Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Glomerular hyperfiltration(GHF), as an early manifestation of prediabetes and diabetic kidney disease, occurs mainly by the mechanism of glomerular-tubular feedback and hemodynamic alterations, and the risk of hyperfiltration can be elevated in younger patients, shorter duration of the disease, poor glycemic control, and high-protein, low-salt diet. Currently, there is no recognized standard for the definition of GHF, GHF lacks typical clinical manifestations, imaging diagnostic criteria are unclear, and GHF-related laboratory markers need to be further studied. Hyperfiltration, if not diagnosed and intervened in time, can accelerate the damage of nephron and the rate of nephropathy progression, and increase the risk of complications and death. Sodium-glucose cotransporter 2 inhibitor(SGLT2i), glucagon-like peptide-1 receptor agonist(GLP-1RA)and so on can effectively reverse the hyperfiltration state. Clinical attention should be paid to the diagnosis of diabetic hyperfiltration and the prevention of its poor prognosis.

Glomerular hyperfiltration(GHF), as an early manifestation of prediabetes and diabetic kidney disease, occurs mainly by the mechanism of glomerular-tubular feedback and hemodynamic alterations, and the risk of hyperfiltration can be elevated in younger patients, shorter duration of the disease, poor glycemic control, and high-protein, low-salt diet. Currently, there is no recognized standard for the definition of GHF, GHF lacks typical clinical manifestations, imaging diagnostic criteria are unclear, and GHF-related laboratory markers need to be further studied. Hyperfiltration, if not diagnosed and intervened in time, can accelerate the damage of nephron and the rate of nephropathy progression, and increase the risk of complications and death. Sodium-glucose cotransporter 2 inhibitor(SGLT2i), glucagon-like peptide-1 receptor agonist(GLP-1RA)and so on can effectively reverse the hyperfiltration state. Clinical attention should be paid to the diagnosis of diabetic hyperfiltration and the prevention of its poor prognosis.

Moral distress generally exists in the nursing interns and has a far-reaching impact. This paper analyzed and summarized the current situation, influencing factors and coping strategies of the nursing interns at home and abroad, in order to provide reference for promoting the professional development of nursing students, strengthening their professional beliefs and stabilizing the nursing team.

Objective:To systematically review the experience of nurses′ in providing home-based hospice care, so as to provide a basis for improving the quality of home-based hospice care and the nursing service system.Methods:Qualitative researches on nurses′ experience of providing home-based hospice care were retrieved from the Cochrane Library, PubMed,Web of Science, EBSCO, Medline, China National Knowledge Internet, China Biomedical Literature Database, Wanfang Database, VIP Database from inception to April 1, 2022. Adopting Joanna Briggs Institute Critical Appraisal Tool (2016) to evaluate the quality of included studies, the Meta-synthesis was used to explain and integrate the research results.Results:A total of 9 articles were included. This study extracted 23 clear results, 8 new categories, and 3 integrated results, including the significance of nurses′ acceptance of home-based hospice care; positive and negative emotions coexist when nurses provide home-based hospice care; challenges in implementing home-based hospice care.Conclusions:The development of home-based hospice care service is helpful to provide continuous care for the terminally ill patients and improve their quality of life, but at the same time, the ability of home-based hospice care of nurses should be further improved and the related policy guarantee should be perfected to promote the steady development of home-based hospice care in China.

Objective:To systematically evaluate and integrate the qualitative research of the practical experience and practical difficulties of advance care planning (ACP), so as to provide a reference for subsequent clinical nurses to better carry out ACP.Methods:PubMed, Web of Science, Embase, Cochrane Library, CINAHL, CNKI, Wanfang, VIP, Chinese Biomedical Literature Database were collected the qualitative research on the practical experience and practical difficulties of nurses′advance care planing, and the search time was the database establishment until August 1, 2022. Literature quality evaluation was conducted by the Joanna Briggs Institute (JBI) (2016), and the results were summarized using Meta integration method.Results:A total of 13 studies were included, and 39 studies were summarized into 11 new categories, forming 4 integrated results: nurses′ cognition of ACP practice, emotional experience of nurses′ ACP practice, personal factors that hinder ACP practice, and external environmental factors that hinder ACP practice.Conclusions:In ACP practice, nurses should be actively guided to have positive cognitive and emotional experience to improve their competence in ACP practice. At the same time, government departments should be united to support, integrate hospitals, society and other forces to formulate coping strategies against obstacles, so as to promote the development and practice of ACP.

Objective:To compare the effect of uPWS R15 software based on deep learning with MIM-Maestro 6.9 software based on atlas library to automatically delineate the organs at risk of prostate cancer in order to provide a reference for clinical application.Methods:The CT data of 90 prostate cancer patients admitted to the Department of Oncology Radiotherapy of the Affiliated Hospital of North Sichuan Medical College from 2018 to 2022 were retrospectively selected. Based on the uPWS R15 software developed by Shanghai United Imaging Medical Technology Company and the MIM-Maestro 6.9 software developed by Beijing Mingwei Vision Medical Software Company, the effects of uPWS and MIM software on automatic delineation of organs at risk were evaluated according to five parameters, including delineation time (T), Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), Hausdorff distance (HD) and the mean distance to agreement (MDA).Results:The sketching time of uPWS software was less than that of MIM software. There were no significant differences in the sketching effect of femoral head and skin between the two software (all P>0.05). The delineation of right kidney ( tMDA=-3.43, zDSC=-4.03, zJSC=-4.16, P<0.05), left kidney ( tMDA=-3.87, zDSC=-4.18, zJSC=-4.41, P<0.05), small intestine ( tMDA=-8.57, zDSC=-9.99, tJSC=14.21, P<0.05) and rectum ( zMDA=-4.00, tDSC=-9.98, tJSC= 9.72, P< 0.05) except HD, was statistically different. The bladder ( z=-7.88, -9.00, -8.17, -8.74, P<0.05) and spinalcord ( z=-3.87, -4.43, 4.03, 3.05, P<0.05) were also delineated with significant differences. The DSC automatically delineated by uPWS software was >0.7, while the DSC automatically delineated by MIM software was >0.7 for all other organs at risk except small intestine and rectum. In addition, the HD, MDA and JSC values of the organs at risk (bilateral femoral head, bilateral kidneys, spinal cord, bladder, skin, rectum and small intestine) automatically delineated by uPWS software were generally better than those with MIM software. Conclusions:The uPWS software outlines better than the MIM software, but the MIM software can also be used clinically with modifications to the small bowel and rectum, saving a great deal of time in preparation for radiation therapy.

【Objective】 To explore the precautions of pre-transfusion examination in patients with antibodies to erythrocyte protective solution, discrepant ABO blood typing results, and positive unexpected antibodies, so as to ensure the safety of blood transfusion. 【Methods】 The screen cells were divided into two groups according to the presence or absence of washing reagent red blood cells in normal saline. One group had untreated forward typing cells, antibody screening cells and identification panel, and the other group had saline-washed reverse typing cells, antibody screening cells and identification panel. The experiments were carried out by microcolumn gel method, saline medium method and polyamine method to analyze the effect of red blood cell preservation solution on serum agglutination reaction of specific patients. 【Results】 Among the 8 patients, forward typing was AB (+ ) in 1 patient, B (+ ) in 4, and A(+ ) in 3, and the reverse typing were interfered. The plasma of 8 patients agglutinated with unwashed reverse typing cells (saline tube method), screen cells and identification panels (saline tube method plus cassette method), while not agglutinated with the polybrene method. The interference was eliminated as using washed reverse typing cells (salinetube method), screen cells and identification panels (saline tube method plus cassette method). 【Conclusion】 The erythrocyte preservation solution affected patients’ blood group typing, but not affected the outcome of blood transfusion as no adverse reactions occurred.

Objective:To investigate whether the hypervirulent Klebsiella pneumoniae (hvKP) induces liver abscess through activating NLRP3 inflammasome. Methods:K1-hvKP and K35-non-hvKP bacterial suspensions were intraperitoneally injected into C57BL/6 mice to establish the models of liver abscess. Human peripheral blood neutrophils were sorted by immunomagnetic beads with CD45 + and Gr-1 + , and the purity was detected by flow cytometry. The concentrations of capsular polysaccharide of K1-hvKP and K35-non-hvKP were detected by total carbohydrate assay kit. The expression of IL-18 and IL-33 by neutrophils at mRNA and protein levels was detected by real-time fluorescence quantitative PCR and ELISA, respectively. The activation of NLRP3 inflammasome in neutrophils was detected by Western blot. Neutrophil extracellular trap formation (NETosis) was observed under confocal laser scanning microscope. Results:The C57BL/6 mice with K1-hvKP infection had significantly serious liver abscess as compared with the K35-non-hvKP-infected mice. The purity of human neutrophils was more than 95%. The concentration of capsular polysaccharide in K1-hvKP was significantly higher than that in K35-non-hvKP. Compared with K35-non-hvKP, K1-hvKP significantly promoted the neutrophils to express IL-18 and IL-33 at both mRNA and protein levels, enhanced the activation of NLRP3 and induced NETosis.Conclusions:This study suggested that hvKP could promote NETosis by activating NLRP3 inflammasome to cause liver abscess.

Objective:To report a Chinese family with a novel ABCD1 gene mutation at c.332T>G (p.V111G) site and discuss its clinical characteristics and molecular mechanism.Methods:The clinical data, laboratory examination, and imaging examination results were analyzed to make the clinical diagnosis of a middle-aged onset patient from the First Affiliated Hospital of Zhengzhou University in May 2017. High-throughput sequencing was used to discover a novel ABCD1 gene mutation. Sanger sequencing was used to find out whether other family members contain the same ABCD1 gene mutation. The pathogenicity of this mutation was explored by protein structure prediction and pathogenicity analysis. Adrenoleukodystrophy protein-green fluorescent protein (ALDP-GFP) and ALDP-GFP (V111G) plasmids were constructed and human embryonic kidney 293 cells were transfected, then immunofluorescence and Western blotting were used to explore the molecular mechanism of this mutation (completed in Henan Provincial People′s Hospital).Results:The proband (a 39-year-old male) was diagnosed as adrenomyeloneuropathy, a subset of X-linked adrenoleukodystrophy, with a novel heterozygous missense mutation in the ABCD1 gene at c.332T>G (p.V111G) site, and his mother and two daughters were all carriers. Protein structure prediction and pathogenicity results suggested that this mutation is pathogenic. Overexpression of ALDP-GFP (V111G) in the human embryonic kidney 293 cells resulted in a significant decrease in the expression levels of ALDP and the abnormal localization from the peroxisomal membrane to the cytoplasm, accompanied by significant down-regulation of LC3-Ⅱ/LC3-Ⅰ and beclin-1.Conclusion:c.332T>G (p.V111G) is a novel pathogenic mutation in the ABCD1 gene, which causes adrenomyeloneuropathy by impairing autophagy.