Culture-based susceptibility-guided tailored versus empirical concomitant therapy as first-line Helicobacter pylori treatment: A randomized clinical trial.

BACKGROUND: With the increasing resistance to antimicrobial agents, susceptibility-guided tailored therapy has been emerging as an ideal strategy for Helicobacter pylori treatment. However, susceptibility-guided tailored therapy requires additional cost, time consumption, and invasive procedure (endoscopy) and its superiority over empirical quadruple therapy as the first-line H. pylori treatment remains unclear. AIMS: To compare the efficacy of culture-based susceptibility-guided tailored versus empirical concomitant therapy as the first-line Helicobacter pylori treatment. METHODS: This open-label, randomized trial was performed in four Korean institutions. A total of 312 Patients with H. pylori-positive culture test and naïve to treatment were randomly assigned in a 3:1 ratio to either culture-based susceptibility-guided tailored therapy (clarithromycin-based or metronidazole-based triple therapy for susceptible strains or bismuth quadruple therapy for dual-resistant strains, n = 234) or empirical concomitant therapy (n = 78) for 10 days. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment. RESULTS: Prevalence of dual resistance to both clarithromycin and metronidazole was 8%. H. pylori eradication rates for tailored and concomitant groups were 84.2% and 83.3% by intention-to-treat analysis (p = 0.859), respectively, and 92.9% and 91.5% by per-protocol analysis, respectively (p = 0.702), which were comparable between the two groups. However, eradication rates for dual-resistant strains were significantly higher in the tailored group than in the concomitant group. All adverse events were grade 1 or 2 based on the Common Terminology Criteria for Adverse Events and the incidence was significantly lower in the tailored group. The proportion of patients discontinuing treatment for adverse events was comparable between the two groups (2.1% vs. 2.6%). CONCLUSIONS: The culture-based susceptibility-guided tailored therapy failed to show superiority over the empirical concomitant therapy in terms of eradication rate. Based on these findings, the treatment choice in clinical practice would depend on the background rate of antimicrobial resistance, availability of resources and costs associated with culture and susceptibility testing.

Differences in environmental microbial community responses under rice-crab co-culture and crab monoculture models under cyanobacterial bloom.

Cyanobacterial blooms (CBs) present significant challenges to Chinese mitten crab (CMC) culture, posing hazards to the aquatic microbial ecology. However, the current focus on the microbial ecological changes within the CMC culture system under the influence of CBs is somewhat insufficient. There's an urgent need to analyze the microbial ecosystem of the CMC culture system under CBs. This study employed 16S rRNA gene amplicon sequencing to investigate the dynamics of the environmental microbial community in both the rice-crab co-culture (RC) and crab monoculture (CM) models. The results revealed that cyanobacteria reached high levels in the CM water in July, while they began to increase in the RC water in August. Notably, OTU147 (uncultured bacterium g_Planktothrix NIVA-CYA 15), identified as the dominant taxon associated with CBs, showed a significant linear relationship with TP, NO2 --N, and the N:P ratio. TP, TN, NO2 --N, and CODMn had a more pronounced impact on the structure of bacterial communities and cyanobacterial taxa in the water. The bacterial community structure involved in carbon metabolism displayed temporal succession in the water. The co-occurrence network of the bacterial community primarily consisted of Chloroflexi, Proteobacteria, and Firnicutes in the sediment, and Actinobacteria, Proteobacteria, Chloroflexi, and Bacteroidota in the water. In contrast, the co-occurrence network included different peripheral species in the sediment and water. Keystone species were predominantly represented by OTU22 (uncultured actinobacterium g_ hgcI clade) and OTU12 (uncultured Opitutae bacterium g_ norank) in the RC water, and by OTU25 (uncultured bacterium g_ Limnohabitans) in the CM water. TP, TN, NO2 --N, and CODMn were identified as the primary environmental factors influencing these keystone taxa within the culture water. In conclusion, this study on the microbial ecology of the CMC culture system under the influence of CBs provides valuable insights that can be instrumental in subsequent management efforts.

A long non-coding RNA associated with H3K7me3 methylation negatively regulates OsZIP16 transcription under cadmium stress.

Cadmium (Cd) is a toxic environmental pollutant, posing a high risk to crop production and human health. However, the genetic mechanisms for regulation of Cd accumulation in crops are poorly understood. In this study, we functionally identified a novel long non-coding RNA (lncRNA, TCONS_00502780) that repressed a locus encoding an uncharacterized metal transporter ZIP16 (ZRT/IRT-like Protein) in rice. LncRNA-OsZIP16 (L16) is resident in the antisense strand of OsZIP16. Both L16 and OsZIP16 were transcriptionally expressed during the life cycle, but under Cd stress the L16 transcription was repressed, whereas the OsZIP16 expression was upregulated. OsZIP16 is localized to the endoplasmic reticulum. Knocking out OsZIP16 by CRISPR-Cas9 (C16) resulted in Cd sensitivity, manifested by reduced plant growth and intense cellular damage with a slightly higher Cd translocation from roots to shoots, suggesting that OsZIP16 expression is required for rice growth and development under Cd stress. Conversely, OsZIP16 constitutive overexpression (OE16) lines displayed a growth phenotype compatible to the wide-type with lower Cd translocation ratio from roots to shoots. L16 knock-down lines by RNA interference (L16-R) showed a similar phenotype to the OE16 lines, while the L16 overexpression (L16-OE) lines were phenotypically similar to the C16 lines. The OsZIP16 transcription was upregulated in the L16-R lines but downregulated in the L16-OE lines. Using an antibody against the trimethylation of histone H3 lysine 27 (H3K27me3) followed by chromatin immunoprecipitation (ChIP), we found the reduced H3K27me3 methylation marks surrounding the OsZIP16 gene under Cd stress. Further examination of H3K27me3 in the L16-R lines revealed that the methylation levels were also significantly lower than those in WT. Taken together, these data suggest that the L16 could negatively regulate the OsZIP16 transcriptional expression through an epigenetic mechanism for rice adaption to Cd stress.

Delayed Perforation Occurring after Gastric Endoscopic Submucosal Dissection: Clinical Features and Management Strategy.

Background/Aims: Delayed perforation is a rare but serious adverse event of gastric endoscopic submucosal dissection (ESD). The aim of this study was to clarify the clinical features and appropriate management strategy of patients with delayed perforation. Methods: Among 11,531 patients who underwent gastric ESD, the clinical features and outcomes of patients who experienced delayed perforation were retrospectively reviewed and compared with those of the control group. Results: Delayed perforation occurred in 15 of 11,531 patients (0.13%). The patients with delayed perforation were significantly older than those without delayed perforation (p=0.027). The median time to diagnosis of delayed perforation was 28.8 hours (range, 14 to 71 hours). All 15 patients with delayed perforation complained of severe abdominal pain after gastric ESD and underwent subsequent chest X-rays (CXRs) for evaluation. In subsequent CXR, free air was found in 12 patients (80%). For three (20%) patients without free air in CXR, delayed perforation was finally diagnosed by computed tomography. Leukocytosis was significantly less frequent in the patients without free air in CXR (p=0.022). A perforation hole smaller than 1 cm in size was more frequently observed in the six patients who underwent successful non-surgical treatments than in the nine patients who underwent surgery (p<0.001). There was no mortality related to delayed perforation. Conclusions: One-fifth of the patients with delayed perforation did not show free air in CXR and exhibited less leukocytosis than those with free air. Non-surgical treatments including endoscopic closure might be considered as an initial treatment modality for delayed perforation smaller than 1 cm.

Outcomes following hypofractionated radiation therapy alone for surgically unfit early esophageal squamous cell carcinoma patients; a retrospective single center analysis.

BACKGROUND AND PURPOSE: To report the feasibility of hypofractionated radiation therapy (RT) alone for early stage esophageal squamous cell carcinoma (ESCC) patients. MATERIALS AND METHODS: The oncologic outcomes of 60 cT1-2 N0 ESCC patients who received hypofractionated RT (54 âˆ¼ 60 Gy by 3.0 Gy per fraction) from 2004 to 2018 were retrospectively evaluated. RESULTS: The 5-year rates of local control (LC), progression-free survival, cancer-specific survival, and overall survival were 81.1 %, 44.2 %, 73.7 %, and 54.5 %, respectively. In Cox regression analysis, tumor length < 3 cm was correlated with favorable LC (HR 0.167, p = 0.090), and the 5-year LC rates were 95.7 % and 72.0 % in < 3 cm and ≥ 3 cm subgroups, respectively (p = 0.053). Grade ≥ 2 esophagitis was observed in 44 patients (73.3 %) and grade ≥ 2 esophageal strictures developed in five (8.3 %), respectively. The patients with ≥ 3 cm tumor more frequently suffered from grade ≥ 2 esophagitis (13/24 vs. 31/36, p = 0.006) and grade ≥ 2 esophageal stricture (0/24 vs. 5/36, p = 0.056), respectively. The patients with cT2 tumor suffered from grade ≥ 2 esophagitis more frequently than those with T1 tumor (29/44 vs. 15/16, p = 0.03). CONCLUSIONS: Hypofractionated RT alone, with the merit of short treatment course, could be used as feasible option in treating the early stage ESCC patients who are unfit for surgical resection or chemoradiation. Especially, tumor length < 3 cm seems a good indication of this treatment scheme based on favorable LC rate with low incidence of esophageal toxicities.

Neoadjuvant Nivolumab Therapy for Esophageal Squamous Cell Carcinoma: A Single-Arm, Phase II Study.

PURPOSE: Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC. MATERIALS AND METHODS: Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]). RESULTS: Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9). CONCLUSION: Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Curcumin plays an anti-osteoporosis role by inhibiting NF-κB signaling pathway to reduce oxidative stress damage to osteogenesis / 中国药理学通报

Aim To investigate the mechanism of curcumin inhibition of oxidative stress on osteogenic differentiation and its dose-dependent anti-osteoporosis effect. Methods Cellular oxidative stress models were used, different concentrations of curcumin were added to determinethebone formation markers, and the potential signaling pathways involvedwere detected. Meanwhile, the mouse model of osteoporosis ( ovariecto- mized, 0VX) was used to confirm its effect against osteoporosis. Results In vitro experiments found that low concentrations of curcumin (1-10 μmol · L

Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ2=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

Correlation between Content of Active Ingredients of Aurantii Fructus and Soil Factor / 中国实验方剂学杂志

ObjectiveTo study the correlation between the content of active ingredients of Aurantii Fructus in different main production areas and soil factors， so as to provide a theoretical basis for implementing ecological regulation of soil， improving the quality of Aurantii Fructus， and revealing the origin of genuine medicinal materials. MethodThe content of naringin， neohesperidin， total flavonoids， volatile oil， total nitrogen， total phosphorus， total potassium， and 17 soil factor-related indicators in 25 batches of Aurantii Fructus from different production areas were determined. The main soil factors affecting the content of active ingredients of Aurantii Fructus were analyzed by Pearson correlation analysis， principal component analysis， and grey correlation analysis. ResultThe pH value of the soil is between 4.83 and 8.21， and the soil is weakly acidic and neutral in general. Soil fertility exceeds the average. Pearson correlation analysis shows that the soil factors most related to the four active ingredients of Aurantii Fructus are total phosphorus， available copper， available zinc， exchangeable magnesium， available sulfur， available phosphorus， and available molybdenum. Principal component analysis shows that total nitrogen， alkali-hydrolyzable nitrogen， organic matter， available phosphorus， and available zinc are the main characteristic factors in soil. Grey correlation analysis shows that the main soil factors affecting the active ingredients of Aurantii Fructus are total phosphorus， total nitrogen， available zinc， available copper， exchangeable magnesium， and pH. ConclusionIn the cultivation of Aurantii Fructus， the medicinal material quality of Aurantii Fructus could be improved by adjusting the level of beneficial factors in the soil and improving the soil texture.

Outcomes of Primary Esophagectomy and Esophagectomy after Endoscopic Submucosal Dissection for Superficial Esophageal Squamous Cell Carcinoma: A Propensity-Score-Matched Analysis.

Even though the conventional treatment for T1 esophageal cancer is surgery, ESD is becoming the primary treatment. Currently, it is unknown whether secondary esophagectomy after endoscopic submucosal dissection (ESD) is comparable to primary esophagectomy when considering outcomes in patients with T1 esophageal cancer. We compared short- and long-term clinical outcomes between the two groups. Primary surgery (esophagectomy) was performed in 191 patients between 2003 and 2014, and 62 patients underwent secondary surgery (esophagectomy) after ESD for T1 esophageal cancer between 2007 and 2019. Propensity matching was performed for age, sex, Charlson Comorbidity Index (CCI), location, pathology, degree of differentiation, tumor size, and invasion depth. Lymph node metastasis (LNM), overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and post-operative complications were compared between groups. Sixty-eight patients were included after propensity score matching; LNM, OS, DSS, and RFS were comparable between the two groups. Comparing primary and secondary surgery, the respective LNM rates were 23.5% and 26.5%, 6-year OS 78.0% and 89.7%, p = 0.15; DSS were 80.4% and 96.8%, p = 0.057; and RFS were 80.8% and 89.7%, p = 0.069. Comparing the adverse events between the two groups, there was no significant difference in the overall adverse events. However, more early complications were observed in the primary surgery group than in the secondary surgery group (50% vs. 20.6%, p = 0.021). Secondary surgery did not increase the risk of LNM. The long-term outcomes were comparable. Therefore, attempts to perform upfront ESD for superficial esophageal squamous cell cancers are justified.

Distribution and Ultrastructural Features of Telocytes in the Pars Distalis of the Rat Pituitary Gland.

Telocytes (TCs), a novel type of interstitial cells, are characterized by their smaller cellular body and extremely long, thin processes which are called telopodes (Tps). They have been described in multiple organs from diverse animals. Currently, the existence of TCs in rat pars distalis (PD) has remained unexplored. This investigation was undertaken to visualize the distribution and structural features of TCs in the PD using immunofluorescence (IF) and further validated by transmission electron microscopy (TEM). HE staining revealed the presence of interstitial cells in the peri-sinusoidal vessels spaces of the PD. Using IF, CD34/vimentin double-positive interstitial cells were identified as TCs in accordance with identification standards. TEM further verified the presence of TCs based on their unique ultrastructural features. TCs exhibited communication structures including cell connections and extracellular vesicles (EVs). Interestingly, TCs were in close proximity to the nerves. Most importantly, Tps extended toward the nerves, blood vessels, and glandular cells. TCs could be the structural foundation of a third regulatory system in rat PD according to the tight connections of TCs with sinusoid vessels, glandular cells, EVs and most crucially the nerves. Taken together, these morphological and structural findings demonstrate that TCs are vital components of the rat PD.

Effect of ω-9MUFAs in Fat Emulsion on Serum Interleukin-6 in Rats with Lipopolysaccharide-induced Lung Injury.

AIM: This study aimed to investigate how ω-9 MUFAs in fat emulsion affect serum IL-6 levels in rats with lipopolysaccharide (LPS)-induced lung injury. BACKGROUND: Research suggests that acute lung injury (ALI) develops acute respiratory distress syndrome (ARDS) due to the activation of many inflammatory factors. ALI may be treated by reducing inflammation. Fat emulsion is used in parenteral nutrition for critically ill patients to regulate the body's inflammatory response. It is mostly made up of ω-9 MUFAs (Clinoleic), which can regulate the inflammatory response. OBJECTIVE: The effect of ω-9MUFAs on the secretion of IL-6 in ALI rats was studied in order to provide a basis for the rational use of fat emulsion in clinical practice and provide new ideas for the diagnosis and treatment of ALI. METHODS: The control, model, and -9MUFAs groups consisted of 18 female Sprageue-Dawley (SD) young rats (180 ± 20 g). The SD young rats received normal saline and were not operated. LPS-induced ALI animals received tail vein injections of normal saline. SD young rats were first triggered with acute lung injury by LPS (3 mg/kg) and then injected with 3 mg/kg of ω-9MUFAs via the tail vein. The expression levels of IL-6, an activator of signal transduction transcription 3 (STAT3), transforming growth factor-ß (TGF-ß), and glycoprotein 130 (GP130) in serum and lung tissues were determined by ELISA and Western blot methods. RESULTS: Compared with the model group, the survival rate of rats in the ω-9 MUFAs group was significantly increased, and the difference was statistically significant (p<0.05). Compared with the model group, the lung pathology of rats in the ω-9 MUFAs group was significantly improved, and the expression levels of IL-6, TGF-ß1, GP130, IL-1 and other proteins were significantly decreased. The difference was statistically significant (p<0.05). CONCLUSION: In LPS-induced lung injury, ω-9MUFAs may alleviate symptoms by inhibiting the IL-6/GP130/STAT3 pathway.

Antithrombotic Therapy Increases the Risk of Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Propensity Score-Matched Analysis.

Whether antithrombotic agent (ATA) usage increases the risk of gastric post-endoscopic submucosal dissection (ESD) bleeding remains controversial. The aim of this study was to elucidate the effects of usage, type, and cessation timing of ATA on post-ESD bleeding. A total of 4775 early gastric cancer patients undergoing ESD were analyzed; 1:3 propensity score matching between ATA and non-ATA groups resulted in 318 and 767 matched patients in each group, respectively. Outcomes were compared between the two groups using a generalized estimating equation method. After matching, post-ESD bleeding rates in ATA users and non-users were 9.1% and 4.2%, respectively (p = 0.001). In multivariable analysis, ATA usage was independently associated with an increased risk of post-ESD bleeding (adjusted odds ratio: 2.28, 95% confidence interval: 1.34-3.86). Both the continued or insufficient cessation groups and the sufficient cessation group had an increased incidence of post-ESD bleeding compared to their matched controls (12.5% versus 5.2%, p = 0.048; 8.1% versus 3.9%, p = 0.014). Post-ESD bleeding rates in antiplatelet agent users were significantly higher than those of their matched controls (8.3% versus 4.2%, p = 0.010). ATA usage increased the risk of post-ESD bleeding even after its sufficient cessation. Careful observation after ESD is required regardless of the cessation status of ATA.

Combination of neutrophil-to-lymphocyte ratio and albumin concentration to predict the prognosis of esophageal squamous cell cancer patients undergoing esophagectomy.

Background: Esophageal squamous cell cancer (ESCC) is an aggressive cancer with high incidence and mortality. It is crucial to predict prognosis of these patients individually. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic indicator in several tumors, including esophageal cancer. Besides inflammatory factors, nutritional status can impact survival of cancer patients. Albumin (Alb) concentration is an easily obtained indicator to reflect nutritional status. Methods: In this study, we retrospectively collected the data of patients with ESCC and used univariate and multivariate analysis to investigate the relationship between combination of NLR and Alb (NLR-Alb) and survival. Meanwhile, we compared clinical features among NLR-Alb cohorts. Results: Univariate analysis showed that age (P=0.013), gender (P=0.021), surgical type (P=0.031), preoperative therapy (P=0.007), NLR-Alb (P=0.001), and tumor-node-metastasis (TNM) status (P<0.001) were associated with 5-year overall survival (OS). In multivariate analysis, NLR-Alb [hazard ratio (HR) =2.53, 95% confidence interval (95% CI): 1.38-4.63, P=0.003] and TNM status (HR =4.76, 95% CI: 3.09-7.33, P<0.001) were independent predictive factors for 5-year OS. The 5-year OS rates were 83%, 62%, and 55% for NLR-Alb 1, NLR-Alb 2, and NLR-Alb 3, respectively (P=0.001). Conclusions: In summary, pre-operative NLR-Alb is a favorable and cost-effective index to predict prognosis of patients with ESCC individually.

Hypercontractile Esophagus: Clinical and Manometric Features From a Multicenter Korean Cohort.

Background/Aims: Hypercontractile esophagus (HE) is a heterogeneous disorder with variable clinical presentations and a natural course, leading to management challenges. This study aims to investigate the characteristics of HE and evaluate its treatment outcomes. Methods: Four Korean referral centers recruited subjects with at least 1 hypercontractile swallow (distal contraction integral > 8000 mmHg·s·cm) in this retrospective observational study. Subjects were classified according to the Chicago classification version 2.0 (CC v2.0), CC v3.0, and CC v4.0. criteria. The clinical and manometric features were also investigated. The treatment modalities and outcomes of subjects with CC v4.0 were evaluated. Results: In total, 59 subjects with at least 1 hypercontractile swallow were analyzed. Among them, 30 (50.8%) had increased integrated relaxation pressure values without meeting the criteria for achalasia. Among the remaining 29 patients, 6 (20.7%) had only 1 hypercontractile swallowing symptom (CC v2.0) and 23 (79.3%) met both the CC v3.0 and v4.0 criteria for HE. Dysphagia (91.3%) was the most prevalent symptom, followed by chest pain (56.5%), regurgitation (52.2%), globus (34.8%), heartburn (21.7%), and belching (8.7%). Twenty (87.0%) patients received medical treatment, and 8 (47.1%) and 5 (29.4%) showed moderate and significant improvements, respectively. Proton pump inhibitors were the most common option (n = 15, 65.2%), followed by calcium channel blockers (n = 6, 26.1%). One patient received peroral endoscopic myotomy and showed significant symptom improvement. Conclusions: Sixty-one percent of patients who meet the diagnostic criteria for the high-resolution manometry are diagnosed with symptomatic HE based CC v4.0. Chest pain and regurgitation were also observed in over half of them. The overall medical treatment efficacy was moderate.

An n-Type Polythiophene Derivative with Excellent Thermoelectric Performance.

Typical n-type conjugated polymers are based on fused-ring electron-accepting building blocks. Herein, we report a non-fused-ring strategy to design n-type conjugated polymers, i.e. introducing electron-withdrawing imide or cyano groups to each thiophene unit of a non-fused-ring polythiophene backbone. The resulting polymer, n-PT1, shows low LUMO/HOMO energy levels of -3.91 eV/-6.22 eV, high electron mobility of 0.39 cm2  V-1 s-1 and high crystallinity in thin film. After n-doping, n-PT1 exhibits excellent thermoelectric performance with an electrical conductivity of 61.2 S cm-1 and a power factor (PF) of 141.7 µW m-1 K-2 . This PF is the highest value reported so far for n-type conjugated polymers and this is the first time for polythiophene derivatives to be used in n-type organic thermoelectrics. The excellent thermoelectric performance of n-PT1 is due to its superior tolerance to doping. This work indicates that polythiophene derivatives without fused rings are low-cost and high-performance n-type conjugated polymers.

Incidence, Morbidity, and Mortality of Achalasia: A Nationwide, Population-Based Cohort Study in South Korea.

Background/Aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). Conclusions: In this nationwide study, achalasia was associated with increased risk of mortality. Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.

Effect of renal insufficiency on the short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer: Propensity score-matched analysis.

OBJECTIVES: It is unclear whether renal insufficiency (RI) itself is a risk factor for adverse outcomes after gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the safety and efficacy of gastric ESD in patients with and without RI using propensity score-matching analysis. METHODS: In all, 4775 patients with 4775 early gastric cancer lesions undergoing ESD were analyzed. 1:1 propensity score-matching was performed between patients with and without RI using 12 variables. After matching, logistic regression and survival analyses were performed for short- and long-term outcomes of ESD, respectively. RESULTS: The matching yielded 188 pairs of patients with and without RI. In both univariable and multivariable analyses, the presence of RI was not significantly associated with postprocedural bleeding (unadjusted odds ratio 1.81, 95% confidence interval 0.74-4.42; adjusted odds ratio 1.86, 95% confidence interval 0.74-4.65, respectively). When RI patients were subclassified into patients with estimated glomerular filtration rate (eGFR) 30-59 mL/min/1.73 m2 and eGFR <30 mL/min/1.73 m2 , no significant differences in bleeding rates were found compared to their matched controls in both groups. Perforation, en bloc resection, en bloc and R0 resection, and curative resection rates of RI patients were 2.1%, 98.4%, 91.0%, and 78.2%, respectively, which were comparable to those of non-RI patients. During a median follow-up of 119 months, there was no difference in gastric cancer-specific survival between patients with and without RI (P = 0.143). CONCLUSION: The outcomes of ESD were comparable in patients with and without RI. Decreased renal function itself may not be a reason to keep patients with RI from receiving gastric ESD.

Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1 and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background/Aims: There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. Methods: Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebo group (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. Results: Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological well-being (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. Conclusions: The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.