A single photoreceptor splits perception and entrainment by cotransmission.

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3-6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7-15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the Drosophila R8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light-dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.

Isolation and characterization of a novel parvovirus from a red-crowned crane, China, 2021.

BACKGROUND: Parvoviruses are icosahedral, nonenveloped viruses with single-stranded DNA genomes of approximately 5 kb in length. In recent years, parvoviruses have frequently mutated and expanded their host range to cause disease in many wild animals by altering their tissue tropism. Animal infection mainly results in acute enteritis and inflammation of other organs. In this study, we used a viral metagenomic method to detect a novel parvovirus species in a red-crowned crane that died due to severe diarrhea in China. RESULTS: The presence of the viral genome in the kidney, lung, heart, liver, and intestine were confirmed by PCR. Histopathological examination of the intestine showed a large number of infiltrated inflammatory cells. The JL21/10 strain of the red-crowned crane parvovirus was first isolated from the intestine. Whole-genome sequence analysis showed that JL21/10 shared high identity with the red-crowned crane Parvovirinae strains yc-8 at the nucleotide level (96.61%). Phylogenetic analysis of the complete genome and NS1 gene revealed that the JL21/10 strain clustered with strains in chicken and revealed a close genetic relationship with the red-crowned crane parvovirus strains.The complete of VP2 gene analysis showed that JL21/10 shared identity with the red-crowned crane yc-8 strains (97.7%), chicken (55.4%),ducks(31.0%) and geese(30.1%) at the amino acid level. The result showed that red-crowned crane parvovirus may be cross-species transmission to chicken. However, There is little possibility of transmission to ducks and geese. CONCLUSION: This is the first isolation and identification of a parvovirus in red-crowned crane that was associated with severe diarrhea.

Homoharringtonine deregulates MYC transcriptional expression by directly binding NF-κB repressing factor.

Homoharringtonine (HHT), a known protein synthesis inhibitor, has an anti-myeloid leukemia effect and potentiates the therapeutic efficacy of anthracycline/cytarabine induction regimens for acute myelogenous leukemia (AML) with favorable and intermediate prognoses, especially in the t(8;21) subtype. Here we provide evidence showing that HHT inhibits the activity of leukemia-initiating cells (Lin-/Sca-1-/c-kit+; LICs) in a t(8;21) murine leukemia model and exerts a down-regulating effect on MYC pathway genes in human t(8;21) leukemia cells (Kasumi-1). We discovered that NF-κB repressing factor (NKRF) is bound directly by HHT via the second double-strand RNA-binding motif (DSRM2) domain, which is the nuclear localization signal of NKRF. A series of deletion and mutagenesis experiments mapped HHT direct binding sites to K479 and C480 amino acids in the DSRM2 domain. HHT treatment shifts NKRF from the nucleus (including nucleoli) to the cytoplasm by occupying the DSRM2 domain, strengthens the p65-NKRF interaction, and interferes with p65-p50 complex formation, thereby attenuating the transactivation activity of p65 on the MYC gene. Moreover, HHT significantly decreases the expression of KIT, a frequently mutated and/or highly expressed gene in t(8;21) AML, in concert with MYC down-regulation. Our work thus identifies a mechanism of action of HHT that is different from, but acts in concert with, the known mode of action of this compound. These results justify further clinical testing of HHT in AML.

Identification of a t(X;17)(q28;q21) generating a KANSL1-MTCP1 gene fusion leading to dysregulated expression of MTCP1 in acute myeloid leukemia.

Chromosomal translocations and generating fusion genes are closely associated with disease initiation and progression in acute myeloid leukemia (AML). In this study, we identified a novel t(X;17)(q28;q21) chromosomal rearrangement in a patient with acute monocytic leukemia. Using RNA-sequencing, we identified a KANSL1-MTCP1 and a KANSL1-CMC4 fusion gene. 5'-UTR sequences of the KANSL1 gene were found to become fused upstream of the coding sequence region of the MTCP1 and CMC4 genes, respectively, resulting in an aberrantly high expression of these genes. Functional studies revealed that overexpression of the MTCP1 gene induced an increased cell proliferation and partial blockage of cell differentiation, suggesting that the aberrant expression of MTCP1 is of critical importance in leukemogenesis.

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway.

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1-15 µM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg-1·d-1, ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

Molecular survey of duck circovirus infection in poultry in southern and southwestern China during 2018 and 2019.

BACKGROUND: Duck circovirus (DuCV) is a potential immunosuppressive virus that causes feather disorders in young ducks. In this study, DuCV obtained from various species of ducks was investigated by polymerase chain reaction (PCR) in southern and southwestern China (Guangdong, Guangxi and Yunnan provinces) from 2018 to 2019. RESULTS: A total of 848 bursa samples were collected from dead Mulard, Cherry Valley Pekin, Muscovy and Mallard ducks from duck farms. The positivity rate of DuCV in the total sample was approximately 36.91%. We found that the prevalence of DuCV in Yunnan (43.09%) was higher than those in Guangxi (34.38%) and Guangdong (34.4%). However, the positivity rates of DuCV in the four duck species were not significantly different (P > 0.05). Nineteen randomly selected complete viral genomes were sequenced. The complete genomes of the DuCV were 1987 to 1995 nt in length, and were 81.7-99.3% homologous to the other 57 sequences in GenBank. Phylogenetic analyses based on the complete genomes of 76 DuCVs showed that the 19 novel DuCV sequences from Guangdong and Guangxi provinces mainly belonged to the DuCV-1 and DuCV-2 genetic groups, respectively. However, the two genotype groups coexisted in Yunnan Province. In addition, recombination analysis showed putative recombination sites in 3 strains in Yunnan that originated from strains Guangdong and Guangxi. Interestingly, the epidemiological investigation showed that Mulard ducks, Cherry Valley Pekin ducks and Muscovy ducks more than 4 weeks old were more susceptible to infection with the novel DuCV than ducks less than 4 weeks old. CONCLUSIONS: These data provide insight into the molecular epidemiology and genetic diversity of DuCVs circulating in southern and southwestern China for the first time.

Age-standardized mortality, disability-adjusted life-years and healthy life expectancy in different cultural regions of Guangdong, China: a population-based study of 2005-2015.

BACKGROUND: Guangdong province is dominated by three cultural regions: Canton, Hakka and Hoklo. However, little is known about the disease burden within these regions, particularly because different population,environmental and socioeconomic risk factors might cause different patterns of mortality, disability-adjusted life-years (DALY), life expectancy and healthy life expectancy (HALE). We aimed to compare the patterns of disease burden in Canton, Hakka and Hoklo regions between 2005 and 2015. METHOD: We calculated the mortality, YLL, YLD for 116 diseases for different cultural regions between 2005 and 2015. We calculated the DALYs for 116 causes as the sum of YLLs and YLDs. We estimated the life expectancy and HALE by using sex-specific mortality rates and YLDs for the three cultural regions. RESULTS: With a respective reduction of 22.3, 15.8 and 17.8% in 2015 compared with 2005, the age-standardized DALY rates in 2015 was 19,988.0, 14,396.5 and 20,436.6 in Hakka, Canton and Hoklo region. Canton region had a significantly lower mortality and DALYs in most diseases, followed by Hoklo and Hakka regions. The life expectancy and HALE at birth were highest in Canton region in both 2005 and 2015, than in Hoklo and Hakka region. CONCLUSIONS: Our findings call for improved public health care via the refinement of policy and effective measures for disease prevention. Understanding the environmental and culture-related risk factors of diseases in Hoklo and Hakka regions may help inform public health sectors to reduce the disease burden and the between-region inequality.

First isolation and characterization of Getah virus from cattle in northeastern China.

BACKGROUND: Getah virus (GETV) is a neglected mosquito-borne Alphavirus that causes pyrexia, body rash, and leg oedema in horses and foetal death and reproductive disorders in pigs. Infected animals may play a critical role in the amplification and circulation of the virus. The present study aimed to investigate GETV infection in clinically infected cattle and vector mosquito species in northeastern China. RESULTS: Serum samples were collected from beef cattle that presented sudden onset of fever in forest grazing areas, and metagenomic sequencing was conducted, revealing 29 contigs from ten serum samples matching the GETV genome. Quantitative RT-PCR (RT-qPCR) was performed with GETV RNA from 48 beef cattle serum samples, showing that the overall prevalence of GETV in the beef cattle samples was 6.25% (3/48). Serological investigation indicated that GETV neutralizing antibodies were detected in 83.3% (40/48, 95% CI 67-100) of samples from the study region. The GETV JL1808 strain was isolated from clinically infected cattle showing fever. Sequence comparisons showed high identity with the HuN1 strain, a highly pathogenic swine epidemic isolate obtained in Hunan province in 2017, at the nucleotide level (99.5%) and at the deduced amino acid level (99.7-99.9%). The phylogenetic analysis of JL1808 clustered in Group III, and also revealed a close genetic relationship with the HuN1 strain. Additionally, about 12,000 mosquitoes were trapped in this region. The presence of GETV infection was detected in mosquitoes, suggesting that the minimum infection rate (MIR) was 1.50‰, with MIRs of 1.67‰ in Culex pseudovishnui, 1.60‰ in Culex tritaeniorhynchus, and 1.21‰ in Anopheles sinensis. CONCLUSIONS: To the best of our knowledge, this is the first report of GETV infection in cattle. These results demonstrated that a highly pathogenic, mosquito-borne swine GETV can infect and circulate in cattle, implying that it is necessary to conduct surveillance of GETV infection in animals in northeastern China.

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast-enhanced magnetic resonance imaging.

To investigate the suppressive effects of xanthatin on glioma growth in a nude mouse xenograft model and rat orthotopic implantation model using magnetic resonance imaging (MRI) to dynamically monitor the antitumour growth and antiangiogenesis effects of xanthatin. The nude mouse xenograft tumour model and rat orthotopic implantation model were established to observe the antitumour effects of xanthatin in vivo. In the rat orthotopic implanted tumour model, MRI scanning was used to dynamically monitor the antitumour growth effect and evaluate the antiangiogenesis effect of xanthatin. We found that xanthatin at a dose of 0.4 mg/10 g dramatically decreased the growth of xenograft tumours in nude mice. The antiangiogenesis effect of xanthatin C6 glioma was evaluated by dynamic contrast-enhanced (DCE) MRI via comparison of the volume transfer constant (Ktrans ) value, a parameter that reflects vessel permeability. We found that xanthatin at the doses of 8 and 16 mg/kg significantly decreased the Ktrans value, which suggests that xanthatin has antiangiogenesis effects. These data demonstrate the suppressive effects of xanthatin on C6 glioma occur via antiangiogenesis. Meanwhile, this study also provides evidence for the application of quantitative parameters of DCE-MRI for dynamically evaluating the growth and angiogenesis of intracranial tumours and for experimental and clinical research.

MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats.

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

[Nicotine- and tar-free cigarette smoke extract reduces the penile erectile function of rats].

OBJECTIVE: To evaluate the impact of nicotine- and tar-free cigarette smoke extract (fCSE) on the serum testosterone (T) level and erectile function of male rats. METHODS: We randomized 30 male SD rats to three groups of equal number to receive subcutaneous injection of PBS (1.0 ml / 300 g body weight per day), fCSE (1.0 ml/300 g body weight per day), and reduced glutathione hormone (GSH, 200 mg per kg body weight per day) in addition to fCSE (fCSE + GSH), respectively, all for 8 weeks. Then we evaluated the erectile function of the rats by measuring the maximal intracavernous pressure (MICP), mean arterial pressure (MAP), ICP/MAP ratio, time of stimulation to MICP (Tmax), and cavernosal filling fate (CFR). We determined the serum T level, the activities of superoxide dismutase (SOD) , malondialdehyde (MDA), and nitric oxide synthase (NOS) in the cavernosal tissue, and also observed the morphological changes of the corpus cavernosum. RESULTS: Compared with the controls, the rats of the fCSE group showed obvious decreases in the levels of serum T ([5.37 ± 1.43] vs [3.22 ± 1.11] µg/L), NOS ([2.90 ± 0.27] vs [1.67 ± 0.18] U/mg) , and SOD ([18.41 ± 1.09] vs [13.36 ± 1.18] U/mg prot) and erectile function-related indexes MICP ([85.92 ± 6.36] vs [58.99 ± 10.76] mmHg), MICP/MAP (0.86 ± 0.09 vs [0.56 ± 0.08]), and CFR (2.14 ± 0.44 vs 0.89 ± 0.44), but markedly increased Tmax ([29.90 ± 5.78] vs [42.90 ± 8.56]s), with a positive correlation between the serum T level and CFR (r = 0. 364, P < 0.05). Masson staining revealed a lower ratio of the corpus cavernosum smooth muscle tissue to collagen fiber in the fCSE group (0.27 ± 0.04) than in the control (0.98 ± 0.12). Compared with the fCSE group, the fCSE + GSH group exhibited significantly improved MICP ([58.99 ± 10.76 ] vs [77.95 ± 7.71] mmHg), MICP/MAP (0.56 ± 0.08 vs 0.77 ± 0.09), and CFR (0.89 ± 0.44] vs 1.76 ± 0.42) and shortened Tmax ([42.90 ± 8.56 ] vs [32.10 ± 5.84 ] s). The ratio of the corpus cavernosum smooth muscle tissue to collagen fiber was higher in the fCSE + GSH than in the fCSE group (0.77 ± 0.09 vs 0.27 ± 0.04) but still lower than in the control (0.98 ± 0.12). CONCLUSION: Nicotine- and tar-free cigarette smoke extract reduces the serum T level and erectile function of rats, which is related to oxidative stress. Antioxidant therapy can improve erectile function but has a limited value for morphological protection of the penile tissue.

A meta-analysis of the intervention effect of mindfulness training on athletes' performance.

Objective: To explore the intervention effect of mindfulness training on athletes' performance using meta-analysis method. Methods: A total of 11 articles and 23 effect sizes were included through retrieval of Chinese and English databases, with a total sample size of 582. Result: Mindfulness training improves the level of mindfulness [SMD =1.08, 95%CI (0.30, 1.86), p < 0.01], fluency (The optimal competitive psychological state of the athlete, the athlete's attention is all focused on the task, and other things no longer attract their attention) [SMD =1.47, 95%CI (0.87, 2.08), p < 0.001] and performance [SMD =0.92, 95% CI (0.40, 1.43), p < 0.01], reduced psychological anxiety [SMD = -0.87, 95% CI (-1.54, -0.20), p < 0.05], and all reached the level of large effect size. Conclusion: The effect of mindfulness training on athletes' sports performance is effective, and it can be used as an effective psychological skill intervention method to improve athletes' sports performance. In the future, we should further expand the sample size, strengthen the comparative study of different sports and intervention modes, and pay attention to the difference between the time effect and trait mindfulness level in fluency state.

Clinical application value of Ultrafast Pulse Wave Velocity in early cardiovascular injury of Immunoglobulin A nephropathy.

AIM: To investigate the application and the related influencing factors of ultrafast pulse wave velocity (ufPWV) in the evaluation of carotid artery elasticity in patients with Immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS: A total of 156 IgAN patients and 50 healthy individuals were selected as the control group. The ufPWV technique was employed to measure carotid arterial elasticity parameters, including carotid intima-media thickness (cIMT), pulse wave velocity at the beginning of systole (BS-PWV) and pulse wave velocity at the end of systole (ES-PWV). RESULTS: Across the three groups (control group, IgAN patients with normal renal function, and IgAN patients with renal dysfunction) there was an increasing trend observed in cIMT, BS-PWV, and ES-PWV. Additionally, ES-PWV exhibited higher sensitivity than BS-PWV. Correlation analysis revealed that BS-PWV and ES-PWV were positively correlated with age, body mass index (BMI), systolic blood pressure (SBP), high-sensitivity C-reactive protein (hs-CRP), creatinine (Cr), blood urea nitrogen (BUN), and uric acid (UA) and negatively correlated with estimated glomerular filtration rate (eGFR). CONCLUSION: The ufPWV technique allows for the rapid and direct measurement of arterial elasticity parameters in the neck and represents a novel approach for the early diagnosis and quantitative assessment of arterial stiffness risk in IgAN patients.

Research progress on venous thrombosis development in patients with malignant tumors.

The coexistence of venous thromboembolism (VTE) within patients with cancer, known as cancer-associated thrombosis (CAT), stands as a prominent cause of mortality in this population. Over recent years, the incidence of VTE has demonstrated a steady increase across diverse tumor types, influenced by several factors such as patient management, tumor-specific risks, and treatment-related aspects. Furthermore, mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes. We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT. This review elucidates the risks, mechanisms, reliable markers, and risk assessment methodologies that can significantly guide effective interventions in clinical practice.

Patterns and drivers of avian taxonomic and phylogenetic beta diversity in China vary across geographical backgrounds and dispersal abilities.

Geographical background and dispersal ability may strongly influence assemblage dissimilarity; however, these aspects have generally been overlooked in previous large-scale beta diversity studies. Here, we examined whether the patterns and drivers of taxonomic beta diversity (TBD) and phylogenetic beta diversity (PBD) of breeding birds in China vary across (1) regions on both sides of the Hu Line, which demarcates China's topographical, climatic, economic, and social patterns, and (2) species with different dispersal ability. TBD and PBD were calculated and partitioned into turnover and nestedness components using a moving window approach. Variables representing climate, habitat heterogeneity, and habitat quality were employed to evaluate the effects of environmental filtering. Spatial distance was considered to assess the impact of dispersal limitation. Variance partitioning analysis was applied to assess the relative roles of these variables. In general, the values of TBD and PBD were high in mountainous areas and were largely determined by environmental filtering. However, different dominant environmental filters on either side of the Hu Line led to divergent beta diversity patterns. Specifically, climate-driven species turnover and habitat heterogeneity-related species nestedness dominated the regions east and west of the line, respectively. Additionally, bird species with stronger dispersal ability were more susceptible to environmental filtering, resulting in more homogeneous assemblages. Our results indicated that regions with distinctive geographical backgrounds may present different ecological factors that lead to divergent assemblage dissimilarity patterns, and dispersal ability determines the response of assemblages to these ecological factors. Identifying a single universal explanation for the observed pattern without considering these aspects may lead to simplistic or incomplete conclusions. Consequently, a comprehensive understanding of large-scale beta diversity patterns and effective planning of conservation strategies necessitate the consideration of both geographical background and species dispersal ability.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism.

BACKGROUND: The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear. AIM: To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation. METHODS: A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH. RESULTS: MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones. CONCLUSION: MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

[Analysis of deaths caused by secondary damages of road traffic accidents: 17 fatal cases].

OBJECTIVE: To explore the forensic identification points of deaths caused by secondary damages of road traffic accidents. METHODS: Seventeen deaths caused by secondary damages of road traffic accidents were collected. Through scene investigation and necropsy, the basic information of the accidents, distribution and property of the injuries, and other information were collected. According to the collected data, the scene was reconstructed in order to confirm the injury process, analyze the way, mechanism and severity of injury, distinguish antemortem injury from postmortem injury, and determine the cause of deaths. RESULTS: Certain features such as serious injuries, multiple traumas, combined injuries, co-existence of antemortem and postmortem injuries, multiple causes of wounds, complex injury mechanism, as well as the mutual damaging and overlapping injuries were quite characteristically noted in these secondary traffic accident cases. CONCLUSION: Forensic assessment of deaths caused by secondary damages of road traffic accidents should be synthetically analyzed and judged through scene investigation and necropsy.

Hypoxia-inducible factor-1 up-regulates the expression of Toll-like receptor 4 in pancreatic cancer cells under hypoxic conditions.

BACKGROUND & AIMS: Hypoxia is a common characteristic of solid tumors. Recent studies confirmed that Toll-like receptor 4 (TLR4) plays a significant role in cancer invasion and progression. In this study, the correlation between the expression of TLR4 and the change of the protein level of Hypoxia-inducible factor-1 alpha (HIF-1α) was studied. METHODS: We examined 84 human pancreatic cancer tissues for expression of HIF-1α and TLR4 proteins. Panc-1 cells were exposed to normoxia (20% O(2)) or hypoxia (<1% O(2)) or treated with CoCl(2). TLR4 protein was analyzed by flow cytometry and immunostaining. Growth studies were conducted on cells with the HIF-1α inhibition isolated from stable transfected cell lines. Finally, TLR4 protein was detected by immunohistochemistry in vivo tumors. RESULTS: There was a positive correlation between TLR4 and HIF-1α protein in pancreatic cancer tissues. Hypoxic stress induced TLR4 mRNA and protein expression in Panc-1 cells. Cells transfected with HIF-1α siRNA showed attenuation of hypoxia stress-induced TLR4 expression. In vivo growth decreased in response to TLR4 and HIF-1α inhibiton. Transient HIF-1α siRNA treatment could effectively curb tumor growth in vivo. CONCLUSION: These results suggest that TLR4 expression in pancreatic cancer cells is up-regulated via HIF-1α in response to hypoxic stress and underscore the crucial role of HIF-1α-induced TLR4 in tumor growth.

Identification of a Nomogram with an Autophagy-Related Risk Signature for Survival Prediction in Patients with Glioma.

BACKGROUND: Glioma is a common type of tumor in the central nervous system characterized by high morbidity and mortality. Autophagy plays vital roles in the development and progression of glioma, and is involved in both normal physiological and various pathophysiological progresses. PATIENTS AND METHODS: A total of 531 autophagy-related genes (ARGs) were obtained and 1738 glioma patients were collected from three public databases. We performed least absolute shrinkage and selection operator regression to identify the optimal prognosis-related genes and constructed an autophagy-related risk signature. The performance of the signature was validated by receiver operating characteristic analysis, survival analysis, clinic correlation analysis, and Cox regression. A nomogram model was established by using multivariate Cox regression analysis. Schoenfeld's global and individual test were used to estimate time-varying covariance for the assumption of the Cox proportional hazard regression analysis. The R programming language was used as the main data analysis and visualizing tool. RESULTS: An overall survival-related risk signature consisting of 15 ARGs was constructed and significantly stratified glioma patients into high- and low-risk groups (P < 0.0001). The area under the ROC curve of 1-, 3-, 5-year survival was 0.890, 0.923, and 0.889, respectively. Univariate and multivariate Cox analyses indicated that the risk signature was a satisfactory independent prognostic factor. Moreover, a nomogram model integrating risk signature with clinical information for predicting survival rates of patients with glioma was constructed (C-index=0.861±0.024). CONCLUSION: This study constructed a novel and reliable ARG-related risk signature, which was verified as a satisfactory prognostic marker. The nomogram model could provide a reference for individually predicting the prognosis for each patient with glioma and promoting the selection of optimal treatment.