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 clinical characteristics and offer diagnostic and therapeutic approaches for adult-onset idiopathic hypogonadotropic hypogonadism(AIHH).Methods:Clinical, laboratory, and imaging data, as well as follow-up information, of three male patients diagnosed with AIHH at the Department of Endocrinology and Metabolism of Nanfang Hospital, Southern Medical University, were systematically reviewed and analyzed.Results:All three patients were male, with a median age of 39 years(range, 22 to 40). Two patients reported symptoms of enlarged breasts and reduced sexual function, while one case solely reported a decline in sexual function. Physical examination showed that the median length of the penis was 6 cm(range, 5 to 6 cm), and the bilateral testicular volume was 7.96 mL(4.70-8.82 mL). Basal hormone levels at the time of initial visit to our hospital as follows: the median testosterone level was 0.32 ng/mL(0.24-2.96 ng/mL), median follicle stimulating hormone(FSH) level was 0.56 mIU/mL(0.1-0.75 mIU/mL), and the median luteinizing hormone(LH) level was 0.69 mIU/mL(0.1-1.03 mIU/mL). The levels of other hormones secreted by the anterior pituitary gland were normal. Hypothalamic-pituitary magnetic resonance imaging(MRI) showed that 1 patient had a pituitary microadenoma. Three patients were treated with pulsatile GnRH or gonadotropins, one of which had hypothalamic-pituitary-gonadal(HPG) axis function reversal after GnRH pulse pump therapy and lasted for 1 year, but then still had irreversible reduction.Conclusion:AIHH is marked by adult-onset disease and idiopathic hypogonadism. Enhancing fertility remains a critical requirement for these patients. Pulsatile GnRH treatment or gonadotropin therapy, as viable treatments, exhibit therapeutic effects, albeit with occasional fluctuations. Therefore, the emphasis lies in the timely consideration of fertility preservation.

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.

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 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.

Diabetic cardiomyopathy is a myocardial complication associated with abnormal glucose metabolism and dyslipidiaemia, which increases the risk of death and heart failure in diabetic patients. Mitochondrial dysfunction is involved in the occurrence and development of diabetic cardiomyopathy. Recent studies have confirmed that scavenging damaged mitochondria in cardiomyocytes through mitophagy can restore mitochondrial homeostasis, reduce oxidative stress and improve diabetic cardiomyopathy. Therefore, this article provides a comprehensive review of the mechanisms and characteristics of mitochondrial autophagy in diabetic cardiomyopathy. It aims to offer new insights and theoretical basis for the prevention and treatment of diabetic cardiomyopathy.

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 investigate pregnancy outcomes and neurodevelopment in fetuses with ventriculomegaly. Methods This was a cohort study of 173 gravidas with singleton pregnancy who were diagnosed with fetal ventriculomegaly by ultrasound in Prenatal Diagnostic Center of Nanfang Hospital Affiliated to Southern Medical University from March 2010 to July 2016. Thirty normal gravidas who received antenatal care in the same hospital and at the same period were selected as control. Clinical data were collected. Gravidas who had chosen to continue their pregnancy were followed up to monitor the variations of fetal ventricular. Fetal mild and moderate ventriculomegaly were respectively defined as a ventricular atrial width of 10-12 mm and >12 mm but <15 mm. Isolated ventriculomegaly (IVM) indicated those without any other ultrasound abnormalities, otherwise the case would be defined as non-isolated ventriculomegaly (NIVM). Among the 173 gravidas, 54 cases were mild IVM, 53 mild NIVM, 26 moderate IVM and 40 moderate NIVM. Fetuses with chromosome abnormalities were excluded from the study. Neonatal behavioral neurological assessment (NBNA) was used to analyze the neonatal neurodevelopment at the age of 7 days, and Bayley scales of infant development was used to evaluate the development of nervous system at the age of 6 months through analyzing their mental development index (MDI) and psychomotor development index (PDI). Statistical methods included t test, χ2 test (or Fisher's exact test), nonparametric test, Mann-Whitney test and multiple Kruskal-Wallis H test. Results (1) Among the 107 fetuses with mild ventriculomegaly, 72.9％ (78), 23.4％ (25) and 3.7％ (4) of them regressed, stabilized and progressed,respectively; however, among the 66 moderate cases, the figures were 45.4％ (30), 37.9％ (25) and 16.7％ (11) respectively (χ2=15.769, P<0.001). For those in the IVM and NIVM subgroups within the moderate ventriculomegaly group, significant difference was shown [17(65.4％), 8(30.8％) and 1(3.8％) vs 13(32.5％), 17(42.5％) and 10(25.0％), χ2=8.552, P=0.014], but not within the mild groups (χ2=2.412, P=0.299). (2) There were 164 gravidas who continued their pregnancy and delivered. Significant differences in NBNA score were observed between the ventriculomegaly group and the control (37.70±1.80 vs 38.53±1.38, t= - 2.424, P<0.05). Numbers of neonates with NBNA score < 36 and ≥ 36 points were 5(4.7％) and 101(95.3％) in the mild group, and 8(13.8％) and 50(86.2％) in the moderate group (χ2=4.231, P=0.004). There was significant difference in NBNA score between the IVM and NIVM subgroup within neither mild nor moderate group (χ2 were 0.210 and 0.201, P were 1.000 and 0.720). (3) Totally, 137 cases completed the assessment of nervous system development at the age of 6 months. There was significant difference in PDI score between the ventriculomegaly group and the control (90.50±10.85 vs 95.80±9.65, t= - 2.471, P=0.014), but not in MDI score (95.42+11.20 vs 99.50+12.00, t= - 1.786, P=0.076). (4) The comparison of the proportion of excellent, average and poor PDI scores: Significant differences were found between the IVM and NIVM subgroup within the moderate ventriculamegaly group and in the different intrauterine outcome groups [IVM vs NIVM groups: 3(15.0％), 16(80.0％) and 1(5.0％) vs 1(3.1％), 24(75.0％) and 7(21.9％),Z= - 2.097, P=0.036;intrauterine regression, stable and progress group: 9(10.6％), 75(88.2％) and 1(1.2％);3(6.5％), 37(80.4％) and 6(13.1％) vs 0, 2(2/6) and 4(4/6), χ2=19.808, P<0.001], but not between the mild and moderate vetriculamegaly group, or between the subgroups within the mild ones (Z were - 1.869 and - 1.946, P were 0.062 and 0.052). (5) The comparison of the proportion of excellent, average and poor scores of MDI: Significant difference was only found among the different intrauterine outcome groups[13(15.3％), 71(83.5％), 1(1.2％); 2(4.4％), 41(89.1％), 3(6.5％) vs 0, 5(5/6), 1(1/6); χ2=7.980, P=0.018], but not in any other comparisons (all P>0.05). Conclusions Prognosis of fetal ventriculomegaly is affected by co-existed abnormalities and intrauterine progression. Fetus with mild ventriculomegaly can also have risk of abnormal neural development, suggesting that we should pay much attention to such cases and a regular follow-up is required.

Objective To evaluate the clinical outcome of fetus diagnosed as mild and moderate isolated ventriculomegaly(IVM)and its correlation with imaging follow-up. Methods Totally,161 cases of single pregnancy whose fetus was diagnosed as mild or moderate IVM by ultrasound were administrated. Data of prenatal ultrasound examination, pregnancy outcomes, and the postnatal MRI results were collected. New borns' growth and development, language expression, movement coordination, auditory and visual function were followed up to evaluate the neurodevelopment. Results (1)Before birth:80.1%(129/161) of IVM disappeared before the delivery, 16.1%(26/161)remained stable, and 3.7%(6/161)continued to deteriorate.(2)Postnatal MRI: 8 cases(9.6%, 8/83)were diagnosed IVM, of which 3 cases were found additional abnormalities(1 case was the corpus callosum dysplasia and 2 cases were leukodystrophy). The additional abnormal detection rate was 3/8.(3)Postnatal assessments: There were 7 cases(8.9%, 7/79) neunatal behavioral neurological assessment (NBNA), 6 cases (7.6%, 6/79) Bayley scales of infant development (BSID)-psychomotor developmental index(PDI) and 3 cases (3.8%, 3/79) BSID-mental development index(MDI) whose scores were low. There was no significant difference of the NBNA and BSID scores between mild and moderate IVM (NBNA: x2=2.042,P=0.210; BSID-PDI: x2=-1.359,P=0.174; BSID-MDI: x2=-1.205,P=0.228). Follow-up of 9 cases(11.4%, 9/79)with low BSID score, 6 of them were found to be stable in the medial ventricle of the uterus, and the size of the lateral ventricle was normal after birth by ultrasound and MRI. Conclusions The majority of IVM fetuses have good prognosis, but there is also a risk of neurodevelopmental dysplasia. The postnatal follow-up should be paid attention to, and MRI should be performed as the postnatal imaging evaluation.

Objective To analysis the common abnormalities in fetus with ventriculomegaly and clinical significance. Methods Collected from March 2010 to December 2016,298 cases of pregnant women whose fetus with ventriculomegaly and accepted the prenatal diagnosis of pregnancy,including 109 cases of isolated cerebral ventriculomegaly(IVM),and 189 cases of non-isolated cerebral ventriculomegaly(NIVM).They were divided into mild groups(10.0-11.9 mm),moderate group(12.0-14.9 mm)and severe group(≥15.0 mm)according to the width of the lateral ventricle. Results(1)The most common abnormality of the NIVM were neurodevelopmental system(37.30%,94/252);The second was ultrasonic soft index(27.78%,70/252).(2)The most frequent combi-nation in mild group was ultrasonographic soft mark anomalies(44.76%,47/105),followed by other ultrasonic indi-cators(18.10%,19/105).The abnormal incidence of central nervous system was higher in middle group(45.16%, 42/93),followed by ultrasonic soft index abnormality(21.51%,20/93).The abnormality of the central nervous sys-tem was 62.96%(34/54)in severe group,followed by an abnormal(14.81%,8/54).(3)There was a difference in the nervous system and the ultrasonic-soft indicator between the non-isolated lateral ventricle dilation with different lateral ventricle widths(P<0.001).There was no difference in cardiovascular abnormalities. Conclusion Prena-tal ultrasound revealed that fetus with cerebral ventriculomegaly should carefully examine whether other abnormali-ties existed to determine the prognosis of the fetus and whether intervention should be taken.There was a difference between the different types of lateral ventricle and the prognosis.