Hypoglycemic and H2O2-induced oxidative injury protective effects and the phytochemical profiles of the ethyl acetate fraction from Radix Paeoniae Alba.

Radix Paeonia Alba (RPA) is often used as food and medicine. This study aimed to enrich and identify the antioxidant and hypoglycemic bioactive compounds from RPA. The results indicated that the ethyl acetate fraction (EAF) showed the highest total phenolic content, DPPH, ABTS+ scavenging ability, and α-glucosidase inhibition ability (IC50 = 7.27 µg/ml). The EAF could alleviate H2O2-induced oxidative stress in HepG2 cells by decreasing the MDA and ROS levels, improving cell apoptosis, increasing the enzyme activity of GPX-Px, CAT, SOD, Na+/K+-ATP, and Ca2+/Mg2+-ATP, and stimulating T-AOC expression, which also enhanced the glucose uptake of insulin-resistant HepG2 cells. In addition, the EAF significantly reduced the fasting blood glucose level and improved glucose tolerance in diabetic mice. An HPLC-QTOF-MS/MS analysis displayed that procyanidin, digallic acid isomer, methyl gallate, tetragalloylglucose isomer, dimethyl gallic acid, and paeoniflorin were the major compounds in the EAF. These findings are meaningful for the application of the EAF in the medicinal or food industry to prevent and treat oxidative stress and diabetes mellitus.

Urolithin A alleviates advanced glycation end-product formation by altering protein structures, trapping methylglyoxal and forming complexes.

Urolithin A (UroA) is a first-in-class natural compound derived from the gut microbiota-derived metabolites of ellagitannins. This research for the first time evaluates the mechanisms of UroA inhibiting advanced glycation end-product (AGE) formation by fluorescence spectroscopy, molecular docking, liquid chromatography (LC) and LC-Oribitrap tandem mass spectrometry. The results indicated that UroA exhibited a good suppression effect on the formation of AGEs in human serum albumin (HSA)-fructose and HSA-methylglyoxal (MGO) systems. Further mechanism analysis revealed that UroA alleviated AGE formation by changing the conformational structure of HSA, trapping reactive MGO to form mono-MGO-UroA complexes, promoting the exposure of chromophores to a more hydrophobic micro-environment, and forming stable UroA-HSA complexes. UroA bound with HSA in an equimolar manner, the binding was an exothermic spontaneous process, subdomain IIIA was the preferred binding pocket, and hydrogen bonding, hydrophobic interactions and van der Waals forces were the major interaction forces. The number of glycation sites detected in glycated HSA was reduced by 1 and 2, respectively, when 181.82 and 363.64 µM UroA was added. These could provide an insight into the mechanism of UroA inhibiting HSA glycation, and highlight its value as a promising glycation inhibitor in the prevention of diabetic complications.

Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China.

BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively). CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.

Transjugular intrahepatic portosystemic shunt in patients treated with a balloon tamponade for variceal hemorrhage without response to high doses of vasoactive drugs: A real-world multicenter retrospective study.

OBJECTIVE: To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) and non-TIPS therapy (endoscopy and/or nonselective beta-blockers [NSBB]) in patients with cirrhosis and active variceal hemorrhage who did not respond to high-dose vasoactive drugs and required balloon tamponade for hemostasis. METHODS: Medical records of cirrhotic patients who did not respond to high-dose vasoactive drugs and required balloon tamponade for hemostasis at five university hospitals in China between January 2011 and December 2018 were reviewed. Treatment outcomes were compared between the TIPS and the non-TIPS groups. RESULTS: Treatment failure of variceal hemorrhage within 5 days was reported in six patients of the non-TIPS group (N = 70) and none of the TIPS group (N = 66) (P = .028). The TIPS group had a higher 1-year variceal rebleeding-free rate compared with the non-TIPS group (95.5% vs 60.0%, P < .001). One patient treated with TIPS and nine with non-TIPS therapy experienced rebleeding within 5 days and 6 weeks after the intervention (P = .009). The cumulative 1-year survival rate was higher in the TIPS group than in the non-TIPS group (93.9% vs 78.6%, P = .01). The TIPS group had a higher incidence of hepatic encephalopathy within one year compared with the non-TIPS group (18.2% vs 4.3%, P = .026). CONCLUSION: For patients with cirrhosis and active variceal bleeding who do not respond to high-dose vasoactive agents and require a balloon tamponade for hemostasis, TIPS may be an appropriate treatment choice.

Use of over-the-scope clip for ulcer hemostasis after failure of both surgery and interventional therapy: A case report.

RATIONALE: Non-variceal gastrointestinal bleeding is a common critical disease worldwide, and according to relevant guidelines, surgery and interventional treatment are the final therapies. However, few studies have reported on therapeutic strategies to employ when the ultimate treatment fails. This report offers a reasonable option for hemostasis after surgery and interventional treatment both fail. PATIENT CONCERNS: A 47-year-old man with recurrent bleeding had undergone endoscopy, surgery, and interventional therapy; however, effective hemostasis was not achieved. DIAGNOSIS: This patient's clinical manifestations and typical gastroscopic findings confirmed duodenal bulb ulcer with hemorrhage INTERVENTIONS:: A Billroth II + Bancroft operation, interventional treatment, and endoscopic hemostasis with an over-the-scope clip (OTSC) system were administered. OUTCOMES: The bleeding was successfully controlled, and the patient remained well during long-term follow-up. LESSONS: The OTSC system can represent a reasonable option for ulcer hemostasis after surgery when other interventional therapies have failed.

Factors affecting the accuracy of endoscopic ultrasound-guided fine needle aspiration for the diagnosis of small (≤20 mm) pancreatic lesions.

To explore the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for small, solid or semi-solid pancreatic lesions (≤20 mm) and the factors affecting its accuracy. METHODS: Altogether 92 patients with small, solid or semi-solid pancreatic lesions who underwent EUS-FNA at the Nanjing Drum Tower Hospital from November 2009 to January 2019 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the factors affecting the accuracy of EUS-FNA for detecting these lesions. RESULTS: Among the 92 cases, 56 (60.9%) were diagnosed as having malignant lesions and 36 (39.1%) as benign lesions, respectively. The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of small, solid or semi-solid pancreatic lesions were 71.4%, 100% and 82.6%, respectively. When considering the impact of the presence of a tissue core on the diagnosis, the sensitivity, specificity, and accuracy of EUS-FNA with tissue core compared with those based on cytology alone were 77.3% vs 50.0%; 100% vs 100%; and 86.8% vs 62.5%, respectively. The multivariate analysis showed that larger tumor size (>15-20 mm) (odds ratio [OR] 4.200, 95% confidence interval [CI] 1.21-14.53, P = 0.023) and histologic diagnosis based on tissue core (OR 4.593, 95% CI 1.03-20.47, P = 0.046) were related to a higher accuracy of EUS-FNA. Adverse events were observed in three patients, all were treated conservatively and recovered within 3 days. CONCLUSIONS: EUS-FNA is effective and safe for diagnosing small pancreatic lesions. Tumor size and presence of tissue core are related to higher accuracy of the EUS-FNA.

Effects of small nucleolar RNA SNORD44 on the proliferation, apoptosis and invasion of glioma cells.

To master the effect of small nucleolar RNA, SNORD44, on the proliferation, apoptosis and invasion of glioma cells and its relevant mechanism. SNORD44 and GAS5 expression in glioma tissues and cells was detected through qRT-PCR. Then, the glioma cell lines (U87 and U251) were divided into different groups with different treatments. Cell proliferation was determined by MTT assay, while the abilities of the cell migration and invasion were measured by wound-healing test and Transwell assay, respectively. Cell apoptosis were detected by flow cytometry and TUNEL assay. The expression of apoptosis proteins was quantified through Western blotting. Finally, the xenograft models were established on nude mice to investigate the effects of SNORD44 on the growth of glioma and the expressions of Ki67, MMP2 and MMP9 in vivo. SNORD44 and GAS5 were down-regulated in glioma tissues and cells in a positive correlation. Either SNORD44 or GAS5 overexpression decreased the proliferation, invasion and migration of U87 and U251 cells with the up-regulation of apoptosis rates, as well as the expressions of cleaved PARP, caspase 3, caspase 8 and caspase 9. Moreover, the in vivo experiment showed that overexpression of SNORD44 blocked the growth of glioma xenograft in nude mice accompanying with the inhibition of Ki67, MMP2 and MMP9 expressions. The combination overexpression of SNORD44 and GAS5 gained better inhibitory effects on glioma cells. Overexpression of SNORD44 and GAS5 activate the caspase-dependent apoptosis pathway to facilitate the apoptosis with the inhibited proliferation, invasion and migration of glioma cells.

Long noncoding RNA H19 is a critical oncogenic driver and contributes to epithelial-mesenchymal transition in papillary thyroid carcinoma.

BACKGROUND: Growing evidence has indicated that the long noncoding RNA H19 (lncRNA H19), frequently deregulated in almost all tumor types tested, acted as a pivotal contributor to both cancer initiation and progression. However, the role of lncRNA H19 in human papillary thyroid carcinoma (PTC) remains controversial. The aim of the study was to investigate the expression and potential function of lncRNA H19 in human PTC. PATIENTS AND METHODS: The lncRNA H19 level was determined by quantitative real-time (RT)-PCR analyses in 58 PTC tissue samples and their paired paracancerous tissue samples. RNA interference, RT-PCR analysis, and Western blot assay were used to determine the impact of lncRNA H19 on epithelial-mesenchymal transition (EMT) markers in human PTC cells. The migratory and invasive capacities of PTC cells were determined by wound-healing and transwell migration and invasion assays. RESULTS: lncRNA H19 expression was 2.417-fold higher in PTC tissues than their paired paracancerous tissue (95% CI: 1.898-2.935, P<0.0001). Higher level of lncRNA H19 was correlated to elevated expression of Vimentin, ZEB2, Twist, and Snail2. Inhibition of lncRNA H19 resulted in upregulation of E-cadherin and downregulation of Vimentin both at mRNA and protein levels. Conversely, enforced expression of the exogenous lncRNA H19 led to E-cadherin mRNA and protein downregulation and relative upregulation of Vimentin. Moreover, wound-healing and transwell migration and invasion assays showed that lncRNA H19 could promote the migratory and invasive abilities of PTC cells. CONCLUSION: The level of lncRNA H19 was significantly higher in PTC tissues than paired paracancerous tissue or normal tissues. Overexpression of lncRNA H19 was correlated with higher tumor burden of PTC. It also contributes to EMT process, as well as promotes migration and invasion of PTC cells.

The impact of endoscopic ultrasound in preoperative evaluation for ampullary adenomas.

OBJECTIVE: We aimed to evaluate the efficacy of endoscopic ultrasonography (EUS) in assessing locoregionally and determining therapeutic options for ampullary adenomas and the related factors. METHODS: Patients undergoing EUS and surgical or endoscopic resection for biopsy-proven ampullary adenomas between 2009 and 2016 were retrospectively analyzed. The depth of tumor invasion, intraductal extension, and regional lymph node staging evaluated by EUS were compared with post-treatment pathological findings. RESULTS: Altogether 120 patients were enrolled in this study. The overall accuracy for EUS in T staging was 81.7%. The sensitivity and specificity of EUS for T staging were 93.9%, 45.5% for adenoma and T1, 50.0% and 96.5% for T2, 66.7% and 97.4% for T3, 50.0% and 97.5% for T4 lesions, respectively. The sensitivity, specificity, and accuracy of EUS for the diagnosis of any intraductal extension were 89.5%, 86.1%, and 86.7%, respectively. The overall accuracy of EUS for regional lymph node staging was 75.0%. The sensitivity and specificity of EUS for diagnosing N1 were 62.5% and 87.5%. By multivariate analysis no factors were found to be independently associated with EUS accuracy for tumor invasive depth. However, small lesion size (≤15 mm) and dilated duct were associated with an overestimation in intraductal extension. CONCLUSION: EUS may be a useful diagnostic tool for selecting endoscopic or surgical treatment for ampullary adenomas.

Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa.

AIM: To investigate the relationship between histological mixed-type of early gastric cancer (EGC) in the mucosa and submucosa and lymph node metastasis (LNM). METHODS: This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated (pure D), pure undifferentiated (pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. Furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC. RESULTS: Of the 298 patients, 165 (55.4%) had mucosa-confined EGC and 133 (44.6%) had submucosa-invasive EGC. Only 13 (7.9%) cases of mucosa-confined EGC and 30 (22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion (OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type (OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixed-type (OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixed-type group (P = 0.012) and pure U group (P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group (P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixed-type (P = 0.012) and pure U group (P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group (P = 0.375). Multivariate logistic analysis showed that only female sex (OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion (OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC (P = 0.106). CONCLUSION: For mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

[Study on differences of Ainsliaea fragrans from different sources based on UFLC-Q-TOF-MS/MS and PCA analysis].

A rapid and accurate method of UFLC-Q-TOF-MS/MS combined with multivariate statistical analysis was established for the identification of Ainsliaea fragrans from different origins in this study. The A. fragrans from different producing areas of Jiangxi, Yunnan, Henan and Jiangsu were determined by UFLC-Q-TOF-MS/MS in the negative ion mode. And the data of the study were analyzed by the Markerview and other software for the PCA and OPLS-DA cluster analysis as well as t test. The results of the principal component analysis(PCA)showed that the main components from different origins were well distinguished. And the results of multivariate statistical showed the differences and similarities between different producing areas. Besides, 40 different compounds were identified in the negative ion mode. This method for identifying A. fragrans from different producing areas has the advantages of rapid accuracy and simplicity, which laid the foundation for the evaluation of the quality of the A. fragrans.

CCR10 activation stimulates the invasion and migration of breast cancer cells through the ERK1/2/MMP-7 signaling pathway.

CCR10, a member of the chemokine receptor subfamily, is overexpressed in several tumors and play a crucial role in cancer development and progression. However, the functions of CCR10 in breast cancer are unknown. Here, we detected the protein levels of CCR10 in breast cancer cells by western blotting, and examined CCR10 expression in breast cancer tissues via immunohistochemical assay. The results showed that CCR10 expression was elevated in breast cancer MCF7, BT-474 and MDA-MB-231 cells. Further, 63 of 89 cases (70.8%) had positive CCR10 staining, and the CCR10 level was closely related to capsular invasion, lymph node metastasis and tumor stage. Moreover, CCL27, the ligand of CCR10, dose-dependently stimulated the invasion and migration of breast cancer cells, and promoted MMP-7 expression and ERK1/2 activation. CCR10 knockdown in breast cancer cells through siRNA transfection attenuated CCL27-induced cell invasiveness, and suppressed MMP-7 expression and ERK1/2 activation. Additionally, blocking the ERK1/2 pathway inhibited the CCL27/CCR10-promoted cell invasion of breast cancer cells. Together, these data suggest that CCL27/CCR10 interaction induces the ERK1/2 pathway, which then increases MMP-7 expresion and subsequently promotes breast cancer cell invasion and migration. Thus, CCR10 may be a key regulator in breast cancer cell invasion and migration.

Profiling of carbonyl compounds in serum by stable isotope labeling - Double precursor ion scan - Mass spectrometry analysis.

Carbonyl compounds are considered as the potential biomarkers for oxidative stress and many types of diseases; therefore their determination may serve as indicator for early clinical diagnosis. Here we developed a strategy based on isotope labeling combined with liquid chromatography-double precursor ion scan-mass spectrometry (IL-LC-DPIS-MS) analysis for comprehensive profiling and relative quantitation of carbonyl compounds in human serum. First, we chose labeling reagents (2-(2-hydrazinyl-2-oxoethyl)isoquinolin-2-ium bromide, HIQB; N,N,N-triethyl-2-hydrazinyl-2-oxoethanaminium bromide, THB; Girard reagent T, GT; Girard reagent P, GP), all of which contain reactive group, isotopically labeled moiety and ionizable group to selectively label carbonyl compounds. Since HIQB labeling offered the best detection sensitivities for carbonyl compounds among these labeling reagents, we used HIQB and the corresponding isotope-labeled reagent of d7-HIQB as the optimal isotope-labeled reagent. The HIQB and d7-HIQB labeled carbonyl compounds can generate two characteristic product ions of m/z 130.1/137.1 under collision-induced dissociation (CID), which contain an isotope tag and therefore were used for double precursor ion scans in mass spectrometry analysis. Using this strategy, 156 carbonyl compounds candidates were detected in human serum, 12 of which were further identified by commercial standards. Subsequently, a targeted method using multiple reaction monitoring (MRM) detection mode was developed for relative quantification of carbonyl compounds in human serum from myelogenous leukemia (ML) patients and healthy controls. As a result, 44 carbonyl compounds were found to have significant difference between ML patients and healthy controls, suggesting that these carbonyl compounds may play certain roles in ML and also can serve as indicators for ML. Taken together, the isotope labeling combined with tandem mass spectrometry analysis demonstrated to be a powerful strategy for identification and quantification of carbonyl compounds in serum samples.

DNA hydroxymethylation age of human blood determined by capillary hydrophilic-interaction liquid chromatography/mass spectrometry.

BACKGROUND: Aging is a complex phenomenon and characterized by a progressive decline in physiology and function of adult tissues. However, it hasn't been well established of the correlation between aging and global DNA methylation and hydroxymethylation that regulate the growth and development of higher organisms. RESULTS: We developed an on-line trapping/capillary hydrophilic-interaction liquid chromatography/electrospray ionization-mass spectrometry method for ultra-sensitive and simultaneous quantification of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in genomic DNA from human blood. Limits of detection for 5-mC and 5-hmC were 0.04 and 0.13 fmol, respectively. The imprecision and recovery of the method were determined with the relative standard deviations (RSDs) and relative errors being <11.2 and 14.0 %, respectively. We analyzed the contents of 5-mC and 5-hmC in genomic DNA of blood from 238 healthy people aged from 1 to 82 years. The results showed that 5-hmC content was significantly decreased and highly correlated with aging process, while 5-mC only showed slight correlation with age. We then established a DNA hydroxymethylation age model according to 5-hmC content with a mean absolute deviation (MAD) of approximate 8.9 years. We also calculated the mean relative error (MRE) using the predicted ages based on the age model and the chronological ages. The results showed that the MRE was 18.3 % for samples with ages from 20 to 82 years (95 % confidence interval, N = 190). CONCLUSIONS: The global DNA hydroxymethylation represents a strong and reproducible mark of chronological age, which could be potentially applied in health assessment and prevention of diseases. The identification of biological or environmental factors that influence DNA hydroxymethylation aging rate may permit quantitative assessments of their impacts on health.

Glutathione S-transferase M1 null genotype and hepatocellular carcinoma susceptibility in China and India: evidence from an updated meta-analysis.

BACKGROUND: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTM1 null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. MATERIALS AND METHODS: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. RESULTS: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80- 4.20], P=0.15). CONCLUSIONS: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.

Effectiveness of peroral endoscopic myotomy in the treatment of achalasia: a pilot trial in Chinese Han population with a minimum of one-year follow-up.

OBJECTIVE: To investigate the outcomes of Chinese Han patients who underwent peroral endoscopic myotomy (POEM) for achalasia. METHODS: Patients undergoing POEM for achalasia at the Affiliated Drum Tower Hospital of Nanjing University Medical School were prospectively enrolled in this study, with a follow-up duration of at least one year. Their outcomes were evaluated by analyzing esophageal manometry, timed barium esophagogram and 36-Item Short Form Health Survey (SF-36), which were performed before surgery, 5 days after surgery and at the last follow-up. Patients' symptom relief was considered the primary outcome. Secondary outcomes included lower esophageal sphincter (LES) pressure, esophageal emptying, patients' quality of life (QoL) and procedure-related complications. RESULTS: Eighty-seven patients were included in the study. Eckardt score after POEM was remarkably lower than the preoperative score (0.4 ± 0.7 vs 7.1 ± 2.1, P = 0.001). The preoperative LES pressure was 32.4 ± 15.3 mmHg, which was decreased to 3.8 ± 3.9 mmHg immediately after surgery. The height of the barium column at 1 min after barium swallow was significantly reduced after treatment (11.7 ± 1.2 cm vs 3.2 ± 1.6 cm, P < 0.001). The patients' QoL was also improved, as indicated by obviously increased physical and mental component summary (PCS and MCS) scores of the SF-36. Complications occurred during POEM included cutaneous emphysema, mucosal injury and pneumothorax. CONCLUSION: POEM is an effective approach for treating achalasia, which can relieve the symptoms of achalasia by improving esophageal emptying and lowering LES pressure.

Growth-inhibiting effects of arsenic trioxide plus epigenetic therapeutic agents on leukemia cell lines.

Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia (APL) and other hematopoietic malignancies. We found that ATO down-regulated the global DNA methylation level in HL-60 cells with high-performance capillary electrophoresis (HPCE) assay. Using combination index method of Chou and Talalay, interactions between ATO and epigenetic therapeutic agents were analyzed in three human leukemia cell lines (HL-60, U937, and K562). A synergistic interaction was observed in HL-60 cells between ATO and 5-Aza-2'-Deoxycytidine (DAC), while an antagonistic interaction was found in U937 cells between ATO and valproic acid (VPA). The combination of ATO with trichostatin A (TSA) caused an antagonistic interaction in U937 and K562 cells. These results not only highlight possible diversity of the anti-leukemia mechanisms of ATO, but also provide initial guide for further investigation of leukemia therapies based on the combination of ATO with epigenetic agents.