Melanopsin retinal ganglion cells mediate light-promoted brain development.

During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.

Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999-2018.

OBJECTIVE: Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. METHODS: This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. RESULTS: During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. CONCLUSIONS: This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

Thoracoscopic right upper lobectomy in a patient with displaced posterior segmental bronchus and vascular abnormalities: a case report.

BACKGROUND: Displaced posterior segmental bronchus (B2) accompanied by anomalous pulmonary vessels is a very rare condition. There is a risk of unexpected injuries to bronchi and blood vessels when patients with such anomalies undergo surgery for lung cancer, especially thoracoscopic surgery. METHODS: We reported a case of thoracoscopic right upper lobectomy in a patient with a displaced B2 and pulmonary vascular variation. RESULTS: A 74-year-old woman was admitted to our hospital with a 2.2 cm × 2.1 cm nodule in the right lung. Three-dimensional computed tomography (3D-CT) revealed the combined apical/anterior segmental branch (B1 + 3) taken off the beginning of the right main bronchus (RMB), at the level of the carina. The displaced B2 taken off the end of the RMB. The anomalous central vein (CV), which passed between B2 and B1 + 3, ran dorsal to the main pulmonary artery (MPA) and directly into the left atrium. The patient consequently underwent uniportal thoracoscopic right upper lobectomy and mediastinal lymph node dissection. The intraoperative findings were completely consistent with 3D-CT. CONCLUSIONS: This paper reports a case of a displaced B2 combined with right upper pulmonary vessels malformation. Under the guidance of 3D-CT, the right upper lobectomy was successfully completed by single hole thoracoscopic surgery.

Enhanced recovery after surgery for primary total hip arthroplasty: analysis of post-operative blood indexes.

INTRODUCTION: To explore the clinical efficacy of the enhanced recovery after surgery (ERAS) program in terms of blood management for primary hip arthroplasty patients. METHOD: Ninety cases of total hip arthroplasty in our hospital from October 2020 to January 2022 were selected as the research objects, 45 cases as the control group, and 45 cases as the ERAS group. The control group was given routine care after operation, while the ERAS group was given ERAS management. The leucocytes, haemoglobin, platelets, albumin, D-dimer, C-reactive protein (CRP), total length of stay (LOS), and estimated blood loss after operation were compared between the two groups. RESULTS: The results showed that the Hb, TPO, and Alb of the ERAS group before operation, one day and three days after operation were significantly higher than those of the control group (P < 0.05). The WBC, CRP, and D-dimer in ERAS group were significantly lower than those in the control group (P < 0.05). The LOS in ERAS group was significantly less than that in control group (P < 0.05). DISCUSSION: ERAS scheme can reduce the loss of blood and nutrients from surgery in patients. WBC, CRP, and D-dimer in ERAS group were significantly lower than those in the control group. Humane care from ERAS programs can relieve patients' anxiety to some extent. CONCLUSION: ERAS management contributes to the recovery of hip function in patients undergoing THA, reduces blood loss during peri-operative period, and reduces the effect of operation on blood system.

Curcumin protects retinal neuronal cells against oxidative stress-induced damage by regulating mitochondrial dynamics.

Oxidative stress plays a crucial role in the damage of retinal neuronal cells. Curcumin, the phytocompound, has anti-inflammatory and antioxidative properties. It was shown that curcumin exerted a beneficial effect on retinal neuronal cell survival. However, the role of mitochondrial dynamics in curcumin-mediated protective effect on retinal neuronal cells remains to be elucidated. Here, H2O2 was used to mimic the oxidative stress in retinal neuronal R28 cells. Drp1 and Mfn2 are key regulators of mitochondrial fission and fusion. 100 µM of H2O2 significantly increased the cleavage of caspase-3 and Drp1 expression, but downregulated the expression of Mfn2. Pretreatment with 5 µM curcumin effectively alleviated H2O2-induced alterations in the expression of Drp1 and Mfn2 and mitochondrial fission in R28 cells. In addition, curcumin and Drp1 knockdown prevented H2O2-induced intracellular ROS increment and mitochondrial membrane potential disruption. On the contrary, knockdown of Mfn2 diminished curcumin-mediated protection against ROS increment and mitochondrial membrane potential disruption after H2O2. Moreover, curcumin protected R28 cells against H2O2-induced PINK1 expression, mitophagy, caspase-3 cleavage and apoptosis. Knockdown of Mfn2 significantly alleviated the protective effect of curcumin on R28 cells after H2O2. Taken together, our data indicate that curcumin protects against oxidative stress-induced injury in retinal neuronal cells by promoting mitochondrial fusion.

Research progress of extracellular vesicles in type 2 diabetes and its complications.

Type 2 diabetes is one of the most common chronic diseases in modern society. However, there is still insufficient research on the pathogenesis, diagnosis and treatment of type 2 diabetes and its complications. Extracellular vesicles are small bilayer vesicles secreted by cells. In recent years, the effect of extracellular vesicles in type 2 diabetes and its complications has aroused extensive attention. The research on the influence of protein and nucleic acids carried by extracellular vesicles secreted by stem cells and inflammatory cells on the pathogenesis of type 2 diabetes and its complications provides new ideas for its diagnosis and treatment. This review focuses on the influence of extracellular vesicles on insulin resistance by regulating inflammation and glucose transporter 4 expression. The second part mainly discusses the research progress and limitations of extracellular vesicles use in treating and diagnosing type 2 diabetes and its complications. This review introduces the current research status of type 2 diabetes and its complications, illustrates the biogenesis of extracellular vesicles, their effect on type 2 diabetes pathogenesis and its complications and their potential as therapeutic tools and diagnostic markers in type 2 diabetes and its complications.

Gallbladder-preserving polypectomy for gallbladder polyp by embryonic-natural orifice transumbilical endoscopic surgery with a gastric endoscopy.

BACKGROUND AND AIMS: Cholecystectomy is performed for most gallbladder polyps (GPs). However, cholecystectomy results concerning complications in some patients. For benign GPs, adoption of gallbladder-preserving surgery is worth to recommend. We describe our experiences performing gallbladder-preserving polypectomy for GPs by embryonic-natural orifice transumbilical endoscopic surgery (E-NOTES) with a gastric endoscopy. METHODS: This is a retrospective study of patients with GPs who underwent gallbladder-preserving polypectomy by E-NOTES with a gastric endoscopy from April 2018 to September 2019 in our hospital. The operative time, intraoperative hemorrhage, intraoperative and postoperative complications, gallbladder emptying function were obtained and analyzed. RESULTS: The procedure was performed successfully in all 12 patients with 5 cases of single polyp and 7 cases of multiple polyps. The range of GPs size was 2 mm to 15 mm. The mean operation time was (95.33 ± 23.08) minutes (55-135 min). There were no adverse events including heavy bleeding, mortality and conversion to open surgery during operation. All patients were discharged in 4-5 days after surgery without postoperative complications such as delayed bleeding, fever, peritonitis, intra-abdominal abscess and abdominal wall incisional hernia. All patients were followed up at 1, 3, 6, and 12 months postoperation who had almost no visible incision on the umbilical region, no recurrent GPs. The gallbladder emptying function decreased one month after surgery, and gradually improved 3, 6 and 12 months after surgery. CONCLUSION: E-NOTES gallbladder-preserving polypectomy is a safe and effective option for patients with GPs and is close to scar-free surgery which can be performed in routine clinical practice.

Transmission roles of symptomatic and asymptomatic COVID-19 cases: a modelling study.

Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9-80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0-34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.

Influence of Postoperative Serum Inflammatory Factors, Stress Indicators, Urination Function, Sexual Function and Clinical Efficacy of Laparoscopic Pelvic Floor Reconstruction without Mesh Implantation in the Treatment of Pelvic Organ Prolapse.

Pelvic organ prolapse is seriously harmful to women's health and daily activities, and the incidence rate increases with age, which is more common among middle-aged and elderly women. Common treatment schemes are prone to relapse or complications. The purpose of this article was to study the clinical effect of laparoscopic pelvic floor reconstruction without mesh implantation in the treatment of pelvic organ prolapse and the influence of postoperative serum inflammatory factors, stress indicators, urination function and sexual function. The clinical curative effect of the operation plan was evaluated by the determination of POP-Q value and objective cure rate. The enzyme-linked immunosorbent assay determined the serum inflammatory factors and stress indexes before and after the operation. Urination function was detected by a urodynamics detector, and sexual function was investigated by a PISQ-12 questionnaire. The results show that laparoscopic pelvic floor reconstruction without mesh implantation has good clinical efficacy in the treatment of pelvic organ prolapse, with less stimulation to patients and less inflammation. After the operation, the patient's maximum urine flow rate exceeded 18mL/s, the sexual function score exceeded 45 points, and the urination function and sexual function were effectively improved.

An iteration model for identifying essential proteins by combining comprehensive PPI network with biological information.

BACKGROUND: Essential proteins have great impacts on cell survival and development, and played important roles in disease analysis and new drug design. However, since it is inefficient and costly to identify essential proteins by using biological experiments, then there is an urgent need for automated and accurate detection methods. In recent years, the recognition of essential proteins in protein interaction networks (PPI) has become a research hotspot, and many computational models for predicting essential proteins have been proposed successively. RESULTS: In order to achieve higher prediction performance, in this paper, a new prediction model called TGSO is proposed. In TGSO, a protein aggregation degree network is constructed first by adopting the node density measurement method for complex networks. And simultaneously, a protein co-expression interactive network is constructed by combining the gene expression information with the network connectivity, and a protein co-localization interaction network is constructed based on the subcellular localization data. And then, through integrating these three kinds of newly constructed networks, a comprehensive protein-protein interaction network will be obtained. Finally, based on the homology information, scores can be calculated out iteratively for different proteins, which can be utilized to estimate the importance of proteins effectively. Moreover, in order to evaluate the identification performance of TGSO, we have compared TGSO with 13 different latest competitive methods based on three kinds of yeast databases. And experimental results show that TGSO can achieve identification accuracies of 94%, 82% and 72% out of the top 1%, 5% and 10% candidate proteins respectively, which are to some degree superior to these state-of-the-art competitive models. CONCLUSIONS: We constructed a comprehensive interactive network based on multi-source data to reduce the noise and errors in the initial PPI, and combined with iterative methods to improve the accuracy of necessary protein prediction, and means that TGSO may be conducive to the future development of essential protein recognition as well.

MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans.

A large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. Genetic and pharmacologic evidence in humans and animals suggests that reducing factor XI (FXI) levels has the potential to effectively prevent and treat thrombosis with a minimal risk of bleeding. We generated a fully human antibody (MAA868) that binds the catalytic domain of both FXI (zymogen) and activated FXI. Our structural studies show that MAA868 traps FXI and activated FXI in an inactive, zymogen-like conformation, explaining its equally high binding affinity for both forms of the enzyme. This binding mode allows the enzyme to be neutralized before entering the coagulation process, revealing a particularly attractive anticoagulant profile of the antibody. MAA868 exhibited favorable anticoagulant activity in mice with a dose-dependent protection from carotid occlusion in a ferric chloride-induced thrombosis model. MAA868 also caused robust and sustained anticoagulant activity in cynomolgus monkeys as assessed by activated partial thromboplastin time without any evidence of bleeding. Based on these preclinical findings, we conducted a first-in-human study in healthy subjects and showed that single subcutaneous doses of MAA868 were safe and well tolerated. MAA868 resulted in dose- and time-dependent robust and sustained prolongation of activated partial thromboplastin time and FXI suppression for up to 4 weeks or longer, supporting further clinical investigation as a potential once-monthly subcutaneous anticoagulant therapy.

A novel computational model for predicting potential LncRNA-disease associations based on both direct and indirect features of LncRNA-disease pairs.

BACKGROUND: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with human diseases, and it is useful for the diagnosis and treatment of diseases to get the relationships between lncRNAs and diseases. Due to the high costs and time complexity of traditional bio-experiments, in recent years, more and more computational methods have been proposed by researchers to infer potential lncRNA-disease associations. However, there exist all kinds of limitations in these state-of-the-art prediction methods as well. RESULTS: In this manuscript, a novel computational model named FVTLDA is proposed to infer potential lncRNA-disease associations. In FVTLDA, its major novelty lies in the integration of direct and indirect features related to lncRNA-disease associations such as the feature vectors of lncRNA-disease pairs and their corresponding association probability fractions, which guarantees that FVTLDA can be utilized to predict diseases without known related-lncRNAs and lncRNAs without known related-diseases. Moreover, FVTLDA neither relies solely on known lncRNA-disease nor requires any negative samples, which guarantee that it can infer potential lncRNA-disease associations more equitably and effectively than traditional state-of-the-art prediction methods. Additionally, to avoid the limitations of single model prediction techniques, we combine FVTLDA with the Multiple Linear Regression (MLR) and the Artificial Neural Network (ANN) for data analysis respectively. Simulation experiment results show that FVTLDA with MLR can achieve reliable AUCs of 0.8909, 0.8936 and 0.8970 in 5-Fold Cross Validation (fivefold CV), 10-Fold Cross Validation (tenfold CV) and Leave-One-Out Cross Validation (LOOCV), separately, while FVTLDA with ANN can achieve reliable AUCs of 0.8766, 0.8830 and 0.8807 in fivefold CV, tenfold CV, and LOOCV respectively. Furthermore, in case studies of gastric cancer, leukemia and lung cancer, experiment results show that there are 8, 8 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with MLR, and 8, 7 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with ANN, having been verified by recent literature. Comparing with the representative prediction model of KATZLDA, comparison results illustrate that FVTLDA with MLR and FVTLDA with ANN can achieve the average case study contrast scores of 0.8429 and 0.8515 respectively, which are both notably higher than the average case study contrast score of 0.6375 achieved by KATZLDA. CONCLUSION: The simulation results show that FVTLDA has good prediction performance, which is a good supplement to future bioinformatics research.

CCL18-dependent translocation of AMAP1 is critical for epithelial to mesenchymal transition in breast cancer.

AMAP1 was a GTPase-activating protein that regulates cytoskeletal structures in focal adhesions, circular dorsal ruffles, and promote cell differentiation in tumor cells. But the activation and function of AMAP1 in breast cancer remain largely unexplored. Here we show that AMAP1 was phosphorylated and translocated to plasma membrane and formed a stable complex with Pyk2 in response to CCL18. Moreover, CCL18-dependent AMAP1 translocation interfered the AMAP1-IKK-ß interaction, resulting in nuclear factor-kappaB (NF-κB) activation. Depletion of AMAP1 expression by RNAi efficiently reversed the CCL18-induced epithelial to mesenchymal transition (EMT) of breast cancer cells and as well as CCL18-induced adhesion, migration and invasion. Strikingly, AMAP1 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognosis in breast cancers. Given that AMAP1 mediated CCL18-induce activation of NF-κB and promoted breast cancer metastasis, AMAP1 may represent a therapeutic target for the eradication of breast cancer metastasis.

Triptolide inhibits the proliferation and migration of medulloblastoma Daoy cells by upregulation of microRNA-138.

Medulloblastoma is a primitive neuroectodermal-derived brain tumor and the most common malignant brain tumor in children. Triptolide (TPL) is the major active component extracted from Tripterygium wilfordii Hook F. This study aimed to explore the effects of TPL on medulloblastoma cell proliferation, migration, and apoptosis, as well as the underlying possible molecular mechanism. Viability, proliferation, and apoptosis of Daoy cells were measured using cell counting kit-8 assay, 5-bromo-2'-deoxyuridine incorporation assay, and Guava Nexin assay, respectively. Cell migration was detected using two-chamber transwell assay and wound healing assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to determine the relative expression of microRNA-138 (miR-138) in Daoy cells. Cell transfection was used to change the expression of miR-138 in cells. Western blot analysis was used to analyze the expression of key factors involved in cell apoptosis, cell migration, the phosphatidylinositol 3-kinase (PI3K)/protein kinase 3 (AKT) pathway, and the Notch pathway in Daoy cells. We found that TPL significantly inhibited the viability, proliferation, and migration of Daoy cells but promoted Daoy cell apoptosis. The expression levels of matrix metalloproteinases (MMP)-2 and MMP-9 after TPL treatment were decreased. The expression of miR-138 in Daoy cells after TPL treatment was increased. Suppression of miR-138 obviously reversed the TPL-induced Daoy cell proliferation, migration inhibition, and cell apoptosis enhancement, as well as the inactivation of the PI3K/AKT and Notch pathways. Cyclin-dependent kinase 6 (CDK6) was a direct target gene of miR-138, which might be involved in the antitumor effects of TPL on Daoy cells. In conclusion, our study verified that TPL exerted anticancer effects on medulloblastoma cells possibly via upregulating miR-138 and inactivating the PI3K/AKT and Notch pathways.

Five-year outcomes following hypofractionated stereotactic radiotherapy delivered in five fractions for acoustic neuromas: the mean cochlear dose may impact hearing preservation.

BACKGROUND: The aim of this study was to assess the clinical outcomes of acoustic neuromas (ANs) treated with hypofractionated stereotactic radiotherapy (hypo-FSRT) prescribed at a uniform dose. METHODS: Forty-seven patients with a unilateral AN were treated consecutively with hypo-FSRT between February 2007 and March 2012. Nineteen patients maintained a serviceable hearing status at the beginning of hypo-FSRT. The prescribed dose was 25 Gy delivered in five fractions per week to the isocenter, and the planning target volume was covered by the 80% isodose line. RESULTS: The median follow-up and audiometric follow-up periods were 61 and 52 months, respectively. The estimated tumor control rate at 5 years was 90% (95% CI 76-96). The existence of the cystic component before hypo-FSRT had a significantly worse impact on tumor control (p = 0.02). The estimated hearing preservation rates at 1, 3 and 5 years were 68% (95% CI 42-84), 41% (95% CI 20-62) and 36% (95% CI 15-57), respectively. A borderline significant difference was identified in the mean biological effective dose with an α/ß value of 3 Gy (BED3) to the ipsilateral cochlea between the preserved hearing and hearing loss groups (19 Gy vs. 28 Gy) (p = 0.08). CONCLUSIONS: Hypo-FSRT delivered in five fractions for unilateral ANs may achieve excellent tumor control with no severe facial or trigeminal complications. The mean BED3 in the cochlea may impact the hearing preservation rate. Therefore, the cochlear dose should be as low as possible.

Measles vaccination coverage, determinants of delayed vaccination and reasons for non-vaccination among children aged 24-35 months in Zhejiang province, China.

BACKGROUND: This study was aimed to assess the coverage of two doses of measles vaccine and identify the determinants of the delayed vaccination. METHODS: A cluster survey among 1386 children aged 24-35 months was conducted. Characteristics on demographic and socio-economic and vaccination records was collected. The overall coverage was defined as the proportion of children receiving the first dose of measles vaccination and the second dose of measles vaccination by 24 months of age. The age-appropriate coverage was defined as the proportion of children receiving the measles vaccine doses within one month after its relevant due date. Timeliness was evaluated with the Kaplan-Meier analysis. Cox proportional hazard regression was adopted to identify determinants of the delayed vaccination. RESULTS: The overall coverage was 96.9% for the first dose of measles vaccine and 93.9% for the second dose of measles vaccine. The age-appropriate coverage of the first and the second dose of measles vaccine was 76.6 and 68.2%, respectively. Household having more than one child, non-local children were associated with the delayed vaccination for the first and the second dose of measles vaccine. Children delivered at home, younger mothers, low maternal education background, mothers with a fixed job, and low household income were associated with the delayed vaccination for the second dose of measles vaccine. CONCLUSIONS: The coverage of measles vaccine had been improved for both the first and the second dose, while the timeliness still needed improvement. We suggested the policy-makers pay more attention to the reasons for non-vaccination and determinants of delayed vaccination when planning efforts to ensure the high age-appropriate coverage of measles vaccination.

Expression of a Grape VqSTS36-Increased Resistance to Powdery Mildew and Osmotic Stress in Arabidopsis but Enhanced Susceptibility to Botrytis cinerea in Arabidopsis and Tomato.

Stilbene synthase genes make a contribution to improving the tolerances of biotic and abiotic stress in plants. However, the mechanisms mediated by these STS genes remain unclear. To provide insight into the role of STS genes defense against biotic and abiotic stress, we overexpressed VqSTS36 in Arabidopsis thaliana and tomato (Micro-Tom) via Agrobacterium-mediated transformation. VqSTS36-transformed Arabidopsis lines displayed an increased resistance to powdery mildew, but both VqSTS36-transformed Arabidopsis and tomato lines showed the increased susceptibility to Botrytis cinerea. Besides, transgenic Arabidopsis lines were found to confer tolerance to salt and drought stress in seed and seedlings. When transgenic plants were treated with a different stress, qPCR assays of defense-related genes in transgenic Arabidopsis and tomato suggested that VqSTS36 played a specific role in different phytohormone-related pathways, including salicylic acid, jasmonic acid, and abscisic acid signaling pathways. All of these results provided a better understanding of the mechanism behind the role of VqSTS36 in biotic and abiotic stress.

Epidemiology of human infections with avian influenza A(H7N9) virus in China.

BACKGROUND: The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. METHODS: Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. RESULTS: Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus. CONCLUSIONS: Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.