Objective:To analyze the prognostic factors of children with septic shock in the pediatric intensive care unit.Methods:The clinical data of children diagnosed with septic shock in the pediatric intensive care unit of Guiyang Maternal and Child Health Hospital from April 2018 to April 2022 were retrospectively collected,and the children were divided into the death group and the survival group according to seven days regression.The basic data of the two groups were statistically compared，and the relationship between lactic acid，vasoactive-inotropic score one hour after admission，time of antibiotic initiation，serum potassium，serum sodium，serum calcium，serum troponin T，fluid resuscitation volume in the first hour，glutamyl aminotransferase，creatinine，total leukocyte count，C-reaction protein，brain natriuretic peptide were compared.The risk factors affecting the death of children were analyzed by Logistic regression.The relationship between fluid resuscitation volume in the first hour and prognosis was analyzed using the receiver operator characteristic (ROC) curve.Results:（1）A total of 67 children were included，19 died and 48 survived.（2）The first-hour liquid resuscitation dose in the survival group was lower than that in the death group，and the difference was statistically significant（ P<0.05）.（3）The ROC curve showed that the optimal cut-off of the first-hour liquid resuscitation dose was 25 mL/kg，with a sensitivity of 57.9% and a specificity of 72.9%.（4）In unifactorial analysis，lactic acid in the first hour of admission，early lactic acid after resuscitation，serum calcium，serum troponin T，alanine aminotransferase，combined septic encephalopathy，Glasgow coma score，and pediatric critical illness score were all risk factors for death in children within seven days（ P<0.05）.(5) Multivariate Logistic regression analysis showed that serum calcium（ OR=1.435， P=0.001）and lactic acid value after resuscitation（ OR=0.040， P=0.021）were independent risk factors for death in septic shock. Conclusion:The higher the total fluid resuscitation in the first hour，the higher the fatality rate.Serum calcium and early lactic acid after resuscitation are independent risk factors for death in children within seven days.

Efferocytosis refers to the process by which apoptotic cells are engulfed and cleared by phagocytes， including professional phagocytes， such as macrophages and dendritic cells， and non-professional phagocytes， such as epithelial cells. Liver macrophages are the main cells with the function of efferocytosis in the liver. In recent years， an increasing number of studies have shown that various acute and chronic liver diseases are associated with the efferocytosis function of liver macrophages， including acute liver injury， alcoholic liver disease， nonalcoholic fatty liver disease， autoimmune liver disease， liver fibrosis， and liver cancer. This article elaborates on the expression of molecules associated with the efferocytosis function of macrophages， the process of efferocytosis， and the role of efferocytosis function in different liver diseases， so as to provide new ideas for the treatment of liver diseases.

Primary biliary cholangitis （PBC） is an autoimmune liver disease characterized by progressive and non-purulent inflammation of small- and medium-sized bile ducts in the liver. Recent studies have shown that abnormal lipid metabolism is relatively common in patients with PBC， and 76% of PBC patients have dyslipidemia. The effects and harms of dyslipidemia have attracted much attention. Lipid metabolism disorders play an important role in the progression of PBC. This article mainly reviews the research advances in the manifestation， role， diagnosis， and treatment of lipid metabolism disorders in PBC， so as to provide new ideas for the treatment of PBC.

T-cell immunoglobulin and mucin domain-containing molecule-3(Tim-3)is a member of the Tim family and has been a research hotspot in recent years.As a negative regulatory factor,Tim-3 exerts different effects by binding to different ligands.Tim-3 is expressed in various types of immune cells,such as natural killer cells,dendritic cells,and monocytes,and Tim-3 has a regulatory effect on the functions of these immune cells.In recent years,a large number of studies have shown that Tim-3 is closely associated with the development and progression of liver diseases.This article reviews the studies on the role and mechanism of Tim-3 in different liver diseases and cells in recent years,in order to provide richer perspectives and ideas for the clinical diagnosis and treatment of liver diseases.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Background/Aims: We aimed to investigate the role and working mechanism of Homo sapiens circular RNA_0003602 (hsa_circ_0003602) in colorectal cancer (CRC) development. Methods: The expression of circ_0003602, miR-149-5p, and solute carrier family 38 member 1(SLC38A1) was detected by quantitative real-time polymerase chain reaction. RNase R assays were conducted to determine the characteristics of circ_0003602. CCK-8 assays, flow cytometry analysis, transwell invasion assays, wound healing assays and tube formation assays were employed to evaluate cell viability, apoptosis, invasion, migration, and angiogenesis. All protein levels were examined by Western blot or immunohistochemistry assay. The glutamine metabo-lism was monitored by corresponding glutamine, α-ketoglutarate and glutamate assay kits. Dual-luciferase reporter assay was utilized to confirm the targeted combination between miR-149-5p and circ_0003602 or SLC38A1. A xenograft tumor model was established to analyze the role of circ_0003602 in CRC tumor growth in vivo. Results: Circ_0003602 was upregulated in CRC tissues and cell lines. Circ_0003602 silencing suppressed CRC cell viability, migration, invasion, angiogenesis, and glutaminolysis; induced cell apoptosis in vitro; and blocked tumor growth in vivo. Moreover, circ_0003602 directly interacted with miR-149-5p to negatively regulate its expression, and circ_0003602 knockdown suppressed the malignant behaviors of CRC cells largely by upregulating miR-149-5p. MiR-149-5p directly bound to the 3’ untranslated region of SLC38A1 to induce its degradation, and miR-149-5p overexpression reduced the malignant potential of CRC cells largely by downregulating SLC38A1. Circ_0003602 positively regulated SLC38A1 expression by sponging miR-149-5p in CRC cells. Conclusions Circ_0003602 knockdown impedes CRC development by targeting the miR-149-5p/SLC38A1 axis, which provides a novel theoretical basis and new insights for CRC treatment.

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

【Objective】 To explore the current status and development trend of research on external therapies in traditional Chinese medicine (TCM) for insomnia over the past 10 years through bibliometrics and visual analysis, to provide references for further research on the topic. 【Methods】 Literature relating to TCM external therapies for insomnia from January 1, 2012 to December 31, 2021 was retrieved from Chinese databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and from the Web of Science Core Collection (WOSCC) for English articles. CiteSpace, VOSviewer, Scimago Graphica, and NoteExpress software were used to analyze publication volumes of the papers and how they were distributed in different journals, as well as to visualize the data of the countries, authors, institutions, and keywords. 【Results】 A total of 6 085 papers were obtained, of which 5 592 were from the Chinese databases and 493 were from the English database, with their publication volumes growing steadily year on year. Approximately 45 countries and regions were found to have published research on the topic. In terms of Chinese publications, the author with the most papers published was CHEN Yunfei from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine. The closest collaboration was between LIU Chengyong from the Affiliated Hospital of Nanjing University of Chinese Medicine and YUE Zenghui from Hunan University of Chinese Medicine. In terms of English publications, the author with the most papers published was MAO Junj from Sloan-Kettering Cancer Research Center, USA, and LAO Lixing from the University of Hong Kong was his closest partner in collaboration. Heilongjiang University of Chinese Medicine was the institution with the most Chinese publications, and Shanghai University of Traditional Chinese Medicine was the one with the most English papers published. Studies on the topic were published in 386 Chinese journals and 205 English journals, respectively. Nowadays, the clinical application of TCM external treatments for insomnia, the selection of meridians and acupoints, therapies for insomnia and its related diseases are research hotspots. The combined use of different TCM external therapies is a trend in the treatment of insomnia and its concomitant diseases, especially in the fields of oncology, nursing, and psychiatric disorders. The exploration of mechanisms of TCM external therapies for insomnia is also a key direction for future research. In clinical practice, the commonly used external therapies for insomnia include acupuncture, ear-acupressure with beans, acupoint application, etc. The commonly selected acupoints are auricular points, Sishencong (EX-HN1), Shenmen (HT7), etc. The frequently studied meridians are Ren, Du, Qiao, etc. The insomnia concomitant diseases are depression, stroke, anxiety, etc. 【Conclusion】 A wealth of research results have been accumulated in the treatment of insomnia by TCM external therapies, but authoritative research results are not so many. Therefore, institutions in different countries should strengthen communications and cooperation, and researchers should be encouraged to make innovations and breakthroughs on the basis of inherited TCM external therapies, so as to produce more valuable research results and improve TCM external therapies for providing better treatments for patients with sleep disorders.

Objective:To compare and analyze the clinical characteristics between acute fatty liver of pregnancy (AFLP) and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.Methods:This is a retrospective cohort study. The clinical data of 13 cases with AFLP and 34 cases with HELLP syndrome were collected from three tertiary referral centers in Yunnan (the First Affiliated Hospital of Kunming Medical University, the Second Affiliated Hospital of Kunming Medical University, and Yan'an Hospital of Kunming City) from January 2016 to December 2021. The patients were diagnosed to AFLP and HELLP syndrome according to the Swansea criteria and the Tennessee classification system. The general characteristics, clinical features, laboratory results within 24 hours after admission, complications, maternal and neonatal outcomes were compared to analysis the differences between the two groups.Results:① Maternal characteristics: compared with HELLP syndrome group, AFLP group had lower body mass index (BMI) and blood pressure at admission (both P < 0.01). ②Clinical features: the most common symptoms in AFLP patients were skin jaundice, abdominal pain, nausea and vomiting, edema. The main manifestations of patients with HELLP syndrome were albuminuria, hypertension, edema, headache. Some patients had multiple symptoms concurrently. ③ Laboratory results: compared with HELLP syndrome group, the levels of platelet count (PLT), total bilirubin (TBil), direct bilirubin (DBil), γ-glutamyl transferase (γ-GGT), alkaline phosphatase (ALP), total bile acid (TBA), serum creatinine (SCr) and international standardized ratio (INR) in AFLP group were significantly increased within 24 hours after admission [PLT (×10 9/L): 107.69±51.13 vs.76.71±43.25, TBil (μmol/L): 121.60 (83.20, 170.00) vs.15.25 (7.22, 29.05), DBil (μmol/L): 86.50 (58.60, 104.00) vs. 4.30 (2.22, 10.10), γ-GGT (U/L): 87.00 (37.00, 127.00) vs. 41.00 (19.00, 64.42), ALP (U/L): 199.10 (109.00, 349.20) vs. 125.50 (90.50, 155.25), TBA (μmol/L): 51.50 (16.20, 117.40) vs. 4.15 (2.02, 6.95), SCr (μmol/L): 155.80 (129.00, 237.00) vs. 79.00 (65.43, 113.70), INR: 1.28 (1.17, 1.63) vs. 0.94 (0.88, 1.08), all P < 0.05], prothrombin time (PT) was significantly prolonged [seconds: 16.10 (14.50, 19.20) vs. 12.40 (11.43, 13.40), P < 0.05]. The level of blood glucose (GLU), fibrinogen (FIB) and the activity of antithrombin Ⅲ (ATⅢ) decreased significantly [GLU (mmol/L): 5.18±1.33 vs. 6.33±1.19, FIB (g/L): 1.96±1.46 vs. 3.81±1.58, ATⅢ (%): 40.61±25.84 vs. 66.39±24.11, all P < 0.05]; ④ Complications: compared with HELLP syndrome group, the incidence of patients with hypoglycemia [30.77% (4/13) vs. 0% (0/34)], acute liver failure [53.85% (7/13) vs. 5.88% (2/34)], acute renal insufficiency [69.23% (9/13) vs. 8.82% (3/34)], coagulopathy [76.92% (10/13) vs. 38.24% (13/34)], disseminated intravascular coagulation (DIC) [53.85% (7/13) vs. 5.88% (2/34)], and multiple organ dysfunction syndrome (MODS) [53.85% (7/13) vs. 5.88% (2/34)] were significantly higher in AFLP group (all P < 0.05). ⑤ Maternal and neonatal outcome: all patients delivered after admission. The total length of hospital and intensive care unit stay were significantly longer in the AFLP group than in the HELLP syndrome group [days: 17.00 (11.00, 25.00) vs. 9.00 (7.00, 12.00), 12.00 (4.00, 22.00) vs. 3.91 (0, 7.00), both P < 0.01]. Two AFLP patients died, including one due to intracranial venous thrombosis and one due to multiple organ failure and cardiopulmonary arrest. There were no deaths in the HELLP syndrome group. Conclusions:There are significant differences in maternal characteristics, laboratory results and complications between AFLP and HELLP syndrome. TBil, γ-GGT, SCr, FIB, INR and ATⅢ activity may help to distinguish the two diseases.

OBJECTIVE: To investigate the role of NOV/CCN3 in regulating the proliferation of mesenchymal stem cells (MSCs) and its regulatory mechanism and assess the value of CCN3 as a proliferative factor in bone tissue engineering. METHODS: Mouse embryonic fibroblasts (MEFs) were used as the MSC model, in which CCN3 expression was up-regulated and downregulated by transfection with the recombinant adenovirus vectors Ad-CCN3 and Ad-siCCN3, respectively. Flow cytometry was used to analyze the changes in cell cycle and apoptosis of the transfected cells. Western blotting was used to detect the expression levels of the proliferation indicators (PCNA, cyclin E, and cyclin B1) and the apoptosis indicators (Bax and Bcl-2) to assess the effect of modulation of CCN3 expression on MEF proliferation and apoptosis. CCN3 protein secretion by the cells was detected using ELISA. RT-qPCR and Western blotting were employed to analyze the changes in the expressions of Notch1, ligand DLL1, the downstream key proteins or genes (Hey1, P300, H3K9) and MAPK pathway-related proteins ERK1+2 and p-ERK1+2. RESULTS: Flow cytometry showed that compared with the control cells, MEFs transfected with Ad-CCN3 exhibited significantly increased cell proliferation index ( CONCLUSIONS CCN3 over-expression promotes the proliferation and inhibits apoptosis of MEFs possibly by inhibiting the classical Notch signaling pathway and activating the MAPK pathway
Animals ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Fibroblasts ; Mice ; Nephroblastoma Overexpressed Protein