Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Objective To establish a rat model of acute antibody-mediated rejection (AMR) in kidney transplantation and investigate the preventive effect of dihydroartemisinin (DHA) on acute AMR. Methods BN rats were used as donors and Lewis rats as recipients. Kidney transplantation was performed 2 weeks after skin transplantation for sensitization. After establishing the acute AMR model in rat kidney transplantation, the recipients of experimental groups included the syngeneic kidney transplantation group (6 rats), the allogeneic kidney transplantation group (6 rats), the syngeneic skin transplantation followed by kidney transplantation group (12 rats), and the allogeneic skin transplantation followed by kidney transplantation group (24 rats). The groups for investigating the preventive effect of DHA on acute AMR included the control group (allogeneic skin transplantation followed by kidney transplantation) and the DHA group (allogeneic skin transplantation followed by kidney transplantation + DHA), with 12 rats in each group. The survival time of recipient rats, serum donor-specific antibody (DSA) levels and graft pathological changes were used to identify the acute AMR model. On this basis, DSA levels, pathological changes in the transplant kidneys and peripheral blood B-cell levels were detected to assess the preventive effect of DHA on acute AMR. Results Compared with the allogeneic kidney transplantation group, skin transplantation sensitization significantly shortened the survival time of recipient rats (P<0.01). Compared with the syngeneic skin transplantation followed by kidney transplantation group, the allogeneic skin transplantation followed by kidney transplantation group showed significantly elevated serum DSA-IgG levels from 7 days after skin transplantation to 5 days after kidney transplantation (P<0.01), and significantly elevated DSA-IgM levels at 7 and 14 days after skin transplantation(all P<0.01). The transplant kidneys in the allogeneic skin transplantation followed by kidney transplantation group showed a small number of inflammatory cell infiltrations, tubular necrosis, capillaritis, and C4d deposition starting from 1 day after kidney transplantation, with these pathological changes worsening as the post-transplantation days increased. The kidney damage became significant starting from 3 days after transplantation. The above pathology manifestations were consistent with the characteristics of acute AMR. On the basis of establishing the acute AMR model, DHA treatment significantly prolonged the survival time of recipient rats (P<0.01) , and reduced serum DSA-IgG and DSA-IgM levels. DHA treatment significantly alleviated the pathological manifestations of acute AMR, including kidney damage, inflammatory cell infiltration, capillaritis and tubular necrosis, and also reduced C4d deposition in the transplant kidneys, inflammatory cell infiltration and peripheral blood CD19⁺ B-cell levels. Conclusions An acute AMR model is established by performing kidney transplantation 2 weeks after allogeneic skin transplantation in rats. It is discovered that DHA has immunosuppressive effects and may effectively prevent acute AMR, which provides a new strategy for the management of clinical AMR.

Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

Objective To explore the predictive value of methylenetetrahydrofolate reductase(MTHFR)gene C677T polymorphism and serum homocysteine(Hcy)level for adverse pregnancy outcomes.Methods The clinical data of 698 pregnant women who received antenatal care and deliv-ered at Ji'an Central People's Hospital were retrospectively collected.According to the research pur-pose,the pregnant women were divided into internal study cohort(n=483)or external validation co-hort(n=215).Each cohort was further divided into adverse pregnancy group and normal pregnancy group based on whether adverse pregnancy outcomes occurred.The MTHFR gene C677T polymor-phism and serum Hcy level of all pregnant women were detected.Binary Logistic regression analysis was used to investigate the relationships of MTHFR gene C677T polymorphism,Hcy level,and other indicators with adverse pregnancy outcomes.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive efficacy of different indicators when used alone and their combina-tion.Results In the internal study cohort,compared with the normal pregnancy group,the detection frequency of the CC genotype at the MTHFR gene C677T locus was lower,while the detection frequencies of the CT and TT genotypes were higher in the adverse pregnancy group(P＜0.001).The proportion of pregnant women with high Hcy levels was higher in the adverse pregnancy group than that in the normal pregnancy group(P＜0.001).Binary Logistic regression analysis showed that age,folic acid level during pregnancy,MTHFR gene C677T polymorphism,and Hcy level were all independ-ent influencing factors for adverse pregnancy outcomes(P＜0.05).The ROC curve indicated that the area under the curve(AUC)of the combined prediction model was 0.938,which was greater than that of each indicator.In the external validation cohort,the AUC of the combined prediction model was 0.917,validating the stability and clinical applicability of the model.Conclusion The TT and CT genotypes at the MTHFR gene C677T locus and high Hcy level are all independent risk factors for adverse pregnancy outcomes.The prediction model constructed by combining these factors with age and folic acid level during pregnancy has a high predictive efficacy for adverse pregnancy outcomes.

Objective To investigate the effects of goal-directed fluid therapy(GDFT)based on pulse pressure variation(PPV)on postoperative cognitive function in patients undergoing Da Vinci robot-assisted radical resection of gynecological malignancies.Methods A total of 60 patients who underwent robot-assisted radical resection of gynecological malignancies were randomly divided into control group and observation group using a random number table method,with 30 patients in each group.The control group received conventional fluid replacement regimen,while the observation group received GDFT regimen based on PPV.The surgical conditions,hemodynamic indices[heart rate(HR),mean arterial pressure(MAP),PPV],cerebral oxygen saturation(rSO2),gastrointesti-nal function,renal function,cognitive function[Mini-Mental State Examination(MMSE)score],and postoperative conditions of the two groups were compared.Results The amount of crystalloid fluid and urine output in the observation group were less than those in the control group,while the amount of colloid fluid was more than that in the control group,with statistically significant differences(P＜0.05).Five minutes after anesthesia induction,the levels of MAP,HR and rSO2 in the observation group were higher than those in the control group,with statistically significant differences(P＜0.05).Five minutes after anesthesia induction,1 hour after the Trendelenburg position,and imme-diately after the end of surgery,the PPV levels in the observation group were lower than those in the control group,with statistically significant differences(P＜0.05).After surgery,the levels of lactic acid and urea nitrogen in both groupswere higher than those before surgery,but those in the observa-tion group were lower than those in the control group,with statistically significant differences(P＜0.05).After surgery,the creatinine levels in both groups were lower than those before surgery,but those in the observation group were higher than those in the control group,with statistically signifi-cant differences(P＜0.05).The time to first flatus in the observation group was earlier than that in the control group,with a statistically significant difference(P＜0.05).On days 3,7 and 30 after surgery,the MMSE scores in the observation group were higher than those in the control group,with statistically significant differences(P＜0.05).The drainage tube indwelling time and hospital stay in the observation group were shorter than those in the control group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the overall incidence of postoperative complications between the two groups(P＞0.05).Conclusion GDFT based on PPV can stabilize the hemodynamic status and rSO2 in patients undergoing Da Vinci robot-assisted radical resection of gynecological malignancies and reduce postoperative cognitive impairment.

Objective To investigate the differences in physical fitness and physiological indexes of male soldiers stationed at different altitudes and to analyze the determinants of physical fitness of these soldiers.Methods A total of 13 648 male soldiers at different altitudes were included,whose results of annual military physical assessment and physiological indexes in 2023 were collected and comparatively analyzed.Results The 3000-meter running performance,30-meter × 2 serpentine running performance and resting blood oxygen saturation of high-altitude soldiers gradually declined with the increase of altitudes.The pull-up performance dropped significantly when the altitude＞2000 m.Soldiers ≥30 years old demonstrated a marked decline in physical fitness across different training programs.Moderate altitude acclimatization was conduciveto the recovery of physical fitness of soldiers,while exposure to high-altitude environment ≥5 years led to overall deterioration.Conclusion The high-altitude environment significantly impacts the aerobic endurance,speed,agility,and strength of soldiers.Altitude ≥4000 m,age ≥30 years,and prolonged exposure ≥5 years may contribute to the decline in physical fitness of soldiers.

Objective: To investigate the expression of ribosomal protein L26 ( RPL26) in gastric cancer cells (GC) and its effect on cell apoptosis and proliferation . Methods: The expression of RPL26 in GES-1 and GC cell lines was detected by Western blot. GC cell line HGC-27 was used to construct RPL26 overexpression cell line , and GC cell lines HGC-27 and AGS cells were used to construct RPL26 knockdown cell line . The overexpression and knockdown efficiency of RPL26 were detected by Western blot. Cell counting kit-8 (CCK-8) , colony formation assay and Transwell assay were used to detect the effects of the overexpression and knockdown of RPL26 on the pro- liferation and migration of GC cells . Western blot was used to detect the expression of Phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) signaling pathway related factors PI3K , AKT , phosphorylated phosphatidylinosi- tol-3-kinase (p-PI3K) , phosphorylated protein kinase B ( p-AKT) and downstream factors B-Cell lymphoma-2 (Bcl-2) , Bcl-2 associated X protein (Bax) and Cyclin A , G1 /S-specific Cyclin D1(Cyclin D1) , Cyclin-depend- ent kinases (CDK)4 and CDK2 in overexpression and knockdown of RPL26 stably transfected cell lines . Results: Compared with GES-1 , RPL26 was highly expressed in HGC-27 cells ( tHGC-27 = 4. 97 ; P < 0. 01) and elevated in AGS , but the difference was not statistically significant. In HGC-27 and AGS cells , CCK-8 and colony formation assays showed that the proliferation ability of cells decreased after the knockdown of RPL26. Transwell assay showed that the migration ability of cells decreased after the knockdown of RPL26. Western blot showed that Bcl-2 expression was decreased in HGC-27 , AGS cells after the knockdown of RPL26 ( tHGC-27 = 11 . 50 , tAGS = 4. 77 ; P < 0. 001 , P < 0. 01) , and Bax expression increased ( tHGC-27 = 9. 63 , tAGS = 4. 05 ; P < 0. 001 , P < 0. 05) . In HGC-27 cells , the ratios of p-PI3K/PI3K and p-AKT/AKT significantly decreased after the knockdown of RPL26 ( tp-PI3K/PI3K = 3 . 86 , tp-AKT/AKT = 8. 29 ; P < 0. 05 , P < 0. 01) . Cyclin A , Cyclin D1 , CDK4 , CDK2 protein expressions de- creased ( t = 9. 61 , 5 . 10 , 11 . 64 , 7. 81 ; P < 0. 01 or P < 0. 001) , while the overexpression of RPL26 in HGC-27 cells showed the opposite trend . Conclusion The knockdown of RPL26 may arrest the cell cycle in G1 /S phase by inhibiting the PI3K/AKT signaling pathway , thereby inhibiting cell proliferation and promoting apoptosis .

Objective To establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics. Methods Allogeneic BALB/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed. Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment [(28.2±4.1) d vs. (7.0±0.7) d, P < 0.01]. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation and worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells. Conclusions Mouse allogeneic heart transplantation combined with CTLA4-Ig successfully establishes a CR model, which provides a basis for subsequent studies on the pathogenesis and intervention of CR.

This study aims to inquire about the fluctuations of ubiquitin-specific protease 47 on neu-roblastoma cells(Neuro-2a,N2a)infected by rabies virus(RABV).USP47 expression levels were detected after RABV infection in N2a cells through RT-qPCR,protein immunoblotting,and virus titer determination.The levels of RABV nucleoprotein and phosphoprotein gene and protein,and RABV titers in supernatants were analyzed during overexpression and knockdown of USP47.The results showed that RABV infection increased USP47 gene level in N2a cells.When overexpression of USP47,the levels of RABV N and P were increased,and the virus titers were also improved.Mo-reover,the level of interleukin-6(IL-6)genes decreased.Knocking down USP47 expression reduced levels of RABV N and P genes and proteins,lowered the virus titer,and elevated the IL-6 gene lev-el.The results suggest that USP47 promotes RABV infection and suppresses IL-6 expression.This finding lays the foundation for further investigation into the molecular mechanisms by which USP47 regulates RABV infection.

Objective To investigate the multi spiral CT findings of ovarian endometrioid adenofibroma.Methods The clinical and CT imaging data of 7 patients with ovarian endometrioid adenofibroma were retrospectively analyzed,and the characteristic CT findings were summarized.Results All 7 patients of ovarian endometrioid adenofibroma in this group were unilateral,with tumors presenting as round or lobulated masses.Most cases were cystic-solid lesions.The density of cystic fluid was higher than that of water or urine,and fibrous septa of varying thickness were visible.Enhanced scanning showed solid part and fibrous septa with moderate enhancement.Conclusion The CT findings of ovarian endometrioid adenofibroma have certain characteristics,measuring the density of cystic fluid and enhancing scanning can improve it's diagnostic accuracy.