The Potential of Berberine to Target Telocytes in Rabbit Heart.

A brand-new class of interstitial cells, called telocytes, has been detected in the heart. Telocytes can connect and transmit signals to almost all cardiomyocytes; this is highly interrelated with the occurrence and development of heart diseases. Modern studies have shown that berberine has a therapeutic effect on cardiovascular health. However, berberine's mechanism of action on the cardiovascular system through cardiac telocytes is unclear. Interestingly, 5 µm of berberine remarkably decreased the concentration of intracellular calcium and membrane depolarization in cultured telocytes, upregulated the expression of CX43 and ß-catenin, and downregulated the expressions of TRPV4 and TRPV1. Here, telocytes were identified in the vascular adventitia and intima, endocardium, myocardium, adventitia, and heart valves. Moreover, telocytes were broadly dispersed around cardiac vessels and interacted directly through gap junctions and indirectly through extracellular vesicles. Together, cardiac telocytes interact with berberine and then deliver drug information to the heart. Telocytes may be an essential cellular target for drug therapy of the cardiovascular system.

Effect of administration routes of oxytocin on hemoglobin in neonates with delayed umbilical cord clamping: a multi-centre randomized controlled clinical trial.

PURPOSE: To evaluate the effect of intravenous infusion versus intramyometrial injection of oxytocin on hemoglobin levels in neonates with delayed umbilical cord clamping during cesarean section. METHODS: The multi-centre randomized controlled trial was performed at three hospitals from February to June 2023. Women with term singleton gestations scheduled for cesarean delivery were allocated to receive an intravenous infusion of 10 units of oxytocin or a myometrial injection of 10 units of oxytocin during the surgery. The primary outcome was neonatal hemoglobin at 48 to 96 h after birth. Secondary outcomes were side-effects of oxytocin, postpartum haemorrhage, phototherapy for jaundice, feeding at 1 month, maternal and neonatal morbidity and re-admissions. RESULTS: A total of 360 women were randomized (180 women in each group). The mean neonatal hemoglobin did not show a significant difference between the intravenous infusion group (194.3 ± 21.7 g/L) and the intramyometrial groups (195.2 ± 24.3 g/L) (p = 0.715). Secondary neonatal outcomes, involving phototherapy for jaundice, feeding at 1 month and neonatal intensive care unit admission were similar between the two groups. The maternal outcomes did not differ significantly between the two groups, except for a 200 mL higher intraoperative infusion volume observed in the intravenous group compared to the intramyometrial group. CONCLUSION: Among women undergoing elective cesarean delivery of term singleton pregnancies, there was no significant difference in neonatal hemoglobin at 48 to 96 h after birth between infants with delayed cord clamping, whether the oxytocin was administrated by intravenous infusion or intramyometrial injection. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2300067953 (1 February 2023).

Built environment and schizophrenia re-hospitalization risk in China: A cohort study.

BACKGROUND: Built environment exposure, characterized by ubiquity and changeability, has the potential to be the prospective target of public health policy. However, little research has been conducted to explore its impact on schizophrenia. This study aimed to investigate the association between built environmentand and schizophrenia rehospitalization by simultaneously considering substantial built environmental exposures. METHODS: We recruited eligible schizophrenia patients from Hefei, Anhui Province, China between 2017 and 2019. The main outcome for this study was the time interval until the first recurrent hospital admission occurred within one year after discharge. For each included subject, we estimated the built environment exposures, including population density, walkability, land use mix, green and blue space, public transportation accessibility and road traffic indicator. Lasso (Least Absolute Shrinkage and Selection Operator) analysis was used to select the key variables. Multivariable Cox regression model was applied to obtain hazard ratio (HR) and its corresponding 95% confidence intervals (CI). Further, we also evaluated the joint effects of built environment characteristics on rehospitalization for schizophrenia by Quantile g-computation model. RESULTS: A total of 1564 hospitalized schizophrenia patients were enrolled, with 347 patients (22.2%) had a rehospitalization within one-year after discharge. Multivariable Cox regression analysis indicated that the re-hospitalization rate for schizophrenia would be higher in areas with a high population density (HR: 1.10, 95%CI: 1.04-1.16). Nonetheless, compared to the reference (Q1), participants who lived in a neighborhood with the highest walkability and NDVI (Normalized Difference Vegetation Index) (Q4) had a 76% and 47% lower risk of re-hospitalization within one year (HR:0.24, 95%CI: 0.13-0.45; and 0.53, 95%CI:0.32-0.85), respectively. Moreover, quantile-based g-computation analyses revealed that increased walkability and green space significantly eliminated the adverse effects of population density increases on schizophrenia patients, with a HR ratio of 0.61 (95%CI:0.48,0.79) per one quartile change at the same time. CONCLUSION: Our study provides scientific evidence for the significant role of built environment in schizophrenia rehospitalization, suggesting that optimizing the built environment is required in designing and building a healthy city.

The impact of hazes on schizophrenia admissions and the synergistic effect with the combined atmospheric oxidation capacity in Hefei, China.

OBJECTIVES: Currently, most epidemiological studies on haze focus on respiratory diseases, cardiovascular diseases, etc. However, the relationship between haze and mental health has not been adequately explored. The purpose of this study was to investigate the influence of hazes on schizophrenia admissions and to further explore the potential interaction effect with the combined atmospheric oxidative indices (Ox and Oxwt). METHODS: We collected 5328 cases during the cold season from 2013 to 2015 in Hefei, China. By integrating the Poisson Generalized Linear Models with the Distributed Lag Non-linear Models, the association between haze and schizophrenia admissions was evaluated. The interaction between hazes and two combined oxidation indexes was tested by stratifying hazes and Ox, and Oxwt. RESULTS: Haze was found to be significantly linked to an increased risk of hospitalization for schizophrenia, and a 9-day lag effect on schizophrenia (lag 3-lag 11), with the largest effect on lag 6 (RR = 1.080, 95% confidence interval (CI): 1.046-1.116). Males, females, and <40 y (people under 40 years old) were sensitive to hazes. Furthermore, in the stratified analysis, we found synergies between two combined oxidation indexes and hazes. The interaction relative risk (IRR) and relative excess risk due to interaction (RERI) between Ox and hazes were 1.170 (95% CI: 1.071-1.277) and 0.149 (95% CI: 0.045-0.253), respectively. For Oxwt, the IRR and RERI were 1.179 (95% CI: 1.087-1.281) and 0.159 (95% CI: 0.056-0.263), respectively. It is noteworthy that this synergistic effect was significant in males and <40 y when examining the various subgroups in the interaction analysis. CONCLUSIONS: Our findings suggest that exposure to haze significantly increases the risk of hospitalization for schizophrenia. More significant public health benefits can be obtained by prioritizing haze periods with high combined atmospheric oxidation capacity.

The global burden of schizophrenia and the impact of urbanization during 1990-2019: An analysis of the global burden of disease study 2019.

BACKGROUND AND HYPOTHESIS: The burden of schizophrenia is increasing. Assessing the global distribution of schizophrenia and understanding the association between urbanization factors and schizophrenia are crucial. STUDY DESIGN: We conducted a two-stage analysis utilizing public data from GBD (global burden of disease) 2019 and the World Bank. First, the distribution of schizophrenia burden at the global, regional, and national levels as well as temporal trends was analyzed. Then, four composite indicators of urbanization (including demographic, spatial, economic, and eco-environment urbanization) were constructed from ten basic indicators. Panel data models were used to explore the relationship between urbanization indicators and the burden of schizophrenia. RESULTS: In 2019, there were 23.6 million people with schizophrenia, an increase of 65.85% from 1990, and the country with the largest ASDR (age-standardized disability adjusted life years rate) was the United States of America, followed by Australia, and New Zealand. Globally, the ASDR of schizophrenia rose with the sociodemographic index (SDI). In addition, six basic urbanization indicators including urban population proportion, employment in industry/services proportion, urban population density, the population proportion in the largest city, GDP, and PM2.5 concentration were positively associated with ASDR of schizophrenia, with the largest coefficients being urban population density. Overall, demographic, spatial, economic, and eco-environment urbanization all had positive effects on schizophrenia, and the estimated coefficients indicated that demographic urbanization was the most significant influence. CONCLUSIONS: This study provided a comprehensive description of the global burden of schizophrenia and explored urbanization as a factor contributing to the variation in the burden of schizophrenia, and highlighted policy priorities for schizophrenia prevention in the context of urbanization.

The Cellular Mechanism of Acupuncture for Ulcerative Colitis based on the Communication of Telocytes.

Acupuncture can ameliorate or treat diseases according to the meridian theory in traditional Chinese medicine (TCM); however, its mechanism has not been scientifically clarified. On the other hand, telocytes (TCs) are morphologically in accordance with the meridian system, which needs further cytological investigations and acupuncture confirmation. The present study showed that acupuncture could activate TCs in several ways, alleviating rabbit ulcerative colitis. TCs could cytologically communicate the acupoints, the acupuncture sites in skin with their corresponding large intestine by TC homo-cellular junctions, exosomes around TCs, and TC-mediated nerves or blood vessels. TCs expressed transient receptor potential vanilloid type 4, the mechanosensitive channel protein that can transduce the mechanical stimulation of acupuncture into biochemical signals transferring along the extremely thin and long TCs. Collectively, a cellular mechanism diagram of acupuncture was concluded based on TC characteristics. Those results also confirmed the viewpoint that TCs were the key cells of meridian essence in TCM.

Cellular Evidence for Telocytes Mediating Electroacupuncture to Ameliorate Obesity in Mice.

Electroacupuncture has been generally applied to target obesity, the principle of which is based on the meridian in traditional Chinese medicine. Although Telocytes (TCs) have been reported as the potential essence of meridians, their specific role in the electroacupuncture treatment of obesity remains unclear. Thus, we investigated the cellular evidence for TC-mediated electroacupuncture to alleviate obesity. Mice were divided into three groups as follows: electroacupuncture group (EA), control group (CG), and normal group (NG). The present study showed that the weight of perirenal white adipose tissue (rWAT), the serum level of total cholesterol, and the low-density lipoprotein cholesterol were all significantly decreased after electroacupuncture. Ultrastructurally, the prolongations (telopodes, Tps) of TCs were in direct contact with adipocytes, and lipid droplets were distributed on the surface of Tps. The proportions of double-positive fluorescent areas of TCs (CD34 and PDGFRα) were significantly elevated with concomitant elongated Tps in EA mice, as compared to those in CG mice. The expression of Cx43 and CD63 (gap junction and exosome markers) was significantly enhanced. These characteristics facilitated the transmission of electroacupuncture stimulation from skin to rWAT. We conclude that electroacupuncture relieved obesity by activating TCs morphologically, upregulating the gap junctions between TCs, and increasing the exosomes around TCs.

The modification of air particulate matter on the relationship between temperature and childhood asthma hospitalization: An exploration based on different interaction strategies.

The influence of temperature on childhood asthma was self-evident, yet the issue of whether the relationship will be synergized by air pollution remains unclear. The study aimed to investigate whether the relationship between short-term temperature exposure and childhood asthma hospitalization was modified by particulate matter (PM). Data on childhood asthma hospitalization, meteorological factors, and air pollutants during 2013-2016 in Hefei, China, were collected. First, a basic Poisson regression model combined with a distributed lag nonlinear model was used to assess the temperature-childhood asthma hospitalization relationship. Then, two interactive strategies were applied to explore the modification effect of PM on the temperature-childhood asthma hospitalization association. We found a greater effect of cold (5th percentile of temperature) on asthma during days with higher PM2.5 (RR: 2.16, 95% CI: 1.38, 3.38) or PM10 (RR: 1.87, 95% CI:1.20, 2.91) than that during days with lower PM2.5 (RR: 1.64, 95% CI: 1.06, 2.54) or PM10 (RR: 1.52, 95% CI: 0.98, 2.36). In addition, we observed a greater modification effect of PM2.5 on the cold-asthma association than did PM10, with a per 10 µg/m3 increase in PM2.5 and PM10 associated with increases of 0.065 and 0.025 for the RR corresponding to the 5th temperature percentile, respectively. For the temperature-related AF, moderate cold showed the largest change magnitude with the PM levels rising compared with other temperature ranges. For the subgroup, Females and those aged 6-18 years were more sensitive to the modification effect of PM2.5 or PM10 on the cold-asthma association. Our findings demonstrated that particulate matter could modify the associations between temperature and childhood asthma hospitalization.

Association between exposure to a mixture of metals, parabens, and phthalates and fractional exhaled nitric oxide: A population-based study in US adults.

The effects of environmental endocrine-disrupting chemicals (EDCs) (e.g., phthalates) on fractional exhaled nitric oxide (FeNO) in children have received much attention. However, few studies evaluated this relationship in adults, and the previous studies have considered only a unitary exposure or a set of similar exposures instead of mixed exposures, which contain complicated interactions. We aimed to evaluate simultaneously the relationship between three types of EDCs (six phthalate metabolites and two parabens in urine, two heavy metals in blood) and FeNO (as a continuous variable) in adults. Data of adults aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES, 2007-2012) were collected and analyzed. The generalized linear (GLM) regression model was used to explore the association of chemicals with FeNO. The combined effect of 10 chemicals on the overall association with FeNO was evaluated by the weighted quantile sum regression (WQS) model. In addition, The Bayesian kernel machine regression (BKMR) model was explored to investigate the interaction and joint effects of multiple chemicals with FeNO. Of the 3296 study participants ultimately included, among the GLMs, we found that mercury (Hg) (ß = 0.84, 95%CI:0.32-1.36, FDR = 0.01) and methyl paraben (MPB) (ß = 0.47, 95%CI:0.16-0.78, FDR = 0.015) were positively correlated with FeNO. In the WQS model, the combined effect of chemicals almost had a significantly positive association with FeNO and the top three contributors to the WQS index were Hg (40.2%), MECPP (22.1%), and MPB (19.3%). BKMR analysis showed that there may be interactions between MPB and Hg, Mono (carboxyoctyl) phthalate (MCOP) and Hg and the overall effect of the mixture showed a positive correlation with FeNO. In conclusion, our study strengthens the credibility of the view that EDCs can affect respiratory health. In the future, we should be particularly careful with products containing Hg, MECPP, MPB, and MEHP for the prevention of respiratory diseases.

Association between sequential extreme precipitation-heatwaves events and hospitalizations for schizophrenia: The damage amplification effects of sequential extremes.

OBJECTIVES: In the context of frequent global extreme weather events, there are few studies on the effects of sequential extreme precipitation (EP) and heatwaves (HW) events on schizophrenia. We aimed to quantify the effects of the events on hospitalizations for schizophrenia and compare them with EP and HW alone to explore the amplification effect of successive extremes on health loss. METHODS: A time-series Poisson regression model combined with a distributed lag non-linear model was applied to estimate the association between sequential EP and HW events (EP-HW) and schizophrenia hospitalizations. The effects of EP-HW with different intervals and intensities on the admission of schizophrenia were compared. In addition, we calculated the mean attributable fraction (AF) and attributable numbers (AN) per exposure of extreme events to reflect the amplification effect of sequential extreme events on health hazards compared with individual extreme events. RESULTS: EP-HW increased the risk of hospitalization for schizophrenia, with significant effects lasting from lag0 (RR and 95% CI: 1.150 (1.041-1.271)) to lag11 (1.046 (1.000-1.094)). Significant associations were found in the subgroups of male, female, married people, and those aged≥ 40 years old. Shorter-interval (0-3days) or higher-intensity EP-HW (both precipitation ≥ P97.5 and mean temperature ≥ P97.5) had a longer lag effect compared to EP-HW with longer intervals or lower intensity. We found that the mean AF and AN caused by each exposure to EP-HW (AF: 0.074% (0.015%-0.123%); AN: 4.284 (0.862-7.118)) were higher than those induced by each exposure to HW occurring alone (AF:0.032% (0.004%-0.058%); AN:1.845 (0.220-3.329)). CONCLUSIONS: Sequential extreme precipitation-heatwaves events significantly increase the risk of hospitalizations for schizophrenia, with greater impact and disease burden than independently occurring extremes. The impact of consecutive extremes is supposed to be considered in local sector early warning systems for comprehensive public health decision-making.

Seasonal characteristics of temperature variability impacts on childhood asthma hospitalization in Hefei, China: Does PM2.5 modify the association?

OBJECTIVES: Evidence of childhood asthma hospitalizations associated with temperature variability (TV) and the attributable risk are limited in China. We aim to use a comprehensive index that reflected both intra- and inter-day TV to assess the TV-childhood asthma relationship and disease burden, further to identify seasonality vulnerable populations, and to explore the effect modification of PM2.5. METHODS: A quasi-distributed lagged nonlinear model (DLNM) combined with a linear threshold function was applied to estimate the association between TV and childhood asthma hospitalizations during 2013-2016 in Hefei, China. Subgroup analysis was conducted by age and sex. Disease burden is reflected by the attributable fraction and attributable number. Besides, modifications of PM2.5 were tested by introducing the cross-basis of TV and binary PM2.5 as an interaction term. RESULTS: The risk estimates peaked at TV0-3 and TV0-4 in the cool and the warm season separately, with RR of 1.051 (95%CI: 1.021-1.081) and 1.072 (95%CI: 1.008-1.125), and the effects lasted longer in the cool season. The school-age children in the warm season and all subgroups except pre-school children in the cool season were vulnerable to TV. It is estimated that the disease burden related to TV account for 6.2% (95% CI: 2.7%-9.4%) and 4% (95% CI: 0.6%-7.1%) during the cool and warm seasons in TV0-3. In addition, the risks of TV were higher under the high PM2.5 level compared with the low PM2.5 level in the cool season, although no significant differences between them. CONCLUSIONS: TV exposure significantly increases the risk and disease burden of childhood asthma hospitalizations, especially in the cool season. More medical resources should be allocated to school-age children. Giving priority to pay attention to TV in the cool season in practice could obtain the greatest public health benefits and those days with high TV and high PM2.5 need more attention.

Clinical outcomes of patients with pigmented villonodular synovitis of the shoulder after arthroscopic synovectomy.

BACKGROUND: Shoulder pigmented villonodular synovitis (PVNS) is a severe clinical condition, while few studies have focused on this situation due to its rarity. This study was to investigate the efficacy of arthroscopic treatment of patients diagnosed with shoulder PVNS. METHODS: From Jan 1st, 2010 to Dec. 31st, 2019, 6 patients (5 females and 1 male) diagnosed with shoulder PVNS underwent arthroscopic synovectomy in our hospital and combined rotator cuff repair was performed in 3 of them. The outcomes of this study include Constant score, Visual Analogue Scale (VAS), University of California, Los Angeles (UCLA) score and American Shoulder and Elbow Surgeons (ASES) score. The data were retrieved from the patients' medical records. RESULTS: With a mean follow-up of 52.0 months (range, 28-92 months), the mean difference of Constant, VAS, UCLA and ASES scores were 27.83 ± 21.60, 2.83 ± 2.56, 11.67 ± 10.93 and 17.83 ± 25.35, respectively. Statistically significant improvements were detected in all the patient-reported outcomes except ASES score. One of the patients suffered from recurrence. Two patients suffered from mild complications after the surgeries while both of them achieved satisfactory recovery finally. CONCLUSION: Arthroscopic synovectomy in the setting of shoulder PVNS can improve patients' function. A concurrent rotator cuff repair is recommended if it is needed. The conclusion still needs testifying by further high-quality research with larger sample size.

Is higher ambient temperature associated with acute appendicitis hospitalizations? A case-crossover study in Tongling, China.

Existing studies suggested that ambient temperature may affect the attack of acute appendicitis. However, the identification of the quantitative effect and vulnerable populations are still unknown. The purposes of this study were to quantify the impact of daily mean temperature on the hospitalization of acute appendicitis and clarify vulnerable groups, further guide targeted prevention of acute appendicitis in Tongling. Daily data of cases and meteorological factors were collected in Tongling, China, during 2015-2019. Time stratified case-crossover design and conditional logistic regression model were used to evaluate the odds ratio (OR) of ambient temperature on hospitalizations for acute appendicitis. Stratified analyses were performed by sex, age, and marital status. The odds ratio (OR) of hospitalizations for acute appendicitis increased by 1.6% for per 1 ℃ rise in mean temperature at lag3[OR = 1.016, 95% confidence interval (CI): 1.004-1.028]. In addition, our results suggest it is in the women that increased ambient temperature is more likely to contribute to acute appendicitis hospitalizations; we also found that the married are more susceptible to acute appendicitis hospitalizations due to increased ambient temperature than the unmarried; people in the 21-40 years old are more sensitive to ambient temperature than other age groups. The significant results of the differences between the subgroups indicate that the differences between the groups are all statistically significant. The elevated ambient temperatures increased the risk of hospitalizations for acute appendicitis. The females, married people, and patients aged 21-40 years old were more susceptible to ambient temperature. These findings suggest that more attention should be paid to the impact of high ambient temperature on acute appendicitis in the future.

Pre-gelatinization and cellulase addition improve fermentation performance and antioxidant activity of black rice wine.

BACKGROUND: Black rice contains a variety of bioactive substances that contribute to the high nutritional value of black rice wine (BRW). However, the dense bran layer of black rice retards the fermentation rate and reduces the dissolution of active components. Hence, this study aims to investigate the effects of pre-gelatinization (PG) before cooking and cellulase (CE) addition during fermentation on the fermentation performance of BRW and its antioxidant activity. RESULTS: PG combined with CE treatments (PGCE) increases the alcohol content, free amino acid content, volatile flavor content and total antioxidant activity of BRW by 90.81%, 15.36%, 38.05% and 19.56%, respectively, compared with the control group. Scanning electron microscopy, low-field nuclear magnetic resonance and texture properties analysis indicate that PG treatment increases gelatinization degree of starch during cooking, decreases bound water content in cooked black rice and promotes unbound water release. CE destroys the aleurone layer structure, facilitates the release of unbound water and the exposure of rice starch, thus increasing the reaction area and extravasation content significantly, which is beneficial to microbial growth and fermentation. Incomplete aleurone layer also promotes the dissolution of anthocyanins, phenols and other active substances, increasing the antioxidant activities of BRW. CONCLUSION: PG and CE treatments reduce the fermentation time and improve the quality of BRW by destroying the black rice structure. © 2022 Society of Chemical Industry.

Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer.

Gastric cancer has the fifth highest incidence of disease and is the third leading cause of cancer-associated mortality in the world. The etiology of gastric cancer is complex and needs to be fully elucidated. Thus, it is necessary to explore potential pathogenic genes and pathways that contribute to gastric cancer. Gene expression profiles of the GSE33335 and GSE54129 datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were compared and identified using R software. The DEGs were then subjected to gene set enrichment analysis and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Survival analyses based on The Cancer Genome Atlas database were used to further screen the essential DEGs. A knockdown assay was performed to determine the function of the candidate gene in gastric cancer. Finally, the association between the candidate gene and immune-related genes was investigated. We found that GPNMB serves as an essential gene, with a high expression level, and predicts a worse outcome of gastric cancer. Knockdown of GPNMB inhibited gastric cancer cell proliferation and migration. In addition, GPNMB may augment the immunosuppressive ability of gastric cancer by recruiting immunosuppressive cells and promoting immune cell exhaustion through PI3K/AKT/CCL4 signaling axis. Collectively, these data suggest that GPNMB acts as an important positive mediator of tumor progression in gastric cancer, and GPNMB could exert multimodality modulation of gastric cancer-mediated immune suppression.

4.1B suppresses cancer cell proliferation by binding to EGFR P13 region of intracellular juxtamembrane segment.

BACKGROUND: Gastric cancer (GC) has high incidence and mortality worldwide. However, the underlying mechanisms that regulate gastric carcinogenesis are largely undefined. 4.1B is an adaptor protein found at the interface of membrane and the cytoskeleton. Previous studies demonstrated that 4.1B serves as tumor suppressor. RESULTS: We showed that 4.1B expression was decreased or lost in most GC patients. The expression pattern of it was tightly correlated with tumor size, TNM stage and overall survival (OS). We further showed that 4.1B inhibited the proliferation of two GC cell lines, MGC-803 and MKN-45, by impeding the EGFR/MAPK/ERK1/2 and PI3K/AKT pathways. A similar phenotype was also observed in immortalized mouse embryonic fibroblasts (MEF) derived from wild type (WT) and 4.1B knock-out (BKO) mice. Additionally, immunofluorescence (IF) staining and Co-IP showed that protein 4.1B bound to EGFR. Furthermore, the FERM domain of 4.1B interacted with EGFR through the initial 13 amino acids (P13) of the intracellular juxtamembrane (JM) segment of EGFR. The binding of 4.1B to EGFR inhibited dimerization and autophosphorylation of EGFR. CONCLUSION: Our present work revealed that 4.1B plays important regulatory roles in the proliferation of GC cells by binding to EGFR and inhibiting EGFR function through an EGFR/MAPK/ERK1/2 pathway. Our results provide novel insight into the mechanism of the development and progression of GC.

Enhanced magnifying endoscopy for differential diagnosis of superficial gastric lesions identified with white-light endoscopy.

BACKGROUND: Various techniques using magnifying endoscopy (ME) and chromoendoscopy are being developed to enhance images of gastrointestinal tumor. The aim of this study was to evaluate the diagnostic performance of ME enhanced by acetic acid-indigo carmine mixture (ME-AIM) and ME enhanced with narrow-band imaging (ME-NBI) for differential diagnosis of superficial gastric lesions identified with conventional white-light endoscopy (WLE). METHODS: Patients with superficial gastric lesions picked up with WLE were enrolled in the study. ME-NBI and ME-AIM were used to further characterize the lesions. All images of the lesions were evaluated by four skilled endoscopists blinded to the clinical data. The microarchitectural patterns in the lesions were analyzed with reference to the "VS classification" system. RESULTS: A total of 643 lesions (mean diameter, 7 mm) from 508 patients (316 men, 192 women; mean age, 63 years) were evaluated. Pathologically, 24 of the 643 lesions were diagnosed as gastric cancer; the others were noncancerous lesions. For diagnosis of gastric cancer, the negative predictive value of each of the three magnified findings (irregular microvascular pattern, irregular microsurface pattern, and demarcation line) was high (nearly 100 %). According to the "VS classification" system, either ME-NBI or ME-AIM had a higher specificity (99.5 % or 99.4 % vs. 89.5 %, P < 0.001) and accuracy (99.2 % or 98.9 % vs. 89.0 %, P < 0.001) than WLE, and ME-AIM was not superior to ME-NBI for identifying carcinoma. CONCLUSIONS: Enhanced ME is useful for correctly diagnosing early gastric cancer, and in contrast with ME-AIM, ME-NBI is a more feasible and efficient method for clinical practice.

Ischemia preconditioning protects rat submandibular glands from ischemia/reperfusion injuries.

To investigate the effects of ischemia/reperfusion on rat submandibular glands without denervation and the possible protective effects of ischemia preconditioning on the glands that experienced ischemia/reperfusion, in-situ ischemia/reperfusion and ischemia preconditioning experimental models of submandibular glands of healthy male Wistar rats were conducted. For ischemia/reperfusion groups, the glands were subjected to 90 min of ischemia without denervation, followed by 1, 12, 24, or 72 h of reperfusion. Ischemia preconditioning was achieved by 3 min of ischemia following 3 min of reperfusion, performed three times before ischemia/reperfusion. Salivary secretion, histological changes, alterations of tight junctions, myeloperoxidase activity, cellular apoptosis, and reactive oxygen species levels were detected. In ischemia/reperfusion glands, rising acute-inflammation responses, reduced tight-junction width, and increased myeloperoxidase activity, reactive oxygen species levels, and apoptotic cell numbers were observed, along with secretory dysfunction, especially at 1 and 12 h post-reperfusion, which seemed to gradually return to normal by 72 h post-reperfusion. In contrast, ischemia preconditioning showed the potential to ameliorate the injury-stress responses caused by ischemia/reperfusion. Our study revealed that ischemia/reperfusion could cause a series of injury-stress responses and ultimately lead to hyposecretion, independently of the parasympathetic nerve supply, which might play an important role in the early-phase dysfunction of the transplanted glands. Ischemia preconditioning could protect the involved glands and improve ischemia/reperfusion-induced hyposecretion.