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Background Central adrenal insufficiency (CAI) is defined as the inability of the adrenal glands to release sufficient corticosteroids due to a series of diseases or injuries of the hypothalamus or pituitary. Signs and symptoms of CAI are insidious, ambiguous, and debilitating. Preceding studies suggest that elderly patients with CAI may present with hyponatremia as a characteristic manifestation, but little is mentioned about gastrointestinal (GI) symptoms. Herein we report a rare case of an elderly male patient with a radio-chemotherapy history for nasopharyngeal carcinoma, in whom prolonged exogenous glucocorticoid replacement and infectious stress from two bouts of bacterial pneumonia combined to cause severe CAI with prodromal symptoms of persistent, intractable nausea and vomiting. Case presentation A 71-year-old man presented to the gastroenterology department with persistent nausea and vomiting. Gastroscopy, brain magnetic resonance imaging (MRI), and contrast-enhanced abdominal computed tomography (CT) were performed to exclude organic lesions. The diagnosis of CAI was confirmed by checking the levels of basal cortisol and adrenocorticotropic hormone. After replacement therapy with hydrocortisone, the patient's GI symptoms resolved rapidly, hyponatremia was corrected. At subsequent follow-ups, he was doing well with no hospitalizations. Conclusion CAI in elderly patients can start with persistent, refractory nausea and vomiting, and is featured by uncorrectable and insidious hyponatremia. Timely hydrocortisone replacement therapy averts life-threatening adrenal crises.

The aim of the present study was to retrospectively investigate the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in tricuspid valve replacement (TVR). A total of 73 TVR patients who had NT-proBNP measured on the first postoperative morning during a period of 10 years from February 2008 to December 2018 were included in the study. The endpoint was postsurgery all-cause in-hospital mortality. The outcome-based cut-point optimization was performed using X-tile software. NT-proBNP with the maximum χ2 score and the minimum P value will be used as the optimal cut-point. Kaplan–Meier analysis and log-rank test were adopted to calculate and compare survival rates stratified by tertiles and the cut-point. Predictive capabilities of NT-proBNP were tested using univariable and multivariable Cox regression. Overall, 20 (27.3%) in-hospital deaths occurred. Postsurgery hospital stay was 21 days (interquartile range, 16–32 day). NT-proBNP were divided into low (

Background: Cervical cancer (CC) is one of the most common malignancies in females worldwide. Traditional treatments have been used widely, but the prognosis remains poor. Therefore, new strategies are needed to improve outcomes. Immunotherapy has been used to treat various types of solid tumors. Subtypes of the tumor microenvironment (TME) are associated with the response to immunotherapy, so understanding complexity of TME is pivotal for immunotherapy.Methods: In this study, we used two methods, “ssGSEA” and “xCell”, to estimate the immune profile in CC. R packages “Corrplot” was used to analysis the correlation of immune cells. “ConsensusClusterPlus” was used to cluster CC based on infiltration of immune cells. “Limma” was used to identify differentially expressed genes (DEGs), and “clusterprofile” was used to perform enrichment analysis. “survival”and “glmnet”was used to construct perdition model. RT-PCR was used to detect Keratin, type I cytoskeletal 23 (KRT23) expression。Cytometric bead arrays and ELISA were used to detect CCL5expression. Transwell assay was used to detect migration of CD8+T cells.Results: We subdivided CC into “hot” and “cold” tumors, in which hot tumors had infiltration of more immune cells and longer survival. Enrichment analyses of DEGs revealed that the number of activated immune signaling pathways was higher in hot tumors. KRT23 showed high expression in cold tumors and its expression was negatively correlated with infiltration of immune cells. In vitro experiments, knockdown of KRT23 expression promoted secretion of CCL5, and promoted recruitment of CD8+T cells. We also constructed a model based on DEGs that had high efficacy for predicting the survival of CC and patients receiving immunotherapy.Conclusion: Our study provides deep insights in infiltration of immune cells into CC. KRT23 may act as an immunotherapeutic target. Our model can predict the prognosis of CC patients and may guide immunotherapy.

Objective: To evaluate the mid-term survival rate after tricuspid valve replacement (TVR). Methods: We retrospectively studied 110 consecutive patients who underwent TVR from January 2007 to November 2017. A survival analysis was performed with the Kaplan-Meier method and the log-rank test. Results: The median survival was 65.81 months. Mean age was 50 (range 39 to 59) years. Forty-eight patients (43.6%) were male, and 62 patients (56.4%) were female. Most of the patients (78.5%) were categorized into the New York Heart Association (NYHA) functional classes III/IV. Seventy-two patients (65.5%) had isolated TVR. Six-three patients (57.3%) had previously undergone heart surgery. The Kaplan-Meier survival rates at one year, three years, and five years were 59.0%±5%, 52.0%±6%, and 48.0%±6%, respectively. A Cox regression analysis demonstrated that the risk factors for mid-term mortality were advanced NYHA class (hazard ratio [HR] 2.430, 95% confidence interval [CI] 1.099-5.375, P=0.028), need for continuous renal replacement therapy (CRRT) treatment (HR 3.121, 95% CI 1.610-6.050, P=0.001), and need for intra-aortic balloon pump (IABP) treatment (HR 3.356, 95% CI 1.072-10.504, P=0.038). Conclusion: In TVR, impaired cardiac function before the operation and a need for CRRT or IABP treatment after the operation is independently associated with increased mid-term mortality.

Multiple sclerosis (MS) is caused by immune-mediated damage of myelin sheath. Current therapies aim to block such immune responses. However, this blocking is not sufficiently specific and hence compromises immunity, leading to severe side effects. In addition, blocking medications usually provide transient effects and require frequent administration, which further increases the chance to compromise immunity. In this regard, myelin-specific therapy may provide the desired specificity and a long-lasting therapeutic effect by inducing myelin-specific regulatory T (Treg) cells. Tolerogenic dendritic cells (TolDCs) are one such therapy. However, ex vivo generated TolDCs may be converted into immunogenic DCs in a proinflammatory environment. In this study, we identified a potential novel myelin-specific therapy that works with immunogenic DCs, hence without the in vivo conversion concern. We showed that immunization with DCs, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase for de novo synthesis of a focally high 1,25-dihydroxyvitamin D concentration in the peripheral lymphoid tissues, induced Treg cells. In addition, such engineered DCs, when pulsed with a myelin antigen, led to myelin-specific suppression of ongoing experimental allergic encephalomyelitis (an MS animal model), and the disease suppression depended on forkhead-box-protein-P3(foxp3)+ Treg cells. Our data support a novel concept that immunogenic DCs can be engineered for myelin-specific therapy for MS.—Li, C.-H., Zhang, J., Baylink, D. J., Wang, X., Goparaju, N. B., Xu, Y., Wasnik, S., Cheng, Y., Berumen, E. C., Qin, X., Lau, K.-H. W., Tang, X. Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis.

Current therapies for gut inflammation have not reached the desired specificity and are attended by unintended immune suppression. This study aimed to provide evidence for supporting a hypothesis that direct in vivo augmentation of the induction of gut-homing regulatory T (Treg) cells is a strategy of expected specificity for the treatment of chronic intestinal inflammation (e.g., inflammatory bowel disease). We showed that dendritic cells (DCs), engineered to de novo produce high concentrations of both 1,25-dihydroxyvitamin D, the active vitamin D metabolite, and retinoic acid, an active vitamin A metabolite, augmented the induction of T cells that express both the regulatory molecule Foxp3 and the gut-homing receptor CCR9 in vitro and in vivo. In vivo, the newly generated Ag-specific Foxp3+ T cells homed to intestines. Additionally, transfer of such engineered DCs robustly suppressed ongoing experimental colitis. Moreover, CD4+ T cells from spleens of the mice transferred with the engineered DCs suppressed experimental colitis in syngeneic hosts. The data suggest that the engineered DCs enhance regulatory function in CD4+ T cell population in peripheral lymphoid tissues. Finally, we showed that colitis suppression following in vivo transfer of the engineered DCs was significantly reduced when Foxp3+ Treg cells were depleted. The data indicate that maximal colitis suppression mediated by the engineered DCs requires Treg cells. Collectively, our data support that DCs de novo overproducing both 1,25-dihydroxyvitamin D and retinoic acid are a promising novel therapy for chronic intestinal inflammation.

Takayasu arteritis (TA) patients with active disease often have elevated serum C-reactive protein (CRP) levels, which usually decline with the disease remission. The serum CRP concentration has been showed to be related to CRP gene polymorphisms in previous studies. The present study aims to investigate the associations of serum level of CRP and CRP polymorphisms with TA. A total of 178 unrelated Chinese Han TA patients and 229 unrelated Chinese Han individuals without documented disease were enrolled in our studies. After a systemic search in the HapMap database, four single-nucleotide polymorphisms (SNPs) were selected, namely, rs1800947, rs3093077, rs1205, and rs2808630. The ligase detection reaction (LDR) was used in genotyping. CRP concentrations were determined using turbidimetric immunoassay. Genotype frequencies and allele frequencies of CRP variations were similar between TA patients and controls. CRP haplotype frequencies in patients were not significantly different from those of controls. No significant association between serum CRP concentrations and genotypes was found. Moreover, no association was found in CRP concentration between patients with types I, II, and III TA or between patients with or without pulmonary involvement. By contrast, serum CRP concentration was directly correlated with disease severity. In conclusion, CRP polymorphisms were not associated with TA susceptibility or serum CRP levels in the Chinese Han population. However, higher CRP level was correlated with a more serious disease status, which implies that CRP possibly contributes to the progression of TA.

Cardiac pacing can be used to treat carotid sinus syndrome (CSS), but clinical studies have shown conflicting results. We conducted a systematic review and meta-analysis to evaluate the role of pacing for CSS. A systematic search of publications in PubMed, Embase, and the Cochrane Library without language restriction was performed. Prospective randomized studies that compared cardiac pacing with standard therapy or pacing with different algorithms were included if the recurrence of syncope or the number of falls was observed. Eight studies enrolling 540 patients were identified. In open-label studies, the recurrence of syncope was reduced significantly by cardiac pacing compared with standard therapy. The recurrence of syncope was not different between single- and dual-chamber pacing, but a lower rate of patients with pre-syncope was observed in the group with dual-chamber pacing. Double-blind clinical studies failed to observe the role of cardiac pacing for preventing falls in patients with CSS. The results of meta-analysis supported the use of cardiac pacing for patients with dominant cardioinhibitory CSS.

Background. Studies revealed that metabolic factors might contribute substantially to osteoarthritis (OA) pathogenesis. There has been an increasing interest to understand the relationship between knee OA and the metabolic syndrome (MetS). The purpose of this study was to explore the association between metabolic syndrome and knee osteoarthritis using meta-analysis.Methods. Databases, including PUBMED, EMBASE, and the Cochrane Library, were searched to get relevant studies. Data were extracted separately by two authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated.Results. The meta-analysis was finished with 8 studies with a total of 3202 cases and 20968 controls finally retrieved from the database search. The crude pooled OR is 2.24 (95% CI = 1.38–3.64). Although there was significant heterogeneity among these studies, which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study. The pooled adjusted OR remained significant with pooled adjusted OR 1.05 (95% CI = 1.03–1.07,p<0.00001). No publication bias was found in the present meta-analysis.Conclusions. The synthesis of available evidence supports that metabolic syndrome increases the risk for knee osteoarthritis, even after adjustment for many risk factors.

The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.

Objective: Previous case-control studies have suggested that the variations of the oxidized-lipoprotein receptor 1 (OLR1) gene (G501C, 3′-UTR-C188T) are associated with coronary artery disease (CAD). However, other studies have not confirmed this relationship. The objective of this study was to assess the relationship between OLR1 variations and CAD. Methods: We conducted a meta-analysis. Databases, including PubMed, EMbase, Chinese Biological Medical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI), were searched to obtain genetic association studies. Data were extracted by two authors, and pooled odds ratios (OR) with 95% CI were calculated. Results: The meta-analysis included 8 studies with 4,963 cases and 14,864 controls for 3′-UTR-C188T and 9 studies with 5,660 cases and 15,405 controls for G501C. The pooled OR for 3′-UTR-188T was 1.29 (95% CI 1.05–1.58, p = 0.02) compared to the C allele in the dominant model, and it was 1.38 (95% CI 1.09–1.74, p = 0.007) in the recessive model. The pooled OR for 501C was 0.79 (95% CI 0.57–1.10, p = 0.16) compared to the G allele in the dominant model, and it was 0.86 (95% CI 0.71–1.04, p = 0.12) in the recessive model. No publication bias was found in the present meta-analysis. Conclusion: The synthesis of available evidence supports that OLR1 3′-UTR-188T increases the susceptibility to CAD. However, G501C is not associated with CAD.

The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.