Recent advances of m6A methylation modification in esophageal squamous cell carcinoma.

In recent years, with the development of RNA sequencing technology and bioinformatics methods, the epigenetic modification of RNA based on N6-methyladenosine (m6A) has gradually become a research hotspot in the field of bioscience. m6A is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs). m6A methylation modification can dynamically and reversibly regulate RNA transport, localization, translation and degradation through the interaction of methyltransferase, demethylase and reading protein. m6A methylation can regulate the expression of proto-oncogenes and tumor suppressor genes at the epigenetic modification level to affect tumor occurrence and metastasis. The morbidity and mortality of esophageal cancer (EC) are still high worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common tissue subtype of EC. This article reviews the related concepts, biological functions and recent advances of m6A methylation in ESCC, and looks forward to the prospect of m6A methylation as a new diagnostic biomarker and potential therapeutic target for ESCC.

Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer.

BACKGROUND: Platinum-based chemotherapy is a mainstay for treating esophageal cancer patients. In this manuscript, we have provided clues for influence of platinum on overall m6A level and further investigated the potential regulatory mechanism. METHODS: qRT-PCR was used to measure SNHG3 and miR-186-5p expression; ELISA and western blot were used to measure the expression of METTL3. CCK8 was used to measure the cell proliferation rate. Caspase 3/7 activity was used to measure the apoptosis rate. Dual luciferase reporter gene assay and RNA pull down assay were used to investigate the potential crosstalk between miR-186-5p and SNHG3; and miR-186-5p and METTL3. RESULTS: m6A level was increased when treated with platinum (CDDP, CPB and L-OHP). Besides, SNHG3 expression was induced and miR-186-5p expression was suppressed by platinum. Furthermore, SNHG3 could promote the m6A level, however miR-186-5p inhibited the m6A level through targeting METTL3. SNHG3 interacts with miR-186-5p to negatively regulate the expression of miR-186-5p; and miR-186-5p might bind to the 3'UTR of METTL3 to regulate its expression. CONCLUSION: Platinum can increase the overall m6A level of esophageal cancer. SNHG3/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. Our manuscript has provided clues that regulating m6A level might be a novel way to enhance the platinum efficacy.

Circular RNAs and esophageal cancer.

As a new kind of RNA, circular RNA (circRNA) is a endogenous non-coding RNA with circular structure, which has the characteristics of universality, stability, conservatism and specificity. CircRNA can specifically bind to microRNAs (miRNAs) in the form of competitive endogenous RNA, thus directly or indirectly regulating the expression of related genes. In addition to the role of sponge, circRNA also regulates parental gene expression, transcriptional translation and protein modification; and it can be used as a biomarker to develop potential diagnosis and treatment methods and evaluate prognosis. Due to changes in dietary habits and genetic factors, the morbidity and mortality of esophageal cancer (EC) in the world are still high, and are prone to early metastasis. Although the diagnosis and treatment techniques have been improved in recent years, the early diagnosis of EC is not common, and the 5-year survival rate of patients is still very low. This article reviews the function and significance of circRNA and discusses the research progress of circRNA as biomarkers in EC.

Linc-PINT acted as a tumor suppressor by sponging miR-543 and miR-576-5p in esophageal cancer.

This manuscript aimed to investigate linc-PINT's role as a tumor suppressor and its downstream microRNAs (miRNAs) in esophageal cancer. Log-rank, Cox, and nomogram were used for survival analysis. Quantitative real-time polymerase chain reaction was used to evaluate the expression. Cell counting kit-8 was used for proliferation tests. As for in vivo experiments, low expression of linc-PINT was associated with better prognosis; besides, the nomogram indicated that linc-PINT, miR-543, and miR-576-5p served well in predicting the survival rate. As for the in vitro experiments, linc-PINT could directly regulate miR-543 and miR-576-5p to inhibit the proliferation of Eca-109 cell line. In conclusion, linc-PINT-miR-543/miR-576-5p pathway could predict the prognosis and provide novel therapeutic targets for esophageal cancer.

Function, Significance, and Regulation of Rap1b in Malignancy.

Ras-associated protein 1(Rap1) is a member of the RAS family of small G proteins and regulates several signal pathways involved in carcinogenesis. Rap1 consists of two highly homologous isoforms, Rap1a and Rap1b. Increasing data suggest that the deregulated activation of Rap1b is involved in a spectrum of malignancies. Accumulating evidence also indicates effects of Rap1b on cell proliferation, metastasis, angiogenesis, and treatment resistance. Rap1b overexpresses in many tumors and has prognostic values, which are regulated by A2br, miRNAs, and other upstream effectors. This article aims to review research progress in function, significance, and regulation of Rap1b in malignancy.

Synthesis of [H22·Zr5·WO4·10 P2O7]n·26n H2O by response surface methodology to adsorb Ca(II) in manganiferous wastewater.

The presence of calcium challenges the manganese recovery from manganiferous wastewater. In this paper, a kind of mesoporous material named [H22·Zr5·WO4·10 P2O7]n·6n H2O is investigated as an ion exchanger to remove calcium ion from manganese slag percolate. The synthesis of zirconium tungstopyrophosphate (ZWPP) was optimized by response surface methodology , and its adsorption capacity and equilibrium were tested. The adsorption data have been confirmed by the use of various techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy and Brunauer, Emmett and Teller. An empirical formula of ZWPP was obtained by X-ray diffraction and thermal analysis. The adsorption process conformed to pseudo-second-order kinetics and the Langmuir isotherm, which described the equilibrium powerfully. Furthermore, different thermodynamic parameters were evaluated. And it was found that Gibbs free energy change is negative, indicating the adsorption process was spontaneous, whereas the enthalpy change and entropy change are positive indicating endothermy and increased randomness nature of the adsorption process. As a result, ZWPP could be a possible ion exchanger material in the area of removing Ca2+ from processing water or wastewater.

Construction of adsorptive nanorods from polyoxometalates and ionic liquid and their adsorption properties for silver ion from AMD.

A new structure of hybrid nanorods adsorbent ([n-BBIM]9PW9O34) was synthesized by a simple molecular assembly of polyoxometalates with ionic liquids (ILs). The nanocomposite was characterized by Fourier transform infrared (FT-IR), ultraviolet-visible (UV-Vis), scanning electron microscope, energy dispersive X-ray and X-ray diffractometer. Adsorption of silver from acid mine drainage (AMD) was studied using batch experiments. The impact of several parameters, like ion concentration, pH, adsorbent dosage, and temperature was elucidated and optimization was carried out by single-factor experiment and response surface methodology. Analysis of variance of the quadratic model suggested that experimental data were excellently fitted to the quadratic model. Optimum conditions for removal of Ag(+) from AMD were determined to be an initial concentration 143 mg/L, adsorbent dosage 2.69 g/L, temperature 35 °C to achieve the maximum adsorption of Ag(+) 99.03%, which was very close to the predicted value (100%). The adsorption was confirmed as oxidation-reduction mechanism following a complexation process, and has been verified according to results from FT-IR and UV-vis spectra. The selective experiment suggested that the nanorods adsorbent could adsorb silver ions in AMD well. Based on the adsorption/desorption study result, the adsorbent can be efficiently recovered.

A study on fluorescence properties of carboxymethyl-quaternary ammonium oligochitosan and its performances as a tracing agent.

Carboxymethyl-quaternary ammonium oligochitosan (CM-QAOC) exhibited high inhibition to scaling and microbial formation and also remarkable fluorescence. In this paper its fluorescent properties and application as a fluorescent tracing chemical for industrial water treatment were studied in detail. The fluorescence intensities of CM-QAOC were in good linear agreement with its content in the concentration range of 5 to 500 mg/L and in the range of pH 7 to 9, which shows CM-QAOC can trace itself directly. The results showed the fluorescence would not be influenced by common phosphorus-containing organic and inorganic water treatment chemicals and N-dodecyl-N,N-dimethyl-benzenemethanaminium chloride. This means CM-QAOC is compatible with those chemicals. The metal ions Ca2+, Mg2+, Fe3+ and Cu2+ from raw water or corrosion products could cause obvious enhancement in fluorescence intensities and sometimes blue-shifts in the fluorescence maxima, which demonstrated CM-QAOC could also be used as tracer to monitor damages like corrosion and scaling in water systems, by varying changes of fluorescence intensities and maximum emission wavelength. The fluorescence of CM-QAOC may be influenced by NaClO, and be quenched by sunshine slightly. Its ratio of biochemical oxygen demand to chemical oxygen demand was 0.53, which indicates CM-QAOC is a biodegradable chemical. Therefore, CM-QAOC can be applied as a tracer and environmental-friendly chemical for industrial cooling water treatment.

The Relationship Between Psychological Conditions and Gastrointestinal Symptoms of Medical Students During the COVID-19 Pandemic.

Objective: This study aims to explore the nexus between students' psychological well-being and the manifestation of gastrointestinal symptoms (GISs) amid the health lockdown enforced in Xi'an, focusing on the student populace of Xi'an Medical College and Shaanxi University of Traditional Chinese Medicine. Materials and methods: A survey encompassing psychological parameters and GISs was administered to a randomized cohort of 1327 college students drawn from Xi'an Medical College and Shaanxi University of Traditional Chinese Medicine. The survey instrument was developed utilizing the Questionnaire Star platform. Subsequent to data collection, analysis was performed using GraphPad Prism 9 and SPSS 22.0. Results: Comparative analysis revealed statistically significant disparities (P < 0.05) in various GISs between the periods during and preceding the health lockdown, encompassing symptoms such as nausea/vomiting, acid reflux, postprandial fullness/early satiety, anorexia, decreased appetite, bloating, abdominal discomfort, abdominal pain, diarrhea, and constipation. Notably, the mean score for Generalized Anxiety Disorder 7 (GAD-7) was 3.31±3.92, indicating mild anxiety, while the mean score for Patient Health Questionnaire-2 (PHQ-2) was 1.15±1.28, suggesting mild depression. Detailed evaluation of anxiety revealed prevalence rates of 34% among respondents, with 34.2% of these individuals reporting concurrent GISs, while among those evaluated for depression (38.8% of the sample), 44.2% reported concurrent GISs. Furthermore, multiple linear regression analysis unveiled a negative correlation between GISs during the health lockdown and lifestyle scores, while positive correlations were observed with GISs preceding the lockdown, anxiety, and depression. The formulated multiple linear regression equation for GISs during the health lockdown is delineated as follows: 14.693-0.342 life style + 0.725GISs before health lockdown + 0.218anxiety + 0.564 depression. Conclusion: This investigation underscores the substantial impact of anxiety and depression on the student body, accentuating their role in precipitating GISs during health lockdown situations. The psychological well-being of medical students during exigent circumstances such as natural disasters warrants heightened attention, necessitating proactive measures aimed at emotional regulation to mitigate the onset of GISs.

Role of epigenetic modifications mediated by vitamins and trace elements in inflammatory bowel disease.

Graphical abstract [Formula: see text] Numerous environmental factors frequently emerge as primary determinants of inflammatory bowel disease (IBD). Diet is a major component of environmental factors, and the consumption of vitamins (A, B, C and D) and trace elements (calcium, iron, zinc and selenium) exerts an impact on the progression of IBD through epigenetic modifications. Intake of vitamins A, B, C and D, as well as excessive amounts of iron and calcium, can modulate the condition of IBD by regulating the levels of DNA methylation, histone acetylation and miRNA. Zinc and selenium alleviate the progression of IBD by regulating the levels of promoter methylation or histone ubiquitination, respectively. Graphical Abstract was adapted from 'Epigenetic levels (layout)', by BioRender.com. Retrieved from https://app.biorender.com/biorender-templates.

First-line treatment options for advanced gastric/gastroesophageal junction cancer patients with PD-L1-positive: a systematic review and meta-analysis.

Lately, many trials have paid much attention on the oncological outcomes of immunotherapy combined with chemotherapy as a first-line treatment. The authors perform a systematic meta-analysis to assess the efficacy and safety of programmed death 1 inhibitor plus chemotherapy for first-line treatment in advanced gastric/gastroesophageal junction cancer. Materials and methods: Literature search through major databases in English and Chinese: PubMed, Embase, Cochrane library, web of Science and CNKI updated on 10 March 2023. Randomized controlled trials were selected to investigate chemotherapy plus programmed death 1 inhibitor versus chemotherapy. Results: A total of 7 randomised controlled trials including 5788 participants were included. The overall survival (hazard ratio=0.79;95% CI: 0.74-0.85, P<0.01), progression-free survival (hazard ratio=0.72; 95% CI: 0.67-0.77, P<0.01) and objective response rate (risk ratio=1.24,95% CI: 1.18-1.31, P<0.05) were longer than chemotherapy alone in the pooled analysis. For subgroup analyses of overall survival, programmed death 1 inhibitors plus chemotherapy had a significant advantage in patients with combined positive score greater than or equal to 5, in Asia, in men and in those younger than 65 years (P<0.01), as were immune-mediated adverse events (odds ratio=8.86;95% CI: 1.26-62.47,P<0.05) and treatment-related grade 3-5 adverse events (odds ratio=1.40,95% CI:1.20-1.62, P<0.01). Conclusion: Programmed death 1 inhibitors plus chemotherapy have significant antitumour activity compared to chemotherapy alone. However, it is riskier in terms of toxicity than chemotherapy. The authors recommend programmed death 1 inhibitors plus chemotherapy as the optimal treatment regimen for patients with positive programmed death ligand 1 expression, in Asia, male and less than 65 years of age. More well-designed studies are needed to investigate the efficacy and safety of different immune plus chemotherapy drug doses and regimens.

Using Herbal-Cake-Separated Moxibustion for the Treatment of Rats with Chronic Renal Failure.

In the process of moxibustion in clinical practice, subjects need to be in a stable mood and comfortable posture to avoid problems such as moxa ash falling, scalding skin, and poor curative effect. Such problems also exist in the rat moxibustion experiment. To simulate clinical practice, it is necessary to introduce an experimental instrument in animal experiments, that is, a moxibustion device with fixed rats and moxibustion treatment synchronization, which can make experimental rats receive moxibustion treatment quietly and comfortably under non-anesthesia. Our research group designed a rat moxibustion experimental platform. The device was framed by a wooden board with a supporting base plate, multiple fixed components, and partitioned components. The device can achieve the operation mode of moxibustion in rats without binding, avoiding anesthesia and scalding and simultaneously exposing multiple acupoints on the back. This operation can avoid physical and mental injury to rats and operators, which improves the research efficiency and further promotes the development and research of moxibustion animal experiments. The device has a simple structure, is easy to operate and popularize, is comprehensively and innovatively designed, reusable, and is suitable for rat experiments mainly based on moxibustion. This article mainly introduces the structure of the experimental platform device for rat moxibustion, the basic procedure of herbal-cake-separated-moxibustion in experimental rats using the device and describes the establishment of a rat model of chronic renal failure (CRF) and representative experimental results.

MAD2L1 is transcriptionally regulated by TEAD4 and promotes cell proliferation and migration in colorectal cancer.

The molecular mechanism of network regulation in the occurrence and development of colorectal cancer (CRC) has been constantly improved. Here, we investigated the biological effects of TEAD4-MAD2L1 axis on proliferation and metastasis of human CRC cells. This study revealed that the expressions of MAD2L1 and TEAD4 in CRC tissues and CRC cell lines were significantly higher than those in adjacent epithelial tissues and normal intestinal epithelial cell line NCM460, and their expressions were significantly positively correlated; Moreover, inhibiting the expression of MAD2L1 or TEAD4 can inhibit the proliferation and migration of CRC cells and promote apoptosis. In addition, the promoter region of MAD2L1 gene has a TEAD4 binding site (motif sequence), and the transcription of MAD2L1 is positively regulated by TEAD4 protein; The inhibition of promotion/migration and promotion of apoptosis of CRC cells by silencing TEAD4 can be saved by the high expression of MAD2L1. In conclusion, our study suggests that the transcription and expression of MAD2L1 is regulated by TEAD4, which further promotes the proliferation and migration of CRC cells in vitro and in vivo, and inhibits apoptosis. MAD2L1 and TEAD4 are potential biomarkers for colorectal cancer.

Oral Nanotherapeutics of Andrographolide/Carbon Monoxide Donor for Synergistically Anti-inflammatory and Pro-resolving Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology affecting the colon and rectum. Current therapeutics are focused on suppressing inflammation but are ineffective. Combining anti-inflammatory therapeutic approaches with pro-resolution might be a superior strategy for UC treatment. Andrographolide (AG), an active compound from the plant Andrographis paniculata, presented anti-inflammatory effects in various inflammatory diseases. Gaseous mediators, such as carbon monoxide (CO), have a role in inflammatory resolution. Herein, we developed a dextran-functionalized PLGA nanocarrier for efficient delivery of AG and a carbon monoxide donor (CORM-2) for synergistically anti-inflammatory/pro-resolving treatment of UC (AG/CORM-2@NP-Dex) based on PLGA with good biocompatibility, slow drug release, efficient targeting, and biodegradability. The resulting nanocarrier had a nano-scaled diameter of ∼200 nm and a spherical shape. After being coated with dextran (Dex), the resulting AG/CORM-2@NP-Dex could be efficiently internalized by Colon-26 and Raw 264.7 cells in vitro and preferentially localized to the inflamed colon with chitosan/alginate hydrogel protection by gavage. AG/CORM-2@NP-Dex performed anti-inflammatory effects by eliminating the over-production of pro-inflammatory mediator, nitric oxide (NO), and down-regulating the expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), while it showed pro-resolving function by accelerating M1 to M2 macrophage conversion and up-regulating resolution-related genes (IL-10, TGF-ß, and HO-1). In the colitis model, oral administration of AG/CORM-2@NP-Dex in a chitosan/alginate hydrogel also showed synergistically anti-inflammatory/pro-resolving effects, therefore relieving UC effectively. Without appreciable systemic toxicity, this bifunctional nanocarrier represents a novel therapeutic approach for UC and is expected to achieve long-term inflammatory remission.

[Significance of identification of fungi in gastric juice of patients with artificial airway in intensive care unit].

OBJECTIVE: To investigate the direct relationship and significance between the pH value of gastric juice and positive fungi in culture critical patients with artificial airway in intensive care unit (ICU) by analyzing and identifying the type of fungi and their sensitivity to antifungal therapy. METHODS: A prospective study was conducted.One hundred and sixty patients (between December, 2008 and October, 2011) with artificial airway lasting longer than 48 hours were studied in the ICU at the First Affiliated Hospital of Shenzhen University. The gastric juice specimens were collected through a nasogastric tube, their pH values were measured using precise litmus paper. These samples were divided into six groups according to their pH values: pH ≤ 2.0, pH 2.1-3.0, pH 3.1-4.0, pH 4.1-5.0, pH 5.1-6.0 and pH 6.1-7.0, and then fungi were cultured in these specimens with different pH values. Susceptibility of different fungicide drugs were also investigated. The susceptibility of fungi to gastric juice with different pH values was also investigated. The relationship between 28-day survival rate and the presence of fungi in gastric juice was analyzed in order to analyze the relationship of the presence of fungi in gastric juice and clinical outcome. RESULTS: (1) No fungal growth was found in the gastric juice with pH value lower than 4.0, and the positive rate of fungal culture was significantly increased when the pH value of gastric juice raised. (2) The positive rate of fungal growth was 27.9% (55/197), in which, the positive rate of Candida and non-Candida fungi was 38.2% (21/55) and 61.8% (34/55) respectively, and the difference was significant statistically [χ(2) = 4.16, P < 0.05]. (3) The fungal positive rate was 40.0% (22/55) and 60.0% (33/55) respectively, in survivors (102 cases) and non-survivors (58 cases). The percentage of Candida infection and non-Candida infection was 54.5% (12/22) and 45.5% (10/22) respectively, in survivors, and it was 27.3% (9/33) and 72.7% (24/33), respectively, in non-survivors. The rate of resistance of Candida and non-Candida fungi was 4.7%-14.3% (mean 10.1%) and 0-60% (mean 28.5%) respectively. CONCLUSIONS: Positive fungus culture rate was higher in critical patients with artificial airway and higher gastric juice pH values. Non-Candida fungi were mainly found in gastric juice with increasing resistance rate. Candida was more commonly found in survivors, and non-Candida fungi were more commonly found in non-survivors.

[The effects of fluid resuscitation with different crystalloid-colloid ratio on extravascular lung water index in severe acute pancreatitis].

OBJECTIVE: To investigate the effects of fluid resuscitation with different crystalloid-colloid ratio on extravascular lung water (EVLW) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of 24 SAP patients,who had undergone intrathoracic blood volume index (ITBVI <750 ml/m(2)),were analyzed retrospectively, in Department of Critical Care Medicine in the First Affiliated Hospital of Shenzhen University, during January of 2009 to December of 2010. ITBVI 850-1 000 ml/m(2) was confirmed the end criterion of the end point of resuscitation. Low crystalloid-colloid ratio group (n=13) and high crystalloid-colloid ratio group (n=11) were divided according to crystalloid-colloid ratio (3:1) as the borderline . Hemodynamic parameters, extravascular lung water index (EVLWI), oxygenation index (PaO(2)/FiO(2)), bladder pressure (ICP) and B type natriuretic peptide (BNP) were observed at the time point of before fluid resuscitation, and 0, 24,48, 72 hours after resuscitation, EVLWI was measured with thermal dilution pulse index continuous cardiac output (PiCCO), and BNP with radioimmunoassay. RESULTS: (1)Hemodynamic parameters can be improved at early fluid resuscitation stage in both groups.(2) The total amount of fluid [(16 438±1 758) ml], amount of crystalloid fluid [(13 459±425) ml] and crystalloid-colloid ratio (4.50±0.23) of the high crystalloid-colloid ratio group was significantly higher than that of the low crystalloid-colloid ratio group [(13 895±1 783) ml, (6 945± 454) ml, 2.32±0.18, respectively, P<0.05 or P<0.01] at the time point of 72 hours after resuscitation. (3) Compared with low crystalloid-colloid ratio group, PaO(2)/FiO(2)(mm Hg, 1 mm Hg=0.133 kPa) in high crystalloid-colloid ratio group was lowered significantly at 48 hours and 72 hours after resuscitation (48 hours: 186.51±42.26 vs. 268.35±34.18, 72 hours : 172.85±21.50 vs. 263.95±24.20); but EVLWI, ICP and BNP were increased significantly [EVLWI (ml/kg) 48 hours: 14.52±1.08 vs. 10.40±1.16, 72 hours: 14.92±0.86 vs. 10.52±1.02; ICP (cm H(2)O, 1 cm H(2)O=0.098 kPa) 48 hours: 16.23±1.32 vs. 13.05±1.70, 72 hours: 17.39±1.56 vs. 13.42±1.65; BNP (ng/L) 48 hours: 424.29±74.25 vs. 225.32±53.58, 72 hours: 620.49±79.53 vs. 288.28±68.78, P<0.05 or P<0.01]. (4) The Pearson correlation analysis showed that: EVLWI with PO(2)/FiO(2) was correlated negatively (r=-0.71, P<0.01), but with the BNP, ICP showed positive correlation (r(1)=0.63, r(2)=0.56, both P<0.01). CONCLUSION: In order to guide early fluid resuscitation,EVLW, ICP and BNP should be monitored and limited fluid resuscitation strategy with an increasing colloid ratio should be adopted for SAP patients.

Construction and evaluation of prognostic models for esophageal cancer patients with distant and non-distant metastases: providing a reference process for clinical diagnosis and treatment.

BACKGROUND: Although the current treatment for esophageal cancer has great technological progress, the 5-year survival rate of patients is not optimistic. About 70% of patients with esophageal cancer are at an advanced stage at first diagnosis. These patients are prone to distant metastasis, and the prognosis is poor. Therefore, understanding the risk factors for distant metastasis in patients with esophageal cancer, combined with the prognosis of the patient, can aid in choosing the optimal diagnosis and treatment plan. Ultimately, it will improve the patient's survival time and quality of life. This research aims to construct a model for the risk assessment of distant metastasis in patients with esophageal cancer and prognostic models for patients with distant and non-distant metastases. METHODS: The Surveillance Epidemiology and End Results (SEER) database was used to select patients with esophageal cancer from 2010 to 2015. The optimal cutoff point was selected for the age and tumor size variables using X-tile. The nomogram was constructed using R software (The R Foundation for Statistical Computing). RESULTS: Gender, grade, T stage, N stage, and tumor size were independent risk factors associated with distant metastasis in patients with esophageal cancer. The concordance index (C-index) of the nomogram prediction model for whether the patient will have distant metastasis was 0.609. Age, grade, T stage, N stage, and tumor size were independent risk factors affecting the prognosis without distant metastasis. The C-index of the nomogram prediction model for patients with distant metastases was 0.590. Age and T stage were independent risk factors affecting the prognosis of patients with distant metastases. The C-index of the nomogram prediction model was 0.543. The combination of radiotherapy, chemotherapy, and primary surgery yielded the best overall survival for both patients with distant metastases and patients with non-distant metastases. CONCLUSIONS: A comprehensive assessment of the risk of distant metastasis in patients with esophageal cancer, combined with prognosis prediction, is necessary to provide patients with a reasonable treatment plan.

[Positive lymph node ratio ≥0.16 is an independent risk factor affecting the prognosis of patients with esophageal cancer].

OBJECTIVE: To investigate the value of positive lymph node ratio (LNR) in predicting the prognosis of patients with esophageal cancer. METHODS: We retrieved the data of a total of 862 patients with esophageal cancer with complete clinical pathology data archived in SEER database in 2010 to 2015. The best cutoff point of LNR was selected using X-tile software. Univariate and multivariate COX proportional hazard models were used to assess the value of LNR in predicting the prognosis of patients after propensity score matching (PSM). RESULTS: The best cut-off point of LNR determined using X-tile 3.6.1 software was 0.16. The patients with LNR < 0.16 and those with LNR≥0.16 showed significant differences in the number of positive lymph nodes, pathological type, T stage and M stage. After 1:1 propensity score matching, the two groups showed no significant difference in the clinical data or pathological parameters. Matched univariate and multivariate COX regression analyses showed that LNR, primary tumor site and M staging were all independent risk factors affecting the prognosis of patients, and among them LNR had the most significant predictive value (LNR < 0.16 vs LNR≥0.16: HR=1.827, 95% CI: 1.140-2.929; P=0.000). The median survival time of patients with LNR < 0.16 was 31 months (95%CI: 22.556-39.444 months), as compared with 16 months (95%CI: 12.989-19.011) in patient with LNR≥0.16 (Log Rank χ2=27.392, P < 0.0001). LNR had a better accuracy than N stage for assessing the patients' prognosis with an area under the ROC curve of 0.617 (95%CI: 0.567-0.666), as compared with 0.515 (95%CI: 0.463-0.565) of N stage (z=3.008, P=0.0026). CONCLUSIONS: LNR≥0.16 is an independent risk factor affecting the prognosis of patients with esophageal cancer and has better prognostic value than N stage.

[Esophageal pH-impedance monitoring of reflux patterns in non-erosive reflux disease, reflux hypersensitivity and functional heartburn].

OBJECTIVE: To analyze the differences in reflux patterns in 24-hour esophageal pH-impedance monitoring in patients with non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) and explore the possible mechanism of symptoms in patients with heartburn and negative endoscopic findings. METHODS: Seventy-nine patients with heartburn as the main symptoms but negative endoscopic findings, including 35 with NERD, 16 with RH and 28 with FH, were enrolled in this study.All the patients underwent 24-h esophageal pH-impedance monitoring and esophagogastroscopy, and the results were compared among the 3 groups. RESULTS: Acid reflux episode was significantly increased and weakly alkaline reflux episode was significantly decreased in NERD group in comparison with RH group and FH group (P < 0.05).The patients in NERD group showed significantly increased total reflux episode, mixed reflux episode, proximal acid reflux episode, proximal weak acid reflux episode, total proximal reflux episode, percentage of proximal acid reflux, percentage of proximal weak acid reflux, and percentage of total proximal reflux as compared with the other two groups (all P < 0.05).Bolus clear time was significantly prolonged in NERD group compared with that in the other two groups (P < 0.05).Analysis of the reflux acidity showed that the percentages of different reflux episodes differed significantly among the 3 groups (P < 0.05);acid reflux was the main reflux in NERD, while weak acid reflux was the main reflux in RH and FH groups, which had also significantly increased weakly alkaline reflux episodes compared with NERD group. CONCLUSIONS: Patients with NERD, RH and FH had different reflux patterns.Acid reflux is predominant in the NERD, while weakly alkaline reflux is significantly increased RH and FH.In patients with normal esophageal acid exposure but without symptoms or without recorded symptoms during esophageal pH-impedance monitoring, analysis of the total reflux episode, mixed reflux episode, proximal acid reflux episode and percentage can help in the differential diagnosis between RH and FH.

Genome-wide identification and expression analyses of R2R3-MYB transcription factor genes from two Orchid species.

MYB transcription factors play important roles in different plant biological processes during plant growth, development and stress response. In this study, 101 (DoMYB1-101) and 99 (PaMYB1-99) R2R3-MYB genes were identified in the genomes of Dendrobium officinale and Phalaenopsis aphrodite, respectively. To classify the isolated candidate genes, the R2R3-MYB genes from A. thaliana were selected as references. As a result, all identified DoMYB and PaMYB genes were classified into 22 subfamilies. Phylogenetic analysis revealed that S21 had the largest number of members of all the subfamilies. The numbers of introns, exons and conserved sequences in all of the identified genes are different. In addition, 20 DoMYB genes from six subfamilies were selected for further analysis of tissue-specific expression and responses to various abiotic stresses treatments. The results showed that all of the DoMYB genes in S4 and S19 subfamilies exhibited the highest relative expression levels in flowers. And five DoMYB genes including DoMYB31, DoMYB40, DoMYB49, DoMYB52 and DoMYB54, responded to the stress response. These results may provide useful information for further studies of the R2R3-MYB gene family.