Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

A patient who suffered soft tissue defects of all 5 digits of left hand was referred to the Department of Hand and Foot Surgery, Affiliated Nanhua Hospital, University of South China in January 2020. A quadruple paddled posterior interosseous artery flaps was used to cover the defect in index, middle, ring and little fingers and a free hallux nail flap was used to repair the defect in thumb. Two years after operation, the appearance and texture of the flaps of all digits in the left hand were good. The function of the digits was good as well. There were slightly noticeable scars left in both the donor sites of left forearm and right foot.

Objective:To investigate the relationship between the E2 and E4 alleles of apolipoprotein E (apoE) gene and myocardial infarction (MI) in type 2 diabetes Mellitus (T2DM) patients, and to explore the relationship between apoE polymorphism and blood lipid metabolism.Methods:This case control study was conducted from August 2016 to March 2020 in China-Japan Friendship Hospital, 3 459 inpatients with T2DM were included including 3 044 patients without MI (T2DM group) and 415 patients with MI (T2DM+MI group). Real time fluorescent quantitative PCR was used to detect apoE polymorphism. Automatic biochemical analyzer was used to detect lipid levels. Logistic regression analyses were performed to determine the association of apoE with risk of MI in patients with T2DM.Results:(1) The frequency of E4 allele in T2DM+MI group (12.29%, 102/830) was significantly higher than in T2DM group (9.13%,556/6 088), while the frequency of E2 allele in T2DM+MI group (7.35%,61/830) was significantly lower than that in T2DM group (8.21%,500/6 088), P=0.012. Logistic regression analyses showed that E4 allele carrier (E3/E4+E4/E4) faced a higher risk for MI in T2DM patients ( OR=1.48, 95% CI 1.14-1.92, P=0.003), while E2 allele carrier(E2/E3+E2/E2)did not face a higher risk of MI in T2DM patients ( OR=0.88, P=0.642). (2) The levels of apoE polymorphism and blood lipid: The levels of TC, LDL-C and apoB increased in the order of E4 allele, wild type and E2 allele ( P<0.05). The levels of HDL-C, apoA1 and apoE decreased in the order of E4 allele, Wild type and E2 allele ( P<0.05). Conclusion:The E4 allele is a risk factor for MI in T2DM patients, and apoE polymorphism can affect blood lipid level in this patent cohort.

Objective: To investigate the relationships between behavioral problems and family environment in obese children aged 6-15 years to provide a dereference for the analysis of behavioral problems among obese children and the construction of their family environmet . Methods: Family environment dimensions and behavioral problems were investigated among 2 376 obese children and 2 376 non-obese children with Family Environment Scale Symptoms Questionnaire and Achenbach Child Behavior Checklist. Data were analyzed by SPSS 17.0. Results: The incidence of the behavioral problems in obese children (21.12%) was higher than that of non-obese children (15.53%)(χ2=24.93，P<0.01).The scores of Family Environment Scale Symptoms Questionnaire differed between obese children and nonobese children (Z=-2.44, -2.98, -3.38, P<0.05). Binary logistic regression results showed that for obese boys and girls aged 6 to 11 years, high maternal education levels(OR=0.78, 95%CI=0.69-0.88), family cohesion(OR=0.75, 95%CI=0.67-0.84) and less family conflicts(OR=0.81, 95%CI=0.75-0.87) were related to less behavioral problems; for obese boys and girls aged 12 to 15 years, family cohesion(OR=0.79, 95%CI=0.70-0.90) and less family conflicts(OR=0.78, 95%CI=0.71-0.86) were related to less behavioral problems. Conclusion Family cohesion and less family conflicts might help low the risk of behavioral problems among obese children. The role of family environment on behavioral problems should not be neglected in future mental health promotion and social work service for obese children.

Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) or high glucose on the toll-like receptor 4 (TLR4) expression,inflammatory cytokines and fibrotic factors in human tubular epithelial cells (HK-2),revealing the innate immune-related pathogenesis of diabetic nephropathy (DN) which may have clinical implications.Methods Three TLR4 siRNA sequences were designed and synthetized.After transfection,the most effective siRNA was selected to use for further expriments.The experiment consisted of 2 parts.Part 1:Cells were divided into three groups:normal-glucose group (NG,5.5mmol/L glucose),mannose group (M,5.5 mmol/L glucose + 19.5 mmol/L mannose),High-glucose group (HG,25 mmol/L glucose),preliminary validated the effects of high glucose and high osmotic pressure.Part 2:Cells were divided into seven groups:NG group,HG group,Ang Ⅱ group,Ang Ⅱ + negative group,HG+ negative group,Ang Ⅱ + siRNA group and HG+ siRNA group.Real time PCR was used to analyze the mRNA expression of TLR4,myeloid differentiation factor 88 (MyD88),heat shock protein 47 (HSP47).Western blotting was used to observe the protein expression of TLR4,MyD88,HSP47,NF-κB,type Ⅳ collagen (ColⅣ).ELISA was used to detect the expression of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6).Results Compared with NG group,TLR4,MyD88,HSP47 mRNA and TLR4,MyD88,NF-κB,ColⅣ,HSP47 protein were highly expressed under high glucose or Ang Ⅱconditions (P ＜ 0.01),and the expression levels of MCP-1 and IL-6 also increased significantly (P ＜ 0.01).Compared with HG or Ang Ⅱ group,the above indicators were obviously inhibited in the TLR4 siRNA groups (P＜0.01).Comparison between blank vector transfected groups and HG group as well as Ang Ⅱ group indicated no statistic significance (P ＞ 0.05).Conclusions Both Ang Ⅱ and high glucose stimulate TLR4 expression,which result in the up-regulation of inflammatory and fibrotic factors in HK-2.Specific target of TLR4 gene silencing can block the TLR4 pathway that is activated by high glucose and Ang Ⅱ,and thus reduce the inflammatory and fibtogenic factors' release.TLR4 signal is the common innate immune response pathway which induces the release of inflammatory and fibrotic factors in HK-2 under high glucose or high angiotension conditions.

Objective To explore the influences of family-centered health education on compliance of segregation in children with respiratory infectious disease. Methods The patients of observation group received family-centered health education and included 247 children with respiratory infectious disease who were hospitalized in Hu′nan Children′s Hospital from August to December in 2014 and their parents. The patients of control group received normal health education and included 285 children with respiratory infectious disease who were hospitalized from January to July in 2014 and their parents. The compliance of segregation of the children and their parents were compared between two groups. Results The cognition of the awareness, category and requirement of the segregation, as well as parents′ effective segregate practice of the observation group were significantly higher than that of the control group (χ2 =38. 7,57. 71,30. 36;P<0. 01). Conclusions Family-centered health education can highly improve the compliance of segregation in children with respiratory infectious disease. It can also prevent cross infection and ensure children′s health.

Objective To strengthen nursing risk assessment for critical patients and improve their healthcare outcomes.Methods It formed the dynamic closed-loop management mode around the management system, early risk warning system, nurses′ observation ability, emergency procedures, information communication on account of predicting risk factors no timely,disease observation inaccuracy,emergency procedures nonstandard.Results Compared 2009 year with 201 5 year,the numbers of preventing nursing accidents by timely and effective observation increased 37 from 1 0;obviously improvement on reporting illness, communication ability,observing illness satisfied doctors(P <0.01 );the numbers of nursing adverse events was significantly decreased.The abilities of emergency situation judgment,reaction and coping measures in nurses were improve.Conclusions The closed-loop management mode can effectively improve each step′s quality and quality of critically patients care continuously.

Objective To identify the influencing factors of nursing related medication errors , and put forward the effective prevention and control measures .Methods One thousand three hundred and forty-three cases with medication errors from 15 tertiary hospitals in Shanghai Nursing Quality Control Center were chosen . The influencing factors were analyzed by the research tools which were constructed by the level of influencing factors depending on the international classification of patient safety ( ICPS ) through the method of content analysis.Results The occurrences of medication errors were most frequent (62.84%) in the early morning (8:00-16:00), and were related to the most therapeutic nursing .The nursing related medication errors happened frequently in elderly patients with more than 70 years old (32.45%), and which suggested that the abilities of self-care and communication in elderly patients were weak , and the elderly patients were the highest risk of medication errors .The results of safety events of patients in the ICPS were divided into 5 levels including the no, mild, moderate, severe, death.The percent of medication errors including the no , mild, moderate, severe, death in 1 343 cases were respectively 91.88%, 3.35%, 2.76%, 2.01%, 0%.The frequencies of influencing factors of nursing related medication errors in 1 343 cases were 3 185, and the frequencies from high to low were respectively routine violations ,“negligence” and “fault” in the technical mistakes ,“misapplication of good rules” in the error of rule, knowledge-based mistake, communication and illusion.Conclusions Application of the influencing factor of ICPS is helpful to discriminate the system and process defect from the perspective of human error in the nursing managers , and can improve the level of management of patient safety .

BACKGROUND: Whether horizontal and vertical impacts cause craniocerebral injury of the same degree, and whether serum myelin basic protein (MBP) changes is associated with the direction of impact have been scarcely addressed in previous studies.OBJECTIVE: To observe the change in the serum MBP levels and morphological changes of the brain tissue rabbits with craniocerebral injury resulting from impacts from different directions.DESIGN: A randomized controlled experiment.SETTING: Department of Neurosurgery of a hospital affiliated to a medical university.MATERIALS: This study was conducted in the Central Laboratory of Shenyang Medical College between October 2003 and January 2004. Totally 30 healthy rabbits of either sex were randomly divided into two equal groups to receive vertical and horizontal impact on the head.METHODS: All the rabbits were anesthetized and fixed in prone position onto a table equipped with a device for inducing impact on the head from different directions. Venous blood of 1 mL was taken from the edge of the ear of each rabbit for detecting MBP before injury. The rabbits in vertical impact group received the impact of a hammer falling directly on the parietal bone of the skull. In the horizontal group, the rabbits were subjected to horizontal impact on the lateral side of the skull. Forty-eight hours after the injury, venous blood were again taken for MBP measurement. The rabbits were then killed for pathological examination of the brain.MAIN OUTCOME MEASURES: Changes in serum MBP and pathomorphology of the brain tissues in the two groups after the impact.RESULTS: ① According to intention to treat analysis, all the 30 animals were involved in the experiment. There was no significant difference in serum MBP levels between the two groups before the impact, nor 48 hours after the impact( P ＞ 0.05). In the vertical impact group, serum MBP levels before the impact was( 1.68 ± 0. 86) μg/L, which was significantly lower than that after the impact[ (5.25 ± 1.96) μg/L, t = 3. 226, P ＜ 0. 05]. ② In the horizontal strike group, serum MBP also significantly increased from the level of( 1.70 ± 0.91 ) μg/L before impact to(5.73 ± 2.07) μg/L after that( t = 3. 080, P ＜ 0.05) . ③ After the impact, vasodilation and congestion in the cortex near the midline of the bilateral parietal region and edema in the deep layer of the white matter were observed in the vertical impact group, along with significant enlargement of the extravascular and extracellular space. In the horizontal group, similar changes except those near the midline of the bilateral parietal region took place after the impact; the same pathological changes were also observed in the basal plane, with nearly identical pathological changes in the deep layer of the white matter.CONCLUSION: Vertical and horizontal impacts can both result in almost identical brain injuries demonstrated by similar changes in serum MBP and the pathomorphology of the brain tissues after the impacts.

Objective: To explore the clinical efficacy and characteristics of Tuina and herbal and magnetic application in the treatment of cervical spondylopathy, Method: 302 subjects were treated with above methods and their efficacy were assessed according to the patterns. Results: Among the 302 cases, 153 cases were cured, 131 got marked effects, 14 cases were improved and 4 cases failed; the total effective rate was 98.7%. Conclusion: Tuina in combination with herbal and magnetic application has good effects on various pattern of cervical spondylopathy.