Exosomes derived from M1 macrophages inhibit the proliferation of the A549 and H1299 lung cancer cell lines via the miRNA-let-7b-5p-GNG5 axis.

Background: Almost all cells are capable of secreting exosomes (Exos) for intercellular communication and regulation. Therefore, Exos can be used as a natural therapeutic platform to regulate genes or deliver drugs to treat diseases. M1 macrophages inhibit tumor growth by releasing pro-inflammatory factors. This study explored the applicability of M1 macrophage exosomes (M1-Exos) as gene carriers and the effects on GNG5 protein, and further examined whether macrophage repolarization could inhibit tumor activity. Methods: M0 macrophages were polarized toward M1 using vitexin. Exos were obtained from M1 macrophages by ultra-centrifugation. The transwell non-contact co-culture system was used to co-culture M1 macrophages with HLF-α human lung epithelial cells or A549 or H1299 lung cancer cells. MTT, scratch, and transwell assays were used to detect the cell viability, migration, and invasion ability of cells in the four groups. Flow cytometry was used to detect the apoptosis rate of each group, and western blot (WB) analysis was performed to detect the change in the expression of proliferation- and apoptosis-related proteins. We screened the differentially expressed microRNAs using quantitative polymerase chain reaction technology. Luciferase reporter analysis was performed to explore the interaction between miRNA and protein. We used Xenografted A549 tumors in nude mice to study the effect of M1-Exos on tumor cell growth in vivo. Results: The results showed that, under the M1 macrophage co-culture system, lung cancer cell viability, invasion, and migration ability decreased, and the number of apoptotic cells increased, will all indicators being statistically significant (P < 0.05). The expression levels of PCNA, KI67, and Bcl-2 decreased significantly, but that of Bax increased (P < 0.05). Exosomes can have the same effect on tumor cells as M1 macrophages. Exosomes can transport miR-let-7b-5p to tumor cells, and miR-let-7b-5p can inhibit tumor cell proliferation and promote tumor cell apoptosis by regulating the GNG5 protein level. Conclusions: M1-Exos inhibit the proliferation, invasion, and metastasis of lung cancer cells through miRNA-let-7b-5p and GNG5 signaling pathways and inhibit the anti-apoptotic ability of lung cancer cells.

Risk monitoring and pharmacovigilance of programmed cell death protein 1 / programmed cell death 1 ligand 1 in cancer patients after solid organ transplantation.

INTRODUCTION: Several medications are available for the treatment of cancer, and monoclonal antibodies that target PD-1 and PD-L1 represent first-line options for cancer. PD-1 promotes the ability of the immune system to recognize and attack cancer cells by activating T cells. PD-1 also activates the autoimmune system. This activation causes healthy cells in the body to be attacked by the immune system, resulting in immune-related adverse events (irAE). The objective of this study was to comprehensively evaluate the adverse events of rejection reactions in real-world solid organ transplant patients using monoclonal antibodies that target PD-1/PD-L1. METHODS: Data from 2016-2021 were extracted from the U.S. Food and Drug Administration(FDA) Adverse Reporting System (FAERS) to describe the rejection reaction in patients with solid organ transplantation cases after using PD-1/PD-L1 inhibitors approved by the FDA. The reporting odds ratio (ROR) with 95% confidence interval (CI) for rejection reaction was calculated for each PD-1/PD-L1 inhibitor. A disproportionality signal was defined when the lower limit of 95% CI>1. RESULTS: The FAERS database recorded 11,935 adverse events related to solid organ transplantation. Among these reports, 117 showed that various PD-1/PD-L1 inhibitors exhibited a strong correlation with solid organ transplantation rejection. The 3 medicines with the incidence of rejection reaction include avelumab (1), nivolumab (79) and pembrolizumab (37). The average time of solid organ transplantation rejection associated with PD1 / PD-L1 inhibitors was 40.64 days. Of those patients who experienced solid organ transplant rejection, a total of 24.79% died. CONCLUSION: This study found that PD-1/PD-L1 inhibitor use in patients with solid organ transplantation was associated with donor organ rejection. This information serves as a pharmacovigilance signal that we need to continue to track in the real world.

Stratification Based on Risk Factors at Diagnosis Could Predict Progression in Patients with Pancreatic Cysts.

BACKGROUND: Predicting the risk of malignant transformation in pancreatic cyst patients is challenging. AIM: We retrospectively investigated the risk factors for malignant transformation in pancreatic cyst patients. METHODS: Patients with pancreatic cysts diagnosed using imaging tests were followed from November 2008 to December 2021. A significant change was defined as the additional development of high-risk stigmata (HRS), worrisome features (WFs), or pancreatic cancer during monitoring. RESULTS: In total, 479 patients were analyzed, with a median observation period of 50 months. Forty-four patients (9.2%) showed significant changes, and eight (1.7%) developed pancreatic cancer. The univariate analysis showed that the cyst diameter at diagnosis (≥ 14 mm), main pancreatic duct (MPD) diameter at diagnosis (≥ 3 mm), presence of multilocular cysts, and an inconsistent MPD caliber were significant predictive factors for a significant change. One point was assigned for each significant factor. We grouped the patients into three groups: the low-risk group (total score 0), medium-risk group (score 1-2), and high-risk group (score 3-4). The high-risk group had a higher risk of a significant change than the medium- and low-risk groups (age-adjusted HRs for the medium-risk and high-risk groups were 3.0 and 5.2 compared with the low-risk group). CONCLUSION: Stratification based on risk factors may help predict the development of significant changes in pancreatic cyst patients.

The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis.

Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in the etiopathology of cardiac fibrosis, but giving their heterogeneity and the antagonizing roles of macrophage subtypes in fibrosis, targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. By using single cell RNA sequencing analysis of immune cells in the same model, we establish the functional heterogeneity of macrophages and define an early pro-fibrogenic phase of NICM that is driven by Ccl5-expressing Ly6chigh monocytes. Among cardiac macrophage subtypes, WWP2 dysfunction primarily affects Ly6chigh monocytes via modulating Ccl5, and consequentially macrophage infiltration and activation, which contributes to reduced myofibroblast trans-differentiation. WWP2 interacts with transcription factor IRF7, promoting its non-degradative mono-ubiquitination, nuclear translocation and transcriptional activity, leading to upregulation of Ccl5 at transcriptional level. We identify a pro-fibrogenic macrophage subtype in non-ischemic cardiomyopathy, and demonstrate that WWP2 is a key regulator of IRF7-mediated Ccl5/Ly6chigh monocyte axis in heart fibrosis.

Aristolone in Nardostachys jatamansi DC. induces mesenteric vasodilation and ameliorates hypertension via activation of the KATP channel and PDK1-Akt-eNOS pathway.

BACKGROUND: Nardostachys jatamansi DC. is a common medicinal herb used to treat cardiovascular diseases, particularly hypertension. Previously, our lab characterized the chemical compounds of N. jatamansi. However, the bioactive compounds of N. jatamansi and their mechanisms of action on blood pressure and blood vessels are unknown. PURPOSE: The vasorelaxant effects of the methanolic extract (MeOH ext.) of the roots and rhizomes of N. jatamansi, its main compounds, and their underlying mode of action, were investigated. METHODS: The main compounds of N. jatamansi were isolated and identified using UHPLC-TOF MS. The antihypertensive effect of N. jatamansi extracts and (-)-aristolone were determined using spontaneously hypertensive rats. The extracts, fractions, and compounds were also evaluated for their vasorelaxant effects on U46619 contractile responses in isolated thoracic aortic and mesenteric arterial rings. The endothelial-dependent relaxation, as well as the regulatory pathways and targets of (-)-aristolone, were studied in-vitro and ex-vivo. Molecular docking and biophysical characterization (Surface plasmon resonance) studies were utilized to investigate the molecular interaction between (-)-aristolone and the target protein. RESULTS: MeOH ext. (200 mg/kg) reduces the systolic and diastolic blood pressure in spontaneously hypertensive rats. MeOH ext. and its ethyl acetate fraction (EtOAc Fr.), but not the H2O fraction, had a significant relaxing effect on the thoracic aorta. (-)-aristolone and kanshone H from EtOAc Fr. induced vasorelaxation of the thoracic aorta and mesenteric artery. In human umbilical vein endothelial cells, (-)-aristolone treatment upregulated phosphorylation of Akt (T308) and eNOS. Molecular docking and surface plasmon resonance experiments revealed an interaction between (-)-aristolone and phosphoinositide-dependent protein kinase 1 (PDK1), an upstream protein kinase that phosphorylates Akt at T308. Treatment with PDK1 inhibitor PHT-427 and eNOS inhibitor L-NAME consistently inhibited (-)-aristolone-induced vasorelaxation. In addition, KATP channel inhibitor glibenclamide dramatically inhibited the vasorelaxant effects of (-)-aristolone and kanshone H in the endothelium-denuded thoracic aorta. Finally, (-)-aristolone lowers hypertensive rats' systolic and diastolic blood pressure. CONCLUSIONS: The extracts of N. jatamansi promote vasorelaxation and alleviate hypertension. The essential chemicals responsible for producing vasorelaxation effects are (-)-aristolone and kanshone H, which activate the PDK1-Akt-eNOS-NO relaxing pathway and stimulate the opening of the KATP channel. These findings point to N. jatamansi and aristolone as possible antihypertensive agents.

SIRT2 Is Critical for Sheep Oocyte Maturation through Regulating Function of Surrounding Granulosa Cells.

Oocyte in vitro maturation is crucial for in vitro embryo production technology, which provides oocytes resources for in vitro fertilization and somatic cell nuclear transfer. Previous studies proved that SIRT2, a member of the sirtuin family, plays a role in oocyte meiosis, but its role in sheep oocyte maturation and its regulating mechanism remains unknown. Firstly, we confirmed the role of Sirt2 in sheep oocytes maturation by supplementation of SIRT2 inhibitor and activator. To further explore the specific mechanism, we performed knockdown of Sirt2 in granulosa cells and then cocultured them with oocytes. Moreover, we determined the effects of Sirt2 on granulosa cell oxidative apoptosis, cell migration, and diffusion, and examined its effects on granulosa cell mitochondrial function, mitophagy, and steroid hormone levels. The results showed that supplementation of SIRT2 inhibitor decreased the oocytes maturation rate (69.28% ± 1.28 vs. 45.74% ± 4.74, p < 0.05), while resveratrol, a SIRT2 activator, increased its maturation rate (67.44% ± 1.68 vs. 78.52 ± 1.28, p < 0.05). Knockdown of Sirt2 in sheep granulosa cells also reduced the oocytes maturation rate (47.98% ± 1.43 vs. 33.60% ± 1.77, p < 0.05), and led to decreased cell migration and expansion ability, oxidative apoptosis, abnormal mitochondrial gene expression, decreased mitochondrial membrane potential and ATP level, and increased mitophagy level. Overexpression of Sirt2 improved mitochondrial membrane potential and ATP level and improved mitochondrial function. Furthermore, we found that Sirt2 knockdown in granulosa cells promotes the secretion of P4 through regulating p-ERK1/2. In conclusion the present study showed that SIRT2 is critical for sheep oocyte maturation through regulating the function of ovarian granulosa cells, especially affecting its mitochondrial function.

[Research Updates: The Role of Interaction between Oral Microbiota, Immune Cells, and Epithelial Barrier in Oral Mucosal Homeostasis and Pathogenesis].

In a healthy state, the interaction between the oral microorganisms, mucosal immune cells and epithelial barrier can maintain the oral microecological stability. However, the oral microecology is disrupted under a diseased state and various pathogenic bacteria and their virulence factors and metabolites irritate the immune system, which causes direct or indirect damage to the epithelial barrier, promotes the pathogenesis and progression of oral mucosal diseases, and triggers immune inflammatory response or the irreversible transformation from inflammation into cancer. We herein reviewed the interaction between oral microorganisms, immune cells and epithelial barrier from two perspectives, the maintenance of the oral homeostasis and the pathogenesis of oral mucosal diseases. We intended to gain further understanding of the oral mucosal homeostasis and the mechanism of action of the pathogenesis and progression of oral mucosal diseases, and to provide thereby ideas and scientific and theoretical basis for developing new strategies for the diagnosis and treatment of oral mucosal diseases through re-establishing mucosal homeostasis.

Comparison of colonoscopy after colonic diverticulitis and positive fecal immunochemical tests for the detection of colorectal neoplasia.

Background and study aims The relationship between acute colonic diverticulitis and colorectal cancer (CRC) is unclear, but colonoscopy is recommended to exclude malignancy. We compared the detection rates for colorectal neoplasia in patients with colonic diverticulitis and asymptomatic patients who had positive fecal immunochemical tests (FITs). Patients and methods In total, 282 patients with acute colonic diverticulitis were hospitalized in our hospital from February 2011 to December 2019. Of them, 143 patients with diverticulitis and 1819 with positive FITs patients during the same period underwent colonoscopy without a prior colonoscopy within 5 years. We retrospectively compared these patients in terms of the invasive CRC rate, advanced neoplasia detection rate (ANDR), adenoma detection rate (ADR), and polyp detection rate (PDR). Results Compared to the diverticulitis group, the FIT-positive group had a significantly higher CRC rate (0 vs 2.7 %, P  = 0.0061), ANDR (5.6 vs. 14.0 %, P  = 0.0017), ADR (19.6 vs. 53.2 %, P  < .0001), and PDR (44.1 vs. 91.0 %, P  < .0001). Using 1:1 propensity score matching based on age and sex, we obtained 276 matched patients in both groups. After matching, no difference was found in the CRC rate (0 vs 0.7 %) or ANDR (5.8 vs 7.3 %) between groups, but the ADR and PDR were significantly higher in the FIT-positive group (20.3 vs 43.5 %, P  < .0001; 45.7 % vs 86.2 %, P  < .0001). Conclusion Patients with acute diverticulitis had lower ADRs and PDRs than patients with positive FITs.

Radiation exposure dose of fluoroscopy-guided gastrointestinal procedures: A single-center retrospective study.

Background and study aims Fluoroscopy-guided gastrointestinal procedures (FGPs) are increasingly common. However, the radiation exposure (RE) to patients undergoing FGPs is still unclear. We examined the actual RE of FGPs. Patients and methods This retrospective, single-center cohort study included consecutive FGPs, including endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), enteral stenting, balloon-assisted enteroscopy, tube placement, endoscopic injection sclerotherapy (EIS), esophageal balloon dilatation and repositioning for sigmoid volvulus, from September 2012 to June 2019. We measured the air kerma (AK, mGy), dose area product (DAP, Gycm 2 ), and fluoroscopy time (FT, min) for each procedure. Results In total, 3831 patients were enrolled. Overall, 2778 ERCPs were performed. The median AK, DAP, and FT were as follows: ERCP: 109 mGy, 13.3 Gycm 2 and 10.0 min; self-expandable enteral stenting (SEMS): 62 mGy, 12.4 Gycm 2 and 10.4 min; tube placement: 40 mGy, 13.8 Gycm 2 and 11.1 min; balloon-assisted enteroscopy: 43 mGy, 22.4 Gycm 2 and 18.2 min; EUS cyst drainage (EUS-CD): 96 mGy, 18.3 Gycm 2 and 10.4 min; EIS: 36 mGy, 8.1 Gycm 2 and 4.4 min; esophageal balloon dilatation: 9 mGy, 2.2 Gycm 2 and 1.8 min; and repositioning for sigmoid volvulus: 7 mGy, 4.7 Gycm 2 and 1.6 min. Conclusion This large series reporting actual RE doses of various FGPs could serve as a reference for future prospective studies.

Long non-coding RNA MT1JP exerts anti-cancer effects in breast cancer cells by regulating miR-92-3p.

MT1JP is a LncRNA that is reportedly involved in gastric cancer development, but a biological role and mechanism for MT1JP in breast cancer is unknown. Quantitative RT-PCR was performed to detect the level of MT1JP and miR-92a-3p, and Western blotting assays ware performed to measure the expression of CDK2, cyclinE1, P21, CD151, CD147, MMP2 and MMP9 in breast cells. Subsequently, cell viability was analyzed with CCK-8 assay. Cell migration and invasion were analyzed with Transwell and Scratch Test, respectively. The results demonstrated that MT1JP was significantly down-regulated in breast cells. Additionally, we found that overexpression of MT1JP in breast cancer cells significantly inhibited cell proliferation, migration and invasion, and regulate the expression of CDK2, cyclinE1 and P21. We then investigated a possible mechanism for these results, MT1JP significantly inhibited CD151, CD147, MMP2 and MMP9 protein expression in breast cancer cells. Moreover, we found that MT1JP binds to and negatively regulates miR-92-3p, which is known to be an oncogene in some human cancers. Our data indicate that MT1JP functions as an anti-tumor LncRNA and downregulates miR-92-3p, CD151 and CD147, and may serve as a novel diagnostic and therapeutic marker in breast cancer.

[Bioinformatics analysis of programmed cell death ligand 1 co-expression genes and their regulatory network in head and neck squamous cell carcinoma].

OBJECTIVE: This study aimed to construct a network of programmed celldeath ligand 1 (PD-L1) co-expression genes and screen potential biomarkers for PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) by bioinformatics analysis. Moreover, the genes and pathways participating in PD-L1 and regulating the tumor immune status were determined. METHODS: The HNSCC transcriptomic dataset in TCGA was selected to retrieve gene sets on the cBioPortal platform, where PD-L1 co-expressional genes were acquired. With these genes, GO-BP, KEGG, and string analyses were performed in R clusterProfiler. Cytoscape was used for network analysis and hub gene screening. RESULTS: A total of 117 co-expression genes were obtained, most of which were enriched in immune regulation and response to viral processes. Node degree analysis indicated that STAT1, IFNG, CXCL10, CCR5, FCGR3A, CXCL9, GBP5, CD86, GZMB, IRF1 were the highest connected genes and functioned as hub genes. Survival analysis of these hub genes resulted in CCR5, CXCL9, and GZMB as the prognostic biomarkers for patients with HNSCC, all of which were involved in immune regulation and their expression levels were related to PD-L1 (Pearson correlation coefficient was 0.30, 0.35, 0.39; P<0.01). High expression levels of these three hub genes were protective factors in patients with HNSCC. CONCLUSIONS: PD-L1 co-expression hub genes are related to immunity, among which CCR5, CXCL9, and GZMB are prognostic markers with the possibility to be involved in programmed cell death protein 1 (PD-1)/PD-L1-induced tumor immune escape. These genes provide new clues to study the mechanism and precision target medicine of PD-1/PD-L1 in HNSCC.

Follicular cholangitis mimicking cholangiocarcinoma treated with right hepatectomy: A case report and review of published works.

Follicular cholangitis is a new, rare disease that causes severe biliary stricture. We herein describe the findings from a resected case of follicular cholangitis, suggesting a distinct disease entity that causes benign biliary stricture. A 60-year-old man who was referred to our hospital due to elevated γ-glutamyl transpeptidase levels and dilatation of the B8 bile duct. Although bile juice cytology and bile duct brushing cytology showed no malignancy, the dilatation was progressive. Therefore, right hepatectomy combined with caudate lobectomy was carried out on suspicion of intrahepatic cholangiocarcinoma. The wall of the resected bile duct was markedly thickened due to severe fibrosis under the mucosal layer. Histology of the mucosal epithelium indicated no malignancy. Infiltration of plasma cells characterized by remarkable formation of lymphoid follicles with germinal centers was observed around the bile ducts. The patient was diagnosed with follicular cholangitis based on histological findings. We thus observed a rare case of follicular cholangitis. This case and review of published reports suggest that, despite its rarity, follicular cholangitis should be considered at the differential diagnosis of biliary stricture. This case report could contribute to a better understanding of how to address this disease.

Full-Cell Cycling of a Self-Supporting Aluminum Foil Anode with a Phosphate Conversion Coating.

Aluminum foil is a promising candidate anode material for lithium-ion batteries (LIBs), due to its high theoretical capacity, low lithiation voltage, and abundance. However, as a matter of fact, it has been a great challenge to make Al foil cycle in full cells at industrially acceptable areal capacities of 2-4 mAh/cm2 for commercial 18650 LIBs and some high-power LIBs. In this study, we defined the concepts of electrochemical true contact area (ECA) (areas with perfect electrolyte/electrode contact) and electrochemical noncontact area (ENA) (referred to regions without electrolyte spread on) for the metal foil anode. An initial ECA/ENA partition would cause severe inhomogeneity of the alloying reaction, cause localized electrode pulverization, and exacerbate ECA/ENA inequality even more. Through a phosphate conversion coating on aluminum foil, we killed two birds with one stone: first, the Al foil with a phosphate conversion coating has improved wettability (characterized by the contact angle that decreased from 35.2 to 15.9°) and favors the elimination of ENA, thus guaranteeing uniform electrochemical contact; also, the coating functions as an artificial solid electrolyte interface, which stabilizes the fragile naturally formed solid electrolyte interface and a "steady-state" electrolyte/electrode interface. Therefore, when pairing the phosphated Al foil anode against a commercial LiFePO4 (LFP) cathode (with ∼2.65 mAh/cm2), it can cycle 120 times without Li excess and stabilizes at 1.27 mAh/cm2.

[Congenital infiltrating lipomatosis of face with seizures: a case report].

Congenital infiltrating lipomatosis of the face is a rare disorder resulting from overgrowth of adipose tissues. This condition presents gradually with swelling along with age, hypertrophy of adjacent bones, and tooth abnormalities. This study reports a case of congenital infiltrating lipomatosis of face with seizures and reviews relevant literature on the etiology, clinical symptom, diagnosis, and treatment of this condition.

Evaluation of the Prostate Imaging Reporting and Data System for Magnetic Resonance Imaging Diagnosis of Prostate Cancer in Patients with Prostate-specific Antigen <20 ng/ml.

BACKGROUND: The European Society of Urogenital Radiology has built the Prostate Imaging Reporting and Data System (PI-RADS) for standardizing the diagnosis of prostate cancer (PCa). This study evaluated the PI-RADS diagnosis method in patients with prostate-specific antigen (PSA) <20 ng/ml. METHODS: A total of 133 patients with PSA <20 ng/ml were prospectively recruited. T2-weighted (T2WI) and diffusion-weighted (DWI) magnetic resonance images of the prostate were acquired before a 12-core transrectal prostate biopsy. Each patient's peripheral zone was divided into six regions on the images; each region corresponded to two of the 12 biopsy cores. T2WI, DWI, and T2WI + DWI scores were computed according to PI-RADS. The diagnostic accuracy of the PI-RADS score was evaluated using histopathology of prostate biopsies as the reference standard. RESULTS: PCa was histologically diagnosed in 169 (21.2%) regions. Increased PI-RADS score correlated positively with increased cancer detection rate. The cancer detection rate for scores 1 to 5 was 2.8%, 15.0%, 34.6%, 52.6%, and 88.9%, respectively, using T2WI and 12.0%, 20.2%, 48.0%, 85.7%, and 93.3%, respectively, using DWI. For T2WI + DWI, the cancer detection rate was 1.5% (score 2), 13.5% (scores 3-4), 41.3% (scores 5-6), 75.9% (scores 7-8), and 92.3% (scores 9-10). The area under the curve for cancer detection was 0.700 (T2WI), 0.735 (DWI) and 0.749 (T2WI + DWI). The sensitivity and specificity were 53.8% and 89.2%, respectively, when using scores 5-6 as the cutoff value for T2WI + DWI. CONCLUSIONS: The PI-RADS score correlates with the PCa detection rate in patients with PSA <20 ng/ml. The summed score of T2WI + DWI has the highest accuracy in detection of PCa. However, the sensitivity should be further improved.

[Viral etiologies of hospitalized pneumonia patients aged less than five years in six provinces, 2009-2012].

OBJECTIVE: To analyze the viral etiologies of hospitalized pneumonia patients aged less than five years in six provinces during 2009-2012, and to describe the seasonality of the detected viral etiologies. METHODS: Eight hospitals were selected in six provinces from a national acute respiratory infection surveillance network. Demographic information, clinical history and physical examination, and laboratory testing results of the enrolled hospitalized patients aged less than five years with pneumonia, including respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV)and human bocavirus (hBoV) were analyzed. The viral etiology spectrum of the enrolled patients was analyzed by age-group, year, and seasonality of the detected viral etiologies were described. RESULTS: 4 508 hospitalized children less than five years old, with pneumonia from 8 hospitals were included, and 2 688 (59.6%) patients were positive for at least one viral etiology. The most frequent detected virus was RSV (21.3%), followed by PIV (7.1%) and influenza (5.2%), hBoV (3.8%), ADV(3.6%) and hMPV(2.6%). The lowest positive rates in hCoV(1.1%). RSV, influenza, PIV, hBoV and hMPV all showed the nature of seasonality. CONCLUSION: RSV was a most common viral etiology in the hospitalized young children less than 5 years of age with pneumonia. Prevention measures should be conducted to decrease its severe impact to the young infants and children in China.

Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013.

BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma.

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.

Diagnostic value of interictal diffusion-weighted imaging in evaluation of intractable temporal lobe epilepsy.

OBJECTIVE: To explore the ability of interictal diffusion-weighted imaging (DWI) to localize the temporal lobe of seizure origin and to predict postoperative seizure control in patients with temporal lobe epilepsy (TLE). METHODS: Twenty-seven patients with intractable TLE considered for surgery and 19 healthy volunteers were studied with conventional magnetic resonance imaging (MRI) and DWI. Apparent diffusion coefficients (ADCs) of bilateral hippocampi in both TLE patients and control subjects were obtained. Lateralization to either temporal lobe with hippocampal ADC was based on the threshold values derived from +/- SD of right/left ratios in normal subjects. And the postoperative pathology was reviewed. RESULTS: Hippocampal ADCs were higher on the side of surgery compared with those on the contralateral side as well as the ipsilateral side in control subjects [resected side (109.8 +/- 7.3) x 10(-5) cm2/s, contralateral side (91.7 +/- 4.7) x 10(-5) cm2/s, control subjects (81.6 +/- 5.2) x 10(-5) cm2/s, all P < 0.01]. Right/left hippocampal ADC ratio and conventional MRI lateralized to the operated temporal lobe in 21 of 27 (77.8%) and in 18 of 27 (66.7%) patients. Lateralization to the surgical side was not associated with postoperative seizure control with right/left hippocampal ADC ratio (P > 0.05). CONCLUSIONS: Conventional MRI is a sensitive method to detect hippocampal sclerosis. Accuracy of the right/left hippocampal ADC ratio for lateralizing to the side of surgery is very high, but it isn't a better predictor of surgical outcome.

Differentiation between benign prostatic hyperplasia and prostate cancer in the transitional zone evaluated by 1H magnetic resonance spectroscopic imaging.

OBJECTIVE: To quantitatively evaluate the metabolic changes of benign prostatic hyperplasia (BPH) and prostate cancer in the transitional zone using magnetic resonance spectroscopic imaging (MRSI), and to analyze the characteristics and differences of the spectra in this zonal area. METHODS: Eighteen patients with prostate cancer in the transitional zone underwent magnetic resonance imaging (MRI)/MRSI examinations. The (Choline + Creatine)/Citrate (CC/Ci) ratio and the Choline/Creatine (Cho/Cr) ratio were evaluated in each voxel with cancer or BPH confirmed by pathological results. Discriminant analysis was used to determine the power of the two ratios in differentiation between cancer and BPH. RESULTS: The CC/Ci ratio and Cho/Cr ratio for cancer voxels were significantly higher than those in the voxels with BPH in the transitional zone (CC/Ci: 2.36 +/- 1.31 vs. 0.85 +/- 0.29, P < 0.01; Cho/Cr: 4.14 +/- 1.79 vs. 1.26 +/- 0.45, P < 0.01). As for the discriminant function with the CC/Ci ratio and the Cho/Cr ratio, the specificity, sensitivity, and accuracy were 98.6%, 85.7%, 92.9% respectively for the differentiation between cancer and BPH. CONCLUSIONS: The prostate cancer is characterized by higher CC/Ci ratio and Cho/Cr ratio compared to BPH in the transitional zone. Both CC/Ci ratio and Cho/Cr ratio have high specificity, sensitivity, and accuracy in their discriminative power between cancer and BPH in this zonal area.