Efficacy of Baclofen as Add-on Therapy for Refractory Gastroesophageal Reflux Disease: A Meta-analysis.

OBJECTIVES: As a GABAB receptor agonist, baclofen has demonstrated efficacy in alleviating symptoms of refractory gastroesophageal reflux disease (r-GERD). This meta-analysis aims to evaluate the safety and effectiveness of baclofen as an add-on therapy for this condition. METHOD: We conducted a comprehensive search of the PubMed, Embase, and Web of Science databases for studies published up until October 2023. Subsequently, we performed a meta-analysis encompassing all eligible trials. RESULTS: From 719 records, 10 studies were included, most of these studies were moderate risk. The findings demonstrated that the addition of baclofen as a supplementary treatment effectively improves symptoms (GERD Q score) in r-GERD (standardized mean difference=-0.78, 95% CI: -1.06 to -0.51, I2=0%). The addition of this treatment also resulted in a decrease in the frequency of nonacidic reflux episodes (standardized mean difference=-0.93, 95% CI: -1.49 to -0.37, I2=63%) and an improvement in DeMeester scores (standardized mean difference=-0.82, 95% CI: -1.61 to -0.04, I2=81%) among patients with r-GERD when compared with the use of proton pump inhibitor (PPI) drugs alone. However, no significant disparity was observed in terms of reducing acid reflux episodes (standardized mean difference=-0.12, 95% CI: -0.49 to 0.19, I2=0%) and proximal reflux (standardized mean difference=-0.47, 95% CI: -1.08 to 0.14, I2=60%). CONCLUSION: Baclofen as an add-on treatment can effectively improve the symptoms of patients with r-GERD and reduce the incidence of nonacidic reflux and improve DeMeester score. However, long-term use of baclofen leads to an increased incidence of side effects and is not effective in reducing the occurrence of acid reflux.

The expression of LRRN4 was correlated with the progression and prognosis of colon adenocarcinoma (COAD) patients.

Our present study aims to investigate the value of LRRN4 in the progression and prognosis of COAD patients. All COAD and adjacent sample data was downloaded from TCGA database. Survival analysis was performed according to Kaplan-Meier method. The real-time quantitative PCR and immunohistochemistry analysis were conducted for validation in cell lines and tissues. The GSEA was conducted to find functional KEGG pathways. Multivariate Cox regression proportional hazard mode was used to determine whether LRRN4 expression was an independent prognostic factor. The LRRN4 expression in COAD samples were significantly higher than that in adjacent samples, which was consistent with our experiments in cell lines and tissues. Along with the increase of TNM Stage, LRRN4 expression had an increasing tendency. The COAD patients with high LRRN4 expression showed undesirable prognoses. Additionally, the TGF-ß signaling pathway, WNT signaling pathway and other 25 pathways were significantly activated in the high LRRN4 expression group. In conclusion, high LRRN4 expression was closely related to the onset of COAD and it was a poor prognostic factor for COAD patients.

Overexpression of cancer susceptibility candidate 2 inhibited progression of hepatocellular carcinoma cells.

OBJECTIVE: Our study was aimed to investigate the effect of cancer susceptibility candidate 2 (CASC2) on the proliferation, cell cycle, apoptosis, and metastasis of hepatocellular carcinoma (HCC) cells. METHODS: CASC2 expression in tumor tissues and HCC cells was tested by quantitative real-time polymerase chain reaction. After manipulating the expression of CASC2 in Hep3B and HepG2 cells, cells viability, including proliferation, apoptosis, cell-cycle distribution, migration, and invasion were examined by colony formation assay, flow cytometry, wound-healing assay, and transwell assay, respectively. The expression levels of proteins associated with the cell cycle and AKT/mTOR pathway were measured by the western blot. Stably transfected HepG2 cells were used to construct nude mice models, and tumorigenesis was evaluated to investigate the in vivo functions of CASC2 in HCC progression. RESULTS: In tissues and cells of HCC, decreased CASC2 expressions were confirmed. Overexpression of CASC2 made cell cycle stagnated at G0/G1 phase and induced apoptosis. Meanwhile, the overexpression of CASC2 played significant roles in inhibiting the proliferation, migration, and invasion of HCC cells. Furthermore, In vivo experiment indicated that CASC2 restrained the growth of tumors. CONCLUSION: Our study suggested that CASC2 promoted cell apoptosis and suppressed cell growth and metastasis in HCC, indicating that CASC2 might be a useful biomarker of HCC.

Systematic review and meta-analysis of laparoscopic mesh versus suture repair of hiatus hernia: objective and subjective outcomes.

BACKGROUND: Hiatus hernia (HH) contributes to the pathophysiology of gastroesophageal reflux disease (GERD). Mesh-augmentation of surgical repair might be associated with a reduced risk of recurrence and GERD. However, recurrence rates, mesh-associated complications and quality of life (QOL) after mesh versus suture repair are debated. The aim of this meta-analysis was to determine HH recurrence following mesh-augmentation versus suture repair. Secondary aims were to compare complications, mortality, QOL and GERD symptoms following different repair techniques. METHODS: A systematic literature search of the PubMed, Medline, Embase, Cochrane Library, and Springer database was performed to identify relevant studies comparing mesh-augmentation versus suture repair of the esophageal hiatus. Data pertinent to the benefit versus risk outcomes for these techniques were extracted and compared by meta-analysis. The odd ratio (OR) and mean differences (MD) with 95% confidence intervals were calculated. RESULTS: Eleven studies (4 randomized, 9 non-randomized) comparing mesh (n = 719) versus suture (n = 755) repair were identified. Mesh-augmentation was associated with a reduced overall recurrence rate compared to suture repair [2.6 vs. 9.4%, OR 0.23 (95% CI 0.14-0.39), P < 0.00001]. There was no significant difference in the incidence of complications (P = 0.400) between groups. Improvement in QOL measured by SF-36 was greater following biological mesh-augmentation compared to suture repair (MD = 13.68, 95% CI 2.51-24.85, P = 0.020), as well as GERD-HRQL. No differences were seen for the GIQLI scores with permanent mesh (P = 0.530). Dysphagia improvements were better following suture repair (MD = 1.47, 95% CI 0.20-2.74, P = 0.020). CONCLUSIONS: Mesh repair of HH conferred some advantages and disadvantages at short-term follow-up. Compared to a suture repair alone, mesh-augmentation might be associated with less short-term recurrences, and biological mesh was associated with improved short-term QOL. However, these advantages were offset by more dysphagia. Long-term outcomes are still needed to determine the place of mesh repair of HH.

Step-up mini-invasive surgery for infected pancreatic necrosis: Results from prospective cohort study.

OBJECTIVES: To investigate the clinical efficacy and success predictors of mini-invasive techniques in the treatment of infected pancreatic necrosis (IPN). METHODS: IPN patients admitted to our clinic for treatment by mini-invasive techniques were included in this study prospectively. Treatment was divided into four sequential phases: percutaneous catheter drainage (PCD), mini-incision drainage (MID), video assisted debridement (VAD) and open surgery. Patients progressed to next phase if the infection cannot be controlled. The frequency of surgery, treatment duration, cure rate, incidence of complication and overall mortality were recorded. Risk factors for failure of PCD and MID procedures were detected by logistic regression including demographics, disease severity and morphologic characteristics. RESULTS: From January 2012 to March 2015, a total of 54 consecutive IPN patients were treated, with an average age of 51.2 ± 3.1 years. Of the 54 cases, 18 (33.3%) were cured after PCD; 13 (24.1%) with uncontrolled infection were cured after MID; and the remaining 19 cases (35.2%) were cured after VAD. No open surgery was performed. Overall mortality was 7.4% (4/54), and the incidence of complications was 12.9% (7/54). In multivariable regression, the following factors were associated with high failure rate for both PCD and MID: heterogeneous fluid collection (odds ratio (OR) = 3.14; 95% confidence interval (CI): 1.32 ï½ž 4.25, P = 0.001 for PCD; OR = 2.99; 95% CI: 1.52 ï½ž 5.10, P = 0.006 for MID), multiple infected collections (OR = 4.51; 95% CI: 2.94 ï½ž 8.63; P = 0.000 for PCD; OR = 4.17; 95% CI: 2.77 ï½ž 8.12, P = 0.000 for MID), CT severity index (0 ï½ž 3/4 ï½ž 6/7 ï½ž 10: OR = 2.16; 95% CI: 1.83 ï½ž 3.62, P = 0.031 for PCD; OR = 2.72; 95% CI: 1.78 ï½ž 4.10, P = 0.005 for MID). CONCLUSIONS: Step-up mini-invasive techniques can be considered a first choice in the treatment of IPN. CT is effective to predict success of PCD and MID.

Elevated DNA damage response in pancreatic cancer.

Pancreatic cancer is one of the most aggressive and intractable human malignant tumors and a leading cause of cancer-related death across the world, with incidence equaling mortality. Because of the extremely high malignance, this disease is usually diagnosed at its advanced stage and recurs even after surgical excision. Pancreatic adenocarcinoma is generally thought to arise from pathological changes of pancreatic duct, and the pancreatic ductal adenocarcinoma accounts for more than 90 % of malignant neoplasms of the pancreas. To date, scientists have revealed several risk factors for pancreatic cancer, including smoking, family history, and aging. However, the underlying molecular mechanism remains unclear. Meanwhile, more mutations of DNA damage response factors have been identified in familial pancreatic cancers, implying a potential link between DNA damage and pancreatic cancer. DNA damage is a recurring phenomenon in our bodies which could be induced by exogenous agents and endogenous metabolism. Accumulated DNA lesions cause genomic instability which eventually results in tumorigenesis. In this study, we showed obvious DNA damages existed in human pancreatic cancer, which activated DNA damage response and the DNA repair pathway including ataxia-telangiectasia mutated, DNA-PK, CHK1, and CHK2. The persistent DNA damage in pancreatic tissue may be the source for its tumorigenesis.

Efficacy evaluation of pepsin in laparoscopic antireflux surgery for gastroesophageal reflux disease.

BACKGROUND: The false positive rate of the PPI test for the diagnosis of typical symptoms of gastroesophageal reflux disease (GERD) is extremely high. OBJECTIVE: This study aims to investigate the effect of the pepsin test on GERD and laparoscopy-assisted anti-reflux surgery for GERD. METHODS: A total of 30 GERD patients were enrolled into this study, and the pre-diagnosis of GERD was determined by symptom evaluation, impedance-pH examination, gastroscopy and pepsin test. All patients underwent surgery. RESULTS: Among the 30 GERD patients, 18 patients were male and 12 were female, and their average age was 58.2 + 12.6 years old. The patients were treated with laparoscopic fundoplication and hiatus hernia repair after preoperative assessment. A total of 28 patients were followed up, one patient developed recurrent symptoms, and one patient developed postoperative dysphagia and received non-operative treatment. Furthermore, the symptom scores were significantly lower at postoperative pepsin detection when compared to the scores before the operation (pepsin: preoperative: 148.8 ± 82.6, postoperative: 30.7 ± 24.6; t= 4.848, P= 0.000). CONCLUSIONS: Laparoscopic fundoplication and hiatus hernia repair may effectively control the symptoms of GERD. Furthermore, the detection of pepsin is non-invasive and easy to operate.

Urotensin II receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCl4-induced cirrhotic rats.

Increased serum urotensin II (UII) levels in human cirrhotic populations have been recently shown, but the long-term effects of UII receptor antagonist on the cirrhosis have not been investigated. To investigate the therapeutic effects of urotensin II receptor (UT) antagonist palosuran on rats with carbon tetrachloride (CCl4)-induced cirrhosis, the hepatic and systemic hemodynamics, liver fibrosis, the metalloproteinase-13 (MMP-13)/tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio, hepatic Rho-kinase activity, and the endothelial nitric oxide synthase (eNOS) activity are measured in CCl4-cirrhotic rats treated with palosuran or vehicle for 4 weeks. Primary hepatic stellate cells (HSCs) are used to investigate the changes in UII/UT expression and the in vitro effect of palosuran. Compared with the vehicle-treated cirrhotic rats, treatment with palosuran can reduce the portal pressure (PP), decrease the risk of liver fibrosis and the level of α smooth muscle actin, collagen-I (COL-I), and transforming growth factor ß expression. However, treatment with palosuran can increase MMP-13/TIMP-1, pvasodilator-stimulated phosphoprotein (p-VASP), and p-eNOS expression. Moreover, in vitro UII/UT mRNA expression increases during HSC activation. MMP-13/TIMP-1, COL-I, and p-VASP are inhibited after palosuran treatment. Our data indicate that long-term administration of palosuran can decrease PP in cirrhosis, which results from decreased hepatic fibrosis and enhanced eNOS-dependent HSC vasodilatation.

Strategy and management of severe hemorrhage complicating pancreatitis and post-pancreatectomy.

PURPOSE: Transcatheter arterial embolization (TAE) is increasingly used as the first-line treatment for hemorrhage complicating pancreatitis and post-pancreatectomy. However, the optimal therapeutic strategy remains unclear. METHODS: Among 1924 consecutive patients, 40 patients with severe pancreatic hemorrhage in Xuanwu Hospital were enrolled between 2005 and 2017. Patients underwent angiography and direct TAE for primary diagnosis and treatment of bleeding. Repeat TAE, watch and wait, and laparotomy were used as the other therapeutic options. Patient data, technical success, and 90-day survival were identified. RESULTS: Pancreatic diseases underlying hemorrhage included acute pancreatitis (n=19, 47.5%), chronic pancreatitis (n=12, 30%), and pancreatic cancer (n=9, 22.5%). A history of percutaneous catheter drainage or pancreatic surgery was seen in 29 patients (72.5%). There were 48 angiographies, 31 embolizations, and 5 laparotomies performed. Rebleeding occurred in 8 patients (20%); 4 of whom underwent re-embolization, 3 had laparotomy, and 1 had conservative treatment. Successful clinical hemostasis was achieved in 37 patients. Complications were observed in only 2 patients with renal failure and 1 patient with hepatic insufficiency. In total, 25 patients (62.5%) were alive at the 90-day follow-up. CONCLUSION: Endovascular management is effective for achieving hemostasis in severe pancreatic hemorrhage with a high success rate and low recurrence, and laparotomy is not suitable for rebleeding cases.

Predictive factors of pancreatic necrosectomy following percutaneous catheter drainage as a primary treatment of patients with infected necrotizing pancreatitis.

Pancreatic necrosectomy (PN) following percutaneous catheter drainage (PCD) is an effective method of treating patients with necrotizing pancreatitis, however, the predictive factors for PN after PCD have not yet been identified. A total of 74 patients with suspected infected necrotizing pancreatitis (INP) and peripancreatic fluid collection were enrolled in the current study between October 2010 and October 2015. These patients received ultrasound or computer topography guided PCD followed by PN. Patients were divided into two groups: i) A PCD-alone group (n=32) and ii) a PCD+necrosectomy group (n=42). Multivariate analysis revealed that reduction of fluid collection after PCD (P=0.021), maximum extent of peripancreatic necrosis (P=0.019) and multiple organ failure (P=0.017) were predictors of PN following PCD. A prediction model was produced to evaluate the aforementioned factors and indicated that the area under the receiver operating characteristic curve was 0.827. The probability of successful PCD was determined using a prognostic nomogram. Thus, the results of the current study demonstrated that a reduction of fluid collection by <50% following PCD, a maximum extent of peripancreatic necrosis of >50% and multiple organ failure are effective predictors of necrosectomy in patients with INP following PCD failure.

Nissen fundoplication vs proton pump inhibitors for laryngopharyngeal reflux based on pH-monitoring and symptom-scale.

AIM: To compare the outcomes between laparoscopic Nissen fundoplication (LNF) and proton pump inhibitors (PPIs) therapy in patients with laryngopharyngeal reflux (LPR) and type I hiatal hernia diagnosed by oropharyngeal pH-monitoring and symptom-scale assessment. METHODS: From February 2014 to January 2015, 70 patients who were diagnosed with LPR and type I hiatal hernia and referred for symptomatic assessment, oropharyngeal pH-monitoring, manometry, and gastrointestinal endoscopy were enrolled in this study. All of the patients met the inclusion criteria. All of the patients underwent LNF or PPIs administration, and completed a 2-year follow-up. Patients' baseline characteristics and primary outcome measures, including comprehensive and single symptoms of LPR, PPIs independence, and satisfaction, and postoperative complications were assessed. The outcomes of LNF and PPIs therapy were analyzed and compared. RESULTS: There were 31 patients in the LNF group and 39 patients in the PPI group. Fifty-three patients (25 in the LNF group and 28 in the PPI group) completed reviews and follow-up. Oropharyngeal pH-monitoring parameters were all abnormal with high acid exposure, a large amount of reflux, and a high Ryan score, associated reflux symptom index (RSI) score. There was a significant improvement in the RSI and LPR symptom scores after the 2-year follow-up in both groups (P < 0.05), as well as typical symptoms of gastroesophageal reflux disease. Improvement in the RSI (P < 0.005) and symptom scores of cough (P = 0.032), mucus (P = 0.011), and throat clearing (P = 0.022) was significantly superior in the LNF group to that in the PPI group. After LNF and PPIs therapy, 13 and 53 patients achieved independence from PPIs therapy (LNF: 44.0% vs PPI: 7.14%, P < 0.001) during follow-up, respectively. Patients in the LNF group were more satisfied with their quality of life than those in the PPI group (LNF: 62.49 ± 28.68 vs PPI: 44.36 ± 32.77, P = 0.004). Body mass index was significantly lower in the LNF group than in the PPI group (LNF: 22.2 ± 3.1 kg/m2vs PPI: 25.1 ± 2.9 kg/m2, P = 0.001). CONCLUSION: Diagnosis of LPR should be assessed with oropharyngeal pH-monitoring, manometry, and the symptom-scale. LNF achieves better improvement than PPIs for LPR with type I hiatal hernia.

The diagnosis and treatment of Rapunzel syndrome.

Trichobezoars are hairballs or hair-like fibers formed by chewing and swallowing hair or any other indigestible materials. Trichobezoars usually form in the gastric body and are thus prepyloric. However, trichobezoars may rarely pass through the pylorus into the duodenum, jejunum, ileum, and even the colon, in a condition referred to as Rapunzel syndrome. Here, we present a case of a 13-year-old girl with this rare syndrome and discuss the diagnosis and treatment of the disease.

Increased expression of urotensin II is associated with poor prognosis in hepatocellular carcinoma.

Urotensin II (UII) and the urotensin II receptor (UT) exhibit mitogenic effects on tumor growth. Our previous study demonstrated that the UII/UT system is upregulated in hepatocellular carcinoma (HCC) and may enhance the proliferation of human hepatoma cells. However, the clinical significance of UII/UT expression in HCC remains unclear. The present study assessed UII messenger RNA (mRNA) expression in 129 surgical specimens obtained from HCC patients using reverse transcription quantitative-polymerase chain reaction. The association between UII mRNA expression and clinicopathological parameters and overall survival rates was also investigated. The results revealed that UII and UT mRNA expression was significantly increased in HCC tissue compared with adjacent non-cancerous liver tissue (P<0.001). Furthermore, a significant correlation was identified between UII expression and histological differentiation (P<0.01), tumor size (P<0.01) and tumor stage (P=0.026). Kaplan-Meier survival analysis indicated that overall survival time was significantly shorter in patients with high UII expression, compared with those with low UII expression (P<0.001). Multivariate analyses indicated that UII expression was an independent predictor of overall survival (odds ratio, 1.12; P<0.001). In addition, UII mRNA was correlated with vascular endothelial growth factor mRNA expression. Therefore, UII expression is an independent biomarker for the prognosis of patients with HCC and thus, the UII/UT system may present a novel therapeutic target for the treatment of HCC.

NIM811 downregulates transforming growth factor­ß signal transduction in vivo and in vitro.

Liver fibrosis is the common histological feature of a number of chronic liver diseases, and leads to cirrhosis and hepatocellular carcinoma (HCC). It has been demonstrated that N­methyl­4­isoleucine cyclosporine (NIM811) attenuates CCl4­induced liver fibrosis and inflammation in rats. The present study investigated whether NIM811 downregulated transforming growth factor (TGF)­ß signaling in rats with CCl4­induced liver fibrosis and in HSC­T6 cells. Liver tissues were obtained from rats with CCl4­induced liver fibrosis, with or without NIM811 treatment. HSC­T6 cells were cultured with or without NIM811 for 18 h under serum­free conditions. Expression of collagen I, α­smooth muscle actin (α­SMA), TGF­ß1, TGF­ß receptor I (TßR­I) and TGF­ß pathway downstream signaling molecules were measured by reverse transcription­quantitative polymerase chain reaction and/or western blotting. Collagen I and TGF­ß1 content in the cell supernatant was measured by ELISA. NIM811 profoundly inhibited collagen I, α­SMA, TGF­ß1 and TßR­I expression in the liver of CCl4­treated rats. Phosphorylation of Smad2, 3 and 1/5/8 was decreased in the liver of NIM811­treated groups, accompanied by increased In addition, Smad7 expression compared with the CCl4­treated rats. NIM811 inhibited collagen I, TGF­ß1 and TßR­I expression in HSC­T6 cells. Smad1 mRNA and phospho­Smad1/5/8 protein levels decreased following NIM811 treatment, accompanied by increased Smad7 expression in HSC­T6 cells compared with normal controls. Furthermore, NIM811 also inhibited collagen I mRNA expression in the liver of rats with CCl4­induced liver fibrosis and in HSC­T6 cells. The results suggest that the antifibrotic effect of NIM811 was due to the inhibition of TGF­ß1 and its downstream signaling molecules.

Post-translational modifications of α-synuclein contribute to neurodegeneration in the colon of elderly individuals.

Synucleinopathies and abnormalities in the nerves of the enteric nervous system are hypothesized to be involved in age-associated motility disorders. The aim of the present study was to investigate the expression of various antigens, including α­synuclein (Syn) and its post­translational modified forms, in the human colon at various ages. In addition, the study aimed to correlate the expression of Syn with neurodegeneration. Immunohistochemistry was used to detect the expression of neurofilament (NF), Syn, as well as its nitrated (N) form in the healthy colonic tissue of 12 young (34.08±5.12 years), 10 middle­aged (51.80±3.52 years), and 11 elderly (75.82±7.70 years) individuals. To the best of our knowledge, the current study is the first to demonstrate the presence of N­Syn in the colonic tissue. N­Syn was identified in the upper layer of the mucosa and submucosa layer. Furthermore, Syn (wild­type) was present in the mucosa and submucosa. The number of NF­positive neurons in the submucosal layer declined significantly with age (P<0.01). In addition, Syn and N­Syn significantly increased during aging (P<0.01). Furthermore, a negative correlation was identified between neuron number and synucleinopathies, indicating the abnormal accumulation of both wild-type Syn and N­Syn in the mucosa, submucosa, muscle layer and myenteric plexus. The present study demonstrates that the Syn pathology may be linked to colic neuronal degeneration during normal aging, and this link may cause functional deficits.

Diagnosis and Anti-Reflux Therapy for GERD with Respiratory Symptoms: A Study Using Multichannel Intraluminal Impedance-pH Monitoring.

BACKGROUND/AIMS: Respiratory symptoms are often associated with gastroesophageal reflux disease (GERD). Although the role of multichannel intraluminal impedance-pH (MII-pH) monitoring in GERD is clear, little is known regarding the characteristics of patients with respiratory symptoms based on MII-pH monitoring and anti-reflux therapy. We evaluated a cohort of GERD patients to identify the MII-pH parameters of GERD-related respiratory symptoms and to assess the anti-reflux therapy outcomes. METHODS: We undertook a prospective study of patients who were referred for GERD evaluation from January 2011 to January 2012. One hundred ninety-five patients underwent MII-pH monitoring and esophageal manometry, and one hundred sixty-five patients underwent invasive anti-reflux therapy that included laparoscopic Toupet fundoplication (LTF) and the Stretta procedure. The patient characteristics and MII-pH parameters were analyzed, and the symptom scores were assessed at baseline and at 1- and 3-year follow-up evaluations. RESULTS: Of the 195 patients, 96 (49.2%) exhibited respiratory symptoms and significantly more reflux episodes (70.7±29.3) than patients without respiratory symptoms (64.7±24.4, p = 0.044) based on the MII-pH monitoring results. Moreover, the group of patients with respiratory symptoms exhibited more proximal reflux episodes (35.2±21.3) than the non-respiratory symptomatic group (28.3±17.9, p = 0.013). One hundred twenty-five patients following the Stretta procedure (n = 60, 31 with respiratory symptoms) or LTF (n = 65, 35 with respiratory symptoms) completed the designated 3-year follow-up period and were included in the final analysis. The symptom scores after anti-reflux therapy all decreased relative to the corresponding baseline values (p<0.05), and there were no significant differences in the control of respiration between the Stretta procedure and LTF (p>0.05). However, LTF significantly reduced the recurrence (re-operation) rate compared with the Stretta procedure (0 vs. 19.4%, p = 0.006). CONCLUSIONS: MII-pH monitoring effectively detected respiratory-related predictive parameters, including total/proximal reflux episodes and symptom correlations. We found that GERD patients with respiratory symptoms exhibited more proximal and total reflux episodes but not more acid-related episodes, as determined by MII-pH monitoring. Thus, such monitoring could be useful for diagnosing atypical GERD patients with respiratory symptoms. Furthermore, LTF exhibited a more significant effect on controlling typical symptoms in all GERD patients and reducing the recurrence rate than the Stretta procedure in patients with respiratory symptoms.

Determination of rutin and isoquercetin contents in Hibisci mutabilis Folium in different collection periods by HPLC.

Hibisci mutabilis Folium (HMF), the dried leaf of Hibiscus mutabilis (Malvaceae), is commonly used in traditional Chinese medicine. This article aimed to establish a high-performance liquid chromatography method for the determination of rutin and isoquercitrin contents in the HMF, and to compare the content variation in all the samples, including nearly withered yellow leaf, in different collection periods, so as to provide research basis for the quality evaluation and determination of the optimal collection period. A reversed-phase HPLC separation method was employed, with a BDS Hypersil C18 column (4.6 m × 250 mm, 5 µm), under the following conditions: acetonitrile-0.3% phosphoric acid (15:85, v/v) solution as the mobile phase, flow rate 1.0 mL/min at 30°C and detection wavelength 254 nm. The calibration curves for rutin and isoquercitrin were linear over the range of 1.5-48 and 0.25-8 µg/mL, and the average recoveries were 99.92 and 100.45% (RSD: 2.39% and 2.11%, respectively)]. Based on the analysis results, it was found that contents of rutin and isoquercitrin in HMF (mature green leaf) harvested in different periods had significant difference, and reached the highest in mid-December. It was also found that the contents of the two components in the mature green leaf were much higher than those in the nearly withered leaf from the same collection period. In conclusion, the results indicated that the HPLC method was easy-to-operate and precise, and could be applied for the determination of rutin and isoquercitrin contents in the HMF. The experimental data also showed that early winter should be the most suitable collection period for HMF.

Human recombinant endostatin Endostar attenuates hepatic sinusoidal endothelial cell capillarization in CCl4­induced fibrosis in mice.

The aim of the present study was to detect the effect of the recombinant human endostatin Endostar on hepatic sinusoidal capillarization in CCl4­induced murine models of liver fibrosis. The liver fibrosis model was induced in BALB/c mice using intraperitoneal injection of CCl4 for 6 weeks. Animals were divided into the following six treatment groups: Group 1, normal animals; group 2, CCl4­induced liver fibrosis; group 3, CCl4+Endostar 20 mg/kg/day for 6 weeks; group 4, CCl4+Endostar 10 mg/kg/day for 6 weeks; group 5, CCl4+Endostar 20 mg/kg/day for 4 weeks; and group 6, CCl4+Endostar 10 mg/kg/day for 4 weeks. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 and 2 expression was detected by western blot analysis. There were significant differences in the number of fenestrae per sinusoid between the normal control and untreated model fibrotic mice (P<0.01), and between the untreated model and Endostar­treated mice (P<0.05). Endostar treatment was associated with reduced levels of VEGFR1 and VEGFR2 in liver tissues (P<0.01), as well as with decreased hepatic sinusoidal endothelial cell capillarization in CCl4­induced mouse models of liver fibrosis, and this effect may involve the VEGF pathway. However, further studies are required to confirm its involvement in other causes of liver fibrosis.

Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice.

Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3: CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, α-smooth muscle actin (α-SMA), TGF-ß1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, α-SMA, and TGF-ß1 were measured by real-time PCR. Collagen I and transforming growth factor ß1 (TGF-ß1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups (P < 0.05). Moreover, Endostar inhibited the hepatic expression of α-SMA, TGF-ß1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P < 0.05). In the HSC-T6 cell line model, Endostar profoundly inhibited the expression of α-SMA, Collagen-1, and TGF-ß1 mRNA. Expressions of Collagen-1 and TGF-ß1 protein were decreased in the Endostar group as compared to the normal controls in the supernatant of HSC-T6 cells (P < 0.05). Endostar decreased both liver fibrosis in CCl4-induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.

Multisystem Langerhans cell histiocytosis with liver dysfunction as the first presentation: A case report.

Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology characterized by oligoclonal proliferation of Langerhans cells. The diagnosis of LCH is complicated by the fact that it may involve multiple organ systems and its clinical presentation and course varies, ranging from an isolated to a multisystem disease. We report a 35-year-old male with LCH involving multiple systems, including the bones, lungs, spleen, liver and bile ducts, whose first clinical presentation was liver dysfunction. The patient was diagnosed following a skull biopsy that revealed infiltration of Langerhans cells. However, a liver biopsy revealed sclerosing cholangitis (SC) with no signs of Langerhans cell infiltration, and the clinical manifestations of the involved organs were atypical, leading to a delayed diagnosis. The patient was in partial remission following chemotherapy. In conclusion, findings of this case may aid our understanding of the pathophysiology of LCH and in improving its diagnosis and treatment.