[Preliminary study of the fourth-generation CAR-T cells targeting CS1 in the treatment of refractory and recurrent multiple myeloma].

Objective: To design the fourth-generation chimeric antigen receptor-T (CAR-T) cells that secrete interleukin-7 (IL7) and chemokine C legend 19 (CCL19) on the basis of the second-generation CAR, and to analyze and compare the differences in proliferation, chemotaxis, tumor cell clearance and persistence in the microenvironment of multiple myeloma (MM) between them. Methods: The fourth-generation CAR vector plasmid was constructed by using 2A self-cleaving peptide technology. The third-generation lentiviral packaging system was used to prepare high-titer lentivirus. Flow cytometry was used to monitor the transduction efficiency of lentivirus and the subtype changes of CAR-T cells. The enzyme-linked immunosorbent assay (ELISA) was used to quantify the IL7 and CCL19 secreted by CAR-T cells.The calculation of absolute number of CAR-T cells during culture was used to analysis cell proliferation activity. Transwell migration assay was used to verify the chemotactic ability of CAR-T cells. The specific killing activity of CAR-T cells was detected by using the luciferase bioluminescence method. The NOD-Prkdcem26Cd52Il2rgem26Cd22/Nju (NOD) mouse xenograft model was used to verify the anti-myeloma activity and safety of CAR-T cells in vivo. Results: Flow cytometry results showed that the stable CAR expression rates of the second-generation anti-CS1 CAR-T and fourth-generation anti-CS1-IL7-CCL19 CAR-T cells were (91.50±0.29)% and (46.7±0.12)%, respectively. CAR-T cells were successfully constructed. Subtype analysis demonstrated that the ratio of stem memory T cell (TSCM) in anti-CS1-IL7-CCL19 CAR-T cells was (67.58±0.59)%, which was significantly higher than (50.74 ± 1.01)% of anti-CS1 CAR-T (P=0.000 1), with more strong immune memory function and better durability. Anti-CS1-IL7-CCL19 CAR-T cells can continuously secrete IL7 and CCL19 compared to MOCK-T and anti-CS1 CAR-T (P<0.000 1). The number of anti-CS1-IL7-CCL19 CAR-T cells reached (22.77±0.79)×10(6) on the 9th day after lentivirus transduction, which was significantly higher than (9.40±0.79)×10(6) of anti-CS1 CAR-T cells (P=0.000 1), with stronger proliferation ability. The number of chemotaxis cells of anti-CS1-IL7-CCL19 CAR-T cells to reactive T cells was (109.0±4.04), which was significantly higher than (9.33±1.20) of MOCK-T (P<0.000 1) and (7.33±0.88) of anti-CS1 CAR-T (P<0.000 1), with stronger chemotactic ability. The specific killing activity showed that both anti-CS1-IL7-CCL19 CAR-T and anti-CS1 CAR-T cells had specific killing efficacies when compared with the MOCK-T cells (P<0.000 1). Animal experiment indicated that anti-CS1-IL7-CCL19 CAR-T cells significantly reduced the tumor burden (P<0.000 1) and extended the overall survival time (P=0.006 1) of tumor-bearing mice. Conclusions: The anti-CS1-IL7-CCL19 CAR-T cells designed in this study show stronger proliferative activity, chemotactic ability, and durability without affecting the anti-myeloma activity in vivo and in vivo, which provides strategies for overcoming the defects of low survival rate, poor durability and inhibition by tumor microenvironment of traditional CAR-T cells, and offers preliminary experimental basis for the clinical application of the fourth-generation CAR-T cells.

The Y-chromosome F haplogroup contributes to the development of Barrett's esophagus-associated esophageal adenocarcinoma in a white male population.

Barrett's esophagus (BE) is a metaplastic condition of the distal esophagus, resulting from longstanding gastroesophageal reflux disease (GERD). BE predisposes for the highly malignant esophageal adenocarcinoma (EAC). Both BE and EAC have the highest frequencies in white males. Only a subset of patients with GERD develop BE, while <0.5% of BE will progress to EAC. Therefore, it is most likely that the development of BE and EAC is associated with underlying genetic factors. We hypothesized that in white males, Y-chromosomal haplogroups are associated with BE and EAC. To investigate this we conducted a multicenter study studying the frequencies of the Y-chromosomal haplogroups in GERD, BE, and EAC patients. We used genomic analysis by polymerase chain reaction and restriction fragment length polymorphism to determine the frequency of six Y-chromosomal haplogroups (DE, F(xJ,xK), K(xP), J, P(xR1a), and R1a) between GERD, BE, and EAC in a cohort of 1,365 white males, including 612 GERD, 753 BE patients, while 178 of the BE patients also had BE-associated EAC. Univariate logistic regression analysis was used to compare the outcomes. In this study, we found the R1a (6% vs. 9%, P = 0.04) and K (3% vs. 6%, P = 0.035) to be significantly underrepresented in BE patients as compared to GERD patients with an odds ratio (OR) of 0.63 (95% CI 0.42-0.95, P = 0.03) and of 0.56 (95% CI 0.33-0.96, P = 0.03), respectively, while the K haplogroup was protective against EAC (OR 0.30; 95% CI 0.07-0.86, P = 0.05). A significant overrepresentation of the F haplogroup was found in EAC compared to BE and GERD patients (34% vs. 27% and 23%, respectively). The F haplogroup was found to be a risk factor for EAC with an OR of 1.5 (95% CI 1.03-2.19, P = 0.03). We identified the R1a and K haplogroups as protective factors against development of BE. These haplogroups have low frequencies in white male populations. Of importance is that we could link the presence of the predominantly occurring F haplogroup in white males to EAC. It is possible that this F haplogroup is associated to genetic variants that predispose for the EAC development. In future, the haplogroups could be applied to improve stratification of BE and GERD patients with increased risk to develop BE and/or EAC.

Interpretation of volumetric laser endomicroscopy in Barrett's esophagus using image enhancement software.

Image interpretation of Barrett's esophagus (BE) with volumetric laser endomicroscopy (VLE) can be enhanced by image processing software that highlights established features using a color-graded scale (intelligent real-time image segmentation, IRIS). This study aims to provide a description of IRIS features of various gastroesophageal tissue types using histologic correlation. A database of 80 VLE laser-marked targets with histologic correlation was reviewed for various tissue types. IRIS was applied off-line to the VLE scans, laser-marked targets were identified, and feature review was performed. Squamous epithelium targets (N = 7) showed IRIS layered architecture with lack of surface hyper-reflectivity and epithelial glands. Gastric cardia targets (N = 10) showed absent layering (100%) and surface hyper-reflectivity with epithelial glands (40%). Nondysplastic BE targets (N = 39) showed surface hyper-reflectivity (64%), epithelial glands (51%), and lack of layering (74%). Targets of BE with early neoplasia (N = 24), showed surface hyper-reflectivity (96%), epithelial glands (67%), and lack of layering (96%). IRIS features that characterize each tissue type appear to mirror the nonenhanced VLE counterparts that define them.

Comparative assessment of atherosclerosis of rabbit femoral artery by Duplex Ultrasound Scanning, Optical Coherence Tomography and Fractional Flow Reserve.

Duplex Ultrasound Scanning (DUS), Frequency-domain optical coherence tomography (FD-OCT) and fractional flow reserve (FFR) remarkably shape our understanding of the significance of coronary stenosis. The present study aimed to compare the assessment results of the atherosclerotic lesions in rabbit superficial femoral artery by DUS with that of FD-OCT and FFR. A total of 20 atherosclerotic lesions were analyzed. Morphological assessments were prospectively compared through DUS, FD-OCT and quantitative superficial femoral angiography (QFA). In addition, the correlation between DUS derived lesion parameters and FFR was determined. The results show that, compared with FD-OCT and QFA, DUS detected larger reference diameter and higher percent stenosis. However, the minimal lumen diameter (MLD) and distance from profunda femoris to MLD were equivalent measured by the three imaging modalities. There was a poor correlation between FFR and DUS-derived percent diameter stenosis (R2=0.198, P=0.049). In conclusion, hemodynamic significance of lesions assessed by FFR was only related with percent diameter stenosis measured by DUS.

Clutch cutter is a safe device for performing endoscopic submucosal dissection of superficial esophageal neoplasms: a western experience.

Although the endoscopic submucosal dissection (ESD) has been established to be more efficacious in the treatment of superficial gastrointestinal neoplasia than the piecemeal resection, its use is still limited due to the concern about serious adverse events particularly in the west. Newer ESD knives have been developed that have been said to be safer than the first-generation devices. We aimed to report a Western single center experience regarding the initial safety and performance of ESD for superficial esophageal neoplasia treated with the Clutch Cutter (DP2618DT; Fujifilm Corporation, Tokyo, Japan). Our main outcome was safety in terms of bleeding or perforation. Secondary outcomes included en bloc resection and the R0 resection. Fourteen patients with superficial esophageal neoplasia underwent 15 ESDs using the Clutch Cutter. The mean age was 65 ± 16.7 years and 10 (71.4%) males. Eight (57%) patients had esophageal adenocarcinoma, 3 (21.4%) had high-grade dysplasia, 1 (7%) had nodular low-grade dysplasia, and 2 (14.3%) had squamous cell carcinoma. Mild anticipated intraprocedural bleeding was present with most procedures. However, no significant postoperative bleeding or perforation was encountered. One patient had mild chest pain postprocedure. En bloc resection was achieved in all lesions 100%. Histological R0 was achieved in 5/12 lesions (41.6%). The mean length of the resected area was 24.8 ± 13 mm (IQR: 17-30 mm). All patients were safely discharged home after overnight observation. In conclusion, this is the largest series of esophageal ESD using the multimodal Clutch Cutter in the United States; we found that the device effectively achieved en bloc resection of superficial esophageal neoplasia without significant adverse events. The use of the Clutch Cutter should be considered as one option to minimize adverse events during ESD in the Western population.

Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma.

Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

Quadruplex priming amplification for the detection of mRNA from surrogate patient samples.

Simple and rapid methods for detecting mRNA biomarkers from patient samples are valuable in settings with limited access to laboratory resources. In this report, we describe the development and evaluation of a self-contained assay to extract and quantify mRNA biomarkers from complex samples using a novel nucleic acid-based molecular sensor called quadruplex priming amplification (QPA). QPA is a simple and robust isothermal nucleic acid amplification method that exploits the stability of the G-quadruplex nucleotide structure to drive spontaneous strand melting from a specific DNA template sequence. Quantification of mRNA was enabled by integrating QPA with a magnetic bead-based extraction method using an mRNA-QPA interface reagent. The assay was found to maintain >90% of the maximum signal over a 4 °C range of operational temperatures (64-68 °C). QPA had a dynamic range spanning four orders of magnitude, with a limit of detection of ~20 pM template molecules using a highly controlled heating and optical system and a limit of detection of ~250 pM using a less optimal water bath and plate reader. These results demonstrate that this integrated approach has potential as a simple and effective mRNA biomarker extraction and detection assay for use in limited resource settings.

Predictive biomarkers for Barrett's esophagus: so near and yet so far.

Barrett's esophagus (BE) is the strongest risk factor for the development of esophageal adenocarcinoma. However, the risk of cancer progression is difficult to ascertain in individuals, as a significant number of patients with BE do not necessarily progress to esophageal adenocarcinoma. There are several issues with the current strategy of using dysplasia as a marker of disease progression. It is subject to sampling error during biopsy acquisition and interobserver variability among gastrointestinal pathologists. Ideal biomarkers with high sensitivity and specificity are needed to accurately detect high-risk BE patients for early intervention and appropriate cost-effective surveillance. To date, there are no available molecular tests in routine clinical practice despite known genetic and epigenetic aberrations in the Barrett's epithelium. In this review, we present potential biomarkers for the prediction of malignant progression in BE. These include markers of genomic instability, tumor suppressor loci abnormalities, epigenetic changes, proliferation markers, cell cycle predictors, and immunohistochemical markers. Further work in translating biomarkers for routine clinical use may eventually lead to accurate risk stratification.

[Effects of neonatal stimulator of interferon genes innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine in infants].

Objective: To explore the effects of neonatal stimulator of interferon genes (STING) innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine (HepB) in their infants. Methods: From November 2019 to June 2022, HBsAg-positive mothers and their infants in the Third People's Hospital of Taiyuan were recruited as the study subjects. The epidemiological and clinical data were collected by questionnaire survey and medical records review. The key molecular proteins of STING innate immune signaling pathway (STING, pIRF3) and immune cells associated with vaccine response (DC, T and B and plasma cells) in neonatal cord blood were detected by flow cytometry. Follow up was conducted for infants for 1-2 months after the full vaccination of HepB. Serum hepatitis B surface antibody (anti-HBs) was detected by chemiluminescence microparticle immunoassay. Unconditional logistic regression model, nomogram and Bayesian network model were used to evaluate the effect of STING innate immune signaling pathway on non/hypo-response to HepB and related factors in infants, and the relationship between various factors. Results: A total of 195 pairs of HBsAg-positive mothers and infants were recruited, the rate of non/hypo-response to HepB in the infants was 12.31% (24/195). High maternal HBV DNA load, low expression of neonatal STING, low expression of pIRF3 and low percentage of plasma cells were risk factors for non/hypo-response to HepB in the infants (OR=4.70, 3.46, 3.18 and 2.20, all P<0.05). The nomogram constructed by these factors had good predictive efficacy (area under curve=0.81, 95%CI: 0.63-0.83). The results of Bayesian network model showed that the infants with a high maternal HBV DNA load had a higher conditional probability of low STING expression (62.50%) and a higher conditional probability of low pIRF3 expression (58.54%). The conditional probabilities of low expression of DC, T, B and plasma cells were 53.16%, 60.20%, 68.42% and 57.14%, respectively. Conclusion: Maternal HBV DNA might inhibit STING innate immune signaling pathways in infants and immune cells associated with HepB response, resulting in non/hypo-response to HepB in infants of HBsAg-positive mothers.

Photodynamic therapy of intraductal papillary mucinous neoplasm.

Intraductal papillary mucinous neoplasm (IPMN) of the main pancreatic duct is usually treated by surgical excision of the affected pancreas. Nonoperative ablative therapies have not been described. We treated IPMN of the pancreatic duct with photodynamic therapy (PDT) in a patient who was a poor operative candidate. Porfimer sodium was administered intravenously, and laser light was delivered by a diffusing catheter placed in the pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP). Imaging and biopsy findings of IPMN resolved after PDT, and symptoms also resolved. Metastatic cancer was diagnosed 2 years after PDT had been initiated. Pancreatic PDT was well tolerated in this case, and may be a therapeutic option for selected patients with IPMN of the main pancreatic duct.

Endoscopic ablative therapy for Barrett's esophagus: a potential cause of eosinophilic esophagitis.

Markedly increased esophageal eosinophils are associated with allergy- or reflux-based eosinophilic esophagitis. Other known disorders that cause this entity are unusual. To characterize the clinical, endoscopic, and histological findings of patients who develop marked esophageal eosinophilic infiltration after ablative therapy for Barrett's dysplasia. All patients who underwent endoscopic ablation of Barrett's esophagus between 1991 and 2009 with photodynamic therapy or radio frequency were screened for a pathologic descriptor of 'eosinophils' on biopsy. Patients whose biopsies demonstrated >15 eosinophils per high power (HPF) field in squamous epithelium after ablation were reviewed and included in the study group. Thirteen of 385 (3.4%) patients underwent ablation for Barrett's esophagus and subsequently had large numbers of intraepithelial eosinophils. All patients had long segment Barrett's (mean 8.0 cm) with low- or high-grade dysplasia or adenocarcinoma. All had undergone photodynamic therapy as their form of ablation. No patients had typical symptoms or endoscopic findings of eosinophilic esophagitis. Eleven patients were on proton pump inhibitors. The time between ablation and onset of esophageal eosinophilia ranged from 83 to 692 days. Intraepithelial eosinophil counts ranged from 30 to 150/HPF (mean 90). The majority of cases showed eosinophilic degranulation, spongiosis, increased papillary height, and basal zone thickening. The natural history of esophageal eosinophilia was variable after ablation, persisting consistently or sporadically on biopsy for up to 6 years. Ablation for Barrett's dysplasia can be followed rarely by eosinophil infiltrates with a histological resemblance to allergy-based eosinophilic esophagitis, but lacking dysphagia. The pathophysiology is unknown.

Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus.

The management of high-grade dysplasia in Barrett's esophagus has clearly changed over recent years. The risk of cancer development is still substantial, with about one in three patients developing cancer, but a number of patients do not develop cancer. The nature of high-grade dysplasia has also been genetically elucidated with more evidence of chromosomal instability being present at this stage than previously thought. Therapy of the condition has evolved more toward endoscopic therapy, given the good results of radio-frequency ablation and photodynamic therapy in eliminating dysplasia and decreasing cancer development in randomized controlled trial. The best candidates for treatment include compliant patients that have relatively short segments of Barrett's esophagus, an anatomically straight segment, lack of nodularity, and an intact p16. However, even with excellent long-term results similar to surgical resection, the risk of recurrence is present in over 14% of patients, which indicates that there will be a need to continue surveillance endoscopy in these patients.

Endoscopic diagnosis and resection of esophageal granular cell tumors.

Granular cell tumors (GCT) are uncommon neoplasms. There is controversy regarding the endoscopic diagnosis and treatment of esophageal GCT. We studied the endoscopic diagnosis and management of esophageal GCT among 23 patients identified in a single-institution pathology database. Medical records, pathology, and endoscopic images were reviewed. All patients underwent endoscopy and endoscopic ultrasonography (EUS), and endoscopic resection was performed in 10 patients. Seven of 23 patients had more than one esophageal GCT. Only six lesions exhibited a classic yellow discoloration. Among patients with a single GCT, three, four, and nine lesions were located in the proximal, middle, and distal esophagus, respectively. EUS showed hypoechoic, smooth-edged lesions usually confined to deep mucosa and submucosa. Standard forceps biopsy was diagnostic in 19 of 23 patients (83%). Ten GCT ≤ 10 mm in diameter underwent successful endoscopic mucosal resection without complication. The endoscopic appearance, location, and number of esophageal GCT are highly variable. Histological proof is still necessary for the differential diagnosis of this rare neoplasm. Endoscopic forceps biopsy is usually diagnostic. Endoscopic resection appears safe and effective in selected cases with lesions ≤ 10 mm.

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND AND STUDY AIMS: The AIM-II Trial included patients with nondysplastic Barrett's esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS: Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barrett's esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS: Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS: In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

Collapsin response mediator protein-2 is a calmodulin-binding protein.

Collapsin response mediator protein-2 (CRMP-2) plays a crucial role in axonal guidance and neurite outgrowth during neural development and regeneration. We have studied the interaction between calmodulin (CaM) and CRMP-2 and how Ca(2+)/CaM binding modulates the biological functions of CRMP-2. We have shown that CRMP-2 binds to CaM directly in a Ca(2+)-dependent manner. The CaM binding site of CRMP-2 is proposed to reside in the last helix of the folded domain, and in line with this, a synthesized peptide representing this helix bound to CaM. In addition, CaM binding inhibits a homotetrameric assembly of CRMP-2 and attenuates calpainmediated CRMP-2 proteolysis. Furthermore, a CaM antagonist reduces the number and length of process induced by CRMP-2 overexpression in HEK293 cells. Take together, our data suggest that CRMP-2 is a novel CaM-binding protein and that CaM binding may play an important role in regulating CRMP-2 functions.

A genomic biomarker-based model for cancer risk stratification of non-dysplastic Barrett's esophagus patients after extended follow up; results from Dutch surveillance cohorts.

Barrett's esophagus is the only known mucosal precursor for the highly malignant esophageal adenocarcinoma. Malignant degeneration of non-dysplastic Barrett's esophagus occurs in < 0.6% per year in Dutch surveillance cohorts. Therefore, it has been proposed to increase the surveillance intervals from 3 to 5 years, potentially increasing development of advanced stage interval cancers. To prevent such cases robust biomarkers for more optimal stratification over longer follow up periods for non-dysplastic Barrett's patients are required. In this multi-center study, aberrations for chromosomes 7, 17, and structural abnormalities for c-MYC, CDKN2A, TP53, Her-2/neu and 20q assessed by DNA fluorescence in situ hybridization on brush cytology specimens, were used to determine marker scores and to perform clonal diversity measurements, as described previously. In this study, these genetic biomarkers were combined with clinical variables and analyzed to obtain the most efficient cancer prediction model after an extended period of follow-up (median time of 7 years) by applying Cox regression modeling, bootstrapping and leave-one-out analyses. A total of 334 patients with Barrett's esophagus without dysplasia from 6 community hospitals (n = 220) and one academic center (n = 114) were included. The annual progression rate to high grade dysplasia and/or esophageal adenocarcinoma was 1.3%, and to adenocarcinoma alone 0.85%. A prediction model including age, Barrett circumferential length, and a clonicity score over the genomic set including chromosomes 7, 17, 20q and c-MYC, resulted in an area under the curve of 0.88. The sensitivity and specificity of this model were 0.91 and 0.38. The positive and negative predictive values were 0.13 (95% CI 0.09 to 0.19) and 0.97 (95% CI 0.93 to 0.99). We propose the implementation of the model to identify non-dysplastic Barrett's patients, who are required to remain in surveillance programs with 3-yearly surveillance intervals from those that can benefit from less frequent or no surveillance.

The plasma membrane calcium pump: a multiregulated transporter.

Activation of many cells, especially nonexcitable cells, results in a Ca(2+) transient that is influenced in part by the kinetics of active extrusion of Ca(2+) across the plasma membrane. The molecular cloning of the plasma membrane Ca(2+)-pump has helped to clarify the relationship between its structure and function. The Ca(2+)-pump is controlled by multiple regulators, including calmodulin, phospholipids and various kinases. Longer term control is achieved through regulation of its gene expression, and the presence of a number of Ca(2+)-pump isoforms that differ in their regulatory domains provides potential functional diversity. In this review, we focus on the mechanisms that regulate the function of the Ca(2+)-pump, and their physiological significance.

Micromachined "Side-Viewing" Optical Sensor Probe for Detection of Esophageal Cancers.

In this paper, we report the design, fabrication and testing of a new miniaturized optical sensor probe with "side viewing" capability for oblique incidence diffuse reflectance spectrometry. The sensor probe consists of a lithographically patterned polymer waveguides chip and two micromachined positioning substrates and source/collection fibers to achieve 45° light incidence and collection of spatially resolved diffuse reflectance. Diffuse reflectance of human esophageal surface has been successfully measured for differentiation of cancerous tissues from normal ones.

[An animal experiment regarding the effect of lipopolysaccharide intervention program on Legionella pneumonia].

Objective: To explore the effect of lipopolysaccharide intervention program on Legionella pneumonia. Methods: C3H/HeN mice (6-8 weeks old) were used as experimental animals. The mice were randomly divided into lipopolysaccharide intervention, non-lipopolysaccharide intervention and control groups. Each group was again divided into three time points: 12 h, 24 h and 48 h. Mice in the lipopolysaccharide intervention group were intraperitoneally injected with E. coli lipopolysaccharide (100 ng per mice), and the rest groups were intraperitoneally injected with normal saline. After 24 hours, mice in the lipopolysaccharide intervention and the non-intervention groups mice were infected with Legionella by tracheal injection and the control group was given the same amount of saline. All the mice were killed at 12, 24 and 48 hours respectively. The mice were anatomized, lungs of the mice were separated and weighed. Organ coefficients (lung weight/body weight of mice) were calculated. 1 ml Orbital blood was collected. Toll-like receptor 4 (TLR4) levels of peripheral blood mononuclear cells were measured by flow cytometry. The contents of TNF-α and IL-1ß in the upper left lung lobe were measured by ELISA. Results: In the lung organs, the coefficients of lipopolysaccharide non-intervention group were higher than the other groups and there was no significant difference seen between the lipopolysaccharide intervention group and the controls. TLR4 peaked at 12 hours in both the lipopolysaccharide intervention and the non-intervention groups while the TLR4 level in the intervention group was higher than that in the non-intervention group. There were no significant differences appeared on the TLR4 expression levels between the two Legionella pneumonia modelled groups at 24 or 48 hours. There was no significant difference seen regarding the concentration of TNF-α and IL-1ß between the intervention and the control groups. The secretion levels of TNF-α and IL-1ß in the non-intervention group were higher than those in the intervention group at each time point. Conclusion: The lipopolysaccharide intervention program may alleviate the inflammatory symptoms of Legionella infection.

[Association between maternal dietary intake and the incidence of babies with small for gestational age].

Objective: To investigate the relations between dietary intake during pregnancy and the incidence of their babies with small for gestational age (SGA). Methods: Data on demographics, dietary intake of protein, fat, and carbohydrates of the pregnant mothers during the first, second and third trimester, were collected. Information related to birth weight and gestational age of the infants were also gathered. A total of 8 102 women, who delivered their babies at the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016, were enrolled in this project. Among them, 961 mothers had infants with SGA but the other 7 141 of them having normal infants. Unconditional logistic regression model was used to analyze the effect of dietary nutrient intake on SGA the first, second and third trimester. Results: We found that low dietary intake of protein during the first trimester and following trimesters during pregnancy were positively associated with higher risk of SGA (OR=1.534, 95%CI: 1.217-1.934; OR=1.268, 95%CI: 1.005-1.599; OR=1.310, 95%CI: 1.036-1.655). When adjusting for maternal pre-pregnancy BMI, we found that when mothers were with a pre-pregnancy BMI less than 18.5 or with low maternal intake of protein during the first trimester, positive association with higher risk of SGA (OR=1.872, 95%CI: 1.033-3.395; OR=1.754, 95%CI: 1.125-2.734), was noticed. However, for mothers with a pre-pregnancy BMI between 18.5 and 24.0 or with low protein intake during the first trimester, significant association with higher risk of SGA (OR=1.465, 95%CI: 1.089-1.972) was found. Conclusions: Through our observation, maternal dietary intake during pregnancy seemed to be associated with the risk of SGA but the effects of dietary intake were different, according to the BMI of pre-pregnancy population. Early pregnancy appeares as the key period for dietary intake which may influence the SGA.