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Myopia has become a global public health problem due to high prevalence. Although the etiological factors of myopia have been gradually recognized, the underlying mechanism remains largely elusive. Choroidal vascular dysfunction is recognized as a critical vision-threatening complication in myopia. Circular RNAs (circRNAs) are shown as the critical regulators in many biological processes and human diseases. In this study, we investigated the role of circRNAs in choroidal vascular dysfunction in myopia. The level of circFoxO1 was significantly upregulated in myopic choroid. circFoxO1 silencing suppressed choroidal endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviated choroidal vascular dysfunction in vivo and ex vivo. circFoxO1 silencing retarded the progression of myopia as shown by reduced extracellular matrix remodeling and improved refractive error and axial elongation. Mechanistically, circFoxO1 acted as the sponge of miR-145 to sequester and inhibit miR-145 activity, thereby inducing VEGFA or ANGPT2 expression. miR-145 could mimic the effects of circFoxO1 silencing on choroidal endothelial phenotypes. Collectively, intervention of choroidal vascular dysfunction via regulating circFoxO1 level is a potential strategy for the prevention and management of myopia.

Background The COVID-19 pandemic and relevant prevention and control measures may affect the mental health and induce depressive symptoms in fathers with concurrent partner delivery exposure. This study aims to investigate the prevalence of depression in fathers with simultaneous exposure to COVID-19 pandemic and the effects of family functions on paternal perinatal depression (PPD) risk. Methods A cross-sectional study was conducted among the perinatal fathers recruited in a large tertiary hospital in Wuhan across the whole pandemic period from 31 December 2019 to 11 April 2020. Edinburgh Postnatal Depression Scale (EPDS) and APGAR family function scale were used to evaluate PPD and family function, respectively. Chi-square test and multivariable-adjusted logistic regression model were applied for data analysis. Results Among the 1187 participants, the prevalence of PPD was 13.82% throughout the COVID-19 pandemic. Compared with that in the time period before the announcement of human-to-human transmission on 19 January 2020, the depression risk was significantly lower during the traffic restriction (OR = 0.54, 95% CI: 0.34, 0.86) and public transportation reopening periods (OR = 0.29, 95% CI: 0.14, 0.59). Poor/fair family functions was associated with elevated depression risk (OR = 2.93, 95% CI: 1.90, 4.52). Individuals reporting a low family income and smoking had high depression risks. Conclusions A declined risk of PPD was observed over the traffic restriction period of the COVID-19 pandemic. An improved family function may help alleviate the risk of PPD during the pandemic. Health authorities are recommended to formulate targeted prevention and control strategies to handle PPD.

Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4α (HNF4A; NR2A1), and retinoid-related orphan receptor γ (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC.

Background/objectives To identify visual trajectories and examine their relationships with physical and cognitive function in older Chinese adults. Design Population-based longitudinal study. Setting The Chinese Longitudinal Healthy Longevity Survey. Participants A total of 16,151 participants aged ≥65 years. Measurements Visual, physical (including activities of daily living [ADL] and instrumental ADL [IADL]), and cognitive function were assessed at baseline and subsequently every 3 years. ADI disability and IADL disability were defined as needing any help in any item of the Katz scale and a modified Lawton's scale, respectively. Cognitive impairment was defined as a Chinese version of the Mini-Mental State Examination score below 24. A group-based trajectory model was used to determine visual trajectories adjusted for age, sex, and education. Associations of visual trajectories with ADL disability, IADL disability, and cognitive impairment were evaluated using generalized estimating equation models adjusted for potential confounders. Results This study identified three distinct visual trajectories, including no decline (32.4%), moderate decline (48.3%), and progressive decline (19.3%) during the follow-up period. Compared with the no decline trajectory, both the moderate decline (ADL disability: OR = 2.75, 95% CI: 2.30-3.28; IADL disability: OR = 3.01, 95% CI: 2.74-3.31; cognitive impairment: OR = 3.37, 95% CI: 3.02-3.76) and the progressive decline (ADL disability: OR = 8.50, 95% CI: 6.55-11.02; IADL disability: OR = 12.96, 95% CI: 9.95-16.87; cognitive impairment: OR = 10.84, 95% CI: 8.89-13.23) trajectories were significantly associated with an increased risk of functional impairment. Compared with the moderate decline trajectory, the progressive decline trajectory was significantly associated with an increased risk of ADL disability (OR = 3.09, 95% CI: 2.46-3.89), IADL disability (OR = 4.30, 95% CI: 3.29-5.61), and cognitive impairment (OR = 3.22, 95% CI:2.63-3.93). Conclusion Older Chinese adults exhibit three distinct visual trajectories and those with decline trajectories in vision have an increased risk of functional impairment than those with a trajectory of no decline in vision.

Background Astrocytes in the rostral ventromedial medulla (RVM) contribute to descending pain modulation, but their role in oro-facial pain induced by persistent experimental dental occlusal interference (PEOI) or following EOI removal (REOI) is unknown. Objective To explore the involvement of RVM astrocytes in PEOI-induced oro-facial hyperalgesia or its maintenance following REOI. Methods Male rats were randomly assigned into five groups: sham-EOI, postoperative day 6 and 14 of PEOI (PEOI 6 d and PEOI 14 d), postoperative day 6 following REOI on day 3 (REOI 3 d) and postoperative day 14 following REOI on day 8 (REOI 8 d). The nociceptive head withdrawal threshold (HWT) and activities of RVM ON- or OFF-cells were recorded before and after intra-RVM astrocyte gap junction blocker carbenoxolone (CBX) microinjection. RVM astrocytes were labelled immunohistochemically with glial fibrillary acidic protein (GFAP) and analysed semi-quantitatively. Results Persistent experimental dental occlusal interference-induced oro-facial hyperalgesia, as reflected in decreased HWTs, was partially inhibited by REOI at day 3 but not at day 8 after EOI placement. Increased GFAP-staining area occurred only in REOI 8 d group in which CBX could inhibit the maintained hyperalgesia; CBX was ineffective in inhibiting hyperalgesia in PEOI 14 d group. OFF-cell activities showed no change, but the spontaneous activity and responses of ON-cells were significantly enhanced that could be suppressed by CBX in REOI 8 d group. Conclusion Rostral ventromedial medulla astrocytes may not participate in PEOI-induced oro-facial hyperalgesia or hyperalgesia inhibition by early REOI but are involved in the maintenance of oro-facial hyperalgesia by late REOI.

Centromeres are chromosomal loci marked by histone variant CenH3 (centromeric histone H3) and essential for genomic stability and cell division. The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast CenH3 (Cse4) for ubiquitination and controls the cellular level of Cse4 for proteolysis, but the underlying mechanism remains largely unknown. Here, we show that Psh1 uses a Cse4-binding domain (CBD, residues 1–211) to interact with Cse4-H4 instead of H3-H4, yielding a dissociation constant (Kd) of 27 nM. Psh1 recognizes Cse4-specific residues in the L1 loop and α2 helix to ensure Cse4 binding and ubiquitination. We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination. Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding. Together, our study reveals a novel Cse4-binding mode distinct from those of known CenH3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding.

Terpenoids represent one of the largest class of chemicals in nature, which play important roles in food and pharmaceutical fields due to diverse biological and pharmacological activities. Microorganisms are recognized as a promising source of terpenoids due to its short growth cycle and sustainability. Importantly, microalgae can fix inorganic carbon through photosynthesis for the growth of themselves and the biosynthesis of various terpenoids. Moreover, microalgae possess effective biosynthesis pathways of terpenoids, both the eukaryotic mevalonic acid (MVA) pathway and the prokaryotic methyl-D-erythritol 4-phosphate (MEP) pathway. In recent years, various genetic engineering strategies have been applied to increase target terpenoid yields, including overexpression of the rate-limited enzymes and inhibition of the competing pathways. However, since gene-editing tools are only built in some model microalgae, fermentation strategies that are easier to be operated have been widely successful in promoting the production of terpenoids, such as changing culture conditions and addition of chemical additives. In addition, an economical and effective downstream process is also an important consideration for the industrial production of terpenoids, and the solvent extraction and the supercritical fluid extraction method are the most commonly used strategies, especially in the industrial production of β-carotene and astaxanthin from microalgae. In this review, recent advancements and novel strategies used for terpenoid production are concluded and discussed, and new insights to move the field forward are proposed. KEY POINTS: • The MEP pathway is more stoichiometrically efficient than the MVA pathway. • Advanced genetic engineering and fermentation strategies can increase terpene yield. • SFE has a higher recovery of carotenoids than solvent extraction.

BACKGROUND AND AIMS Increasing evidence in recent years has suggested that microRNA-7 (miR-7) is an important gene implicated in the development of various diseases including HCC. However, the role of miR-7 in autoimmune hepatitis (AIH) is unknown. APPROACH AND RESULTS Herein, we showed that miR-7 deficiency led to exacerbated pathology in Concanavalin-A-induced murine acute autoimmune liver injury (ALI) model, accompanied by hyperactivation state of CD4+ T cells. Depletion of CD4+ T cells reduced the effect of miR-7 deficiency on the pathology of ALI. Interestingly, miR-7 deficiency elevated CD4+ T-cell activation, proliferation, and cytokine production in vitro. Adoptive cell transfer experiments showed that miR-7def CD4+ T cells could exacerbate the pathology of ALI. Further analysis showed that miR-7 expression was up-regulated in activated CD4+ T cells. Importantly, the transcription of pre-miR-7b, a major resource of mature miR-7 in CD4+ T cells, was dominantly dependent on transcription factor CCAAT enhancer binding protein alpha (C/EBPα), which binds to the core promoter region of the miR-7b gene. Global gene analysis showed that mitogen-activated protein kinase 4 (MAPK4) is a target of miR-7 in CD4+ T cells. Finally, the loss of MAPK4 could ameliorate the activation state of CD4+ T cells with or without miR-7 deficiency. Our studies document the important role of miR-7 in the setting of AIH induced by Concanavalin-A. Specifically, we provide evidence that the C/EBPα/miR-7 axis negatively controls CD4+ T-cell activation and function through MAPK4, thereby orchestrating experimental AIH in mice. CONCLUSIONS This study expands on the important role of miR-7 in liver-related diseases and reveals the value of the C/EBPα/miR-7 axis in CD4+ T-cell biological function for the pathogenesis of immune-mediated liver diseases.

Studying the allele and haplotype distributions of human leukocyte antigen (HLA) loci at 2nd-field level in different populations was important. Allele and haplotype frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 loci in 110 unrelated healthy Kazak individuals living in Xinjiang (China) were analyzed using polymerase chain reaction sequence based typing. Thirty HLA-A, 48 HLA-B, 24 HLA-C, 34 HLA-DRB1 and 18 HLA-DQB1 alleles were detected at the 2nd-field level in the Kazak population. Frequencies of HLA alleles, genotypes, and haplotypes were calculated, and some exhibited significantly different distributions among different populations. A neighbor-joining (NJ) tree, heatmap, multidimensional scaling (MDS) and principal component analysis (PCA) were used to explore the genetic relationships between the Kazak population and 32 reference populations distributed in Asia, Africa, America and Europe using frequency data of HLA-A, -B, -C and -DRB1 loci. The NJ tree, heatmap, and MDS of the 33 populations were constructed based on pairwise DA values of populations obtained by the HLA-A, -B, -C and -DRB1 allele frequencies. Different PCA plots were constructed based on the allele frequencies of HLA-A, -B, -C and -DRB1 or estimated haplotypic frequencies of HLA-A, -B, -C loci. The data obtained in the present research can be used for research on HLA-related diseases or paternity relationships, and aid to finding the best matched donors in stem cell transplantation for Kazak individuals.

Exercise preconditioning (EP) provides protective effects for acute cardiovascular stress; however, its mechanisms need to be further investigated. Autophagy is a degradation pathway essential for myocardium health. Therefore, we investigated whether intermittent myocardial ischemia-hypoxia affected Beclin1 and whether the changes in autophagy levels contribute to EP-induced early myocardial protective effects. Rats were trained on a treadmill using an EP model (four cycles of 10 minutes of running/10 minutes of rest). Exhaustive exercise (EE) was performed to induce myocardial injury. Cardiac troponin I (cTnI) and ischemia-hypoxia staining were used to evaluate myocardial injury and protection. Double-labeled immunofluorescence staining and western blot analysis were employed to examine related markers. EP attenuated the myocardial ischemic-hypoxic injury induced by EE. Compared with the control (C) group, the dissociations of Beclin1/Bcl-2 ratio and Beclin1 expression were both higher in all other groups. Compared with the C group, PI3KC3 and the LC3-II/LC3-I ratio were higher in all other groups, whereas LC3-II was higher in the EE and EEP + EE groups. p62 was higher in the EE group than in the C group but lower in the EEP + EE group than in the EE group. We concluded that EP increases Beclin1 via intermittent myocardial ischemia-hypoxia and induces autophagy, which exerts early myocardial protective effects and reduces the myocardial ischemic-hypoxic injury induced by exhaustive exercise.

In eukaryotes, MEDIATOR is a conserved multi-subunit complex that links transcription factors and RNA polymerase II and that thereby facilitates transcriptional initiation. Although the composition of MEDIATOR has been well studied in yeast and mammals, relatively little is known about the composition of MEDIATOR in plants. By affinity purification followed by mass spectrometry, we identified 28 conserved MEDIATOR subunits in Arabidopsis thaliana, including putative MEDIATOR subunits that were not previously validated. Our results indicated that MED34, MED35, MED36, and MED37 are not Arabidopsis MEDIATOR subunits, as previously proposed. Our results also revealed that two homologous CBP/p300 histone acetyltransferases, HAC1 and HAC5 (HAC1/5) are in fact plant-specific MEDIATOR subunits. The MEDIATOR subunits MED8 and MED25 (MED8/25) are partially responsible for the association of MEDIATOR with HAC1/5, MED8/25 and HAC1/5 co-regulate gene expression and thereby affect flowering time and floral development. Our in vitro observations indicated that MED8 and HAC1 form liquid-like droplets by phase separation, and our in vivo observations indicated that these droplets co-localize in the nuclear bodies at a subset of nuclei. The formation of liquid-like droplets is required for MED8 to interact with RNA polymerase II. In summary, we have identified all of the components of Arabidopsis MEDIATOR and revealed the mechanism underlying the link of histone acetylation and transcriptional regulation.

Background Currently, there is no cure for Alzheimer’s disease (AD). Therapeutics that can modify the early stage of AD are urgently needed. Recent studies have shown that the pathogenesis of AD is closely regulated by an endo/lysosomal asparaginyl endopeptidase (AEP). Inhibition of AEP has been reported to prevent neural degeneration in transgenic mouse models of AD. However, more than 90% of AD cases are age-related sporadic AD rather than hereditary AD. The therapeutic efficacy of AEP inhibition in ageing-associated sporadic AD remains unknown. Methods The senescence-accelerated mouse prone 8 (SAMP8) was chosen as an approximate model of sporadic AD and treated with a selective AEP inhibitor,: δ-secretase inhibitor 11. Activation of AEP was determined by enzymatic activity assay. Concentration of soluble amyloid β (Aβ) in the brain was determined by ELISA. Morris water maze test was performed to assess the learning and memory-related cognitive ability. Pathological changes in the brain were explored by morphological and western blot analyses. Results The enzymatic activity of AEP in the SAMP8 mouse brain was significantly higher than that in the age-matched SAMR1 mice. The half maximal inhibitory concentration (IC50) for δ-secretase inhibitor 11 to inhibit AEP in vitro is was around 150 nM. Chronic treatment with δ-secretase inhibitor 11 markedly decreased the brain AEP activity, reduced the generation of Aβ1–40/42 and ameliorated memory loss. The inhibition of AEP with this reagent not only reduced the AEP-cleaved tau fragments and tau hyperphosphorylation, but also attenuated neuroinflammation in the form of microglial activation. Moreover, treatment with δ-secretase inhibitor 11 prevented the synaptic loss and alleviated dendritic disruption in SAMP8 mouse brain. Conclusions Pharmacological inhibition of AEP can intervene and prevent AD-like pathological progress in the model of sporadic AD. The up-regulated AEP in the brain could be a promising target for early treatment of AD. The δ-secretase inhibitor 11 can be used as a lead compound for translational development of AD treatment.

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA (ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC., Graphical Abstract, Shi et al. provide evidence that a ceRNA-based DLEU2L/TAOK1 axis has an impact on changes in the tumor immune microenvironment and might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.

Ming-Jr Jian,1 Hsing-Yi Chung,1 Chih-Kai Chang,1 Shan-Shan Hsieh,1 Jung-Chung Lin,2 Kuo-Ming Yeh,2 Chien-Wen Chen,3 Feng-Yee Chang,2 Sheng-Kang Chiu,2 Kuo-Sheng Hung,4 Ming-Tsan Liu,5 Ji-Rong Yang,5 Cherng-Lih Perng,1 Hung-Sheng Shang1 1Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 2Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Center for Precision Medicine and Genomics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 5Centers for Disease Control, Taipei, Taiwan, Republic of ChinaCorrespondence: Hung-Sheng ShangDivision of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Kung Road, Neihu, Taipei, 114, Taiwan, Republic of ChinaTel +886920713130Fax +886287927226Email iamkeith001@gmail.comAbstract: The COVID-19 pandemic has caused a global public health crisis. Taiwan experienced two waves of imported cases of coronavirus disease 2019 (COVID-19), first from China in January to late February, 2020 then from other countries starting in early March. As of Dec 14, 2020, 733 cases have been reported in Taiwan, with cases of entire families being infected. This study aimed to investigate the clinical characteristics and differentiation of genetic variation among isolates from a cluster of familial COVID-19 infection. The parents had pneumonia (Case 14, father, and Case 15, mother), the elder son (Case 17) had mild cough, and the younger son (Case 18) was asymptomatic. In this study, four full viral genomes were sequenced by Illumina sequencing directly from specimens. Phylogenetic tree analysis revealed that these sequences came from Italy, not China, indicating that no major strain has been circulating in Taiwan. Several novel mutations were observed in the asymptomatic patient, such as nsp2, nsp12, and nsp14. These mutations may be associated with the severity of COVID-19 infection.Keywords: COVID-19, SARS-CoV-2, imported family infections, whole-genome sequencing, phylogenetic analysis

OBJECTIVES/HYPOTHESIS The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions. STUDY DESIGN The effectiveness evaluation of diagnostic methods. METHODS Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated. RESULTS The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P

Background A certain link between sexual abuse (SA) victimization and suicidal behaviors has been confirmed, but it remains unclear whether this association varies with regard to SA characteristics and gender. Methods Participants were 4034 college students drawn from a cross-sectional study conducted in Hefei, China. Gender-stratified latent class analysis (LCA) and logistic regression models were used to examine the relationships between timing, duration, types and patterns of SA victimization and suicidal behaviors. Results For the males, SA in the elementary school or earlier period was associated with suicidal ideation (OR: 3.29, 95%CI: 2.20-5.38), plans (OR: 3.44, 95% CI: 1.54-7.77) and preparations (OR:3.05, 95% CI: 1.19-7.74). All types of SA were significantly associated with the four types of suicidal behaviors. Dose-response relationship and cumulative effect were found between duration, types of SA victimization and suicidal behaviors. Three latent classes of SA victimization were identified for males and females, respectively. For males, the “moderate SA” class and “persistent SA” class were associated with the four types of suicidal behaviors. For the females, SA during the university period was associated with suicidal ideation (OR: 2.47, 95% CI: 1.24-4.93). Only suicidal ideation was associated with the “moderate SA” class. Limitations The cross-sectional survey design did not allow to conclude any causality. Conclusions The relationship between SA victimization and suicidal behaviors varies in terms of SA victimization characteristics and the relationships were stronger in males than in females.

It remains unclear whether leukocyte-related parameters could be used as biomarkers to differentiate metabolically unhealthy overweight/obesity (MUO) from metabolically healthy overweight/obesity (MHO). We aimed to examine the differences in the distribution of leukocyte-related parameters between older adults with MHO and MUO and the correlations of leukocyte-related parameters with individual components of metabolic abnormality. In the Weitang Geriatric Diseases Study on older Chinese adults aged 60 years or above, 404 individuals with MHO and 480 with MUO contributed to the analysis. Overweight/obesity was defined as body mass index (BMI) of 25 kg/m2 or more. MHO and MUO were discriminated based on the Adult Treatment Panel III (ATP III) criteria. Leukocyte-related parameters were assessed using an automated hematology analyzer. All leukocyte-related parameters except monocytes were elevated in MUO group compared with MHO group (all P 9/L increase of leukocytes after adjusting for confounders in the multiple-adjusted model (P P P for trend P value for interaction

Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR‐660 while miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR‐660, which resulted in an upregulated expression of BAG5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR‐660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305‐mediated miR‐660‐5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression., circ_0008305 was greatly increased in HCC tissues and cells. circ_0008305 can act as a sponge of miR‐660. miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5).

People with end-stage liver disease on the liver transplant waiting list have high symptom burden, which can successfully be addressed by specialist palliative care. Potential tensions with the perceived curative nature of liver transplant make delivering specialist palliative care challenging. This systematic review seeks to establish what is known on the impact of specialist palliative care for patients on liver transplant waiting lists, healthcare professionals' perspectives of providing specialist palliative care for this population, and uptake of advance care planning (ACP). Medline, Embase, and CINAHL were searched to May 5, 2020. Qualitative and quantitative findings were grouped together according to main relevant themes. Eight studies of mixed quality and mainly quantitative, were identified. Findings suggest early palliative care intervention improve patients' symptoms and prompt ACP conversations, but patients on the waiting list receive limited palliative care input. Liver physicians' lack of clarity on referral criteria and liver transplant patients' concerns of being abandoned, were reasons for reluctance to refer to specialist palliative care. They felt referral to specialist palliative care is appropriate only for patients receiving hospice or end of life care. Uptake and understanding of ACP and goals of care designation by patients is poor. This review found evidence of benefit of specialist palliative care for patients on liver transplant waiting lists, but found in a limited understanding of their role. Evidence is limited to studies from North America. Future research is needed to understand better how palliative care could be provided into this clinical environment.

Objectives The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients.

This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76–0.83) and 0.779 (95% CI, 0.74–0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging.

Emerging evidence has shown that circular RNAs (circRNAs) and DNA methylation play important roles in the causation and progression of cancers. However, the roles of circRNAs and abnormal methylation genes in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. Expression profiles of circRNA, gene methylation, and mRNA were downloaded from the GEO database, and differentially expressed genes were obtained via GEO2R, and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Inflammation-associated genes were collected from the GeneCards database. Then, functional enrichment analysis and protein-protein interaction (PPI) networks of inflammation-associated methylated expressed genes were investigated using Metascape and STRING databases, respectively, and visualized in Cytoscape. Hub genes of PPI networks were identified using the NetworkAnalyzer plugin. Also, we analyzed the methylation, protein expression levels, and prognostic value of hub genes in PDAC patients through the UALCAN, Human Protein Atlas (HPA), and Kaplan-Meier plotter databases, respectively. The circRNA_102049/miR-455-3p/CD80 axis was identified by the ceRNA network and hub genes. In vitro and in vivo experiments were performed to evaluate the functions of circRNA_102049. The regulatory mechanisms of circRNA_102049 and miR-455-3p were explored by RT-PCR, western blot, and dual-luciferase assays. In the present study, twelve hub genes (STAT1, CCND1, KRAS, CD80, ICAM1, ESR1, RAF1, RPS6KA2, KDM6B, TNRC6A, FOSB, and DNM1) were determined from the PPI networks. Additionally, the circRNA_102049 was upregulated in PDAC cell lines. Functionally, the knockdown of circRNA_102049 by siRNAs inhibited cell growth, inflammatory factors, and migratory and invasive potential and promoted cell apoptosis. Mechanistically, circRNA_102049 functioned as a sponge of miR-455-3p and partially reversed the effect of miR-455-3p and consequently upregulated CD80 expression. Our findings showed that circRNA_102049 and methylated hub genes play an important role in the proliferation, apoptosis, migration, invasion, and inflammatory response of PDAC, which might be selected as a promising prognostic marker and therapeutic target for PDAC.

Context Icariin (ICA) is the main active ingredient of Epimedium brevicornu Maxim (Berberidaceae), which is used in the immune, reproductive, neuroendocrine systems, and anti-aging. Objective To evaluate the effect of ICA on natural aging rat. Materials and methods 16-month-old Sprague–Dawley (SD) rats were randomly divided into aging, low and high-dose ICA groups (n = 8); 6-month-old rats were taken as the adult control (n = 8). Rats were fed regular feed (aging and adult control) or feed containing ICA (ICA 2 and 6 mg/kg group) for 4 months. HE and Nissl staining were used to assess pathological changes. Western blot was used to test the expression of autophagy (LC3B, p62, Atg5, Beclin1) and p-AMPK, p-mTOR and p-ULK1 (ser 757). Immunofluorescence was used to detect the co-localization of LC3 and neurons. Results ICA improved neuronal degeneration associated with aging and increased the staining of Nissl bodies. Western blot showed that ICA up-regulated autophagy-related proteins LC3B (595%), Beclin1 (73.5%), p-AMPK (464%) protein (p

Despite the accessibility to porous architectures through various biofabrication approaches for tissue engineering, incorporating various active growth regulators within their matrices that act as biochemical cues is also an essential attribute for effective tissue growth. To address these facts, icariin (ICA)-encapsulated polymeric scaffolds are fabricated using a low-temperature extrusion-based three-dimensional (3D) printing technology for efficiently promoting osteogenesis. This approach not only resulted in the generation of porous architectures but also substantially maintained the bio-efficacy of the encapsulated ICA. Moreover, these composite scaffolds based on poly(e-caprolactone) (PCL) and tricalcium phosphate (β-TCP) encapsulated with ICA (ITP scaffolds) are systematically characterized using various techniques before and after printing. Furthermore, various investigations relevant to biodegradability, biocompatibility, ICA release, and osteogenic ability of the ITP scaffolds are explored. The intact physiochemical properties of the materials, sustained release of ICA from the scaffolds, and high biosafety at various levels ranging from cellular to animal efficiently promoted the proliferation of mouse bone marrow mesenchymal stem cells (BMSCs) and their differentiation to osteoblasts. Together, the utilization of low-temperature extrusion approach provides a convenient and eco-friendly means of fabricating highly porous 3D architectures that supply the required growth regulators in their active form for tissue regeneration.

Accumulating studies revealed the vital role of ion channels in cancers, but the prognosis role of ion channels in hepatocellular carcinoma (HCC) remains limited. Here, we developed and validated an ion channel signature for prognostic prediction of HCC patients. In total, 35 differential expressed ion channel genes (DEChannelGs) were identified in HCC and a novel ion channel risk model was established for HCC prognosis prediction using the TCGA cohort, which was validated using the ICGC cohort. Moreover, this risk model was an independent prognostic factor and was associated with the immune microenvironment in HCC. Finally, the mRNA and protein levels of ANO10 and CLCN2 were prominently up-regulated and were related to the poor prognosis of HCC patients. Taken together, these results indicated a novel ion channel risk model as a prognostic biomarker for HCC patients and provided further insight into its immunoregulatory mechanism in HCC progression.

Rui-zhe Li,1 Yun-yun Li,1,2 Hui Qin,1 Shan-shan Li1 1Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of China; 2Department of Stomatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of ChinaCorrespondence: Shan-shan LiDepartment of Pathology, School of Basic Medical Sciences, Zhengzhou University and First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of ChinaTel +86 138 3815 6395Fax +86 371 6796 6155Email lss_path@sina.comBackground: ACTL6A, a regulatory subunit of ATP-dependent chromatin-remodeling complexes SWI/SNF, has been identified as a central oncogenic driver in many tumor types.Materials and Methods: We used immunohistochemistry (IHC) to detect ACTL6A expression in esophageal squamous cell carcinoma (ESCC) tissues. Then, the effect of ACTL6A on proliferation and DNA synthesis was explored by using cell counting kit 8 (CCK8) and EdU retention assays. The potential oncogenic mechanism of ACTL6A in ESCC cells was also analyzed by flow cytometry and Western blotting. We further established an ESCC xenograft mouse model to validate the in vitro results.Results: ACTL6A expression, localized in cancer cell nuclei, was markedly higher in ESCC tissues than in the corresponding noncancerous tissues (P< 0.001) and was positively associated with tumor size, histological differentiation, T stage and tumor-node-metastasis (TNM) stage. Kaplan–Meier analysis revealed that high ACTL6A expression was significantly associated with poor overall survival (OS) (P = 0.008, HR= 2.562, 95% CI: 1.241– 5.289), and decision curve analysis (DCA) demonstrated that ACTL6A could increase the clinical prognostic efficiency of the original clinical prediction model. Further in vitro experiments showed that ACTL6A knockdown led to inhibition of cell proliferation and DNA synthesis in ESCC cell lines, while overexpression of ACTL6A had the opposite effects. ACTL6A knockdown resulted in G1 phase arrest, with downregulation of cyclin D1, CDK2 and S6K1/pS6 pathway proteins and upregulation of p21 and p27, while overexpression of ACTL6A facilitated the entry of more cells into S phase with upregulated cyclin D1, CDK2 and S6K1/pS6 pathway proteins and downregulated p21 and p27. Finally, a xenograft mouse model of ESCC cells validated the results in vitro.Conclusion: ACTL6A expression may affect the proliferation and DNA synthesis of ESCC cells by facilitating ESCC cell cycle redistribution via the S6K1/pS6 pathway. Therefore, ACTL6A may potentially become an alternative therapeutic target for ESCC.Keywords: ACTL6A, esophageal squamous cell carcinoma, cell cycle, proliferation, pS6

Aim: To investigate the role of LINC01160 in nasopharyngeal carcinoma (NPC). Materials & methods: Using NPC cells CNE-2 and HNE-2 in vitro, we performed quantitative PCR to determine mRNA expression and western blotting to determine protein expression. CCK-8, transwell, flow cytometry and wound healing assays were done to examine the function of LINC01160 and STAT1. Chromatin immunoprecipitation PCR (ChIP-PCR) confirmed that STAT1 combines with the LINC01160 promoter region. Xenograft experiments were used to verify the role of STAT1 and LINC01160 in vivo. Results: LINC01160 is upregulated in NPC and can promote a malignant cell phenotype. STAT1 is a transcription factor of LINC01160 and can promote a malignant cell phenotype through upregulating LINC01160 expression. Conclusion: STAT1 can promote a malignant cell phenotype by upregulating LINC01160.

Background Impaction of jujube pits in the upper gastrointestinal (GI) tract is a special clinical condition in the northern Chinese population. Endoscopic removal is the preferred therapy, but there is no consensus on the management strategies. We reported our individualized endoscopic strategies on the jujube pits impacted in the upper GI tract. Methods In this retrospective study, we included 191 patients (male: 57; female: 134) who presented to our hospital with ingestion of jujube pits between January 2015 and December 2017. Demographic information, times of hospital visiting, locations of jujube pits, endoscopic procedures, post-extraction endoscopic characteristics were analyzed. Management strategies including sufficient suction, repeated irrigation, jejunal nutrition and gastrointestinal decompression were given based on post-extraction endoscopic characteristics and impacted locations. Results Peak incidence was in the second quarter of each year (85/191 cases, 44.5%). Among the 191 cases, 169 (88.5%) showed pits impaction in the esophagus, 20 (10.5%) in the prepyloric region and 2 (1.0%) in the duodenal bulb. A total of 185 patients (96.9%) had pits removed with alligator jaw forceps, and 6 (3.1%) underwent suction removal with transparent caps placed over the end of the endoscope to prevent injury on removal of these pits with two sharp painted edges. Post-extraction endoscopic manifestations included mucosal erosion (26.7%), mucosa laceration (24.6%), ulceration with a white coating (18.9%) and penetrating trauma with pus cavity formation (29.8%). All patients received individualized endoscopic and subsequent management strategies and showed good outcomes. Conclusions Individualized endoscopic management for impacted jujube pits in the upper GI tract based on post-extraction endoscopic characteristics and impacted locations was safe, effective, and minimally invasive.

Graphical abstract, Detecting SNPs associated with drug efficacy or toxicity is helpful to facilitate personalized medicine. Previous studies usually find SNPs associated with clinical outcome only in patients received a specific treatment. However, without information from patients without drug treatment, it is possible that the detected SNPs are associated with patients’ clinical outcome even without drug treatment. Here we aimed to detect drug response SNPs based on data from patients with and without drug treatment through combing the cox proportional-hazards model and pairwise Kaplan-Meier survival analysis. A pipeline named Detection of Drug Response SNPs (DDRS) was built and applied to TCGA breast cancer data including 363 patients with doxorubicin treatment and 321 patients without any drug treatment. We identified 548 doxorubicin associated SNPs. Drug response score derived from these SNPs were associated with drug-resistant level (indicated by IC50) of breast cancer cell lines. Enrichment analyses showed that these SNPs were enriched in active epigenetic regulation markers (e.g., H3K27ac). Compared with random genes, the cis-eQTL genes of these SNPs had a shorter protein–protein interaction distance to doxorubicin associated genes. In addition, linear discriminant analysis showed that the eQTL gene expression levels could be used to predict clinical outcome for patients with doxorubicin treatment (AUC = 0.738). Specifically, we identified rs2817101 as a drug response SNP for doxorubicin treatment. Higher expression level of its cis-eQTL gene GSTA1 is associated with poorer survival. This approach can also be applied to identify new drug associated SNPs in other cancers.

OBJECTIVE: This study aimed to retrospectively analyze the blood protective effect of autologous platelet separation in operations for acute aortic dissection. METHODS: A total of 130 patients with acute aortic dissection were enrolled into the present study. The average age of these patients was 52.962±10.5061 years old. These patients underwent the modified aortic arch replacement with the elephant trunk technique or endovascular aortic exclusion with covered stent. Among these patients, 68 patients who underwent autologous platelet separation were assigned to the platelet separation group, while the remaining patients were assigned to the control group. All operations were performed under deep hypothermic circulatory arrest. After anesthesia, 1–2 therapeutic doses of autologous platelets were isolated from patients in the platelet separation group, and these platelets were quickly infused back to these patients after heparin was neutralized by protamine at the end of the cardiopulmonary bypass. The preoperative and postoperative indexes in these two groups were compared. RESULTS: There were no statistically significant differences in age, gender, smoking history, drinking history and hypertension history between these two groups. Compared with controls, the transfusion volume of allogeneic platelets in the perioperative period significantly decreased in the platelet separation group (1.919±1.6226 vs. 0.794±1.1789, P

The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells. Use of a peptide to disturb the TRIB3-MYC interaction together with doxorubicin reduces the tumor burden in MycEμ mice and patient-derived xenografts. The pathophysiological relevance of UBE3B, TRIB3 and MYC is further demonstrated in human lymphoma. Our study highlights a key mechanism for controlling MYC expression and a potential therapeutic option for treating lymphomas with high TRIB3-MYC expression., c-MYC is often deregulated in human cancers including lymphomas. Here, the authors show that a member of the pseudokinase family, tribbles homologue 3 (TRIB3), interacts with c-MYC to suppress c-MYC ubiquitination and degradation, leading to increased proliferation and self-renewal of lymphoma cells.

Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p

Bumble bees are vital to our agro-ecological system, with approximately 250 species reported around the world in the single genus Bombus. However, the health of bumble bees is threatened by multiple factors: habitat loss, climate change, pesticide use, and disease caused by pathogens and parasites. It is therefore vitally important to have a fully developed phylogeny for bumble bee species as part of our conservation efforts. The purpose of this study was to explore the phylogenetic relationships of the dominant bumble bees on the Tibetan plateau and in northern China as well as their placement and classification within the genus Bombus. The study used combined gene analysis consisting of sequence fragments from six genes, 16S rRNA, COI, EF-1α, Argk, Opsin and PEPCK, and the phylogenetic relationships of 209 Bombus species were explored. Twenty-six species, including 152 gene sequences, were collected from different regions throughout China, and 1037 gene sequences representing 183 species were obtained from GenBank or BOLD. The results suggest that the 209 analyzed species belong to fifteen subgenera and that most of the subgenera in Bombus are monophyletic, which is in accordance with conventional morphology-based classifications. The phylogenetic trees also show that nearly all subgenera easily fall into two distinct clades: short-faced and long-faced. The study is the first to investigate the phylogenetic placement of Bombus turneri (Richards), Bombus opulentus Smith, Bombus pyrosoma Morawitz, Bombus longipennis Friese, Bombus minshanensis Bischoff, and Bombus lantschouensis Vogt, all of which are widely distributed throughout different regions of China. The knowledge and understanding gained from the findings can provide a molecular basis to accurately classify Bombus in China and to define strategies to conserve biodiversity and promote pollinator populations.

Activating transcription factor 4 (ATF4) is critical for chondrocyte proliferation and bone formation. Exosomes are considered as promising gene-delivery vehicles for the treatment of osteoarthritis (OA). This study utilized the serum-derived exosomes from OA mice as the gene-delivery vehicles for ATF4 gene therapy and explored their therapeutic effects on OA. Meniscus injury-induced OA model was established by the excision of anterior part of medial meniscus in the right knee of C57BL/6J mice. Exosomes were isolated from serum samples of sham and OA mice, and were referred to as sham-Exo and OA-Exo, respectively. ATF4-overexpressing OA-Exo (ATF4-OA-Exo) was developed by introducing ATF4 mRNA into OA-Exo via electroporation. Four weeks after surgery, OA mice received intra-articular injections of sham-Exo, OA-Exo, and ATF4-OA-Exo, respectively. The results showed that intra-articular injection of ATF4-OA-Exo alleviated articular cartilage degeneration or damage and inflammatory response of OA mice. Autophagy was weakened in knee joint cartilage of OA mice, which was partially restored by intra-articular injection of ATF4-OA-Exo. Further in vitro assays revealed that ATF4-OA-Exo promoted chondrocyte autophagy and inhibited chondrocyte apoptosis in the TNF-α- or tunicamycin-treated chondrocytes. Together, ATF4-modified serum exosomes derived from OA mice protect cartilage and alleviate OA progression by inducing autophagy.

Background Annular pancreas (AP) is a rare congenital abnormal rotation of the pancreas. AP rarely occurs in adults. Pancreatic tumors and ampullary tumors are related to AP, so the discovery and treatment of AP are essential. Case summary This study investigated the clinical manifestations, imaging features, complications, and treatment of six patients diagnosed with AP at the Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jilin University from January 2010 to June 2020. There were four males and two females, with an average age of 56.00 ± 9.86 years old. In this study, abdominal pain and jaundice were the main clinical manifestations. Imaging can show the "crocodile jaw sign" or "double bubble sign". Conclusion For patients with duodenal or biliary obstruction, physicians should give priority to AP when imaging examinations suggest that the duodenum is wrapped with tissue similar to the density of the pancreas. Symptomatic patients should actively undergo surgical treatment.

BACKGROUND Cutaneous metastases originating from pancreatic cancer are relatively rare. The most common reported site of metastasis is the umbilicus, and this manifestation is known as the Sister Mary Joseph’s nodule. Non-umbilical cutaneous metastases are far less common, with only a few cases reported in the literature. Our case is the first case report, to our knowledge, on metastasis involving the labia majora and flat papules. CASE SUMMARY A 49-year-old Chinese female patient presented with a number of red, swollen papules on the vulva for 2 mo. Histological examination of the labia majora lesion revealed metastatic adenocarcinoma. The serum levels of tumor biomarkers CA199, CA242, and CA125 were significantly elevated. B-mode ultrasound-guided needle biopsy of the pancreas demonstrated moderately and poorly differentiated adenocarcinoma. The patient finally declined treatment for financial reasons and died 3 mo later. CONCLUSION Metastatic cutaneous lesions could indicate pancreatic cancer. Serum levels of tumor biomarkers may aid in diagnosing metastatic pancreatic adenocarcinoma.

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn(–)(/ –) mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn(–)(/ –) mice or infecting optn(–)(/ –) mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of Optn(K193R) failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn(–)(/ –) mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP. Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; μCT: micro computed tomography.

Background:. Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. Methods:. This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. Results:. A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P

To investigate the associations between vision impairment (VI), vision correction (VC), and cognitive function.We included 20,677 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (2011-2015). Participants were grouped into no VI, distance VI (DVI) only, near VI (NVI) only, or both distance and near VI (DNVI), and VI(+)/VC(-), VI(+)/VC(+), VI(-)/VC(-), or VI(-)/VC(+) further at baseline. Cognitive function at baseline and subsequently every two years was applied as a dependent variable in a generalized estimating equation model.DVI only, NVI only, and DNVI had significantly worse cognitive function over time than no VI (allCognitive function was worse in middle-aged and older Chinese with VI, especially in those with DNVI. VC was associated with better cognitive function over time regardless of the status of vision.

OBJECTIVE This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [18 F]-fluorodeoxyglucose positron emission tomography. PATIENTS AND MATERIALS A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. RESULTS Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values

The protozoan parasite Giardia duodenalis is known to infect humans and a wide range of animals globally. However, no studies on G. duodenalis infection in Bactrian camels have been reported. In the present study, in order to examine the prevalence and genetic diversity of G. duodenalis in Bactrian camels, 852 fecal samples were collected from 24 sampling sites in three geographical areas (Gansu province, Inner Mongolia, and Xinjiang Uygur autonomous regions) of northwestern China, and subjected to multilocus sequence typing (MLST) analysis targeting the 18S rRNA, β-giardin (bg), glutamate dehydrogenase (gdh), and triosephosphate isomerase (tpi) genes. About 84 fecal samples tested positive for Giardia infection, with an overall prevalence of 9.8%, including three samples from camel calves with diarrhea. Significant differences (χ2 = 80.7, df = 2, P 6 years old. Sequence analysis identified two assemblages, including zoonotic assemblage A and ungulate-adapted assemblage E, with the latter as the dominant G. duodenalis assemblage in each age group and at all sampling sites having positive samples except Hotan. Genetic variations were detected among G. duodenalis isolates in these camels, and eight, three, and seven haplotypes were identified at loci bg, gdh, and tpi, respectively, forming two multilocus genotypes (MLGs) of zoonotic assemblage A and one MLG of assemblage E. To the best of our knowledge, this is the first report on G. duodenalis infection in Bactrian camels, and the data indicate that G. duodenalis have a broad host range.

Cancer stem cells (CSCs) have an established role in cancer progression and therapeutic resistance. The p63 proteins are important transcription factors which belong to the p53 family, but their function and mechanism in CSCs remain elusive. Here, we investigated the role of TAp63α in colorectal CSCs and the effects of sulforaphane on TAp63α. We found that TAp63α was upregulated in spheres with stem cell properties compared to the parental cells. Overexpression of TAp63α promoted self-renewal capacity and enhanced CSC markers expression in colorectal sphere-forming cells. Furthermore, we showed that TAp63α directly bound to the promoter region of Lgr5 to enhance its expression and activate its downstream β-catenin pathway. Functional experiments revealed that sulforaphane suppressed the stemness of colorectal CSCs both in vitro and in vivo. Upregulation of TAp63α attenuated the inhibitory effect of sulforaphane on colorectal CSCs, indicating the role of TAp63α in sulforaphane suppression of the stemness in colorectal cancer. The present study elucidated for the first time that TAp63α promoted CSCs through targeting Lgr5/β-catenin axis and participated in sulforaphane inhibition of the stem cell properties in colorectal cancer.

Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10(−8)): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10(−8), replication p = 1.03 × 10(−4)), 16q12.2 (rs1421085, discovery p = 2.04 × 10(−9), replication p = 6.47 × 10(−14)) and 18q21.32 (rs11152213, discovery p = 3.47 × 10(−8), replication p = 6.69 × 10(−6)). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.

Valganciclovir (VGCV) is the prodrug of ganciclovir (GCV). The objective of this study was to establish a population pharmacokinetic model (PPK) of GCV to investigate the PK characteristics of GCV after administration of VGCV in adult Chinese renal allograft recipients. Seventy Chinese renal allograft recipients were given 450 mg (n = 41) or 900 mg (n = 29) VGCV daily. Blood samples were drawn 0-24 hours after 5 days' therapy, and GCV plasma levels were determined. The PPK model was constructed using nonlinear mixed-effects modeling, and the Bayesian estimation of AUC0-24h was constructed for an individual patient based on limited plasma samples. The PK of GCV was best described by a 2-compartment model with a first-order absorption process. The CL/F, V2 /F, Q/F, V3 /F, Ka , and lag time of GCV were 15.8 ± 0.71 L/h, 10.9 ± 2.38 L, 3.98 ± 0.40 L/h, 167 ± 44.0 L, 0.23 ± 0.0078 1/h, and 0.93 ± 0.017 hours, respectively. Clearance of creatinine was found to have a significant impact on the CL/F of GCV (P < .01). Sampling strategies consisted of plasma concentrations 0 and 2 and 0, 2, and 4 hours after VGCV administration were shown to be suitable for the estimation of the GCV AUC0-24h . The PPK model was acceptable and can describe the PK of GCV in Chinese renal transplant patients administered VGCV. The AUC0-24h of GCV in Chinese renal transplant patients can be calculated by a limited sampling strategy method.

Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain unexplored. This study aimed to uncover the difference in intestinal metabolism of ginseng between normal and cyclophosphamide-induced immunosuppressed rats and further discuss the potential mechanisms involved. Twelve Sprague-Dawley rats (6–8 weeks old) were randomly divided into two groups: the normal group (NG) and immunosuppressed group (ISG). Rats in the NG and ISG groups were intraperitoneally administered normal saline and cyclophosphamide injections (40 mg/kg) on the 1st, 2nd, 3rd and 10th days; on the 12th day, all rats were intragastrically administered ginseng water extract (900 mg/kg). The difference in intestinal metabolism of ginseng was compared using an ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry-based metabolomics approach, and the diversities of gut microbiota were analyzed by 16S rRNA gene sequencing between the two groups. The intestinal metabolomic characteristics of ginseng were significantly different between the normal and immunosuppressed rats, with the ginsenoside F2 (F2), 20S-ginsenoside Rg3 (20(S)-Rg3), pseudo-ginsenoside Rt5 (Pseudo-Rt5), ginsenoside Rd (Rd), ginsenoside Rh1 (Rh1), 20S-ginsenoside Rg1 (20(S)-Rg1), ginsenoside compound K (CK), ginsenoside Rg2 (Rg2) and 20S-panaxatriol (S-PPT) more abundant in immunosuppressed ones (P

Designing desirable adsorbent for highly efficient removal of heavy metal ions is of practical significance, given the cost-effectiveness, environmental benign, natural abundance and easy-handling collection features. Herein, a bead-like adsorbent with high adsorption capacity was prepared by modifying alginate beads using polyacrylate with high density of carboxyl groups. The developed alginate/polyacrylate beads were collaboratively characterized by FT-IR, TGA, SEM, XPS, etc., and various adsorption conditions were tested including the pH of the solution, contact time and the initial concentration. The experimental data were fitted well by the Freundlich isotherm model, and the maximum adsorption capacity was obtained from the Langmuir model was 611.0 mg/g, and adsorption process followed the Pseudo-second-order kinetic model. The adsorption mechanisms conformed to multi-layer adsorption, and mainly dominated by chemical interactions. The bead-like adsorbent exhibited excellent reusability after eight sequential cycles and displayed higher adsorption capacity towards lead ions. This type of adsorbent might possess promising role in treating heavy metals from water by virtue of degradable, cost-effective component and high adsorption efficiency.

We discuss the latest findings on RNA polymerase IV (Pol IV) in plant growth and development, providing new insights and expanding on new ideas for further, more in-depth research on Pol IV.

The warm‐temperate and subtropical climate zones of East Asia are a hotspot of plant species richness and endemism, including a noticeable number of species‐poor Tertiary relict tree genera. However, little is understood about when East Asian Tertiary relict plants diversified, how they responded demographically to past environmental change, and to what extent their current genomic composition (and adaptive capacity) might mitigate the effects of global warming. Here, we obtained genomic (RAD‐SNP) data for 171 samples from two extant species of Euptelea in China (24 E. pleiosperma populations) and Japan (11 E. polyandra populations) to elucidate their divergence and demographic histories, genome‐wide associations with current environmental variables, and genomic vulnerability to future climate change. Our results indicate that Late Miocene changes in climate and/or sea level promoted species divergence, whereas Late Pliocene uplifting in southwest China likely fostered lineage divergence within E. pleiosperma. Its subsequent range expansion into central/east (CE) China bears genomic signatures of climate‐driven selection, yet extant CE populations are predicted to be most vulnerable to future climate change. For E. polyandra, geography was the only significant predictor of genomic variation. Our findings indicate a profound impact of Late Neogene geological and climate change on the evolutionary history of Euptelea, with much stronger signals of local adaptation left in China than in Japan. This study deepens our understanding of the complex evolutionary forces that influence the distribution of genetic variation of Tertiary relict trees, and provides insights into their susceptibility to global change and potential for adaptive responses. Our results lay the groundwork for future conservation and restoration programs for Euptelea.

As a unique form of abiotic stress, the environmental conditions of outer space are expected to induce changes in plant genomes, proteomes and metabolic pathways. However, the effect of outer space conditions on the overall physiology of plants at the protein level has yet to be reported. To investigate the effects of outer space conditions on the growth- and development-related physiological processes and metabolic pathways of rice different stages, the seeds of rice variety DN423 were sent into orbit for 12.5 d aboard the SJ-10 Returning Satellite, and then the seedlings of both treated and control rice were compared at the three-leaf stage (TLS) and tillering stage (TS). In addition to comparing plant growth and reactive oxygen species (ROS) levels, seedling proteomes were also compared using isobaric tags for relative and absolute quantitation (iTRAQ). Space flight increased TLS plant height by 20%, reduced and increased ROS levels of the TLS and TS seedlings, respectively, and affected the expression of 36 and 323 proteins in TLS and TS leaves, respectively. Furthermore, the functions of the differentially abundant proteins were mainly associated with metabolism, energy, and protein synthesis and degradation. These results suggested that the exposure of seeds to outer space conditions affects the subsequent abundance of key signaling proteins, gene expression, and the processes of protein synthesis and degradation, thereby affecting metabolic processes and promoting adaptation to the abiotic stress of outer space. As such, the present study sheds light on the effects of space flight on plants and contributes to a more comprehensive understanding of extraterrestrial biology.

Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high‐glucose and high‐fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high‐glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin ‐induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase [SOD], malondialdehyde [MDA], gp91phox, Cyt‐Cyto C), enhanced cell apoptosis (Bax/Bcl‐2, Cleaved caspase‐3, TUNEL‐positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1‐Foxo1 and PI3K‐Akt pathways.