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To investigate the relationship between systemic inflammatory response and short-term mortality in patients with non-cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil-to-lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet-to lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR).Data were collected from two prospectively enrolled CATCH-LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90-day liver transplant (LT)-free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90-day LT-free mortality. Kaplan-Meier method was used to estimate the 90-year LT-free survival.The prevalence of CSH was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively, for patients with non-cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90-day LT-free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection.NLR may be an independent risk factor for 90-day LT-free mortality in patients with non-cirrhotic chronic liver disease. A NLR of 2.9 as the cut-off value can be used to predict disease aggravation in CSH patients without infection.

The central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.

To explore why young- and middle-aged adults ignore prodromal myocardial infarction symptoms from a life course and sociocultural perspective.A qualitative descriptive study.We applied purposeful sampling to recruit participants from a tertiary hospital in Guangzhou from July to November 2021. Face-to-face interviews were performed. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis methods.Twenty-four young- and middle-aged adults diagnosed with acute myocardial infarction participated in this study. Analysis revealed three main themes: I'm still young, it will not happen to me; to be somebody and different roles, multiple pressures. Age-related self-confidence led to inappropriate perceptions and responses to prodromal symptoms among young- and middle-aged adults. These individuals strived to align their behaviours and attention with social expectations and self-expectations, underestimating the importance of perceiving the warning signs of acute myocardial infarction and seeking medical treatment. Pressure from social roles also prevented them from paying enough attention to prodromal symptoms.Targeted social support, public education and technologies should be provided to these individuals since they are pillars of the family and society. We also highlight how nurses can function these strategies appropriately.This study contributes to a better understanding of the neglect of prodromal symptoms among young- and middle-aged adults. Its results enhance our understanding of the perception of and coping with prodromal symptoms among this population, which will help avoid the burden caused by acute myocardial infarction.The patients involved in our study shared their experiences and insights to provide new perspectives regarding the neglect of prodromal myocardial infarction symptoms among young- and middle-aged adults.

Background: Simulation teaching, which cultivates cooperation and communication in the interprofessional team, has become a suitable type of interprofessional cooperation in college students' health professional courses. This study aimed to explore the intervention effect of simulated interprofessional education (SIPE) on clinical critical thinking of medical nursing students. Methods: This study was a mixed method research including quantitative and qualitative assessment. Results: A total of 30 medical nursing students were randomly divided into a control group (18) and an experimental group (12). The mean scores on interprofessional cooperation and critical thinking of the experimental group were higher than those of the control group (P < 0.05). Quantitative evaluation was conducted using a scale, and qualitative evaluation was conducted through semi-structured interviews. There were three themes emerged: clarifying team positioning, improving team effectiveness, and optimizing the learning experience. Conclusion: This study found that the SIPE program improved medical nursing students' ability to work in interprofessional teams.

Autoimmune liver disease (AILD) has been considered a relatively uncommon disease in China, epidemiological data for AILD in patients with cirrhosis and acute decompensation (AD) is sparse.To investigate the prevalence, outcome and risk factors for AILD in cirrhotic patients complicated with AD in China.We collected data from patients with cirrhosis and AD from two prospective, multicenter cohorts in hepatitis B virus endemic areas. Patients were regularly followed up at the end of 28-d, 90-d and 365-d, or until death or liver transplantation (LT). The primary outcome in this study was 90-d LT-free mortality. Acute-on-chronic liver failure (ACLF) was assessed on admission and during 28-d hospitalization, according to the diagnostic criteria of the European Association for the Study of the Liver (EASL). Risk factors for death were analyzed with logistic regression model.In patients with cirrhosis and AD, the overall prevalence of AILD was 9.3% (242/2597). Prevalence of ACLF was significantly lower in AILD cases (14%) than those with all etiology groups with cirrhosis and AD (22.8%) (AILD was not rare in hospitalized patients with cirrhosis and AD in China, among which PBC was the most common etiology. 90-d LT-free mortality were independently associated with TB, HE and BUN.

To evaluate the diagnostic value and reproducibility of T2 mapping versus apparent diffusion coefficients (ADC) for identifying malignant lymph nodes in patients with non-mucinous rectal adenocarcinoma. High-resolution magnetic resonance imaging, diffusion-weighted imaging, and T2 mapping were performed on patients with suspected metastatic lymph nodes in the mesorectum or around the superior rectal artery with a short-axis diameter of 4–10 mm. The T2 and ADC values of pathology-confirmed metastatic versus non-metastatic lymph nodes were compared using the independent-samples t test and receiver operating characteristic curves. Intra- and inter-observer reproducibility were tested. The cutoff value for T2 relaxation time was determined. In total, 67 lymph nodes underwent histological analysis, with 24 in the non-metastatic and 43 in the metastatic groups. Intra- and inter-observer agreements for T2 values were 0.999 and 0.998, respectively, which were higher than the ADC values of 0.924 and 0.844, respectively. The mean T2 and ADC values for metastatic lymph nodes (65 ± 7.8 ms and 1.17 ± 0.16 × 10−3 mm2/s, respectively) were significantly lower than for benign lymph nodes(83 ± 5.7 ms and 1.29 ± 0.15 × 10−3 mm2/s, respectively). T2 values had a higher AUC value of 0.990 than the AUC value for ADC of 0.729. With a cutoff value of 77 ms, sensitivity and specificity for T2 values were 95% and 96%, respectively. T2 mapping had higher diagnostic efficacy and reproducibility than ADC and may be useful in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. • Mean T2 values were significantly shorter for malignant versus benign LNs in patients with non-mucinous rectal adenocarcinoma. • The diagnostic efficacy and reproducibility of T2 values were excellent and superior to ADC values.

Exploring a collection of naturally occurring imine reductases (IREDs) identified two stereocomplementary IREDs with reducing activity toward sterically hindered 2-aryl-substituted pyrrolines. Using (R)-selective ScIR and (S)-selective SvIR, various chiral 2-aryl-substituted pyrrolidines with excellent enantioselectivity (>99% ee) were stereocomplementarily synthesized in good yield (60-80%), demonstrating the feasibility of IREDs for generating pharmaceutically relevant chiral 2-aryl-substituted pyrrolidine intermediates.

OBJECTIVES: This study aims to evaluate diagnostic performance of radiomic analysis using computed tomography (CT) to identify lymphovascular invasion (LVI) in patients diagnosed with rectal cancer and assess diagnostic performance of different lesion segmentations. METHODS: The study is applied to 169 pre-treatment CT images and the clinical features of patients with rectal cancer. Radiomic features are extracted from two different volumes of interest (VOIs) namely, gross tumor volume and peri-tumor tissue volume. The maximum relevance and the minimum redundancy, and the least absolute shrinkage selection operator based logistic regression analyses are performed to select the optimal feature subset on the training cohort. Then, Rad and Rad-clinical combined models for LVI prediction are built and compared. Finally, the models are externally validated. RESULTS: Eighty-three patients had positive LVI on pathology, while 86 had negative LVI. An optimal multi-mode radiology nomogram for LVI estimation is established. The area under the receiver operating characteristic curves of the Rad and Rad-clinical combined model in the peri-tumor VOI group are significantly higher than those in the tumor VOI group (Rad: peri-tumor vs. tumor: 0.85 vs. 0.68; Rad-clinical: peri-tumor vs. tumor: 0.90 vs 0.82) in the validation cohort. Decision curve analysis shows that the peri-tumor-based Rad-clinical combined model has the best performance in identifying LVI than other models. CONCLUSIONS: CT radiomics model based on peri-tumor volumes improves prediction performance of LVI in rectal cancer compared with the model based on tumor volumes.

Cone-rod dystrophy (CORD) is an inherited retinal degenerative disease characterized by progressive loss of cone and rod photoreceptors. Although several genes have been reported to cause autosomal dominant CORD (adCORD), the genetic causes of adCORD have not been fully elucidated. Here, we identified the ATP1A3 gene, encoding the α3 subunit of Na+, K+-ATPase, as a novel gene associated with adCORD. Using whole-exome sequencing (WES), we found a candidate mutation of ATP1A3 that co-segregated with the disease in an analysis of two affected patients and one healthy relative in an adCORD family. According to our RNA-seq data, we demonstrated that the Atp1a3 mRNA level was extremely high in the murine retina. Overexpression of mutant ATP1A3 in vitro led to a reduced oxygen consumption rate (OCR), reflecting the limited mitochondrial reserve capacity. Furthermore, we generated transgenic mice expressing the ATP1A3 cDNA with patient variant and found decreased electroretinogram (ERG) responses. Moreover, the mutant ATP1A3 is highly expressed in photoreceptor inner segment, where mitochondria are enriched. These results suggest that the ATP1A3 mutation is a new genetic cause responsible for adCORD and indicate that ATP1A3 plays an important role in retinal function.

Background The new 8th TNM system attributes AEG Siewert type II to esophageal classification system. However, the gastric and esophageal classification system which was more suitable for type II remains in disputation. This study aimed to illuminate the 8th TNM-EC or TNM-GC system which was more rational for type II, especially for patients underwent transhiatal approaches. Methods We collected the database of patients with AEG who underwent radical surgical resection from two high-volume institutions in China: West China Hospital (N = 773) and Xi Jing Hospital of Fourth Military University (N = 637). The cases were randomly matched into 705 training cohort and 705 validation cohort. All the cases were reclassified by the 8th edition of TNM-EC and TNM-GC. The distribution of patients in each stage, the hazard ratio of each stage, and the separation of the survival were compared. Multivariate analysis was performed using the Cox proportional hazard model. Comparisons between the different staging systems for the prognostic prediction were performed with the rcorrp.cens package in Hmisc in R (version 3.4.4. http://www.R-project.org/). The validity of these two systems was evaluated by Akaike information criterion (AIC) and concordance index (C-index). Results By univariate analysis, the HRs from stage IA/IB to stage IV/IVB were monotonously increased according to TNM-GC scheme in both cohorts (training 2.63, 3.91, 5.02, 8.64, 15.51 and 29.64; validation 1.54, 3.55, 4.91, 7.14, 11.67, 18.71 and 48.32) whereas only a fluctuating increased tendency was found when staged by TNM-EC. After the multivariate analysis, TNM-GC (P

The dual expression of CD5 and MYC protein (DECM) on B-lymphocytes may arise at a specific stage of de novo diffuse large B-cell lymphoma (DLBCL). This study retrospectively reviewed 210 patients with de novo DLBCL at the Affiliated Hospital of Jiangnan University between 2006 and 2017. DECM was significantly correlated with a worse prognosis than that in either the CD5

To identify novel therapeutic agents to treat cancer, we synthesized a series of diaryl ether derivatives. Structure-activity relationship studies revealed that the presence of a chlorine or hydroxyl at the para-position on the phenyl ring (5h or 5k) significantly enhanced antitumor activity. Compound 5h had stronger growth inhibitory activity in HepG2, A549, and HT-29 cells than compound 5k, with IC50 values of 2.57, 5.48, and 30.04 μM, respectively. Compound 5h also inhibited the growth of other cells lines, including Hep3B, PLC/PRF5, SMMC-7721, HeLa, and A375, with IC50 values of 2.76, 4.26, 29.66, 18.86, and 10.21 μM, respectively. The antitumor activity of compound 5h was confirmed by a colony forming assay. Further, our results indicated that the antitumor activity of compound 5h may be mediated by enhancing expression of p21 and cl-caspase3, and leading to apoptosis of cancer cells.

Difenoconazole is one of the triazole compounds, and is widely used as an environmental fungicide. Recently, it has been suspected that long-term exposure to difenoconazole through drinking water and food may induce health effects including hepatotoxicity and tumorigenesis. However, there is little information regarding the molecular mechanism of difenoconazole-induced cytotoxicity and/or human health risk. The present study aimed to investigate the toxic effects of difenoconazole on human hepatocellular carcinoma HepG2 cells in terms of cell viability, generation of reactive oxygen species (ROS) and cellular apoptosis. Difenoconazole significantly activated apoptosis related proteins, namely caspase-8 and -9, as well as cleavage of poly-ADP ribose polymerase (PARP) in a dose-dependent manner whereas the IC50 value for difenoconazole was calculated to be 70 μM. Correspondingly, intracellular generation of ROS was also markedly increased after exposure to difenoconazole and was observed to occur specifically in mitochondria and the endoplasmic reticulum (ER), suggesting that mitochondria and the ER are target organelles for difenoconazole-induced cytotoxicity. Moreover, phosphorylation of protein kinase-like endoplasmic reticulum kinase (PERK), followed by initiation of ATF4, phosphorylation of eif2α and activation of Chop were observed to be up-regulated by difenoconazole, indicating that difenoconazole is capable of inducing ER-stress in HepG2 cells. More interestingly, activation of caspase-8, -9 combined with cleavage of PARP and induction of ER-stress can be attenuated by pretreatment with either of the antioxidants N-acetylcysteine (NAC) or lipoic acid (LA), indicating that generation of ROS may result in the induction of apoptosis and cell death probably through an ROS-mediated mitochondria and ER-stress dependent signaling pathway.

To improve the scheduling optimization of mass customization collaborative logistics, a scheduling solution developed based on the novel particle swarm optimization algorithm was proposed. A mathematic model based on scheduling strategy of mass customization logistics was designed. The novel dynamic particle swarm optimization algorithm framework was given. And simulation experiments were done to validate algorithm. Experiment results show that the proposed algorithm effectively improves the scheduling optimization of mass customization collaborative logistics, which has direct applications for Logistics scheduling

// Qian Qian Wang 1, 2, * , Xin Yi Zhou 1, 2, * , Yan Fang Zhang 1, 2 , Na Bu 2 , Jin Zhou 3 , Feng Lin Cao 3 , Hua Naranmandura 1, 2 1 Department of Toxicology, School of Medicine and Public Health, Zhejiang University, Hangzhou 310058, China 2 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China 3 Department of Hematology and Oncology, The First Clinical College of Harbin Medical University, Harbin 150086, China * These authors have contributed equally to this work Correspondence to: Hua Naranmandura, e-mail: narenman@zju.edu.cn Keywords: acute promyelocytic leukemia, arsenic trioxide, trivalent arsenicals, arsenic binding proteins, monomethylarsonous acid Received: June 02, 2015 Accepted: July 06, 2015 Published: July 15, 2015 ABSTRACT Arsenic trioxide (As 2 O 3 ) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As 2 O 3 -induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As 2 O 3 , which results in initiation of PML-RARα degradation. However, after injection, As 2 O 3 is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMA III ) and dimethylarsinous acid (DMA III ), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As 2 O 3 (as iAs III ) and its intermediate metabolites (i.e., MMA III /DMA III ) in NB4 cells. Inorganic iAs III predominantly showed induction of cell differentiation, while MMA III and DMA III specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAs III , MMA III showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARα fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation.

Arsenic trioxide (As2O3) has remarkable therapeutic efficacy against leukemia. However, after As2O3 biotransformation, the role of arsenic metabolites in the clinical efficacy against leukemia still needs to be elucidated. Therefore, to explore the contribution of trivalent methylated arsenicals in the therapeutic effects, we investigated and compared the effects of arsenite (iAs(III)), monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) on HL-60 cells. Methylated arsenic species MMA(III) and DMA(III) showed potentially reduced cell survival with IC50 values of 3 and 2 μM, respectively. We found that methylated metabolites caused apoptosis through oxidative stress and loss of mitochondrial membrane potential. Furthermore, we found that the caspase-9 and -3 were markedly activated by exposure to methylated metabolites, with cleavage of poly-ADP ribose polymerase (PARP). Conversely, cellular apoptosis, generation of ROS, activation of caspase-3, -9 as well as PARP cleavage were significantly attenuated by pretreatment with an antioxidant, N-acetylcysteine (NAC). DNA damage was also markedly observed in HL-60 cells exposed to either MMA(III) or DMA(III), while iAs(III) did not show any relevant effects in HL-60 cells. Likewise, phosphorylation of the histone H2A variant (γ-H2AX), a biomarker of DNA damage, significantly occurred in cellular nuclei following exposure to two methylated species, which was reduced in the presence of NAC, suggesting that the induction of DNA damage was predominantly caused by the two metabolites via oxidative stress. In conclusion, we suggest that arsenic intermediate metabolites; MMA(III) and DMA(III) might prove to be of clinical relevance in future as such approaches may help in the treatment of leukemia and other types of cancers.

To observe different effects of moxibustion on extracellular potassium ion in acupoint under physiological and pathological status and provide experimental evidence for exploring action mechanism of moxibustion on acupoint local.Forty female SD rats were randomly divided into a blank group, a blank-moxibustion group, a model group and a model-moxibustion group, 10 cases in each one. The complete Freund's adjuvant(CFA) was adopted to establish model of adjuvant arthritis (AA) in the model group and model-moxibustion group. No treatment was given in the blank group and model group while moxibustion was applied at "Zusan-li" (ST 36) for 30 min in the blank-moxibustion group and model-moxibustion group. The tissue fluid in "Zusanli" (ST 36) was collected with microdialysis and real-time analyzed by electrolytic analyzer. The change of concentration of potassium ion in "Zusanli" (ST 36) was observed.(1) Under physiological status, the concentration of extracellular potassium ion in the blank group was not changed within 150 min (P0.05); before the moxibustion, the concentration of extracellular potassium ion in the blank-moxibustion group was (1.21 +/- 0.31) mmol/L, and after treatment it was gradually increased and reached its peak at (2.38 +/- 0.42) mmol/L after 60 min (P0.05), then it was reduced. 150 min after the treatment, concentration of potassium ion was slightly higher than that before moxibustion as well as that in the blank group. The concentration in the blank-moxibustion group at 60 min was statistically significant compared with that in the blank group (P0.05). (2) Under pathological status, the concentration of extracellular potassium ion in the model group was not changed within 150 min, differences of which at each time point was not statistically significant (all P0.05). Before the moxibustion, the concentration of extracellular potassium ion was (1.09 +/- 0.12) mmol/L in the model-moxibustion group, and it was immediately increased to (1.96 +/- 0.18) mmol/L after moxibustion. 60 min and 90 min after the moxibustion, it still maintained a higher level, which was (1.87 +/- 0.29) mmol/L and (1.59 +/- 0.16) mmol/L respectively (both P0.05). The differences of each time point after moxibustion in the model-moxibustion group were statistically significant compared with those in the model group (all P0.05).The moxibustion could increase the concentration of potassium ion in rat's acupoint local under physiological status but time of effect is short; with moxibustion at "Zusanli" (ST 36) under pathological status, the concentration of local potassium ion is obviously increased and maintains for a long time.