Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human's health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumu-lates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

Background::The ideal blood pressure (BP) target for patients with atrial fibrillation (AF) is still unclear. The present study aimed to assess the effect of the baseline BP on all-cause mortality in patients with AF.Methods::This registry study included 20 emergency centers across China and consecutively enrolled patients with AF from 2008 to 2011. All participants were followed for 1 year ± 1 month. The primary endpoint was all-cause mortality.Results::During the follow-up, 276 (13.9%) all-cause deaths occurred. Kaplan-Meier curves showed that a systolic blood pressure (SBP) ≤110 mmHg or >160 mmHg was associated with a higher risk of all-cause mortality (log-rank test, P = 0.014), and a diastolic blood pressure (DBP) <70 mmHg was associated with the highest risk of all-cause mortality (log-rank test, P = 0.002). After adjusting for confounders, the multivariable Cox regression model suggested that the risk of all-cause mortality was increased in the group with SBP ≤110 mmHg (hazard ratio [HR], 1.963; 95% confidence interval [CI], 1.306-2.951), and DBP <70 mmHg (HR, 1.628; 95% CI, 1.163-2.281). In the restricted cubic splines, relations between baseline SBP or DBP and all-cause mortality showed J-shaped associations (non-linear P <0.001 and P = 0.010, respectively). The risk of all-cause mortality notably increased at a lower baseline SBP and DBP. Conclusions::Having a baseline SBP ≤110 mmHg or DBP <70 mmHg was associated with a significantly higher risk of all-cause mortality in patients with AF. An excessively low BP may not be an optimal target for patients with AF.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human’s health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumulates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human’s health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumulates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared

Objective To study the effect of caffeine on hyperoxic lung injury of premature rats and its relationship with p38 motigen-activated protein kinase( MAPK) signal pathway. Methods Sixty Wistar premature rats were divided into 4 groups(n＝15) according to the random number table:air + normal sa-line group(A+N group),air + caffeine group( A+C group),hyperoxia + normal saline group( H+N group),and hyperoxia + caffeine group(H+C group). Among them,H+N group and H+C group were continually exposed to hyperoxia ( oxygen concentration was 60% ~70%). For A + C group and H + C group,the premature rats were injected with caffeine of 29 mg/(kg·d) into their peritoneal cavities every day after birth. For A+N group and H+N group,the premature rats were injected with normal saline of the same volume into their peritoneal cavities. In each group,the lung tissues of 5 premature rats were randomly select-ed on the third, seventh and fourteenth day respectively. The pathological changes of lung tissue, radiated alveolar count(RAC) and collagen content in lung tissue were observed under a light microscope. The wet/dry ratio ( W/D) was measured. Two-step immunohistochemistry was used to detect the distribution of p38MAPK in lung tissue. The content of phosphorylated p38MAPK( p-p38MAPK) protein was detected by western blot. Results Compared with the air groups,the lung tissues of premature rats in high oxygen expo-sure groups showed different degree of inflammatory changes on the third,seventh,and fourteenth day. The changes were more obvious with the prolonged exposure to hyperoxia. Pulmonary fibrosis was visible on the fourteenth day,which was improved after caffeine intervention. The RAC value of premature rats in hyperoxia exposure groups was significantly lower than that in air-exposure groups(P<0. 05),and the W/D ratio and collagen content in lung tissue increased significantly (P<0. 05),which were improved after caffeine inter-vention(P<0. 05). The results of two-step immunohistochemistry showed that the number of p-p38MAPK positive cells in the lung tissue of premature rats in hyperoxia exposure groups increased and widely distribu-ted, but decreased after caffeine intervention. The results of western blot showed that the content of p-p38MAPK protein in lung tissue of premature rats in hyperoxia exposure groups was significantly higher than that of air groups(P<0. 05),but it decreased after caffeine intervention(P<0. 05). Conclusion Hy-peroxia can promote the formation of pulmonary fibrosis by activating p38MAPK signal pathway. Caffeine can interdict the expression of p38MAPK to alleviate the fibrosis of lung tissue exposed to hyperoxia and thus protects the lung tissue.

Objective To investigate the effect of influenza virus on the expression of collagen triple he-lix repeat containing 1 (CTHRC1). Methods A549 cells were infected with influenza virus. mRNA and protein levels of CTHRC1 were determined by RT-PCR and Western blot , CTHRC1 levels in the cell supernatants and sera of influenza virus infected patients were determined by enzyme-linked immunosorbent assay (ELISA). The difference of CTHRC1 levels between healthy controls and HCV patients was analyzed. Results Compared with controls, mRNA and protein levels of CTHRC1 were higher in A549 cells infected with H3N2. Serum CTHRC1 levels were higher in influenza virus infected patients than in healthy controls (P < 0.05). Conclusion Influenza virus can promote the synthesis and secretion of CTHRC1.

Objective:To explore the relationship of negative life events,parent-child relationship,teacher-child relationship with the altruistic prosocial behaviors in migrant and unattended primary school children. Methods:Totally 1198 migrant children and 1631 unattended children were recruited. The dimension ofaltruistic prosocial behaviorof Child and Adolescent Prosocial Behavior Questionnaire (CAPBQ-A)was used to evaluate altruistic prosocial behaviors,Life Event Questionnaire (LEQ)was used to evaluate negative life events,parent trust and support dimensionof Social Psychological Relationship Questionnaire(SPRQ-P)to evaluate par-ent-child relationship, and teacher trust and support dimension (SPRQ-T ) to evaluate teacher-child relationship. Results:The CAPBQ-A scores were higher in migrant children than in the unattended children (P<0. 001). Being migrant or unattended children (β=-0. 07),LEQ score (β=-0. 04),SPRQ-P score (β=0. 13) and SPRQ-T score (β=0. 31 )predicted the CAPBQ-A score significantly. The SPRQ-P score had significantly stronger predictive effect on the migrant children compared to the unattended children (β=-0. 06 ). Yet the SPRQ-T score predicted the unattended children stronger (β=0. 06 ,Ps<0. 0 1 ). Conclusion:The unattended children's al-truistic prosocial behaviors are much worse than the migrant children. Personal relationships seem to play a more important role than negative life events in shaping children's altruistic prosocial behaviors. Moreover,the parent-child relationship seems to be more important to the migrant children,whereas the teacher-child relationship is more important to the unattended children.

Objective: To investigate the effect of diabetes on the intensity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a)-SUMOylation and SERCA2a activity of myocardium in experimental rats.
Methods: The 8 weeks old SD rats were divided into 2 groups, Diabetic group, with diet-induced type 2 diabetic rats and Control group, with normal rats. The systolic and diastolic cardiac functions were evaluated by echocardiography and left ventricular pressure measurement. The intensity of SERCA2a-SUMOylation was examined by co-immunoprecipitation and SUMOylation kit.
Results: Compared with Control group, Diabetic group had decreased systolic and diastolic cardiac functions, especially for diastolic function;decreased SERCA2a protein expression and intensity of SUMOylation;decreased SUMOylation E2 (Ubc9 ) protein expression. The protein levels of SUMO1, SAE1 and SAE2 were similar between 2 groups.
Conclusion: The intensity of SERCA2a-SUMOylation and Ubc9 decreased in diabetic myocardium which implies that SERCA2a-SUMOylation and Ubc9 were closely related to the damage of diabetic myocardium in experimental rats.