic subjects and a cohort of 121 cases of Chinese cervical spondylotic patients were recruited prospectively from 2011 to 2012. Roussouly Classification was utilized to categorize all subjects and patients according to their thoracic spine, lumbar spine and pelvic alignment. The cervical alignments were evaluated as lordosis, straight, sigmoid or kyphosis. Through the lateral X-ray images of neutral cervical and global spine, a number of parameters were measured and analyzed, including pelvic incidence, pelvic tilt, sacral slope, thoracic kyphosis (TK), lumbar lordosis, global cervical angles (angles between two lines parallel with posterior walls of C2 and C7), practical cervical angles (the addition of different cervical end plate angles from C3 to C7, and inter-vertebral angles from C23 to C67), T1 slope, spinal sacral angles (SSA), Hip to C7/Hip to Sacrum and C0-C2 angle. Results: The percentages of cervical lordosis were 28.3 % and 36.4 % in asymptomatic and spondylotic group, respectively. The cervical spine alignments correlated with Roussouly types of global spine alignment in both asymptomatic and cervical spondylotic group ( P < 0.001). And there were significant differences between Roussouly Type 2 and 4, Type 3 and 4, Type 1 and 3 in cervical angles in spondylotic group ( P < 0.05). In the comparison of the two cohorts, significant differences were found in both general and practical cervical angles in Roussouly Type 4 ( P = 0.00 and 0.01, respectively), and there were significant differences in inter-vertebral angle in Roussouly Type 2 at C4-5 and C5-6 levels ( P = 0.04 and 0.04, respectively), and in Roussouly Type 3 at C6-7 level ( P = 0.01). The SSA showed significant difference between Roussouly Type 2 and 4 in asymptomatic subjects ( P = 0.00), and between Type 1 and 3, 1 and 4, 2 and 3, 2 and 4 in cervical spondylotic patients ( P = 0.01, 0.02, 0.00 and 0.01, respectively). The T1 slope was significantly different among Roussouly types ( P = 0.04) with its largest value in Type 1 in cervical spondylotic group. There are significant differences in C0-C2 angles in all Roussouly types ( P = 0.01, 0.02, 0.00 and 0.01, respectively), as well as in the ratio of Hip to C7/hip to sacrum in Type 2 ( P = 0.01), and Type 3 ( P = 0.00) in the comparison of the two cohorts. The multiple linear regression of all parameters showed both general and practical cervical angles were significantly related to TK, C0-C2 and T1 slope ( P = 0.01, 0.00 and 0.00, respectively). Conclusion: The cervical alignment correlates with their global spine and pelvic curves. And lordosis is not the only presentation in asymptomatic subjects. The degenerative modification of cervical disc angles was the compensation of global spine degeneration for horizontal gaze. Cervical angles are influenced by their TK angles, occipital-C2 joint and the tilt of T1 vertebral body. The occipital-C2 joint has a compensating mechanism in all Roussouly types in cervical spondylosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether apolipoprotein A (apoA)-I glycation and paraoxonase (PON) activities are associated with the severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Methods: Relative intensity of apoA-I glycation and activities of high-density lipoprotein (HDL)-associated PON1 and PON3 were determined in 205 consecutive T2DM patients with stable angina with (n = 144) or without (n = 61) significant CAD (luminal diameter stenosis ≥ 70 %). The severity of CAD was expressed by number of diseased coronary arteries, extent index, and cumulative coronary stenosis score (CCSS). Results: The relative intensity of apoA-I glycation was higher but the activities of HDL-associated PON1 and PON3 were lower in diabetic patients with significant CAD than in those without. The relative intensity of apoA-I glycation increased but the activities of HDL-associated PON1 and PON3 decreased stepwise from 1 - to 3 - vessel disease patients (P for trend < 0.001). After adjusting for possible confounding variables, the relative intensity of apoA-I glycation correlated positively, while the activities of HDL-associated PON1 and PON3 negatively, with extent index and CCSS, respectively. At high level of apoA-I glycation (8.70 ~ 12.50 %), low tertile of HDL-associated PON1 (7.03 ~ 38.97U/mL) and PON3 activities (7.11 ~ 22.30U/mL) was associated with a 1.97- and 2.49- fold increase of extent index and 1.73- and 2.68- fold increase of CCSS compared with high tertile of HDL-associated PON1 (57.85 ~ 154.82U/mL) and PON3 activities (39.63 ~ 124.10U/mL), respectively (all P < 0.01). Conclusions: Elevated apoA-I glycation and decreased activities of HDL-associated PON1 and PON3, and their interaction are associated with the presence and severity of CAD in patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: Many cancer research studies have extensively examined the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway. There are only few reports that suggest that PTEN might affect pain; however, there is still a lack of evidence to show the role of PTEN for modulating pain. Here, we report a role for PTEN in a rodent model of neuropathic pain. Results: We found that chronic constriction injury (CCI) surgery in rats could elicit downregulation of spinal PTEN as well as upregulation of phosphorylated PTEN (phospho-PTEN) and phosphorylated mammalian target of rapamycin (phospho-mTOR). After examining such changes in endogenous PTEN in neuropathic rats, we explored the effects of modulating the spinal PTEN pathway on nociceptive behaviors. The normal rats exhibited mechanical allodynia after intrathecal (i.t.) injection of adenovirus-mediated PTEN antisense oligonucleotide (Ad-antisense PTEN). These data indicate the importance of downregulation of spinal PTEN for nociception. Moreover, upregulation of spinal PTEN by i.t. adenovirus-mediated PTEN (Ad-PTEN) significantly prevented CCI-induced development of nociceptive sensitization, thermal hyperalgesia, mechanical allodynia, cold allodynia, and weight-bearing deficits in neuropathic rats. Furthermore, upregulation of spinal PTEN by i.t. Ad-PTEN significantly attenuated CCI-induced microglia and astrocyte activation, upregulation of tumor necrosis factor-a (TNF-a) and phospho-mTOR, and downregulation of PTEN in neuropathic rats 14 days post injury. Conclusions: These findings demonstrate that PTEN plays a key, beneficial role in a rodent model of neuropathic pain. [ABSTRACT FROM AUTHOR]

To investigate the effects of ischemia/reperfusion on rat submandibular glands without denervation and the possible protective effects of ischemia preconditioning on the glands that experienced ischemia/reperfusion, in-situ ischemia/reperfusion and ischemia preconditioning experimental models of submandibular glands of healthy male Wistar rats were conducted. For ischemia/reperfusion groups, the glands were subjected to 90 min of ischemia without denervation, followed by 1, 12, 24, or 72 h of reperfusion. Ischemia preconditioning was achieved by 3 min of ischemia following 3 min of reperfusion, performed three times before ischemia/reperfusion. Salivary secretion, histological changes, alterations of tight junctions, myeloperoxidase activity, cellular apoptosis, and reactive oxygen species levels were detected. In ischemia/reperfusion glands, rising acute-inflammation responses, reduced tight-junction width, and increased myeloperoxidase activity, reactive oxygen species levels, and apoptotic cell numbers were observed, along with secretory dysfunction, especially at 1 and 12 h post-reperfusion, which seemed to gradually return to normal by 72 h post-reperfusion. In contrast, ischemia preconditioning showed the potential to ameliorate the injury-stress responses caused by ischemia/reperfusion. Our study revealed that ischemia/reperfusion could cause a series of injury-stress responses and ultimately lead to hyposecretion, independently of the parasympathetic nerve supply, which might play an important role in the early-phase dysfunction of the transplanted glands. Ischemia preconditioning could protect the involved glands and improve ischemia/reperfusion-induced hyposecretion. [ABSTRACT FROM AUTHOR]

Objective To investigate the feasibility and efficacy of sight-guided percutaneous unilateral translaminar facet screw fixation (TLFSF) with interbody fusion for treatment of lower lumbar vertebra diseases. Methods Twenty-nine adult patients with lower lumbar disease underwent sight-guided percutaneous unilateral TLFSF combined with microsurgical spinal decompression, discectomy, and interbody fusion from June 2007 to June 2008. All 29 patients had low back pain caused by lumbar disc degeneration (20 cases), in situ recurrent lumbar disc herniation (2), primary diskitis (1), lumbar disc herniation with spinal stenosis (3), and first-degree lumbar degenerative spondylolisthesis (3). Twenty-three cases had lesions at L4,5; three at L5S1, one at L3,4, L4,5, and two at L4,5, L5S1. Results No patient experienced significant postoperative complications. The mean incision length was 4.48 ± 0.55 cm; operative time 1.34 ± 0.22 h; intraoperative blood loss 280 ± 175 mL; and postoperative drainage volume 165 ± 85 mL. Screw position results: type I, 21 cases (23 segments); type II, 7 cases (8 segments); and type III, 1 case (1 segment). Twenty-eight patients were followed up for 24-60 months (average, 47.5 months). Interbody fusion rate was 93.5%). Postoperative intervertebral height recovered significantly; however, loss of intervertebral height oc urred during follow-up. Conclusion Sight-guided percutaneous unilateral TLFSF with interbody fusion for treatment of lower lumbar disease is simple and minimally invasive, with good screw accuracy and security, high fusion rate, and good efficacy. However, specific surgical indications must be strictly followed. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) has recently been introduced as a promising alternative to laparoscopic Heller myotomy for idiopathic achalasia. Several proposed technical modifications are yet to be tested in randomized trials. Objective: The objective of our study was to evaluate efficacy and safety of water-jet (WJ) assisted POEM versus the conventional (C) technique. The clinical trial registration number is NCT01742494. Methods: A prospective randomized trial was carried out in Zhongshan Hospital, Fudan University (Shanghai, China), in 100 consenting achalasia patients between August 2011 and April 2012. Patients eligible for POEM were randomized to use of either the HybridKnife (WJ group) or the conventional technique using injection and triangle tip knife interchangeably (C group). Results: A total of 100 patients with comparable characteristics between groups were included. Procedure time was significantly shorter for the WJ group (22.9 ± 6.7 vs. 35.9 ± 11.7 min; p < 0.0001), mostly due to less replacement of accessories (2.0 ± 2.4 vs. 19.2 ± 7.6; p < 0.0001). Injection volume was larger in the WJ group (45.3 ± 10.2 vs. 35.2 ± 9.5 ml; p < 0.0001) and was associated with fewer minor bleeding episodes (3.6 ± 1.8 vs. 6.8 ± 5.2; p < 0.0001). No severe complications occurred; one case of cutaneous emphysema occurred in the WJ group, and four cases occurred in the C group ( p = 0.17), three cases of pneumonia were encountered in the C group and none in the WJ group ( p = 0.24). Treatment success (Eckardt score ≤3) was achieved in 96.5 % of patients, with no significant differences between groups. Conclusions: The use of the HybridKnife leads to a significant decrease in POEM procedure time and facilitates reinjection, possibly contributing to a lower rate of minor intra-procedural bleeding. [ABSTRACT FROM AUTHOR]

Aims: To analyse the clinical significance and related factors of thirst and xerostomia and to find methods to alleviate thirst and xerostomia in maintenance hemodialysis (MHD) patients. Methods: Forty-two MHD patients were included for observational study and eleven patients were enrolled for crossover trial. Thirst was assessed by 100-mm visual analog scales (VAS) and dialysis thirst inventory (DTI). Meanwhile, xerostomia was assessed by VAS and xerostomia inventory (XI). Depression, kidney disease quality of life (KDQOL), salivary flow rates and inter dialytic weight gain (IDWG) were measured. Data were analyzed by ANOVA and correlation coefficient was used to assess the correlations between continuous variables. The results of crossover trial were investigated by two-sample T-tests. Results: Strong positive correlations among DTI, VAS thirst score, XI and VAS xerostomia score were found (P=0.000). Daily IDWG was positively correlated with VAS thirst score (r=0.315, P=0.042) and DTI(r=0.391, P=0.010). UWS (unstimulated whole saliva) was negatively correlated with VAS xerostomia score (r=-0.308, P=0.048). Residual urine output was negatively correlated with DTI (r=-0.402, P=0.008), VAS xerostomia score (r=-0.461, P=0.002) and XI (r=-0.403, P=0.008). In the crossover trial, DTI, XI, IDWG2d, IDWG3d, VAS thirst and xerostomia score were significantly reduced by the use of chewing gum (P=0.000, 0.001, 0.009, 0.017, 0.038, 0.001). The VAS thirst score, DTI and IDWG3d were significantly reduced by receiveing straw (P=0.016, 0.003, 0.049). Conclusion: Thirst and xerostomia might affect the quality of life in MHD patients. Both chewing gum and straw could decrease thirst and IDWG. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. Study Design: According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups. Results: The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38). Conclusions: Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications. [Copyright &y& Elsevier]

A retrospective analysis was made on 5 cases who had the traumatic carotid artery injury with massive epistaxis (from September 2007 to June 2011). All of them were finally diagnosed by digital substraction angiography (DSA). Among them, 2 cases of traumatic pesudoaneurysm from internal maxillary artery were embolized with polyvinyl alcohol particles and gelatin sponge. One case was carotid-cavernous fistula (CCF) with traumatic pesudoaneurysm located in the sphenoid sinus. This patient's internal carotid artery (ICA) and fistula was blocked with balloon, and then ICA was clipped proximal to the posterior communicating artery. One case with injuried ICA was treated with blocking by balloon. The pesudoaneurysm located in ICA cavernous segment of one case was embolized with coil and liquid glue. No recurrence was found after successful surgeries. Patients with massive epistaxis or recurrent epistaxis after craniofacial trauma should undergo CT angiography (CTA) or DSA examination so as to get proper diagnosis and treatment as early as possible. [ABSTRACT FROM AUTHOR]

Background and objectives: The Fractional Ultrapulsed CO2 laser has been successfully used in treating fine wrinkles, acne scars, and photoaged skin. However, the downtime typically lasts a week or more. The purpose of this study was to observe the efficacy of external cell growth factors after Fractional Ultrapulsed CO2 laser therapy. Methods: The back skin of 20 male guinea pigs were divided into four regions after hair removal, then these four regions were irradiated with Fractional Ultrapulsed CO2 laser, respectively. These 80 incised wounds were randomly divided into three therapeutic groups and a control group. The general condition of the wound healing was observed grossly. The determination of physiological functions was done and biopsies were harvested at different time points to compare the change of skin flexibility and fibroblasts number. Results: The wound healing time of therapeutic groups shortened when compared with the control group. The flexibility of skin and the number of fibroblasts were also more than the control group. The effects of combined application of rhEGF and rb-bFGF therapeutic group were most conspicuous. Conclusions: Combined application of rhEGF with rb-bFGF could be more beneficial to the wound after Fractional Ultrapulsed CO2 laser therapy. It could accelerate the wound healing and increase the flexibility of wound skin, so the significance was important to direct clinical application. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSCs) are regarded as a promising source of cell-based therapy for heart injury. In fact, less than 30% of MSCs contribute to cardiomyocytes differentiation, and the isolation procedure and biological characteristics of this population of cells remain unknown. Here we isolate and investigate the biological characteristics of this subpopulation of MSCs. Twenty four MSC clones were randomly selected using single-cell monoclonal technology. After induced with 5-azacytidine, eight clones displayed cardiomyocyte-like morphologies, and highly (over 90%) expressed cardiac-specific markers cTnT and α-actin, and displayed transient outward K+ current (I to), inwardly rectifying K+ current (I K1) and delayed rectifier K+ current (I KDR), which were typical of cardiomocytes. Other clones merely showed I to current, and the current densities were different from those of cardiomyocytes. In contrast to the other clones, before induced with 5-azacytidine, the eight clones expressed early cardiac markers GATA4 and NKX2.5, but not cTnT, α-actin, CD44 and CD90, and had no potentials for adiopogenesis, osteogenesis or chondrogenesis after induction. Our data suggest that the subgroup of MSCs that contributes to cardiomyocytes differentiation is cardiac progenitor cells. Moreover, we show the preliminary purification of this population of cells with a high potential for cardiomyocytes differentiation using single-cell monoclonal technology. [Copyright &y& Elsevier]

OBJECTIVE: To study the technical method and clinical value of stent implantation through the rendezvous technique of percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) in patients with obstructive jaundice. METHODS: Thirty-six patients with obstructive jaundice underwent the rendezvous technique of PTBD and ERCP after initially unsuccessful ERCP. RESULTS: The procedure of 36 cases were all successful. Sixteen cases underwent PTBD drainage from the bile duct through the right lobe approach and in 20 cases the left lobe approach was used. The one-stage procedure involved in the rendezvous technique of PTBD and ERCP was successful in 23 cases, while the other 13 cases underwent PTBD first and then rendezvous ERCP the next time. The serum total bilirubin 4 days later had decreased by 44.75%, and direct bilirubin had decreased by 45.61%. The main complication was infection of the bile duct. CONCLUSION: Stent implantation using the rendezvous technique of PTBD and ERCP is a new and feasible method to treat obstructive jaundice after initially unsuccessful ERCP. This may be of considerable value in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Drug-eluting stents (DES) constitute a major breakthrough in restenosis prevention after percutaneous coronary intervention (PCI). This study compared the clinical outcomes of PCI using DES versus coronary artery bypass graft (CABG) in patients with multivessel coronary artery disease (MVD) in real-world. Methods: From January 2003 to December 2004, 466 consecutive patients with MVD underwent revascularization, 235 by PCI with DES and 231 by CABG. The study end-point was the incidence of major adverse cardiovascular events (MACEs) at the first 30 days after procedure and during follow-up. Results: Most preoperative characteristics were similar in the two groups, but left main disease (24.7% vs 2.6%, P<0.001) and three-vessel disease (65% vs 54%, P = 0.02) were more prevalent in CABG group. The number of coronary lesions was also greater in CABG group (3.7 ± 1.1 vs 3.3 ± 1.1, P<0.001). Despite higher early morbidity (3.9% vs 0.8%, P = 0.03) associated with CABG, there were no significant differences in composite MACEs at the first 30 days between the two groups. During follow-up (mean 25±8 months), the incidence of death, myocardial infarction, or cerebrovascular event was similar in both groups (PCI 6.3% vs CABG 5.6%, P = 0.84). However, bypass surgery still afforded a lower need for repeat revascularization (2.8% vs 10.4%, p = 0.001). Consequently, overall MACE rate (14.5% vs 7.9%, P = 0.03) remained higher after PCI. Conclusion: PCI with DES is a safe and feasible alternative to CABG for selected patients with MVD. The reintervention gap was further narrowed in the era of DES. Aside from restenosis, progression of disease needs to receive substantial emphasis. [ABSTRACT FROM AUTHOR]

Background: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. Methods: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. Results: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140–3.124), severe agitation (OR 1.846, 95%CL 1.266–2.693), unemployment or retirement (OR 1.614, 95%CL 1.189–2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032–2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436–0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240–0.902) were less likely to be associated with antipsychotic polypharmacy. Conclusion: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy. [ABSTRACT FROM AUTHOR]

Background: ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has rarely been used to determine the response to crizotinib in Chinese patients with NSCLC and ALK overexpression. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC undergoing screening for ALK rearrangements.Methods: A total of 1720 patients with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were included in this analysis. We compared the efficacy and survival of ALK-positive patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in whom the two methods were inconsistent.Results: Among 1720 patients, 187 (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66 received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK-positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR. The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34) by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS; specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK fusion.Conclusions: VENTANA IHC is a reliable and rapid screening tool used in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher association with response to therapy with ALK inhibitors, and some VENTANA IHC-positive, but RT-PCR-negative cases may benefit from crizotinib. [ABSTRACT FROM AUTHOR]

Background: Bone marrow stromal cells (BMSCs) have shown potential to treat chronic pain, although much still needs to be learned about their efficacy and mechanisms of action under different pain conditions. Here, we provide further convergent evidence on the effects of BMSCs in rodent pain models. Results: In an orofacial pain model involving injury of a tendon of the masseter muscle, BMSCs attenuated behavioral pain conditions assessed by von Frey filaments and a conditioned place avoidance test in female Sprague-Dawley rats. The antihyperalgesia of BMSCs in females lasted for <8 weeks, which is shorter than that seen in males. To relate preclinical findings to human clinical conditions, we used human BMSCs. Human BMSCs (1.5 M cells, i.v.) attenuated mechanical and thermal hyperalgesia induced by spinal nerve ligation and suppressed spinal nerve ligation-induced aversive behavior, and the effect persisted through the 8-week observation period. In a trigeminal slice preparation, BMSC-treated and nerve-injured C57B/L mice showed reduced amplitude and frequency of spontaneous excitatory postsynaptic currents, as well as excitatory synaptic currents evoked by electrical stimulation of the trigeminal nerve root, suggesting inhibition of trigeminal neuronal hyperexcitability and primary afferent input by BMSCs. Finally, we observed that GluN2A (N-methyl-D-aspartate receptor subunit 2A) tyrosine phosphorylation and protein kinase Cgamma (PKCγ) immunoreactivity in rostral ventromedial medulla was suppressed at 8 weeks after BMSC in tendon-injured rats. Conclusions: Collectively, the present work adds convergent evidence supporting the use of BMSCs in pain control. As PKCγ activity related to N-methyl-D-aspartate receptor activation is critical in opioid tolerance, these results help to understand the mechanisms of BMSC-produced long-term antihyperalgesia, which requires opioid receptors in rostral ventromedial medulla and apparently lacks the development of tolerance. [ABSTRACT FROM AUTHOR]

The economic and biological significance of blunt snout bream ( Megalobrama amblycephala ) makes this species important to explore the underlying molecular mechanism of hypoxia response. In the present study, we compared the transcriptional responses to serious hypoxia in skeletal muscle among hypoxia tolerant (MT), sensitive (MS) and control (without hypoxia treatment, MC) M. amblycephala obtained according to the time difference of losing balance after hypoxia treatment. A total of 88,200,889 clean reads were generated and assembled into 44,493 unigenes. Transcriptomic comparison revealed 463 genes differentially expressed among different groups. A similar hypoxia-induced transcription patterns suggested a common hypoxia response involved in cell cycle, p53 signaling pathway, apoptosis, heart contraction and blood circulation. Interesting, four genes, heat shock protein beta-8 ( hspb8 ), cysteine/serine-rich nuclear protein 1 ( csrnp1 ), salt-inducible kinase 1 ( sik1 ), and visinin-like 1a ( vsnl1a ) were up-regulated in MT Vs MC but down-regulated in MS Vs MC. Additionally, FoxO signaling pathway was significantly enriched only in MT Vs MC. These results not only provided the first insights into the mechanism that muscle tissue coped with the hypoxia stress in cyprinid species, but offered a theory base for breeding of M. amblycephala with hypoxia-resistant traits. [ABSTRACT FROM AUTHOR]

Various degradable biomaterials have been used to bridge injured peripheral nerve defect; however, drawbacks such as poor mechanical properties, inappropriate degradation rate, and toxic degradation products continue to limit the application of them in nerve repair. Considering the unique properties of zein, such as its biocompatibility, biodegradability and ease of fabrication, we report the use of zein conduits to repair injured rat sciatic nerves with a 10-mm defect. Three-dimensional zein conduits were designed with/without pores, and with/without microtubes including in the lumen of conduits. Zein conduit with microtubes yielded satisfactory results in sciatic function index (SFI), proximal compound muscle action potentials, density of myelinated nerve fibres and myelin thickness, which were not inferior to autograft but slightly superior to the hollow conduit at the 4th month post-implantation. The conduits degraded almost completely within two months, which was shorter than the suggested period of four months. Thus, the use of a porous conduit with microtubes inside as the guidance may play important roles in successful repair. Notably, the regulatory body will more likely approve designs employing a single component, such as the natural polymer zein. [ABSTRACT FROM AUTHOR]

Bushen Quhan Zhiwang decoction (BQZD), a formula in traditional Chinese medicine (TCM), effectively delays bone destruction in rheumatoid arthritis (RA) patients. However, its chemical constituents, absorbed components, and metabolites remain unrevealed, and its mechanism in treating bone destruction in RA needs further investigation. Our objective is to identify the chemical constituents, absorbed components, and metabolites of BQZD and explore the potential mechanisms of BQZD in treating bone destruction in RA. This study systematically identified the chemical constituents, absorbed components, and metabolites of BQZD using ultra-performance liquid chromatography with Q-Exactive Orbitrap mass spectrometry combined with parallel reaction monitoring. The absorbed components and metabolites were subjected to network pharmacology analysis to predict the potential mechanisms of BQZD in treating bone destruction in RA. The in vivo anti-osteoclastogenic and underlying mechanism were further verified in collagen-induced arthritis (CIA) rats. A total of 182 compounds were identified in BQZD, 27 of which were absorbed into plasma and organs and 42 metabolites were identified in plasma and organs. The KEGG analysis revealed that MAPK signaling pathway was highly prioritized. BQZD treatment attenuated paw swelling and the arthritis index; suppressed synovial hyperplasia, bone destruction, and osteoclast differentiation; and inhibited the levels of TNF-α, IL-1β, and IL-6 in CIA rats. Mechanically, BQZD significantly decreased the protein expression levels of TRAF6, NFATc1, p-JNK, and p-p38, which might be related to 9 absorbed components and 1 metabolite. This study revealed the key active components and metabolites of BQZD. BQZD exhibits bone-protective effects via TRAF6/p38/JNK MAPK pathway, which may be associated with 9 absorbed components and 1 metabolite. [Display omitted] • The components and metabolites of BQZD were studied. • BQZD inhibited bone destruction in RA via the TRAF6/p38/JNK MAPK pathway. [ABSTRACT FROM AUTHOR]

Abstract: Background: In our previous prospective and randomized study, we have demonstrated that the concomitant surgical ablation using saline-irrigated cooled tip radiofrequency ablation (SICTRA) system is more effective than subsequent circumferential pulmonary vein isolation (CPVI) combined with substrate modification in treating patients with long-standing persistent atrial fibrillation (LS-AF) and rheumatic heart disease (RHD) undergoing cardiac surgery during middle-term follow-up. Whether this strategy also decreases longer-term arrhythmia recurrence is unknown. This study describes the 4-year efficacy of SICTRA for these patients. Furthermore, we seek to compare the electrophysiological characteristics for recurrent atrial tachyarrhythmia (ATa) at the session of catheter ablation between two groups. Methods: Long-term follow-up was performed in 95 patients who underwent the catheter ablation strategy (n=47, Group A) or SICTRA (n=48, Group B) combined with valvular surgery for symptomatic LS-AF patients with RHD. Results: After one procedure, Group B had a significantly higher freedom from ATa compared with Group A (29/48 vs 15/47, P=0.005) after a mean follow-up of 54months (range 48 to 63months). Catheter-based mapping and ablation of recurrent ATa showed larger amounts of macro-reentrant atrial tachycardias (ATs) in Group B and higher incidence of pulmonary vein (PV) recovery in Group A. After multiple catheter ablations for recurrent ATa, sinus rhythm (SR) could be maintained equally between two groups. Conclusions: Single procedure success seems to be higher with SICTRA but repeated catheter ablation potentially results in comparable outcomes in treating patients with LS-AF and RHD during long-term follow-up. More macro-reentrant ATs and more PV recoveries are identified to be responsible for ATa in SICTRA and catheter ablation group, respectively. [Copyright &y& Elsevier]

Background Context: Langerhans cell histiocytosis (LCH) of the spine is a relatively rare condition with unknown etiology. The diagnosis and treatment protocols for spine LCH remain controversial.Purpose: In this study, we evaluated the efficacy and safety of our proposed diagnosis and treatment protocol introduced in 2009.Study Design: This is a retrospective study.Patient Sample: A total of 110 patients with spine LCH who had been diagnosed and treated in our hospital from October 1997 to November 2015 were included in this study.Outcome Measures: The age, gender, symptoms, neurologic function, lesion distribution, radiological features, pathology, treatment, outcome, and treatment complications of the patients were collected. Visual analog scale (VAS) for pain and Frankel scale for neurologic status were also documented.Methods: We retrospectively reviewed 110 patients with spine LCH who had been diagnosed and treated in our hospital from October 1997 to November 2015. The indications for computed tomography (CT)-guided biopsy and surgery for spine LCH have become more stringent since 2009. In cases of a solitary spinal lesion, immobilization and observation were usually first suggested. Chemotherapy was suggested for cases with multifocal LCH lesions, and low-dosage radiotherapy was restricted to recurrent solitary lesion. This project was supported by our hospital (No. Y71508-01) (¥ 400,000).Result: This series included 69 male and 41 female patients (age range, 1-52 years). Pain was the most common symptom (93.6%, 103/110). Pathologic diagnosis was achieved in 72 cases (65.5%). CT-guided biopsies were performed in 91.3% (42/46) and 73.2% (41/56) of cases before and after 2009, respectively (p=.02). Ninety-eight cases (89.1%) were followed up for a mean 66.3 (range, 24-159) months. Immobilization and observation were performed in 25.9% (14/54) and 75.0% (42/56) of cases before and after 2009, respectively (p<.001). Approximately 35.2% (19/54) and 10.7% (6/56) of cases had surgery (p=.002) before and after 2009, respectively. During the follow-up, no significant difference was found in the outcomes between the two groups treated before and after 2009 (p=.64).Conclusion: Biopsy is not mandatory for typical spine lesions of LCH. Given the self-healing tendency of spine LCH, immobilization and observation remain the first-choice treatments for LCH lesions. Conservative biopsy and treatment protocols might be more appropriate for spinal LCH. [ABSTRACT FROM AUTHOR]

Background Context: Aggressive (Enneking stage 3, S3) vertebral hemangiomas (VHs) are rare, which might require surgery. However, the choice of surgery for S3 VHs remains controversial because of the rarity of these lesions.Purpose: We reported our experience of treating S3 VHs, and evaluated the effectiveness and safety of intraoperative vertebroplasty during decompression surgery for S3 VHs.Study Design: This is a retrospective study.Patient Sample: Thirty-nine patients with a definitive pathologic diagnosis of aggressive VHs who underwent primary decompression surgery in our department were included in this study.Outcome Measures: Basic data such as surgical procedure, surgical duration, estimated blood loss during surgery, and pathology were collected. The modified Frankel grade was used to evaluate neurologic function. Enneking staging was based on radiological findings.Methods: We retrospectively examined aggressive VHs with neurologic deficits. Surgery was indicated if the neurologic deficit was severe or developed quickly or if radiotherapy was ineffective. Decompression surgery was performed. Intraoperative vertebroplasty during posterior decompression has been used since 2009. If contrast-enhanced computed tomography (CT) revealed a residual lesion, we recommended adjuvant radiotherapy with 40-50 Gy to prevent recurrence. Patients' basic and surgical information was collected. The minimum follow-up duration was 18 months. This study was partially funded by Peking University Third Hospital, Grant no. Y71508-01.Results: Average age of the 39 patients with S3 VHs who underwent primary decompression surgery was 46.2 (range, 10-69) years. All patients had neurologic deficits caused by aggressive VHs. Aggressive VH lesions were located in the cervical, thoracic, and lumbar spine in 2, 32, and 5 patients, respectively. The decompression-alone group had 17 patients, and the decompression plus intraoperative vertebroplasty group had 22. There were no statistically significant intergroup differences in preoperative information (p>.05). The average estimated blood losses were 1,764.7 mL (range, 500-4,000 mL) and 1,068.2 mL (range, 300-3,000 mL) in the decompression-alone group and decompression plus vertebroplasty group, respectively (p=.017). One patient who underwent primary decompression alone without adjuvant radiotherapy experienced recurrence after the first decompression. The average follow-up was 50.2 (range, 18-134) months, and no cases of recurrence were observed at the last follow-up.Conclusions: Our results suggest that posterior decompression effectively provides symptom relief in patients with aggressive (S3) VHs with severe spinal cord compression. Intraoperative vertebroplasty is a safe and effective method for minimizing blood loss during surgery, whereas adjuvant radiotherapy or vertebroplasty helps in minimizing recurrence after decompression. [ABSTRACT FROM AUTHOR]

The dried roots of Euphorbia kansui T.N. Liou ex T.P. Wang have been traditionally used for edema in China. However, the severe toxicity caused by Euphorbia kansui has seriously restricted its clinical application. Therefore, in order to study the material basis of the toxicity attenuation effect of processing with vinegar, a rapid, sensitive, validated and reliable UPLC–MS/MS method was developed to determine twelve compounds in ethyl acetate extracts of Euphorbia kansui before and after fry-baked with vinegar simultaneously. Meanwhile, the study of their toxic effect on zebrafish was conducted. Chromatographic separation was accomplished on Waters BEH C 18 UPLC column. 0.3% formic acid in water and acetonitrile were used as mobile phase with a flow rate of 0.40 mL/min and a temperature at 30 °C. The analysis was performed in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). Furthermore, the toxic research results indicated that the toxicity of Euphorbia kansui was decreased after vinegar-processed, which might because of the increase in the content of 5- O -benzoyl-20-deoxyingenol and the decrease in the contents of the remaining terpenoids in ethyl acetate extracts of Euphorbia kansui fry-baked with vinegar. This study demonstrated that the method used is a powerful approach to determine the content of twelve compounds that responsible for the toxic effect of Euphorbia kansui at the same instant. And provided the experimental evidence for the rationale behind the reduction of toxicity. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the anti-inflammatory activity of Musca domestica cecropin-A2 (Mdc-A2) toward Staphylococcus aureus ( S. aureus ) to learn more about their immunological functions. RAW264.7 cells were transfected with recombinant lentiviruses introduce pLEX-Mdc-A2into the RAW264.7 cell line (RAW-Mdc-A2). The RAW264.7 cell line with empty pLEX (RAW-pLEX) was produced in the same manner as a negative control. Real-time quantitative reverse transcription PCR (RT-PCR) was performed to analyze the mRNA expression of TNF-a, IL-1β, NFκB-1 and NFκB-2 in S. aureus -stimulated RAW-Mdc-A2 cells and RAW-pLEX cells in untreated cells and cells treated for 3 h, 6 h, 12 h and 24 h. RT-PCR was performed to analyze the mRNA expression of TNF-a, NFκB-1 and NFκB-2 stimulated by Lipoteichoic acid (LTA). Production of TNF-a was detected by enzyme-linked immunosorbent assay (ELISA). Colony counts were used to calculate the number of CFU per mL of cell culture supernatants. The results showed that compared to RAW-pLEX cells, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by S. aureus significantly down-regulated the mRNA expression of TNF-a transcript variant 1 (TNF-a-tv-1) at 6 h and 12 h and the mRNA expression of TNF-a transcript variant 2 (TNF-a-tv-2) at 3 h, 6 h and 12 h. Compared to RAW-pLEX cells, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by S. aureus significantly down-regulated the mRNA expression of IL-1β-T at 3 h, 6 h and 12 h as well as the mRNA expression of IL-1β at 3 h and 6 h. The expression and production of TNF-a and bacterial burden of cell culture supernatants were significantly down-regulated in RAW-Mdc-A2 cells stimulated by S. aureus , and the expression and production of TNF-a were significantly down-regulated in RAW-Mdc-A2 cells stimulated by LTA. Compared to RAW-pLEX cells, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by S. aureus significantly down-regulated the mRNA expression of NFκB-1 at 3 h, 6 h and 12 h as well as the mRNA expression of NFκB-2 at 6 h. Additionally, stable transfection of Mdc-A2 in RAW264.7 cells stimulated by LTA significantly down-regulated the mRNA expression of NFκB-1. In conclusion, Mdc-A2 possesses potent anti-inflammatory activity and potent antimicrobial activity. Additionally, Mdc-A2 may interact with LTA and execute strong anti-inflammatory activity by blocking the activation of NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have infrequently been reported thus far. In the present study, C57BL/6 mice were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as a control diet with or without DMY (75 and 150 mg/kg/d bw) for 6 weeks. DMY significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and triglyceride deposition induced by chronic alcohol exposure. In addition, DMY dramatically attenuated the alcohol-triggered elevation of the level of inflammatory cytokines and partially recovered hepatic pathological changes. Notably, DMY remarkably modified aberrant expression of CYP2E1, Keap-1 and HO-1 in the liver and simultaneously ameliorated disordered nuclear localization of NF-κB and Nrf2 to exert its hepatoprotective effects. Further mechanistic exploration suggested that DMY activated Nrf2, possibly mediated through the autophagy pathway. Analysis of the crosstalk among p62, Keap-1 and Nrf2 demonstrated that the p62 upregulation caused by DMY contributes to a positive feedback loop in Nrf2 activation. In summary, DMY likely modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate liver steatosis and the inflammatory response in the pathological progression of ALD. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Vertebral hemangiomas (VHs) are called benign tumors but are actually just vascular malformations. The diagnosis and treatment for aggressive VHs is still controversial, due to their rarity. Purpose: To evaluate the safety and efficiency of the present diagnostic methods and treatment choices. Study design: A retrospective study of aggressive VHs with neurologic deficit. Patients sample: A total of 29 consecutive aggressive VH cases were diagnosed and treated in our department since 2001. Outcome measures: We routinely took anteroposterior and lateral spinal roentgenograms, computed tomography, and magnetic resonance images. Methods: Trocar biopsy is indicated in suspected malignant cases. Radiotherapy was usually our first choice if the neurologic deficit was mild or developed slowly. Surgery was indicated if the neurologic deficit was severe or developed quickly or if the radiotherapy was not effective. Results: This series included 12 males and 17 females, and the mean age at diagnosis was 44.0 years (range, 21–72 years). Ten patients had radiculopathy, 1 had cauda equina syndrome, and 18 cases had myelopathy. Twenty-one cases had lesions in the thoracic spine, 5 in the lumbar, and 3 in the cervical region. Eleven cases had untypical image findings, including five cases with pathologic vertebral fracture. The neurologic compression came from only epidural soft tumor mass in 18 cases, whereas it came from both bony compression and soft lesion in the other 11 cases. Ten cases had radiotherapy alone, but two failed and had surgery later. Twenty-one cases had surgery. In the 12 cases having surgical decompression without vertebroplasty, the average estimated blood loss was 1900 mL, and it was 1093 mL for the eight cases having decompression with vertebroplasty. The average follow-up was 51.1 months (range, 24–133 months). There was no recurrence in those cases with radiotherapy, whereas three had local recurrence in those six cases treated by surgical decompression alone without radiotherapy. Conclusions: In aggressive VHs, epidural soft-tissue compression was usually the main reason for neurologic deficit. In cases with rapid progressive and/or severe myelopathy, posterior decompression and stabilization could be combined with intraoperative vertebroplasty to reduce blood loss. [Copyright &y& Elsevier]

Studies have demonstrated poor survival outcomes for patients with resected combined hepatocellular carcinoma-cholangiocarcinoma tumours (CHCC-CC). Our objectives are to report on our institutional experience regarding the clinico-pathological and prognostic features of CHCC-CC and to compare our results with published series. The clinico-pathological features and outcomes of 11 patients with CHCC-CC who had a complete surgical resection for primary liver cancer were reviewed. There were 8 male and 3 female patients. The overall median age was 61 years. Active hepatitis B and hepatitis C infections were present in 6 (54%) and 2 (18%) patients, respectively. Alcoholism was present in one case. Cirrhosis was present in 8 (72%) cases. There were no causative factors identified in 2 patients with non-cirrhotic livers. The median AFP value was 30.56 ng/ml. A single mass located in the right lobe and a single mass located in the left lobe of the liver was noted in 6 (54%) and 4 (36%) patients, respectively. Bilobar involvement was observed in one case. Major and minor resections were performed in 2 (18%) and 9 (81%) cases, respectively. The median tumour size was 3 cm. Tumours measuring >5 cm were identified in only 2 (18%) cases. The majority of the cases were classified as stage I (54%) and stage II (36%). Four patients died 11e50 months after the surgery. Postoperative tumour recurrences were observed in 5 (45.45%) patients within 4 years of surgical resection. The overall 1- and 3-year survival rates in this series were 80% and 69.3%. Our series demonstrated cases of CHCC-CC with more favourable pathological traits and survival outcomes compared with similar studies. [ABSTRACT FROM AUTHOR]

Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G--based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets. [ABSTRACT FROM AUTHOR]

Euphorbia kansui is a toxic Chinese herbal medicine and exhibits promising treatment to the malignant ascites (MA) in its traditional use. Ingenane-type and jastrophane-type diterpenes are demonstrated to be responsible for the toxicity and efficacy of kansui. Two representative compounds, kansuiphorin C (KPC) and kansuinin A (KA) in each type were proved to effectively reduce the ascites. The biological and toxicological effects are closely associated with the gastrointestinal tract, but the possible mechanism and related metabolic functions of KPC and KA treating MA through modulating the gut microbiota remain unclear. To investigate the possible mechanism and related metabolism of KPC and KA ameliorating malignant ascites through modulating gut microbiota. MA rats and normal rats were divided into different groups and administrated with KPC, KA, and positive drug, respectively. 16S rDNA gene sequencing and metagenomes analysis combined with the quantification of short-chain fatty acids of feces were performed to reflect the modulation of gut microbiota. Then, the metabolites of KPC and KA in rat feces under the normal and pathological circumstances were detected by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) to explore the in-vivo bacterial biotransformation. KPC and KA were modulatory compounds for gut microbiota. The richness of Lactobacillus and the decreased abundance of Helicobacter involved in the carbohydrate metabolism and amino acid metabolism could be responsible for their prohibitory effects on malignant ascites. KPC exhibited stronger modulation of gut microbiota through making the abundance of Helicobacter about 3.5 times lower than KA. Besides, in-vivo microbial biotransformation of KPC and KA contained oxidation, hydrolysis, dehydration, and methylation to form metabolites of lower polarity. Besides, at the dosage of 10 mg kg−1, the toxicity of both compounds had weaker influences on the gut microbiota of normal rats. KPC and KA could ameliorate malignant ascites by modulating gut microbiota mainly containing the increase of Lactobacillus and the decrease of Helicobacter and related carbohydrate and amino acid metabolism, providing a basis for their promising clinical usage. Image 1 [ABSTRACT FROM AUTHOR]