Failure of lipid control by PCSK9 inhibitors in compound heterozygous familial hypercholesterolemia complicated with premature myocardial infarction: A case report.

Key Clinical Message: A certain level of low-density lipoprotein receptor activity is crucial for the efficacy of PCSK9i. Therapeutic strategies for familial hypercholesterolemia patients should consider drug efficacy, and genetic testing will be helpful. Abstract: Familial hypercholesterolemia (FH) is a serious autosomal dominant disorder. Managing blood lipids in FH patients poses greater challenges for clinicians. Drug therapy may not always yield satisfactory results, particularly in individuals with low-density lipoprotein receptor (LDLR) negative mutations. Herein, we report a young female harboring an LDLR frameshift mutation. This patient developed xanthomas at 7 months old and underwent several years of treatment involving four classes of lipid-lowering drugs, including PCSK9i. However, the response to drug therapy was limited in this patient and eventually culminated in premature myocardial infarction. The efficacy of PCSK9i depends on the activity of LDLR. The inefficacy of PCSK9i may arise from the extensive mutations which leading to loss of LDLR activity. Therapy plans for these patients should take into account the efficacy of drug therapy. Early genetic testing is crucial for clinicians to make informed decisions regarding therapy options.

The chief culprit of intractable hypoxemia: a case report of rare pulmonary arteriovenous fistula complicated with giant hemangioma.

BACKGROUND: Pulmonary arteriovenous fistula (PAVF) is a rare disease, which can lead to the direct return of unoxidized venous blood to pulmonary veins and left heart, resulting in right-to-left shunt leading to hypoxia. Long term, the right-to-left shunt will cause severe pathophysiological changes in the patient's body and pulmonary circulation, and the prognosis will be poor if PAVF is not treated timely. CASE PRESENTATION: Here, we report the case of a 71-year-old man who presented with chest tightness and shortness of breath. After a series of examinations, PAVF and giant hemangioma were diagnosed, which are difficult to operate.Transcatheter interventional therapy was initiated. The patient recovered on the third day after operation and was discharged smoothly. During the long-term follow-up of nearly 4 years after discharge, the general condition and quality of life of the patient basically returned to normal. CONCLUSIONS: PAVF is rare but very important clinical problem. When the clinical manifestations of persistent unexplained hypoxia appear, it is necessary to fully consider the possibility of PAVF. Once the diagnosis of PAVF is clear, timely treatment is recommended to avoid deterioration of the disease and affecting the prognosis.

Laryngopharyngeal Reflux and Benign Vocal Fold Lesions: A Systematic Review and Meta-analysis.

OBJECTIVE: There is a link between laryngopharyngeal reflux (LPR) and the formation of benign vocal fold lesions (BVFLs). However, previous studies have mainly focused on LPR suggested by symptoms and signs, rather than objectively diagnosed LPR via pharyngeal pH monitoring. We, therefore, conducted a Meta-analysis to evaluate the association between pharyngeal pH monitoring diagnosed LPR and the odds of BVFLs. DATA SOURCES: Relevant observational studies were identified by searching PubMed, Embase, Cochrane Library, and Web of Science. REVIEW METHODS: We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. RESULTS: Thirteen datasets from 9 studies were included. Among them, 493 were diagnosed with LPR and 344 had BVFLs. LPR was related to a higher odds of BVFLs (odds ratio: 3.26, 95% confidence interval: 1.84-5.76, P < .001) with moderate heterogeneity (P for Cochrane Q test = .006, I2 = 57%). Subgroup analyses showed that the association was similar in studies with only pharyngeal pH monitoring (Restech), with double-probe or 3-site pH monitoring, and with 24-hour multichannel intraluminal impedance-pH monitoring (P for subgroup difference = .15). In addition, subgroup analysis showed consistent results in studies from Asia and Europe (P for subgroup analysis = .12), and the association seemed to be consistent for vocal Reinke's edema, nodules, and polyps (P for subgroup difference = .09). CONCLUSION: Pharyngeal pH monitoring diagnosed LPR is associated with the formation of BVFLs.

Efficient FMT reconstruction based on L1-αL2 regularization via half-quadratic splitting and a two-probe separation light source strategy.

Fluorescence molecular tomography (FMT) can achieve noninvasive, high-contrast, high-sensitivity three-dimensional imaging in vivo by relying on a variety of fluorescent molecular probes, and has excellent clinical transformation prospects in the detection of tumors in vivo. However, the limited surface fluorescence makes the FMT reconstruction have some ill-posedness, and it is difficult to obtain the ideal reconstruction effect. In this paper, two different emission fluorescent probes and L 1-L 2 regularization are combined to improve the temporal and spatial resolution of FMT visual reconstruction by introducing the weighting factor α and a half-quadratic splitting alternating optimization (HQSAO) iterative algorithm. By introducing an auxiliary variable, the HQSAO method breaks the sparse FMT reconstruction task into two subproblems that can be solved in turn: simple reconstruction and image denoising. The weight factor α (α>1) can increase the weight of nonconvex terms to further promote the sparsity of the algorithm. Importantly, this paper combines two different dominant fluorescent probes to achieve high-quality reconstruction of dual light sources. The performance of the proposed reconstruction strategy was evaluated by digital mouse and nude mouse single/dual light source models. The simulation results show that the HQSAO iterative algorithm can achieve more excellent positioning accuracy and morphology distribution in a shorter time. In vivo experiments also further prove that the HQSAO algorithm has advantages in light source information preservation and artifact suppression. In particular, the introduction of two main emission fluorescent probes makes it easy to separate and reconstruct the dual light sources. When it comes to localization and three-dimensional morphology, the results of the reconstruction are much better than those using a fluorescent probe, which further facilitates the clinical transformation of FMT.

Evaluation of Platelet Parameters in Patients With Secondary Failure of Platelet Recovery and Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To investigate the clinical significance of changes in platelet parameters in patients with secondary failure of platelet recovery (SFPR) and cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). METHODS: In this retrospective study, 79 patients who had undergone allogeneic HSCT (allo-HSCT), including 40 patients with SFPR and 39 patients without SFPR, were recruited. The evaluated parameters were platelet count (PLT), plateletcrit (PCT), platelet-large cell ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), the incidence of CMV infection after allo-HSCT, and the correlation of SFPR and CMV infection in patients who had undergone allo-HSCT. The control group included 107 healthy donors. RESULTS: The SFPR group had significantly lower megakaryocyte counts, PLT, and PCT and significantly higher P-LCR, MPV, and PDW than the healthy donor and non-SFPR groups. The incidence of CMV infection was higher in SFPR patients than in non-SFPR patients. Among the patients with SFPR, P-LCR, MPV, and PDW were lower in those with CMV DNA >8000 copies/mL than in those with CMV DNA <8000 copies/mL (P < .05 for all); the CMV viral load was slightly negatively correlated with MPV (P = .0297) and P-LCR (P = .0280). CONCLUSION: We demonstrate for the first time that the level of platelet activation in SFPR patients, which was closely related to CMV infection, was higher than that in that in non-SFPR patients, and higher CMV load was associated with the inhibition of platelet activation.

Effects of Acute Exposure to 3500 MHz (5G) Radiofrequency Electromagnetic Radiation on Anxiety-Like Behavior and the Auditory Cortex in Guinea Pigs.

Numerous studies have shown that radiofrequency electromagnetic radiation (RF-EMR) may negatively affect human health. We detected the effect of 3500 MHz RF-EMR on anxiety-like behavior and the auditory cortex (ACx) in guinea pigs. Forty male guinea pigs were randomly divided into four groups and exposed to a continuous wave of 3500 MHz RF-EMF at an average specific absorption rate (SAR) of 0, 2, 4, or 10 W/kg for 72 h. After exposure, malondialdehyde (MDA) levels, antioxidant enzyme activity, anxiety-like behavior, hearing thresholds, cell ultrastructure, and apoptosis were detected. Our results revealed that hearing thresholds and basic indexes of animal behavior did not change significantly after exposure (P > 0.05). However, the MDA levels of ACx were increased (P < 0.05), and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities were decreased (P < 0.05) in the exposure groups compared to the sham group. Ultrastructural changes of ACx, including swollen mitochondria and layered myelin sheaths, were observed. Cytochrome-c relocalization, caspase-9, and cleaved caspase-3 activation were detected in the exposure groups. In conclusion, these results suggest that oxidative stress is an important mechanism underlying the biological effects of RF-EMR, which can induce ultrastructural damage to the ACx and cell apoptosis through a mitochondria-dependent mechanism. Moreover, oxidative stress, apoptosis induction and ultrastructural damage increase in a SAR-dependent manner. However, RF-EMR does not increase hearing thresholds or induce anxiety. Bioelectromagnetics. 43:106-118, 2022. © 2021 Bioelectromagnetics Society.

Nursing Care Plan and Management of Patients With Acute Leukemia.

OBJECTIVE: To provide an overview of the integration of nursing care services for patients with acute leukemia in the past, present and future. DATA SOURCES: Published literature as indexed in Medline, relevant guideline documents, textbooks and clinical experience. CONCLUSION: Patients with acute leukemia have significant nursing care demands that are frequently unmet by routine oncology treatment. The initial introduction of expert nursing care into routine oncology treatment boosts patient-centered results in people with advanced solid tumors, according to research. Recent data suggest that patients with hematologic malignancies who have undergone transplantation of stem cells have similarly improved, and further trials are being conducted to assess nursing care treatments in patients with acute leukemia. NURSING PRACTICE IMPLICATIONS: Nurses are essential in the management of patients with acute leukemia both in and out of the hospital. As a result, having a basic understanding of these illnesses is critical. In the management of oncologic crises, early symptom identification is crucial.

Molecular characterization of long-term survivors of hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most fatal cancers, and the majority of patients die within three years. However, a small proportion of patients overcome this fatal disease and survive for more than five years. To determine the molecular characteristics of long-term survivors (survival ≥ 5 years), we analyzed the genomic and clinical data of hepatocellular carcinoma patients from The Cancer Genome Atlas and the International Cancer Genome Consortium databases, and identified molecular features that were strongly associated with the patients' prognosis. Genes involved in the cell cycle were expressed at lower levels in tumor tissues from long-term survivors than those from short-term survivors (survival ≤ 1 years). High levels of positive regulators of the G1/S cell cycle transition (cyclin-dependent kinase 2 [CDK2], CDK4, Cyclin E2 [CCNE2], E2F1, E2F2) were potential markers of poor prognosis. Hepatocellular carcinoma patients with TP53 mutations were mainly belonged to the short-term survivor group. Abemaciclib, an FDA-approved selective inhibitor of CDK4/6, inhibited the cell proliferation and tumor growth of hepatocellular carcinoma cells in vitro and in vivo. Thus, high G1/S transition-related gene levels and TP53 mutations are promising diagnostic biomarkers for short-term survivals, and abemaciclib may be a potential targeted drug for hepatocellular carcinoma.

Chylous ascites following repair of total anomalous pulmonary venous connection coexisting with a persistent left superior vena cava in a neonate: a case report.

Chylous ascites refers to the accumulation of lymphatic fluid in the peritoneal cavity. The causes of chylous ascites are various, and commonly include traumatic injury and obstruction, which disrupt the lymphatic system. In addition, cardiothoracic surgery may injure the thoracic duct and lead to chylothorax. However, there are very few reported cases of isolated chylous ascites developing following cardiothoracic surgery. In this paper, we report a case of postoperative chylous ascites in a full-term neonate. The infant underwent cardiothoracic surgery via thoracotomy to repair total anomalous pulmonary venous connection coexisting with a persistent left superior vena cava on day of life 17, and there was a significant increase in abdominal girth on postoperative day 12 (day of life 29). Abdominal ultrasound revealed an 8 mm thick ascites without pleural effusion. Abdominal paracentesis was performed and the milky-white peritoneal fluid was positive for Sudan III staining and the chylous test. The triglyceride concentration of the ascitic fluid was 691 mg/dL and the concentration of protein was 39.4 g/L. Additionally, the ascitic fluid also contained 6 360×106/L of white blood cells, predominantly lymphocytes. These results suggested the infant developed chylous ascites. Conservative management with fasting and medium-chain triglycerides-based formula successfully resolved the chylous ascites without reoccurrence. We present our experience of this rare condition and discuss the possible causes of chylous ascites in this case.

Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency.

Background: The role of T cell Ig and ITIM domain (TIGIT) and programmed cell death-1 (PD-1) in colorectal cancer (CRC) with mismatch repair deficiency is unknown.Methods: This was a study of 60 CRC patients with mismatch repair deficiency and 30 healthy controls between June 2015 and October 2015.Results: The expression of Foxp3, PD-1, and TIGIT was higher in cancer tissues compared with adjacent mucosa (all P < .05). Patients with advanced TNM stage had a significantly higher expression of TIGIT (P = .025) and PD-1 (P = .020) than patients with early-stage CRC. The disease-free survival (DFS) of patients with high TIGIT (HR = 3.96, 95%CI: 1.34-11.69, P = .013) or PD-1 (HR = 214.8, 95%CI: 49.88-925.2, P < .001) expression were better. The overall survival (OS) of the patients with CRC and high expression of PD-1 was worse than those with low expression (HR = 4.01, 95%CI:1.26-12.69, P = .019).Conclusion: TIGIT and PD-1 are upregulated in CRC with mismatch repair deficiency and associated with TNM stage and DFS.

Comprehensive Analyses of the Expression, Genetic Alteration, Prognosis Significance, and Interaction Networks of m6A Regulators Across Human Cancers.

Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein-protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators-potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators' roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.

PM2.5 compromises antiviral immunity in influenza infection by inhibiting activation of NLRP3 inflammasome and expression of interferon-ß.

PM2.5, a major component of air pollutants, has caused severe health problems. It has been reported that PM2.5 index is closely associated with severity of influenza A virus (IAV) infection. However, the underlying mechanisms have not been addressed. NLRP3 inflammasome and type I interferon signaling regulate host defense against influenza infection. The present study investigated the potential effects of air pollutants on host defense against influenza infection in vitro and in vivo. In this study, different concentrations of PM2.5 were pre-exposed to macrophages and mice before IAV infection to assess the negative effects of air pollutants in virus infection. We found that exposure to PM2.5 deteriorated influenza virus infection via compromising innate immune responses manifested by a decrease IL-1ß and IFN-ß production in vitro. Meanwhile, mice exposed with PM2.5 were susceptible to PR8 virus infection due to down-regulation of IL-1ß and IFN-ß. Mechanistically, PM 2.5 exposure suppressed the NLRP3 inflammasome activation and the AHR-TIPARP signaling pathway, by which compromised the anti-influenza immunity. Thus, our study revealed that PM2.5 could alter macrophage inflammatory responses by suppressing LPS-induced activation of NLRP3 inflammasome and expression of IFN-ß during influenza infection. These findings provided us new insights in understanding that PM2.5 combining with influenza infection could enhance the severity of pneumonia.

AFAP1-AS1 Promotes Proliferation of Pituitary Adenoma Cells through miR-103a-3p to Activate PI3K/AKT Signaling Pathway.

BACKGROUND: We previously found that AFAP1-AS1 regulates the cell growth of pituitary tumor cells; however, the mechanism still remains unclear. Here, we investigated whether AFAP1-AS1 acts as a competing endogenous RNA of miR-103a-3p to regulate pituitary adenoma growth via the PI3K/AKT pathway. METHODS: The bind between AFAP1-AS1 and rno-miR-103a-3p was measured by luciferase reporter assay, and rno-miR-103a-3p expression was measured by quantitative reverse transcription polymerase chain reaction. Proliferation, cell cycle, and apoptosis were measured by cell counting kit 8 and flow cytometry. Rat growth hormone (GH) and prolactin (PRL) levels in culture supernatant of GH3 and MMQ cells were measured by enzyme-linked immunosorbent assay. RESULTS: AFAP1-AS1 binds to rno-miR-103a-3p in rat pituitary adenoma cells. Additionally, rno-miR-103a-3p overexpression suppressed rat pituitary adenoma cell proliferation, induced cell apoptosis, arrested cell cycle in the G/S phase, reduced GH and PLR secretion, and inhibited the PI3K/AKT signaling pathway. Activated PI3K/AKT signaling pathway revised the effect of rno-miR-103a-3p overexpression on proliferation and GH and PLR secretion. Coexpression of both si-AFAP1-AS1 and rno-miR-103a-3p inhibitor promoted cell proliferation and cell cycle progression, reduced cell apoptosis, enhanced GH and PLR secretion, and activated the PI3K/AKT signaling pathway in rat pituitary adenoma cells. CONCLUSION: We found that AFAP1-AS1 and miR-103a-3p could be a potential therapeutic target for pituitary adenoma.

Diagnostic Potential for Circular RNAs in Gastric Carcinoma: a Meta-Analysis.

BACKGROUND: Circular RNAs (circRNAs) are potential, novel biomarkers for the early diagnosis of gastric carcinoma. Herein, a meta-analysis was conducted to assess the diagnostic potential for circRNAs in gastric carcinoma. METHODS: Online databases were searched for eligible studies. Study quality was judged using the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS) checklist-II tool. STATA 12.0 and Meta-Disc 1.4 software were used for statistical analysis. RESULTS: Twelve studies consisting of 1,278 patients and 1,250 paired controls were considered for meta-analysis. The pooled sensitivity and specificity of circRNAs for gastric carcinoma were compared to normal controls and found to be 0.68 (95% CI: 0.66 - 0.71) and 0.70 (95% CI: 0.68 - 0.73), respectively. A corresponding area under the receiver operating characteristic curve of 0.78 was identified. Moreover, stratified analysis demonstrated an improved diagnostic value for circRNAs when tissue and plasma specimens were combined. CONCLUSIONS: This meta-analysis demonstrates that circRNAs are promising biomarkers for gastric carcinoma.

LL37 Inhibits Aspergillus fumigatus Infection via Directly Binding to the Fungus and Preventing Excessive Inflammation.

The incidence of Aspergillus fumigatus infection and the rate of resistance to antifungal drugs have sharply increased in recent years. LL37 has been reported as a host defense peptide with broad-spectrum antibacterial activities. However, the role of LL37 during A. fumigatus infection remains unclear. Here, we examined the interaction between LL37 and A. fumigatus and found that synthetic LL37 could directly bind to the surface of A. fumigatus, disrupting the integrity of the cell wall in vitro. LL37 inhibited mycelial growth in a concentration-dependent manner, rather than fungicidal effect even at high concentration (e.g., 20 µM). Interestingly, low concentrations of LL37 (e.g., 4 µM) significantly attenuated mycelial adhesion and prevented the invasion and destruction of epithelial cells. Following LL37 treatment, the levels of proinflammatory cytokines released by A. fumigatus-stimulated macrophages decreased significantly, accompanied by downregulation of M1 type markers. In a mouse model of pulmonary A. fumigatus infection, LL37-treated mice showed lower amounts of fungi load, moderate pathological damage, and reduced proinflammatory cytokines. Further, LL37 transgenic mice (LL37+/+) were examined to investigate the effects of endogenous LL37 in an A. fumigatus infection model and showed lower susceptibility to A. fumigatus infection in comparison with wild-type mice. In addition, LL37 also played a protective role in an immunosuppressed mouse model of A. fumigatus infection. Thus, LL37 inhibits A. fumigatus infection via directly binding to mycelia and reducing excessive inflammation. LL37 or its analogs may therefore constitute potential drug components for A. fumigatus infection.

Exposure to Maternal Diabetes Mellitus Causes Renal Dopamine D1 Receptor Dysfunction and Hypertension in Adult Rat Offspring.

Epidemiological and experimental studies suggest that maternal diabetes mellitus programs hypertension that is associated with impaired sodium excretion in the adult offspring. However, the underlying mechanisms are not clear. Because dopamine receptor function is involved in the pathogenesis of hypertension, we hypothesized that impaired renal dopamine D1 receptor function is also involved in the hypertension in offspring of maternal diabetes mellitus. Maternal diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (35 mg/kg) to pregnant Sprague-Dawley rats at day 0 of gestation. Compared with the offspring of mothers injected with citrate buffer (control mother offspring), the diabetic mother offspring (DMO) had increased systolic blood pressure and impaired D1 receptor-mediated diuresis and natriuresis, accompanied by increased renal PKC (protein kinase C) expression and activity, GRK-2 (G protein-coupled receptor kinase-2) expression, D1 receptor phosphorylation, D1 receptor/Gαs uncoupling, and loss of D1 receptor-mediated inhibition of Na+-K+-ATPase activity in renal proximal tubule cells from DMO. Inhibition of PKC reduced the increased GRK-2 expression and normalized D1 receptor function in primary cultures of renal proximal tubule cells from DMO. In addition, DMO, relative to control mother offspring, in vivo, had increased oxidative stress, indicated by decreased renal glutathione and increased renal malondialdehyde and urine 8-isoprostane. Normalization of oxidative stress with tempol also normalized the renal D1 receptor phosphorylation, D1 receptor-mediated diuresis and natriuresis, and blood pressure in DMO. Our present study indicates that maternal diabetes mellitus-programed hypertension in the offspring is caused by impaired renal D1 receptor function because of oxidative stress that is mediated by increased PKC-GRK-2 activity.

Viral infection in community acquired pneumonia patients with fever: a prospective observational study.

BACKGROUND: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. METHODS: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. RESULTS: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death. CONCLUSIONS: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.

Four-and-a-half LIM protein 1 promotes paclitaxel resistance in hepatic carcinoma cells through the regulation of caspase-3 activation.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. AIM: To investigate the mechanisms of paclitaxel resistance in hepatocellular carcinoma cells and find promising molecular target for HCC therapy. MATERIALS AND METHODS: To investigate the effects of FHL1 on chemo resistance in HCC cells, we generated FHL1 knock-down stable cell lines with HepG2 and SMMC7721 cells. Cell viability assay, colony formation and xenograft experiments assay were performed to detect effect of FHL1 on Paclitaxel or Oxaliplatin resistance in vitro and in vivo. Caspase activity assay was performed to explore the activation of caspase-3 and caspase-9 in paclitaxel treated FHL1-knockdown HepG2 cells. RESULT: In the present study we have investigated that four-and-a-half LIM protein 1 (FHL1), which plays an important role in the development of cancer, is associated with both the chemo resistance of hepatocellular carcinomas cells in vitro and in vivo. Knockdown of FHL1 significantly enhanced the sensitivity of paclitaxel, but had no effects on sensitivity of oxaliplatin. Moreover, knockdown of FHL1 promoted the activation of caspase-3 and caspase-9, which were induced by paclitaxel. Interestingly, FHL1 negatively regulates the chemo resistance of HCC in xenografted nude mice. CONCLUSION: FHL1 promote paclitaxel resistance in hepatocellular carcinomas cells through regulating apoptosis induced by paclitaxel, suggesting that FHL1 may be a promising molecular target for HCC therapy.

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients.

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 (P < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group (P < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines.

Abnormally expressed microRNA as auxiliary biomarkers for nasopharyngeal carcinoma: A meta-analysis.

Aberrant expression of microRNA (miRNA) has been highlighted as a helpful indicator to aid in nasopharyngeal carcinoma (NPC) diagnosis. The present meta-analysis aimed to validate the efficacy of miRNA as potential biomarkers for NPC detection. Publication searches were conducted on the online PubMed and EMBASE databases from inception to June 2016. A bivariate meta-analysis was performed to generate the diagnostic parameters based on Meta-Disc 1.4 and Stata 12.0 programs. Sensitivity analysis and meta-regression tests were applied to trace heterogeneity sources among eligible studies. A total of six studies comprising 528 patients with NPC and 252 matched controls were enrolled. Results from the present meta-analysis demonstrated that miRNA testing achieved a pooled sensitivity of 0.78 [95% confidence interval (CI), 0.70-0.84] and specificity of 0.79 (95% CI, 0.73-0.84) in confirming NPC, corresponding to an area under the curve (AUC) value of 0.85. Additionally, the pooled diagnostic odds ratio was estimated to be 9.01 (95% CI, 5.62-14.44), along with a positive likelihood ratio of 2.81 (95% CI, 2.19-3.61) and negative likelihood ratio of 0.35 (95% CI, 0.28-0.44). Additionally, the stratified analyses revealed that paralleled testing of miRNA sustained a pooled accuracy superior compared with that of single miRNA testing (sensitivity, 0.88 vs. 0.70; specificity, 0.85 vs. 0.69; AUC, 0.95 vs. 0.75). Testing of miRNA harbors a moderate diagnostic efficacy and is acceptable as an auxiliary biomarker for NPC diagnosis.