Associations between Proton-Pump Inhibitor Usage, Allergy, and Asthma: An Analysis of NHANES 2005-2006.

INTRODUCTION: Acid suppression medications, such as proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists, are commonly prescribed for the treatment of gastroesophageal reflux disease and other gastrointestinal disorders. However, concerns regarding potential long-term side effects are brought up by the overuse of PPIs. This study aimed to investigate the relationship between PPI usage, allergy, and asthma in the general US population. METHODS: Data of individuals aged ≥20 years who had information on PPI use and questionnaires on allergy and asthma in the US National Health and Nutrition Examination Survey (NHANES) 2005-2006 were analyzed. Univariate and multivariable logistic regression analyses were performed to determine the associations between PPI use, prevalent allergy, and asthma. RESULTS: A total of 4,481 participants (representing 198,543,007 US individuals after weighting) were included in the analyses. PPI use was not significantly associated with the presence of allergy or asthma in the general study population after adjustment. However, in females without steroid exposure, PPI use was significantly associated with increased odds of allergy (adjusted odds ratio [aOR] = 1.69, 95% confidence interval [CI]: 1.002-2.86), among which esomeprazole use was significantly associated with increased odds of allergy (aOR = 2.68, 95% CI: 1.30-5.54) and lansoprazole with increased odds of asthma (aOR = 3.44, 95% CI: 1.50-7.87) as compared to no PPI use. Duration of PPI use was not significantly associated with allergy or asthma. CONCLUSIONS: In US women without steroid exposure, PPI use is associated with increased likelihood of prevalent allergy and asthma.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Cardioprotective effects of gypenoside XVII against ischemia/reperfusion injury: Role of endoplasmic reticulum stress, autophagy, and mitochondrial fusion fission balance.

Gypenoside XVII (GP-17), a tetracyclic triterpene saponin isolated from the functional food Gynostemma pentaphyllum, has been demonstrated protective effects against cerebrovascular and cardiovascular diseases on multiple disease models. In this study, we established a myocardial infarction (MI) model by ligating the left anterior descending coronary artery, and explored whether GP-17 prevent myocardial ischemia/reperfusion (I/R) injuries in mice. Compared with the I/R group, GP-17 significantly improved the cardiac function, reduced the MI, decreased myocardial pathology, activated superoxide dismutase and catalase, and reduced the content of lactate dehydrogenase, creatine kinase, malondialdehyde, and inflammatory factor. The proteomic analysis showed multiple differential proteins between the GP-17 and I/R groups enriched in endoplasmic reticulum and mitochondria. Western-Blot showed that GP-17 significantly decreased the expression of GRP78, ATF6, CHOP, and phosphorylation of PERK, indicating the inhibition of ERS. GP-17 inhibited the expression of ATG5, LC3A/B, and BAX, illustrating the suppression of autophagy and apoptosis. Moreover, both GP-17 and 4-PBA could improve the downregulated Mfn2, meaning that inhibition of ERS regulated the mitochondrial fusion fission balance, thus protected the function of mitochondria. In conclusion, we found that GP-17 prevented against myocardial I/R injury by inhibit ERS-induced cell apoptosis, autophagy, oxidative stress, and mitochondrial division.

Psoralen induces liver injuries through endoplasmic reticulum stress signaling in female mice.

Psoralen is the main coumarin component of Fructus psoraleae. Previously, we have found that psoralen induced hepatocytes apoptosis via PERK and ATF6 related ER stress pathways in vitro. In this study, we investigated the toxicity and ER stress induced by psoralen in female C57 mice. Mice were fed with 80 mg/kg of psoralen intra-gastrically for either 3, 7, or 21 days. Liver and kidney were weighed and their coefficients were calculated. The serum was isolated to examine the biochemical parameters including alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, alkaline phosphatase (ALP) activity, blood urea nitrogen (BUN), total bile acid (TBA), total bilirubin (TBIL), and creatinine (CRE). The transcription and expression of ER stress-related markers were determined by Wes-automated Protein Simple system, Western blot and RT-PCR. Psoralen administration for 3 days significantly increased liver coefficients but decreased kidney coefficients of mice. Histopathological examination showed minimal inflammatory cell foci and vacuolar degeneration in the liver. Besides, serum levels of ALT, TBA, BUN, and CRE were markedly altered by psoralen. Moreover, psoralen significantly increased expression and transcription levels of ER stress related markers, including Grp78, PERK, eIF2α, ATF4, IRE1α, ATF6, and XBP1. These results illustrated that psoralen induced liver injuries through ER stress signaling in female mice.

Prediction of clinical efficacy of subcutaneous immunotherapy for Artemisia sieversiana pollen allergic rhinitis by serum metabolomics.

BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

mTOR Signaling in X/A-Like Cells Contributes to Lipid Homeostasis in Mice.

Gastric mechanistic target of rapamycin (mTOR) signaling is inversely associated with the expression and secretion of ghrelin, a 28-aa peptide hormone produced by gastric X/A-like cells. Ghrelin contributes to obesity and hepatic steatosis. We sought to control global lipid metabolism via the manipulation of gastric mTOR signaling in X/A-like cells. We established a ghrl-cre transgene in which the Cre enzyme is expressed in X/A-like cells under the control of the ghrelin-promoter. mTORflox/flox and tuberous sclerosis 1 (TSC1)flox/flox mice were separately bred with ghrl-cre mice to generate mTOR-ghrl-cre or TSC1-ghrl-cre mice, within which mTOR signaling was suppressed or activated, respectively. Lipid metabolism in liver and adipose depots was analyzed. Under the control of the ghrelin-promoter, the Cre enzyme was exclusively expressed in stomach X/A-like cells in adult animals. Knockout of mTOR in X/A-like cells increased circulating acyl-ghrelin and promoted hepatic lipogenesis with effects on adipose depots. Activation of mTOR signaling by deletion of its upstream inhibitor, TSC1, decreased ghrelin expression and secretion, altering lipid metabolism as evidenced by resistance to high-fat diet-induced obesity and hepatic steatosis. Both ghrelin administration and injection of rapamycin, an inhibitor of mTOR, altered the phenotypes of TSC1-ghrl-cre mice. Conclusion: Gastric mTOR signaling in X/A-like cells contributes to organism lipid homeostasis by regulating hepatic and adipose lipid metabolism. Gastric mTOR signaling may provide an alternative strategy for intervention in lipid disorders.

Psoralen induces hepatic toxicity through PERK and ATF6 related ER stress pathways in HepG2 cells.

Psoralen has potential hepatotoxicity and has a certain promoting effect on the clinical liver injury of Psoralea corylifolia L (Fructus Psoraleae). This study investigated the underlying mechanisms of psoralen-induced hepatotoxicity in vitro. HepG2 cells were treated with psoralen for 6, 12, 24, or 48 h, and an endoplasmic reticulum (ER) stress-specific inhibitor, 4-PBA, was employed to investigate the mechanism of psoralen on ER stress and unfolded protein response (UPR). Cell viability was tested by MTT assay, ATP assay, and cell death by LDH. The apoptosis was reflected by the flow cytometry, caspase-8, and caspase-3 activates. The expression of ER stress-related markers was determined by RT-PCR and western blot. We found that psoralen significantly decreased cell viability, increased activities of caspase-8 and caspase-3, and upregulated expression of CHOP and BAX in a time- and dose-dependent manner. Moreover, psoralen significantly increased the expression and transcription levels of ER stress-related markers, including Grp78, PERK, eIF2α, ATF4, and ATF6, while IRE1α was not significantly affected. And 4-PBA could effectively inhibit psoralen-induced cell death and apoptosis along with the inhibition of ER stress responses. These results suggested that psoralen causes liver injury due to the induction of the ER stress-mediated apoptosis via PERK-eIF2α-ATF4-CHOP and ATF6-CHOP related pathways.

R-spondin3-LGR4 signaling protects hepatocytes against DMOG-induced hypoxia/reoxygenation injury through activating ß-catenin.

BACKGROUND & AIMS: Leucine-rich repeat G-protein-coupled receptor 4 (LGR4) and its ligands R-spondin1-4 (Rspos) have been vastly investigated in embryonic development. The biological functions of Rspos-LGR4 system in liver remains largely unknown. Here, we explored whether it protects hepatocytes against hypoxia/reoxygenation (H/R) induced damage. METHODS: H/R injury was induced by dimethyloxalylglycine (DMOG) in AML12 cells and the effects of Rspo3 on cell proliferation and apoptosis were assessed. Specific shRNAs were used to interfere LGR4 or ß-catenin. RESULTS: DMOG caused hepatocytes damage evidenced by increase in HIF-1α, cell death and apoptosis genes p27 and Bax, with concurrent decrease of cell proliferation genes PCNA and CyclinD1. Of all the Rspos, Rspo3 is predominantly expressed in AML12 hepatocytes. Importantly, Rspo3 demonstrated an alteration in a manner similar to proliferation-related genes during H/R injury. Rspo3 pretreatment rendered hepatocytes less vulnerable to DMOG induced H/R injury. Ablation of LGR4 using shRNA attenuated the protective effects of Rspo3. Wnt3a also protected AML12 cells from damages caused by H/R, showing enhanced proliferation activity. Notably, knockdown of ß-catenin in hepatocytes completely abolished the effect of Rspo3 pretreatment on the expression levels of PCNA and CyclinD1. CONCLUSION: Rspo3-LGR4 axis protects hepatocytes from H/R injury via activating ß-catenin.

Excess Free Fructose Beverages and Allergy in Children and Adolescents: Results From NHANES 2005-2006.

PURPOSE: Our purpose was to investigate the relationship between intake of excess free fructose beverages and allergy among children and adolescents. METHODS: We analyzed data of 860 children (aged 6 to 12 years) and 1,142 adolescents (aged 13 to 19 years) from the National Health and Nutrition Examination Survey 2005-2006. Logistic regression analyses were performed to determine the associations between consumption of excess free fructose beverages and allergic symptoms or allergic sensitization. RESULTS: The pattern of findings was not entirely consistent, but some analyses supported the hypothesis of an association between intake of excess free fructose beverages and allergy. After controlling for the potential confounders, children who consumed nondiet fruit drinks at least 5 times per week had a nearly 2.5-fold greater odds of allergic sensitization than did those who consumed such drinks only 1 to 3 times per month (OR = 2.446; 95% CI, 1.583-3.780). Adolescents who consumed excess free fructose beverages at least 5 times per week or 1 to 4 times per week had about fivefold greater odds of presence of allergic symptoms than did those who seldom consumed these beverages (OR = 5.164; 95% CI, 1.866-14.297 and OR = 4.112; 95% CI, 1.857-9.107, respectively). Adolescents who consumed apple juice at least 5 times per week had a twofold greater odds of presence of allergic sensitization than did the seldom consumers (OR = 2.215; 95% CI, 1.178-4.164). CONCLUSIONS: These findings provide some support for the hypothesis of a link between intake of excess free fructose beverages and allergic symptoms or allergic sensitization in children and adolescents.

A comparison of therapeutic dosages of decitabine in treating myelodysplastic syndrome: a meta-analysis.

Decitabine is used to treat myelodysplastic syndrome (MDS). This meta-analysis evaluated the efficacy and safety of different dosing regimens of decitabine in treating intermediate and/or high-risk MDS. Medline, Cochrane, EMBASE, and Google Scholar databases were searched up to October 23, 2015. Randomized controlled trials, prospective, cohort, and case series studies were included. Fifteen studies were included with a total of 1378 patients. The decitabine 100 mg/m2/course dosing regimen had a greater overall response rate than the 60-75 mg/m2/course (51 vs. 25%; P = 0.003). It also had higher complete response rate compared with the 135 mg/m2/course regimen (24.2 vs.13.7%; P = 0.016). The three dosing regimens were similar with respect to bone marrow complete response and partial response and hematologic improvement (P values > 0.05). Decitabine 135 mg/m2/course regimen had similar hematologic improvement as best supportive care (P = 0.066). The incidence of neutropenia, thrombocytopenia, infections, and anemia was similar across treatment groups (range, 31 to 38%; P values ≥ 0.899). The 100 mg/m2/course decitabine regimen showed benefit with respect to overall response rate compared with the 60-75 mg/m2/course regimen, as well as greater improvement in complete response rate compared with the 135 mg/m2/course regimen. All three dosing regimens had similar frequency of adverse events.

Treatment of multiple solitary plasmacytomas with cytokine-induced killer cells.

BACKGROUND AIMS: Currently available treatment methods for advanced plasmacytoma include surgery, chemotherapy, radiotherapy, immunomodulatory agents, hematopoietic stem cell transplantation and donor lymphocyte infusion. We report a case of advanced refractory multiple solitary plasmacytomas in a 68-year-old Asian man with multiple bone lesions, in whom autologous cytokine-induced killer (CIK) cells were administered in an effort to eliminate residual tumor lesions. METHODS: CIK cells were infused monthly for 21 courses. RESULTS: The patient has survived 63 months since the first hospital visit without disease progression for 40 months. CONCLUSIONS: This case represents the first report of autologous CIK cell immunotherapy used successfully to suppress multiple solitary plasmacytomas and resolve bone lesions.

C1GALT1 induces the carcinogenesis of thyroid cancer through regulation by miR-141-3p and GLUT1.

Core 1 ß 1,3-galactosyltransferase 1 (C1GALT1) acts as an important glycosyltransferase in the occurrence and development of tumor glycosylation. However, the regulatory mechanisms of C1GALT1 in thyroid cancer (TC) is still unclear. In this study, we discovered that the expression level of C1GALT1 was significantly increased in thyroid adenocarcinoma tissues and cell lines (p < 0.01). Meanwhile, gene silencing of C1GALT1 inhibited the proliferation (CCK-8 assay), migration (wound healing), and invasion (Transwell) of TC cells (p < 0.05). Further investigation indicated that miR-141-3p had a negative correlation with C1GALT1 and suppressed cancer carcinogenesis in TC cells. Moreover, we first found that glucose transporter 1 (GLUT1) was a downstream element of C1GALT1 and was positively correlated with C1GALT1 levels in TC. The GLUT1 could reverse the inhibitory effects of siRNA C1GALT1 on cell development (p < 0.05). These data suggest that the miR-141-3p/C1GALT1/GLUT1 axis plays an essential role during TC progression and may be a probable biomarker or therapeutic target for thyroid cancer patients.

High excess-free-fructose beverage consumption is not associated with prevalent allergy in US adults: a population-based analysis of NHANES 2005-2006.

BACKGROUND: A strong association exists between high-excess free fructose (EFF) beverage consumption and prevalent allergy in children and adolescents; however, whether this association exists in the adult population is unclear. Therefore, this study aimed to investigate the relationship between high-EFF beverage intake and prevalent allergy. METHODS: This cross-sectional study extracted data from the National Health and Nutrition Examination Survey 2005-2006. Adults aged ≥ 20 were eligible for inclusion, excluding those without complete information on beverage intake, allergic symptom survey, and allergen-specific immunoglobulin E test results. A total of 2077 adults were included. Univariate and multivariable logistic regression analyses determined the associations between high-EFF beverage consumption, prevalent allergic symptoms, and allergic sensitization. RESULTS: After adjusting for confounders, there were no significant associations between high intake (vs. low) of sum of high-EFF beverage (adjusted odds ratio [aOR] = 1.10, 95% confidence interval [CI] 0.77, 1.57), apple juice (aOR = 0.95, 95% 0.55, 1.65), fruit drinks (aOR = 0.95, 95%CI 0.70, 1.29), soft drinks (aOR = 1.17, 95%CI 0.89, 1.55) and presence of allergic sensitization, or allergic symptoms. Stratified analyses also revealed no associations between high intake of high-EFF beverage in sum, presence of allergic symptoms or sensitization among individuals aged 20-39y, 40-59y, and ≥ 60y. CONCLUSIONS: Our findings indicate no independent association between frequent intake of high-EFF beverage and increased likelihood of allergy in US adults.

Analysis of Radioactive Iodine Trapping Mechanism by Zinc-Based Metal-Organic Frameworks with Various N-Containing Carboxylate Ligands.

This study aimed to develop effective adsorbents for capturing radioactive iodine in nuclear power waste gas. Two zinc metal-organic frameworks (Zn-MOFs) were synthesized and found to have favorable properties such as a large surface area, thermal stability, surface rich in π-electron-containing nitrogen, and redox potential. Adsorption experiments revealed maximum capacities of 1.25 and 1.96 g g-1 for the MOFs at 75 °C, with the pseudo-second-order kinetic model fitting the data well. The Langmuir equation provided a better fit in cyclohexane, with maximum adsorption amounts of 249 and 358 mg g-1 for Zn-MOF-1 and Zn-MOF-2, respectively. The MOFs were also stable during six cycles of adsorption and desorption. Furthermore, electron transfer occurred due to the synergistic adsorption of Zn, N, and O atoms, resulting in the conversion of some iodine to polyiodide. Zn-MOF-2 exhibited better chemisorption than Zn-MOF-1 due to a smaller highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap. Notably, it was discovered that N-containing radicals had stronger interactions with iodine compared to radicals without N. These findings provide valuable insights into MOF synthesis and environmental protection.

Management of allergic rhinitis improves clinical outcomes of difficult-to-treat tic disorders or attention-deficit/hyperactivity disorders.

AIMS: This case series aimed to evaluate the effects of treatment for allergic rhinitis (AR) in AR-diagnosed children with previous diagnosis of tic disorders/attention-deficit/hyperactivity disorders (TD/ADHD) but unresponsive to behavioral or medical treatment. MATERIALS AND METHODS: Between July 2016 and June 2021, children diagnosed with AR in our hospital were enrolled. All were diagnosed with TD/ADHD refractory to behavioral or medical treatment. The demography and clinical information were collected from medical records. The outcomes were visual analogue scale (VAS) for AR severity, Yale Comprehensive Tic Severity Scale (YGTSS) for TD symptoms, and Attention-Deficit Hyperactivity Screening Scale (SNAP-IV) for ADHD symptoms. RESULTS: A total of 27 children (18 boys, 9 girls) were included, with a mean age 7.4 ± 2.9 years (3 - 17 years). They had undergone behavioral or medical treatment of TD/ADHD for 3.6 ± 1.9 years but without significant improvement in TD/ADHD symptoms. After 2-6 months of systematic treatment for AR, VAS was decreased to 0.4 ± 0.1 from 0.8 ± 0.2, YGTSS to 3.5 ± 0.7 from 6.8 ± 1.4, and SNAP-IV to 0.4 ± 0.1 from 0.6 ± 0.2 (all p < 0.001). No recurrence of TD/ADHD symptoms was reported during a mean follow-up of 2.4 ± 1.1 years (0.5 - 5 years). CONCLUSION: AR treatment improves TD/ADHD outcomes in children with difficult-to-treat TD/ADHD. In TD/ADHD children who are unresponsive to behavioral or drug treatment and have AR-related symptoms, AR examination and treatment are recommended for better prognosis.

Self-Reported Allergic Rhinitis Prevalence and Risk Factors in Employees of the China National Railway.

BACKGROUND: Allergic rhinitis (AR) is a common allergic disease globally and its prevalence is increasing year by year. This study aimed to analyze the prevalence and risk factors of self-reported AR among the Chinese National Railway train crew in the China Railway Beijing Group.METHODS: This prospective questionnaire study surveyed 1511 randomly recruited train crewmembers from 20 cities in the China National Railway network, and 494 reported having AR. A structured questionnaire was tailored, designed, and delivered electronically to all subjects. Prevalence of and risk factors for AR were analyzed based on self-reported results.RESULTS: The prevalence of self-reported AR among train crewmembers was 32.6%. Among respondents, 86.03% worked in passenger cars and 64.6% reported having worse AR symptoms while on trains. AR frequencies were 40.15% perennially and 59.85% seasonally. Among the Total Nasal Symptoms Scores (TNSS), significant differences were found between rhinorrhea and sneezing and between nasal itching and sneezing. The Rhino-Conjunctivitis Quality of Life Questionnaire (RQLQ) showed significant correlations between all seven sections. TNSS was significantly associated with the RQLQ. Scores of both the TNSS and RQLQ showed that the severity of AR symptoms (rp = 0.103) and the impact on quality of life (rp = 0.113) correlated significantly with seniority.CONCLUSIONS: The prevalence of self-reported AR among train crew working in passenger cars is higher than that of the general Chinese population. The severity of AR symptoms and the impact on quality of life are associated with seniority, meaning the number of years working on trains.Yu R-L, Ning H-Y, Lan T-F, He H, Zheng C-B, Wang X-Y, Wang H-T, Wang X-Y. Self-reported allergic rhinitis prevalence and risk factors in employees of the China National Railway. Aerosp Med Hum Perform. 2023; 94(11):821-826.

Repeated transfusions of autologous cytokine-induced killer cells for treatment of haematological malignancies in elderly patients: a pilot clinical trial.

The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine-induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL-2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal antibody. The autologous CIK cells (2-3 × 10(9)) were transfused back to patients, followed by a subcutaneous injection of IL-2 (1 mU/day) for 10 consecutive days. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum ß2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow-up, the mean survival time was 20 months. Transfusion with autologous CIK cells plus rhIL-2 treatment is safe and effective for treating haematological malignancies in elderly patients.

Lower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass.

Objective: Roux-en-Y gastric bypass is an effective intervention for metabolic disorder. We aim to elucidate whether ghrelin contributes to weight reduction, and glycemic and lipid control after Roux-en-Y gastric bypass (RYGB). Design: Four-week-old WT and Ghrl-TSC1-/- mice were fed high fat diet for 12 weeks before surgery, and continued to be on the same diet for 3 weeks after surgery. Body weight, food intake, glycemic and lipid metabolism were analyzed before and after surgery. Results: Gastric and circulating ghrelin was significantly increased in mice with RYGB surgery. Hypoghrelinemia elicited by deletion of TSC1 to activate mTOR signaling in gastric X/A like cells demonstrated no effect on weight reduction, glycemic and lipid control induced by Roux-en-Y gastric bypass surgery. Conclusion: Lower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass.

TP53 Co-Mutational Features and NGS-Calibrated Immunohistochemistry Threshold in Gastric Cancer.

PURPOSE: TP53 is the most frequently mutated gene in gastric cancer and it can be potentially used for gastric cancer diagnosis and screening. However, standardized clinical approaches that could accurately and cost-effectively detect TP53 mutations in gastric cancer are largely lagged behind. PATIENTS AND METHODS: We conducted next-generation sequencing (NGS) analysis of 425 cancer-related genes in 42 gastric cancer patients in our cohort. A 1313-patient cohort derived from the cBioPortal database was used for validation. We performed immunohistochemistry (IHC) staining with four commonly used p53 antibodies, and the NGS results were used as the gold standard to optimize the IHC threshold for each antibody. RESULTS: By NGS analysis, we found that around 80% of gastric cancer patients in our cohort harbored TP53 alterations. Genetic alterations of BRCA1/2 or KMT2B were mostly exclusive with TP53 mutations, so were the MSI status or low grade of tumors. These results were further validated using the data from cBioPortal. We then used the NGS-derived TP53 status to optimize four commonly used IHC antibodies for detecting TP53 mutations. We showed that all antibodies could achieve more than 93% accuracy when proper IHC positivity thresholds were used, especially for the SP5 antibody that could reach 100% sensitivity and specificity with the 20% threshold. CONCLUSION: Our results indicated that exclusivity between TP53 and BRCA mutations could be potentially used as a cost-effective way to predict BRCA status. Also, setting proper IHC thresholds for each specific antibody is critical to accurately detect TP53 mutations and facilitate disease diagnosis.

Prevalence of the GJB2 IVS1+1G >A mutation in Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2.

BACKGROUND: Mutations in the GJB2 gene are the most common cause of nonsyndromic recessive hearing loss in China. In about 6% of Chinese patients with severe to profound sensorineural hearing impairment, only monoallelic GJB2 mutations known to be either recessive or of unclear pathogenicity have been identified. This paper reports the prevalence of the GJB2 IVS1+1G>A mutation in a population of Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2. METHODS: Two hundred and twelve patients, screened from 7133 cases of nonsyndromic hearing loss in China, with monoallelic mutation (mainly frameshift and nonsense mutation) in the coding region of GJB2 were examined for the GJB2 IVS1+1G>A mutation and mutations in the promoter region of this gene. Two hundred and sixty-two nonsyndromic hearing loss patients without GJB2 mutation and 105 controls with normal hearing were also tested for the GJB2 IVS1+1G>A mutation by sequencing. RESULTS: Four patients with monoallelic mutation in the coding region of GJB2 were found carrying the GJB2 IVS1+1G>A mutation on the opposite allele. One patient with the GJB2 c.235delC mutation carried one variant, -3175 C>T, in exon 1 of GJB2. Neither GJB2 IVS1+1G>A mutation nor any variant in exon 1 of GJB2 was found in the 262 nonsyndromic hearing loss patients without GJB2 mutation or in the 105 normal hearing controls. CONCLUSION: Testing for the GJB2 IVS 1+1 G to A mutation explained deafness in 1.89% of Chinese GJB2 monoallelic patients, and it should be included in routine testing of patients with GJB2 monoallelic pathogenic mutation.