Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Objective To investigate the expression of centromere protein U(CENPU)in the intestinal tissues of patients with colon cancer,and to analyze the effect of CENPU expression level on the prognosis of patients with colon cancer combined with bioinformatics.Methods Firstly,the expression of CENPU in cancer tissues and normal tissues of colon cancer patients was analyzed by the expression of CENPU in tissues was further verified by real-time quantitative real time polymerase chain reaction(qRT-PCR),Western blot(WB)and immunohistochemistry(IHC).Combined with clinical data,univariate and multivariate Cox regression are used to analyze the correlation between CENPU expression and clinical case parameters of colon cancer patients.Then,the predictive effect of CENPU expression on the prognosis of colon cancer patients are explored by drawing receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.Finally,the possible molecular mechanism of the effect of CENPU expression on the progression of colon cancer are analyzed by bioinformatics.Results By qRT-PCR,WB and IHC experiments,we find that compared with normal tissues,the expression of CENPU in cancer tissues of colon cancer patients is significantly increased.Cox regression analysis show that the expression of CENPU is significantly correlated with the age and TNM stage of patients,and is a risk factor affecting the prognosis of patients.Kaplan-Meier survival curve analysis show that colon cancer patients with high CENPU expression has significantly lower survival rates.ROC curve show that the model based on CENPU expression has a high predictive power for the prognosis of colon cancer patients area under the curve(AUC=0.832).Bioinformatics analysis show that CENPI,CENPN,CENPD,CENPK,CENPP,CENPM,CENPQ,CENPH,NDC80 and ITGB3BP have significant interaction with CENPU gene.CENPU is involved in DNA repair,MYC/TARGETS/V1 and PI3K/AKT/MTOR signaling pathways.Conclusion High expression of CENPU in cancer tissues of patients with colon cancer is significantly associated with poor prognosis of patients,suggesting that CENPU is expected to be a potential target for early diagnosis and prognosis prediction of patients with colon cancer.

Objective:To investigate the effect and possible molecular mechanism of mannan-binding lectin-associated serine protease (MASP) 1 on the biological behavior of hepatocellular carcinoma(HCC) cells.Methods:From January 10 to October 25, 2022, 20 pairs of fresh liver cancer tissue and adjacent (3 cm from cancer tissue) normal tissue samples of patients who underwent hepatic cancer resection at the Affiliated Hospital of Nantong University were collected, and the expression of MASP1 was analyzed. From March 1, 2012 to May 20, 2017, the cancer tissue and adjacent (3 cm from cancer tissue) normal tissue samples of 67 patients with HCC were collected from the tissue sample bank of the Department of Pathology, the Affiliated Hospital of Nantong University and the correlation between the expression level of MASP1 and clinical data of patients with HCC were analyzed. Human hepatoma cells lines SK-Hep1 and Hep3B were cultured, and MASP1 overexpression and MASP1 knockdown cell lines were constructed. SK-Hep1 negative control group, SK-Hep1 MASP1 overexpression group, Hep3B negative control group and Hep3B MASP1 knockdown group were set up. The effect of MASP1 on the proliferation of HCC cells was detected by subcutaneous tumor transplantation experiment in nude mice. The effect of MASP1 on the expression of epithelial-mesenchymal transition related proteins (N-cadherin, matrix metalloproteinase 9(MMP9), and E-cadherin), and the effects of MASP1 on the expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway related proteins and their phosphorylation levels were detected by Western blotting. Independent sample- t test, paired- t test and chi-square test were used for statistical analysis. Results:The results of immunohistochemical staining of 20 pairs of fresh tissue samples showed that the expression level of MASP1 in liver cancer tissue was lower than that in adjacent normal tissue (3.73±1.03 vs. 6.76±1.46), and the difference was statistically significant ( t=16.97, P<0.001). The correlation analysis of MASP1 expression level and clinical data of 67 patients with HCC revealed that the expression level of MASP1 was related to vascular invasion of the tumor, and the difference was statistically significant( χ2=5.20, P=0.023). The subcutaneous tumor transplantation experiment in nude mice showed that the volume and weight of subcutaneous tumor of mice in SK-Hep1 MASP1 overexpression group were lower than those of the SK-Hep1 negative control group((165.42±149.08) mm 3vs. (260.42±179.78) mm 3, (0.13±0.12) g vs. (0.18±0.12) g), and the differences were statistically significant ( t=5.15 and 3.89, both P<0.05). The results of Western blotting showed that the expression levels of N-cadherin and MMP9 in SK-Hep1 MASP1 overexpression group were lower than those of SK-Hep1 negative control group, while the expression level of E-cadherin was higher than that of SK-Hep1 negative control group (0.73±0.01 vs. 1.02±0.02, 0.40±0.01 vs. 0.69±0.01, 0.91±0.02 vs. 0.78±0.02), and the differences were statistically significant ( t=24.23, 36.87 and 9.27, all P<0.001). The expression levels of N-cadherin and MMP9 in Hep3B MASP1 knockdown group were higher than those in Hep3B negative control group, and the expression levels of E-cadherin was lower than that in Hep3B negative control group (1.04±0.01 vs. 0.31±0.01, 0.54±0.02 vs. 0.04±0.01, 0.56±0.01 vs. 0.93±0.01), and the differences were statistically significant ( t=163.20, 53.16, 60.74, all P<0.001). The expression levels of phosphoinositide PI3K, phosphoinositide Akt, and phosphoinositide mTOR of SK-Hep1 MASP1 overexpression group were lower than those of SK-Hep1 negative control group (0.59±0.01 vs.1.02±0.01, 0.64±0.01 vs. 1.12±0.02, 0.10±0.01 vs. 1.05±0.02); the expression levels of phosphoinositide PI3K, phosphoinositide Akt, and phosphoinositide mTOR of Hep3B MASP1 knockdown group were higher than those of Hep3B negative control group (0.96±0.01 vs. 0.55±0.01, 0.99±0.01 vs. 0.38±0.01, 0.93±0.02 vs. 0.06±0.01), and the differences were statistically significant ( t=40.87, 40.91, 87.30, 44.17, 107.50, 67.28, all P<0.001). Conclusions:The expression level of MASP1 is low in HCC tissue, and is significantly correlated with the poor prognosis of HCC patients and the occurrence of tumor vascular invasion. MASP1 may affect the proliferation and migration of liver cancer cells by regulating the PI3K/Akt/mTOR signaling pathway, suggesting that MASP1 may become a key gene in the treatment of HCC.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To examine the expression of transmembrane emp24 domain-containing protein 4(TMED4) in liver tissue of patients with hepatocellular carcinoma, and to investigate the effects of TMED4 gene on the proliferation and migration of hepatocellular carcinoma cells and related molecular mechanisms. Methods:The expression of TMED4 at protein level in liver cancer tissue and paracancerous tissue of patients with hepatocellular carcinoma were detected by Western blotting and immunohistochemical stainning, and the correlation between its expression and clinicopathological features was analyzed. The effects of TMED4 overexpression or knockdown on proliferation, migration and healing ability of hepatocellular carcinoma cells in vitro and in vivo were determined by cell proliferation test, Transwell test, wound healing test and subcutaneous tumor formation in nude mice. The molecular mechanism of TMED4 in regulating the biological behavior of hepatocellular carcinoma cells was preliminarily explored by pathway analysis. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The results of Western blotting showed that the expression of TMED4 at protein level in hepatocellular carcinoma tissue was lower than that in paracancerous tissue(0.52±0.29 vs. 0.83±0.22), and the difference was statistically significant( t=2.54, P=0.022). The results of immunohistochemical examination indicated that the expression of TMED4 at protein level in liver cancer tissue was lower than that in paracancerous tissue(5.46±3.37 vs. 7.58±3.08), and the difference was statistically significant( t=3.49, P<0.001). The expression of TMED4 at protein level was significantly correlated with vascular invasion and Barcelona clinic liver cancer stage( χ2=6.83 and 4.20, P=0.009 and 0.040). The results of cell proliferation assay showed that the absorbance value of SMMC-7721 cells in TMED4 overexpression group was lower than that in control group(1.38±0.05 vs. 2.37±0.08), while the optical density value of HepG2 in TMED4 knockdown group was higher than that in control group(0.76±0.04 vs. 0.54±0.01), and the differences were statistically significant( t=18.23 and 8.85, both P<0.001). The results of Transwell test showed that the number of migrated SMMC-7721 cells in TMED4 overexpression group was less than that in control group(286.30±13.01 vs. 439.70±12.34), while the number of migrated HepG2 cells in TMED4 knockdown group was higher than that in control group(249.00±6.00 vs. 160.00±6.56), and the differences were statistically significant( t=14.81 and 17.34, both P<0.001). The wound healing test showed that the healing rate of SMMC-7721 cells in TMED4 overexpression group was lower than that in control group((0.21±0.01)% vs.(0.45±0.01)%), the healing rate of HepG2 cells in TMED4 knockdown group was higher than that in control group((0.46±0.01)% vs.(0.20±0.01)%), and the differences were statistically significant( t=200.10 and 30.46, both P<0.001). The results of subcutaneous tumor formation assay in nude mice showed that the growth rate of cells in TMED4 overexpression group was slower than that in control group. After cell inoculation for 6 weeks, the subcutaneous tumor volume of mice in TMED4 overexpression group was smaller than that in control group(27.36 mm 3(138.70 mm 3) vs. 1 741.62 mm 3(1 783.39 mm 3)), the tumor weight was lower than that in control group(0.06 g(0.14 g) vs. 1.46 g(1.09 g)), and the differences were statistically significant(both Z=-2.31, both P<0.001). The results of Western blotting showed that the expression of Snail at protein level in SMMC-7721 cells of the TMED4 overexpression group was lower than that of the control group(0.32±0.01 vs. 0.90±0.03), the protein level of Snail in HepG2 cells of TMED4 knockdown group was higher than that of control group(1.03±0.01 vs. 0.97±0.01), and the differences were statistically significant( t=28.49 and 12.31, both P<0.001). The results of real time fluorescent quantitative polymerase chain reaction showed that the expression of Snail at mRNA level in SMMC-7721 cells of TMED4 overexpression group was lower than that of control group(0.13±0.05 vs. 1.00±0.15), the expression of Snail at mRNA level in HepG2 cells of TMED4 knockdown group was higher than that of control group(1.25±0.32 vs. 0.21±0.14), and the differences were statistically significant( t=9.62 and 5.10, P<0.001 and P=0.007). Conclusion:TMED4 may affect the proliferation and migration of hepatocarcinoma cells by regulating the expression of Snail, and which is expected to become a potentially therapeutic target for hepatocellular carcinoma.

Objective To explore the effects of homogeneity management in elderly chronic pain nursing.Methods In Mindong Hospital, Affiliated to Fujian Medical University, we selected 84 elderly patients with chronic pain by convenience sampling as observation group from June 2016 to May 2017 carrying out chronic pain nursing homogeneity management. And we selected 84 patients as control group from January 2015 to May 2016 implementing conventional nursing. The Visual Analogue Scale (VAS), satisfaction questionnaire and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) were used to compare the pain, satisfaction with nursing and life quality of patients between two groups.Results The score of VAS of patients in observation group and control group was (2.09±0.55) and (3.47±0.53) respectively 30 days after intervention with a significant difference (t=16.559,P<0.01). The satisfaction with nursing of observation group and control group was 92.86％ and 67.86％ respectively with a significant difference (χ2=16.630, P<0.01). The dimensions scores of SF-36 of patients in observation group were significantly higher than those in control group three months after intervention (P<0.05).Conclusions Application of homogeneity management has an ideal effect in elderly chronic pain nursing. It can effectively ease patients' pain and improve patients' satisfaction with nursing as well as life quality.

Objective To investigate the correlation between dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) quantitative parameters and pathological grading in esophageal squamous cell carcinoma(SCC). Methods Prospective analysis of esophageal squamous cell carcinoma confirmed by electronic gastrointestinal endoscopy was performed. Thirty nine patients who underwent radical resection of esophageal carcinoma with MRI examination one weeks before operation were included. All patients underwent routine chest MRI and DCE-MRI scans, and DCE-MRI quantitative parameters including volume transfer constant (Ktrans), exchange rate constant (Kep) and extravascular extracellular volume fraction(Ve)were measured.Pathological analysis of postoperative specimens,including pathological grading(highly differentiated,moderately differentiated,poorly differentiated,undifferentiated),gross tumor pathological type(ulcerative type,medullary type,fungating type,sclerotic type)and local infiltration degree (T staging) were performed. Kruskal-Wallis H test was used to compare the differences of quantitative parameters between different pathological T staging,gross tumor pathological types and pathological grades of DCE-MRI,and a Dunn-Bonferroni test for post hoc comparisons.Spearman rank correlation analysis was used to evaluate the correlation between DCE-MRI parameters and pathological grading of esophageal squamous cell carcinoma.The ROC curves was used to evaluate the efficiency of different parameters in the diagnosis of poorly differentiated esophageal squamous cell carcinoma. Result Among the thirty nine patients, they were divided into three group according to pathological findings: well differentiated (12 patients),moderately differentiated(15 patients)and poorly differentiated group(12 patients);ulcerative type (19 patients), fungating type(10 patients), medullary type(10 patients);T1, 2 stage(16 patients), T3 stage(14 patients), and T4 stage(9 patients). There was no significant difference in the value of Ktrans, Kepand Ve between different T staging groups and different tumor pathological types groups(all P>0.05).The differences of Ktrans, Kepand Vebetween different pathological grading groups were statistically significant (all P<0.05). There were positive correlation between Ktrans, Kep, Veand the pathological grading, rs value were 0.874, 0.672, 0.578 respectively, all P<0.01. The ROC curve area of Ktrans, Kepand Vein the diagnosis of poorly differentiated esophageal squamous cell carcinoma was 0.941,0.809 and 0.773 respectively.The diagnostic efficiency of Ktranswas the best.Conclusions The quantitative parameters of DCE-MRI are correlated with the pathological grading of esophageal squamous cell carcinoma. Ktrans, Kepand Vecan reflect the perfusion characteristics of esophageal squamous cell carcinoma.

Objective To investigate the value of T2WI histogram analysis in differential diagnosis of glioblastoma multiform (GBM) from solitary metastasis.Methods Data of 103 patients with pathologically confirmed GBM (GBM group,n=57) and solitary brain metastasis (solitary brain metastasis group,n =46) were retrospectively reviewed.All patients underwent conventional MR scanning,including axial T1WI,T2WI,FLAIR and contrast-enhanced T1WI before surgery.The histogram metrics,including mean,standard deviation (SD),median,kurtosis and skewness were calculated from ROI,which were manually placed on the maximal section of the solid part of tumors on T2WI by using Image J software.ROCs were generated to evaluate differential diagnostic performance of the histogram metrics with significant difference between both groups.Results The values of mean,SD and median were significantly higher in GMB group than those in solitary brain metastasis group (P＜0.05).The areas under ROC curve of mean,SD and median was 0.772 (95％ CI [0.681,0.862],P＜0.001),0.719 (95％ CI [0.616,0.822],P＜0.001) and 0.767 (95％ CI [0.674,0.860],P＜0.001),respectively;and the diagnosis cutoff value of mean,SD and median was 509.575,58.844 and 550.500,respectively.The sensitivity of the three parameters was 0.719,0.702 and 0.719,and the specificity was 0.783,0.652,and 0.826,respectively.Conclusion The value of mean,SD and median of T2WI histogram analysis can be helpful to differentiating GBM and solitary brain metastasis,of which the mean value is the best for differential diagnosis.