A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

The 'double­track sign': A novel CT finding suggestive of the diagnosis of T1a gastric cancer.

Effective identification of T1a stage cancer is crucial for planning endoscopic resection for early gastric cancers. The present study aimed to determine the diagnostic value of the double-track sign in patients with T1a gastric cancer using computed tomography (CT) imaging. A total of 152 patients diagnosed with pathologically proven T1a gastric cancer at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between July 2011 and August 2021 were retrospectively reviewed. The control group consisted of 2,926 patients with gastritis. Clinical data, including patient characteristics and preoperative CT imaging findings with gastric morphological features, were reviewed and analyzed. Out of 51 patients with T1a gastric cancer finally included, 31 (60.8%) exhibited local double-track enhancement changes of the stomach, referred to as the 'double-track sign', on CT images. In addition, four patients (7.8%) had well-enhanced mucosal thickening of the gastric wall. Of the 2,926 control subjects, none had any double-track sign and six patients (0.2%) had local gastric wall thickening with abnormally strengthened enhancement. In conclusion, a double-track sign on CT images is beneficial in the diagnostic differentiation of T1a gastric cancer.

Preoperative prediction of vessel invasion in locally advanced gastric cancer based on computed tomography radiomics and machine learning.

Vessel invasion (VI) is an important factor affecting the prognosis of gastric cancer (GC), and the accurate determination of preoperative VI for locally advanced GC is of great clinical significance. Traditional methods for the evaluation of VI require postoperative pathological examination. Noninvasive preoperative evaluation of VI is therefore crucial to determine the best treatment strategy. To determine the value of preoperative prediction of gastric VI based on portal venous phase computed tomography (CT) radiomic features and machine-learning models, a retrospective analysis of 296 patients with locally advanced GC confirmed through pathological examination was performed. They were divided into two groups, VI+ (n=213) and VI- (n=83), based on pathological results. Using pyradiomics to extract two-dimensional radiomic features of the portal venous stage of locally advanced GC, data were divided into training (n=207) and validation sets (n=89), with a ratio of 7:3, and three feature selection methods were cascaded and merged. Finally, least absolute shrinkage and selection operator (LASSO) regression was used for feature screening to obtain the optimal feature subset. Four current representative machine-learning algorithms were used to construct the prediction model, the receiver operating characteristic curve was constructed to evaluate the predictive performance of the model, and the area under the curve (AUC), accuracy, sensitivity, and specificity were calculated. The differentiation degree, and the Lauren's and CA199 classifications were independent risk factors for locally advanced GC VI. Pyradiomics extracted 864 quantitative features of portal vein images of locally advanced GC. After filtering out low variance features using R, 236 features remained. Next, 18 features were screened using the LASSO algorithm. Extreme gradient boosting (XGBoost), logistic regression, Gaussian naive Bayes, and support vector machine models were constructed based on the 18 best features screened out of the portal venous CT images of advanced GC and three independent risk factors of GC VI in clinical features predicted the training set AUC values of 0.914, 0.897, 0.880, and 0.814, respectively. The predicted validation set AUC values were 0.870, 0.877, 0.859, and 0.773, respectively. The DeLong test results indicated no statistically significant difference in AUC values between the XGBoost and logistic regression models in the training and validation sets. The four machine-learning models showed high predictive performance. The logistic regression model had the highest AUC value in the validation set (0.877), and the accuracy and F1 score were 77 and 87.6%, respectively. CT radiomic features and machine-learning models based on the portal venous phase can be used as a noninvasive imaging method for the preoperative prediction of VI in locally advanced GC. The logistic regression model exhibited the highest diagnostic performance.

A Type III Polyketide Synthase (SfuPKS1) Isolated from the Edible Seaweed Sargassum fusiforme Exhibits Broad Substrate and Catalysis Specificity.

A type III polyketide synthase (SfuPKS1) from the edible seaweed Sargassum fusiforme was molecularly cloned and biochemically characterized. The recombinant SfuPKS1 catalyzed the condensation of fatty acyl-CoA with two or three malonyl-CoA using lactone-type intramolecular cyclization to produce tri- and/or tetraketides. Moreover, it can also utilize phenylpropanoyl-CoA to synthesize phloroglucinol derivatives through Claisen-type cyclization, exhibiting broad substrate and catalysis specificity. Furthermore, the catalytic efficiency (kcat/KM) for acetyl-CoA was 11.8-fold higher than that for 4-coumaroyl-CoA. A pathway for the synthesis of naringenin involving SfuPKS1 was also constructed in Escherichia coli by recombinant means, resulting in 4.9 mg of naringenin per liter.

Diagnostic value and potential clinical significance of duodenal lipoma based on computed tomography imaging data.

BACKGROUND: To explore the diagnostic value of computed tomography (CT) imaging for duodenal lipoma and the potential clinical significance of the findings. METHODS: Clinicopathological and CT data from 57 patients, who were diagnosed with duodenal lipoma at the first affiliated Hospital of Zhengzhou University (Zhengzhou, China) between June 2014 and March 2019, were retrospectively reviewed. Data collected included location and size of the tumor, morphological manifestations (shape, density, boundary), concomitant diseases, pathology and gastroscopy results, and follow-up. Follow-up was performed via telephone, and surgical patients were followed-up for recurrence, metastasis and tumor size, and morphological changes. The follow-up period was up to January 2019. RESULTS: Of the 57 patients with duodenal lipoma, contrast-enhanced scanning was performed in 7 cases. The tumor was located in the descending duodenum in 33 cases, the ascending in 4 cases, the horizontal in 16 cases, and the bulb in 4 cases. Mean tumor size was 13.0 ±â€Š5.8 mm. CT morphological features of the tumor were as follows: tumor shape, round, quasi-round, or oval (n = 42); long strip (n = 3); nodular (n = 2); triangular (n = 1); and irregular lobulated (n = 9). Among the 57 patients, tumor density was homogeneous in 52 cases, inhomogeneous in 4 cases, and nodular with calcification in 1 case. The tumor boundary was classified as clear and with no capsule. Diseases concomitant with the tumor were as follows: gastritis (n = 23), gastric adenocarcinoma (n = 1), and gastric lymphoma (n = 1). Esophageal disease was found in 16 cases, including reflux esophagitis (n = 12) and esophageal cancer (n = 4). There were 13 cases of gallbladder and biliary disease, including cholecystolithiasis and cholecystitis (n = 9), common bile duct disease (n = 2), colorectal cancer (n = 4), lung cancer (n = 2), duodenal carcinoma with obstruction (n = 1), and ureteral space narrowing (n = 1). CONCLUSION: CT was an effective, non-invasive method for diagnosis of duodenal lipoma. CT imaging could clearly discern location, size, shape, and nature of duodenal lipomas. Duodenal lipoma can be associated with digestive tract inflammatory diseases and tumors in different locations, and its diagnosis is potentially valuable for their prevention and treatment.

Comparison of the effectiveness of autologous grafts for anterior cruciate ligament reconstruction: A protocol for an overview of systematic review and network meta-analysis.

BACKGROUND: Anterior cruciate ligament rupture is a common motor system injury, and the most effective treatment is anterior cruciate ligament reconstruction (ACLR). Choosing the right graft is an important factor to ensure the success of the surgery. Current research shows that the clinical effect of autologous ligaments is better than that of allogeneic ligaments and artificial ligaments. However, there are differences between the autogenous ligaments, and how to choose them is still controversial. This study evaluated the published systematic reviews on the efficacy of different autologous ligament grafts in ACLR, and based on this, conducted a network meta-analysis of related randomized controlled trials. METHODS: We searched 8 international and Chinese databases including PubMed, Embase, Web of Science, and Cochrane Library. The methodological quality of systematic reviews will be evaluated by Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR2) measurement tool. Cochrane's risk of bias tool will be used to assess the risk of bias of included randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be used to evaluate the evidence quality. Network meta-analysis will be applied to evaluate the therapeutic effect of different autologous grafts. The main outcome measures are IKDC score, clinical failure rate, Lachman test, Lysholm score, and the incidence of complications. Odds ratio and its 95% confidence interval will be used to synthesize the dichotomy results, while the mean difference and 95% confidence interval of continuous variables will be used for continuous variables. RESULTS: This study will provide comprehensive evidence for the application of autologous grafts in ACLR. CONCLUSION: The results of this study will help clinicians make appropriate decisions. PROTOCOL REGISTRATION NUMBER: INPLASY202090061.

Application of POSSUM and P-POSSUM in Surgical Risk Assessment of Elderly Patients Undergoing Hepatobiliary and Pancreatic Surgery.

PURPOSE: To investigate the efficacy and accuracy of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and Portsmouth-POSSUM (P-POSSUM) scoring systems in the risk assessment of postoperative complications and death in elderly patients undergoing hepatobiliary and pancreatic surgery. PATIENTS AND METHODS: Using POSSUM and P-POSSUM, 274 elderly patients undergoing hepatobiliary and pancreatic surgery were evaluated, and the complications and deaths predicted by the systems were compared with the actual situation. The accuracy and predictive ability of POSSUM and P-POSSUM were evaluated using chi-squared and t-tests, consistency of predicted and actual complication rates (observed/expected, OE ratio), and receiver operating characteristic (ROC) curve. RESULTS: The complication rate predicted by POSSUM (R1) was 22.57%, while the actual postoperative complication rate was 17.88% (P>0.05). The mortality rate predicted by POSSUM (R2) was 4.61%, while the actual rate was 1.09% (P<0.05). The mortality rate predicted by P-POSSUM (R) was 1.42%, while the actual rate was 1.09% (P>0.05). Patients with complications had higher physiology scores (PS), operative severity scores (OS), and POSSUM scores than those without complications (P<0.05). Furthermore, PS, OS, and POSSUM scores were higher in the mortality group than in the survival group. However, the number of individuals in the mortality group was too small to accurately reflect the overall situation. Stratified analysis showed that consistency of the OE ratio in different subgroups was close to 1. The ROC curve showed that the area under the curve for the complication rate predicted by POSSUM was 0.76. CONCLUSION: Although the postoperative mortality rate was higher than the actual value, POSSUM could accurately predict the postoperative complication rate in elderly patients undergoing hepatobiliary and pancreatic surgery. The P-POSSUM accurately predicted the postoperative mortality rate in this population. Patients with complications had higher POSSUM scores.

Mesoatrial Shunt for Budd-Chiari Syndrome.

BACKGROUND: The long-term efficacy of mesoatrial shunt (MAS) for Budd-Chiari syndrome (BCS) is not well studied. The purpose of our study was to investigate the long-term outcome and efficacy of MAS for BCS. METHODS: We retrospectively evaluated 11 patients who underwent MAS for BCS from April 1986 to November 1995. Records of patients' clinical presentations, laboratorial investigation, Doppler duplex ultrasonography, radiologic image, and treatment outcomes were all retrieved and analyzed. RESULTS: Follow-up intervals ranged from 1 year and 2 months to 30 years and 2 months (mean, 17 years and 8 months). Portal pressure decreased significantly from 35.72 ± 3.52 cm H2O to 27.86 ± 5.83 cm H2O post-MAS (P = 0.001). The 5-year, 10-year, and 20-year patency were 72.7%, 54.5%, 36.4%, respectively; 63.3% of patients had survived for more than 10 years and 45.5% for more than 20 years. A male has been alive with patent shunt for 28 years and 1 month. CONCLUSIONS: The MAS with enforced rings is an effective therapeutic modality for BCS with cautious perioperative management.

Laparoscopic Nissen (total) versus anterior 180° fundoplication for gastro-esophageal reflux disease: A meta-analysis and systematic review.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has been the gold standard for the surgical management of Gastro-esophageal reflux disease (GERD). Laparoscopic anterior 180° fundoplication (180° LAF) is reported to reduce the incidence of postoperative complications while obtaining similar control of reflux. The present meta-analysis was conducted to confirm the value of the 2 techniques. METHODS: PubMed, Medline, Embase, Cochrane Library, Springerlink, and China National Knowledge Infrastructure Platform databases were searched for randomized controlled trials (RCTs) comparing LNF and 180° LAF. Data regarding the benefits and adverse results of 2 techniques were extracted and compared using a meta-analysis. RESULTS: Six eligible RCTs comparing LNF (n = 266) and 180° LAF (n = 265) were identified. There were no significant differences between LNF and 180° LAF with regard to operating time, perioperative complications, length of hospital stay, patient satisfaction, willingness to undergo surgery again, quality of life, postoperative heartburn, proton pump inhibitor (PPI) use, postoperative DeMeester scores, postoperative lower esophageal sphincter (LES) pressure, postoperative gas-bloating, unable to belch, diarrhea, or overall reoperation. LNF was associated with a higher prevalence of postoperative dysphagia compared with 180° LAF, while 180° LAF was followed by more reoperation for recurrent reflux symptoms. CONCLUSION: LNF and 180° LAF are equally effective in controlling reflux symptoms and obtain a comparable prevalence of patient satisfaction. 180° LAF can reduce the incidence of postoperative dysphagia while this is offset by a higher risk of reoperation for recurrent symptoms. The risk of recurrent symptoms should need to be balanced against the risk of dysphagia when surgeons choose surgical procedures for each individual with GERD.

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.

Laparoscopic Toupet fundoplication with duodenojejunostomy for the management of superior mesenteric artery syndrome with reflux symptoms.

RATIONALE: The patient had symptoms of GERD and the reflux even caused the symptom of cough. Gaining weight is a risk factor for the treatment of reflux as it could exacerbated symptoms of reflux and the drug treatment is not effective. Surgical intervention becomes necessary when there is failure following conservative medical therapy or the patient. PATIENT CONCERNS: The patient was not satisfied with the drug treatment. DIAGNOSES: Superior mesenteric artery syndrome, gastroesophageal reflux disease. INTERVENTIONS: Laparoscopic Toupet fundoplication with duodenojejunostomy. OUTCOMES: The patient discharged from hospital 10 days after surgery without any postoperative complication. The patient achieved complete relief of symptoms and discontinuation of drug. LESSONS SUBSECTIONS: Superior mesenteric artery (SMA) syndrome may manifest the symptoms of GERD such as heartburn, acid reflux and cough. It is necessary to complete examination to exclude superior mesenteric artery syndrome for these patients. Laparoscopic fundoplication with duodenojejunostomy provided an effective treatment for patients who failed drug treatment.

Increasing the miR-126 expression in the peripheral blood of patients with diabetic foot ulcers treated with maggot debridement therapy.

BACKGROUND: miR-126 may increase angiogenesis in patients with diabetic foot ulcers (DFUs) treated with maggot debridement therapy (MDT). METHODS: Real-time quantitative PCR was used to detect expression of miR-126 mRNA in the peripheral blood among the non-diabetic population, type 2 diabetes mellitus patients without DFU, and patients with DFUs of type 2 diabetes mellitus. The expression of miR-126 mRNA in the peripheral blood of patients with DFUs was observed before and after MDT. Finally, human umbilical vein endothelial cells (HUVEC) were utilized to explore miR-126 mRNA expression with maggot excretions/secretions (ES). RESULTS: In the patients with DFUs, the miR-126 mRNA expression level in the peripheral blood was less than that type 2 diabetes mellitus patients without DFU, and much lower than that in the non-diabetic population (P<0.001). The miR-126 expression level was significantly increased in those DFU patients treated with MDT (P<0.05). Finally, using HUVEC co-cultured with ES, we showed the ES increased miR-126 expression in vitro (P<0.001). CONCLUSION: MDT upregulates the miR-126 expression in the peripheral blood of patients with DFUs.

NAMPT protects against 6-hydroxydopamine-induced neurotoxicity in PC12 cells through modulating SIRT1 activity.

Parkinson's disease (PD) is the second most common progressive neurodegenerative movement disorder. Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate­limiting step in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in mammals, is a substrate for NAD+­dependent enzymes, such as sirtuin 1 (SIRT1), and contributes to cell fate decisions. However, the role of NAMPT in PD has remained to be fully elucidated. In the present study, PC12 cells were treated with the neurotoxin 6-hydroxydopamine (6­OHDA) to establish an in vitro model of PD, following which an obvious inhibitory effect on the levels of NAMPT and NAD+ as well as the NAD+/NADH ratio was detected. In addition, pre­incubation with FK866, a highly specific NAMPT inhibitor, enhanced the inhibitory effects of 6­OHDA on the viability of PC12, while pre­incubation with nicotinamide mononucleotide (NMN), am enzymatic product of NAMPT, had the opposite effect. Furthermore, it was revealed that NMN markedly attenuated 6­OHDA­induced decreases in superoxide dismutase activity and glutathione levels, as well as 6­OHDA­induced increases in malondialdehyde and lactate dehydrogenase in PC12 cells. Furthermore, 6­OHDA significantly reduced SIRT1 activity in PC12 cells, which was inhibited by NMN. The pharmacological activator resveratrol also significantly inhibited 6­OHDA­mediated decreases in PC12 cell viability while reversing 6­OHDA­induced decreases in SIRT1 levels. The results of the present study suggested that NMT protected against 6­OHDA­induced decreases in PC12 cell viability, and that SIRT1 activation had a role in this process. Treatment with NMN to activate SIRT1 may represent a novel therapeutic strategy for treating PD.

Comparison of Stretta procedure and toupet fundoplication for gastroesophageal reflux disease-related extra-esophageal symptoms.

AIM: To compare the outcomes between the Stretta procedure and laparoscopic toupet fundoplication (LTF) in patients with gastroesophageal reflux disease (GERD)-related extra-esophageal symptoms. METHODS: From January 2011 to February 2012, a total of 98 patients diagnosed with GERD-related extra-esophageal symptoms who met the inclusion criteria were enrolled in this study. All patients who either underwent the Stretta procedure or LTF treatment have now completed the 3-year follow-up. Primary outcome measures, including frequency and severity of extra-esophageal symptoms, proton pump inhibitor (PPI) use, satisfaction, and postoperative complications, were assessed. The results of the Stretta procedure and LTF therapy were analyzed and compared. RESULTS: There were 47 patients in the Stretta group and 51 patients in the LTF group. Ninety patients were available at the 3-year follow-up. The total of the frequency and severity scores for every symptom improved in both groups (P < 0.05). Improvement in symptom scores of cough, sputum, and wheezing did not achieve statistical significance between the two groups (P > 0.05). However, the score for globus hysterics was different between the Stretta group and the LTF group (4.9 ± 2.24 vs 3.2 ± 2.63, P < 0.05). After the Stretta procedure and LTF treatment, 29 and 33 patients in each group achieved PPI therapy independence (61.7% vs 64.7%, P = 0.835). The patients in the LTF group were more satisfied with their quality of life than those in the Stretta procedure group (P < 0.05). Most complications resolved without intervention within two weeks; however, two patients in the LTF group still suffered from severe dysphagia 2 wk after the operation, and it improved after bougie dilation treatment in both patients. CONCLUSION: The Stretta procedure and LTF were both safe and effective for the control of GERD-related extra-esophageal symptoms and the reduction of PPI use.

Early and Midterm Outcome After Laparoscopic Fundoplication and a Minimally Invasive Endoscopic Procedure in Patients with Gastroesophageal Reflux Disease: A Prospective Observational Study.

BACKGROUND AND AIMS: Although the minimally invasive endoscopic Stretta procedure is being increasingly used as an alternative strategy to manage gastroesophageal reflux disease (GERD), the benefits of this procedure have to be further evaluated in clinical settings. This prospective observational study assessed the short-term and midterm outcomes associated with laparoscopic Toupet fundoplication (LTF) and the Stretta procedure. PATIENTS AND METHODS: From January 2011 to January 2012, we allocated 80 patients to LTF and 85 to the Stretta procedure. Primary outcome measures, including symptom scores of heartburn, regurgitation, chest pain, belching, hiccup, cough, and asthma, as well as proton pump inhibitor (PPI) use, were analyzed at midterm follow-up (1-3 years). RESULTS: Of the 165 patients, 125 patients following LTF (n=65) or the Stretta procedure (n=60) completed the designated 3-year follow-up and were included in the final analysis. At the end of the 3-year follow-up, the symptom scores were all significantly decreased compared with the corresponding values before the two procedures in both groups (P<.05). After LTF and the Stretta procedure, 47/65 (72.3%) and 41/60 (68.3%) patients, respectively, achieved complete PPI therapy independence (72.3% versus 68.3%, P=.627). Comparing with LTF, however, the Stretta procedure had less effect on improving typical symptoms of heartburn, regurgitation, and chest pain and reducing the rate of re-operation (11.8% versus 0%, P=.006). CONCLUSIONS: LTF and the Stretta procedure were equally effective in controlling GERD symptoms and reducing PPI use. However, LTF can achieve more improvement on typical symptoms and has a lower rate of re-operation.

[Neuroprotective effects of paeonol in a cell model of Parkinson disease].

OBJECTIVE: To investigate the effects of paeonol on neuron cell model of Parkinson disease (PD). METHODS: The cell model of Parkinson disease was induced by treatment of 1-Methyl-4-phenylpyridinium (MPP+) in PC12 cells, the PD model cells were treated with 1 µmol/L, 3 µmol/L or 9 µmol/L paeonol for 24h, respectively. Cell viability and LDH leakage were detected by MTT and lactate dehydrogenase (LDH) assay; the apoptosis of PC12 cells was assessed by Hoechst 33258 staining and flow cytometry; reactive oxygen species (ROS) production was detected by DCFH-DA method; and the ratio of Bax/Bcl-2 and activation of caspase-3 were determined by Western blotting. RESULTS: MPP+ treatment significantly reduced cell viability, increased LDH leakage, enhanced the proportion of apoptotic cells and ROS production. In addition, MPP+ treatment dramatically increased the Bax/Bcl-2 ratio, and the activation of caspase-3. Compared to PD model group, paeonol treatment significantly enhanced cell viability, decreased LDH leakage, inhibited the proportion of apoptotic cells and ROS production, reduced the Bax/Bcl-2 ratio and the activated caspase-3 protein. CONCLUSION: Paeonol can prevent PC12 cells from apoptosis induced by MPP+, and the mechanism may be associated with the down-regulation of ROS production, Bax/Bcl-2 ratio and Caspase-3 activation.

The Role of Interleukin-13 in Patients with Rheumatic Valvular Fibrosis: A Clinical and Histological Study.

BACKGROUND AND AIM OF THE STUDY: Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious diseases, yet few studies have reported its role in valvular fibrosis in patients with rheumatic heart disease (RHD). The study aim was to investigate the role of IL-13 in mitral valvular fibrosis in patients with RHD. METHODS: Peripheral blood samples were collected from surgical patients with RHD (n = 18) and from healthy controls (n = 9). Serum levels of IL-13 and interferon (IFN)-gamma were analyzed using ELISA. Rheumatic mitral valves removed from surgical patients with RHD, and normal mitral valves, were obtained at autopsy. The expression and distribution of collagen I, collagen III, and IL-13Ralpha1 were examined by immunohistochemical staining, the degree of which was measured using computed imaging analysis. RESULTS: Higher IL-13 levels were observed in RHD patients (15.16 +/- 9.62 pg/ml; p < 0.05) than in healthy controls (7.78 +/- 3.87 pg/ml). RHD patients had high levels of IFN-gamma (9.95 +/- 0.77 pg/ml; p <0.05) compared to healthy controls (5.95 +/- 0.69 pg/ml). Immunohistochemistry showed that, compared to normal valves, rheumatic mitral valves expressed high levels of collagen I (0.01931 +/- 0.00159 versus 0.01183 +/- 0.00207; p < 0.05), collagen III (0.00726 +/- 0.00078 versus 0.00342 +/- 0.00124; p <0.05), and IL-13Rcxl (0.00454 +/- 0.00086 versus 0.00017 +/- 0.00008; p <0.01). Collagens I and III were each expressed in heart interstitial cells, while IL-13Ralpha1 was expressed in the endothelial cells and smooth muscle cells of the blood vessels, and in interstitial cells. CONCLUSION: Patients with RHD showed increased serum levels of IL-13 compared to healthy controls. IFN-gamma levels were clearly different among RHD patients and healthy controls. The expression of collagens I and III and IL-13Ralpha1 was higher in rheumatic mitral valves compared to normal mitral valves. IL-13 may induce mitral valvular fibrosis in RHD.

Long-term outcomes of patients with refractory gastroesophageal reflux disease following a minimally invasive endoscopic procedure: a prospective observational study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is the most common digestive disease, affecting one third of the world's population. The minimally invasive endoscopic Stretta procedure is being increasingly used as an alternative strategy to manage refractory GERD. However, long-term benefits of this procedure have to be further evaluated in clinical settings. This prospective observational study was therefore conducted to evaluate the outcome of patients with refractory GERD 5 years after the Stretta procedure. METHODS: A total of 152 patients with refractory GERD underwent the Stretta procedure in our department between April 2007 and September 2008. They were followed up for 5 years, during which the primary outcome measures including symptom scores of heartburn, regurgitation, chest pain, cough and asthma and the secondary outcome measures including proton pump inhibitor (PPI) use and patients' satisfaction were analysed at 6, 12, 24, 36, 48 and 60 months respectively. RESULTS: Of the 152 patients, 138 completed the designated 5-year follow-up and were included in the final analysis. At the end of the 5-year follow-up, the symptom scores of heartburn (2.47 ± 1.22 vs. 5.86 ± 1.52), regurgitation (2.23 ± 1.30 vs. 5.56 ± 1.65), chest pain (2.31 ± 0.76 vs. 4.79 ± 1.59), cough (3.14 ± 1.43 vs. 6.62 ± 1.73) and asthma (3.26 ± 1.53 vs. 6.83 ± 1.46) were all significantly decreased as compared with the corresponding values before the procedure (P < 0.001). After the Stretta procedure, 59 (42.8%) patients achieved complete PPI therapy independence and 104 (75.4%) patients were completely or partially satisfied with the GERD symptom control. Moreover, no severe complications were observed except for complaint of abdominal distention in 12 (8.7%) patients after the Stretta procedure. CONCLUSION: The Stretta procedure may achieve an effective and satisfactory long-term symptom control and considerably reduce the reliance on medication without significant adverse effects in adult patients with refractory GERD, thereby having profound clinical implications.

A preliminary investigation of anti-reflux intervention for gastroesophageal reflux related childhood-to-adult persistent asthma.

BACKGROUND: Childhood-to-adult persistent asthma is usually considered to be an atopic disease. However gastroesophageal reflux may also play an important role in this phenotype of asthma, especially when it is refractory to pulmonary medicine. METHODS: Fifty-seven consecutive GERD patients who had decades of childhood-to-adult persistent asthmatic symptoms refractory to pulmonary medication were enrolled. GERD was assessed by a symptom questionnaire, endoscopy, reflux monitoring, and manometry, and treated by Stretta radiofrequency (SRF) or laparoscopic Nissen fundoplication (LNF). The outcomes were followed up with a questionnaire for an average of 3.3 ± 1.1 years. RESULTS: Upper esophageal sphincter hypotonia, lower esophageal sphincter (LES) hypotonia, shortened LES, and esophageal body dyskinesia were demonstrated by esophagus manometry in 50.9%, 43.9%, 35.1%, and 45.6% of the patients, respectively. The symptom scores for heartburn, regurgitation, coughing, wheezing, and chest tightness significantly decreased from 5.8 ± 2.0, 5.6 ± 2.0, 7.3 ± 1.6, 8.4 ± 1.2, and 8.1 ± 1.5, to 1.2 ± 1.8, 1.1 ± 1.6, 2.8 ± 2.5, 3.8 ± 2.7, and 3.9 ± 2.7, respectively, after anti-reflux treatment (P < 0.001). CONCLUSIONS: Esophagus dysfunction is high in childhood-to-adult persistent asthmatic patients with GERD. SRF and LNF are both effective for esophagus symptoms as well as persistent asthmatic symptoms for these patients. GER may relate with asthmatic symptoms in some patients. Evaluating asthmatic patients for possible treatment of the underlying cause, such as GERD, may improve symptoms and prevent disease persistence.