Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective:To explore the relationship between 18F-fibroblast activation protein inhibitor (FAPI)-42 SUV max of primary gastric cancer and clinicopathological factors of patients. Methods:Fifty-one patients (31males, 20 females, age: 51(47, 65) years) with gastric cancer who underwent 18F-FAPI-42 PET/CT before surgical resection in Nanfang Hospital, Southern Medical University from February 2022 to January 2023 were analyzed retrospectively. The clinicopathological factors that might affect tumor SUV max (including gender, age, tumor location, pathological type, histological grade, Lauren classification, vascular and(or) neural invasion, programmed cell death-ligand 1 (PD-L1) expression, pathologic(p)T stage, pN stage and pTNM stage) were evaluated by the univariate analysis (Mann-Whitney U test or Kruskal-Wallis rank sum test) and multivariate analysis (multiple linear regression analysis). Results:The sensitivity of 18F-FAPI-42 PET/CT in the diagnosis of patients with primary gastric cancer was 82.35% (42/51). The diagnostic sensitivities for early gastric cancer (T1) and locally advanced gastric cancer (T2-T4) were 59.09%(13/22) and 100%(29/29), respectively. The SUV max of primary lesion was 4.90(1.71, 12.51). The univariate analysis showed that SUV max of primary gastric cancer was related to tumor location ( z=-2.00, P=0.046), pT stage ( H=36.94, P<0.001), pN stage ( z=-3.89, P<0.001), pTNM stage ( H=31.49, P<0.001) and vascular and(or) nerve invasion ( z=-5.22, P<0.001), but not related to pathological type, histological grade, Lauren typing, and PD-L1 expression ( z values: from -1.78 to -0.09, all P>0.05). pT stage was found to be a significant independent factor for SUV max in primary gastric lesion by multivariate analysis ( t=2.52, P=0.015). Conclusions:The 18F-FAPI-42 SUV max of primary tumor was related to tumor location, pT stage, pN stage, pTNM stage, and vascular and(or) nerve invasion; pT stage is an independent factor affecting tumor SUV max. The ability of 18F-FAPI-42 PET/CT to detect gastric cancer is mainly affected by pT stage.

Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.

Premature infants are multisystem immature and more prone to extravasation injury of intravenous drugs than mature neonates. Extravasation injury will not only increase the pain of children, prolong hospital stay, increase medical expenses, but also cause limb dysfunction in children, and even leave them disabled. In view of the lack of professional guidelines and consensus on the treatment of extravasation injury in premature infants by intravenous treatment, clinical nurses have certain difficulties in the prevention and treatment of extravasation injury in premature infants. This article reviews the evaluation of risk factors, assessment and management for extravasation injury in premature infants, aiming to provide a practical basis for clinical practice and provide a reference for further development of prevention and treatment strategies.

Objective:To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness.Methods:This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives.Results:30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day.Conclusions:Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

Objective:To investigate the correlation between serum procalcitonin (PCT) level and intracranial atherosclerotic burden (ICASB) in patients with ischemic stroke.Methods:From January 2019 to December 2020, consecutive patients with acute ischemic stroke admitted to the Department of Neurology, Jiangsu Provincial Second Chinese Medicine Hospital were enrolled. Chemiluminescence immunoassay was used to detect serum PCT levels, and ICASB was evaluated based on the results of cranial magnetic resonance angiography. Univariate analysis was used to determine the baseline data among the different ICASB score groups. Then the independent correlation between serum PCT level and ICASB was determined by the ordinal logistic regression analysis. At the same time, the correlation between serum PCT level and ICASB was determined by the linear regression analysis. Results:A total of 291 patients with acute ischemic stroke were enrolled, including 161 male (55.3%), aged 64.5±8.4 years; median serum PCT level was 0.053 μg/L. According to the ICASB score, the patients were divided into 0 group ( n=155, 53.3%), 1-3 group ( n=95, 32.6%) and >3 group ( n=41, 14.1%). Univariate analysis showed that the age, serum homocysteine and PCT level, as well as the proportion of diabetes were significantly higher in the higher ICASB score group, while the proportion of the patients with atrial fibrillation was significantly lower (all P<0.05). Ordinal multivariable logistic regression analysis showed that higher serum PCT level was an independent factor for higher ICASB score (the 4 th quartile vs. the 1 st quartile: odds ratio, 2.015, 95% confidence interval 1.052-3.927; P=0.043). Multiple linear regression analysis showed that the serum PCT level was positively correlated with the ICASB score ( r=0.253, P=0.001). Conclusion:The serum PCT level is correlated with ICASB.

Objective:To observe the therapeutic effect of echinacoside (ECH) on liver injury and glucose metabolism disorder in sepsis rats induced by cecal ligation and puncture (CLP), and to explore its possible mechanism.Methods:Forty eight male Sprague Dawley (SD) rats were randomly divided into four groups: sham group (sham), model group (CLP), treatment group (CLP+ ECH) and inhibitor group (CLP+ ECH+ EX527). The sham group only received laparotomy, and the model group underwent CLP. The treatment group was intragastric administration of echinacea (30 mg/kg) every day after CLP modeling. The inhibitor group was injected with silence information regulator 1 (SIRT1) inhibitor EX527 (5 mg/kg) one hour before CLP, and then treated the same as the treatment group. Fasting blood glucose, insulin and serum biochemical indexes were detected in virous groups. The serum levels of interleukin (IL)-1 β, IL-6 and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). 2′, 7′- dichlorofluorescein diacetate (DCFH-DA) staining was used to observe the production of reactive oxygen species (ROS) in liver tissue of rats in each group; hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue in each group; The expressions of SIRT1, glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and phosphorylated protein ki-nase B(p-AKT) were detected by Western blot.Results:Compared with sham group, the levels of serum glucose, serum insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), ROS, IL-1β, IL-6 and TNF-α in model group increased, while the liver glycogen and survival rate decreased (all P<0.05). After echinacoside treatment, the serum glucose, serum insulin, ALT, AST, ROS , IL-1β, IL-6 and TNF-α levels decreased, and the liver glycogen and survival rate increased (all P<0.05); After SIRT1 inhibitor intervention, the levels of serum insulin, ALT, AST, IL-6 and ROS in the inhibitor group increased ( P<0.05). HE staining showed that there were infiltration and necrosis of inflammatory cells in the liver tissue of model group, and echinacoside could significantly reduce the focal and massive necrosis; Western blot showed that compared with the sham group, the expression levels of SIRT1, p-STAT3 and p-AKT protein in the model group decreased, while the expression levels of G6Pase and PEPCK protein increased ( P<0.05); After echinacoside treatment, the expression levels of SIRT1, p-STAT3 and p-AKT increased, while the expression levels of G6Pase and PEPCK decreased ( P<0.05). After SIRT1 inhibitor intervention, the expression of SIRT1, p-STAT3 and p-AKT protein decreased, and the expression of G6Pase and PEPCK protein increased in the inhibitor group ( P<0.05). Conclusions:Echinacoside is a potential therapeutic agent for sepsis associated liver injury and glucose metabolism disorders, which may play a role by targeting SIRT1 to activate STAT3 and AKT in the liver.

【Objective】 To investigate the unqualified rate of anti-HIV detection of blood screening laboratories in Beijing-Tianjin-Hebei region, and explore the differences in anti-HIV detection ability and influencing factors in each laboratory. 【Methods】 Through filling questionnaires via e-mail, the anti-HIV ELISA unqualified rate and confirmed (WB) positive results (data) from January to December 2018 from 15 blood screening laboratories in Beijing-Tianjin-Hebei region were collected. Our laboratory was responsible for data collection and confirmation, and statistics software SPSS22.0 was used for analysis. 【Results】 1) There was a statistically significant difference among the unqualified rate of anti-HIV ELISA(6.77‱~35.71‱) and confirmed positive rate(0.60‱~3.56‱) in 15 blood screening laboratories in Beijing-Tianjin-Hebei region (P<0.05); 2) There were significant differencse among the ELISA unqualified rate and the confirmed positive rate of 8 reagents for anti-HIV detection(P<0.01), and the sensitivity of the 4th generation detection reagent and the imported reagent was higher than that of the 3rd generation reagent and the domestic reagent. The anti-HIV ELISA unqualified rate of R5 was the highest (19.08‱). 3)There were significant differences in the anti-HIV ELISA unqualified rate of R1, R2, R3, R5 and R7 reagents among different blood station laboratories(P<0.05), and there were no significant differences in the anti-HIV ELISA unqualified rate of R4, R6 and R8 reagents among different blood station laboratories(P>0.05). 4)The unqualified rate of anti-HIV ELISA of laboratories using different regents showed significant differences(P<0.05), except H, J, M. The unqualified rate of imported reagent was significantly higher than that of domestic reagents of laboratories using imported and domestic reagents combinations(P<0.05), except O. 62.5% (5/8) laboratories using domestic 3^rd and 4^th generation reagent combination showed significant differences in the unqualified rates among different reagents(P<0.05); 5) The positive rate of single-reagent(62.02%~95.45%)in 15 blood screening laboratories showed significant difference(P<0.001), and A was the lowest (62.02%). 【Conclusion】 The anti-HIV detection ability among 15 blood screening laboratories in Beijing-Tianjin-Hebei region is quite different. The application of different reagents is the main factor for the difference, and other factors such as personnel, instruments and test strategies also has a great impact on the detection of anti-HIV. It is still necessary to promote the process of homogenization of blood testing quality among blood screening laboratories in Beijing-Tianjin-Hebei region.

The Genome Sequence Archive (GSA) is a data repository for archiving raw sequence data, which provides data storage and sharing services for worldwide scientific communities. Considering explosive data growth with diverse data types, here we present the GSA family by expanding into a set of resources for raw data archive with different purposes, namely, GSA (https://ngdc.cncb.ac.cn/gsa/), GSA for Human (GSA-Human, https://ngdc.cncb.ac.cn/gsa-human/), and Open Archive for Miscellaneous Data (OMIX, https://ngdc.cncb.ac.cn/omix/). Compared with the 2017 version, GSA has been significantly updated in data model, online functionalities, and web interfaces. GSA-Human, as a new partner of GSA, is a data repository specialized in human genetics-related data with controlled access and security. OMIX, as a critical complement to the two resources mentioned above, is an open archive for miscellaneous data. Together, all these resources form a family of resources dedicated to archiving explosive data with diverse types, accepting data submissions from all over the world, and providing free open access to all publicly available data in support of worldwide research activities.