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

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To evaluate early left ventricular myocardial work in patients with metabolic syndrome (MS) by pressure-strain loops (PSL).Methods:From September 2020 to April 2021, 70 MS patients in the First Hospital of Qinhuangdao Affiliated to Hebei Medical University without left ventricular remodeling were selected as MS group and 65 normal controls as control group, PSL was used to obtain the myocardial power parameters, including global work index (GWI), global work efficiency (GWE), global constructive work (GCW) and global wasted work (GWW). The changes of the parameters were compared between the two groups and their correlations with biochemical parameters were performed in MS group.Results:The left ventricular global longitudinal strain (GLS), GWI, GCW and GWE in MS group were lower than those in normal group, while GWW was higher than that in normal group ( P<0.05). Pearson correlation analysis showed that GWI was positively correlated with high-density lipoprotein cholesterol (HDL-C) ( r=0.194, P<0.05), and negatively correlated with diastolic blood pressure (DBP), waist circumference (WC), fasting blood glucose (Glu), triglyceride (TG) and GLS ( r=-0.257, -0.452, -0.239, -0.193, -0.758, all P<0.05). GWE was negatively correlated with SBP, DBP, WC, Glu, TG and GLS ( r=-0.360, -0.269, -0.326, -0.352, -0.265, -0.663, all P<0.01), and positively correlated with HDL-C ( r=0.201, P<0.05). GCW was negatively correlated with WC and GLS ( r=-0.299, -0.737; all P<0.001). GWW was positively correlated with SBP, DBP, WC, Glu, TG and GLS ( r=0.435, 0.308, 0.413, 0.547, 0.272, 0.400, all P<0.01), and negatively correlated with HDL-C ( r=-0.336, P<0.001). Conclusions:PSL can quantitatively evaluate the changes of early myocardial work in MS patients with good repeatability and has certain clinical value.

Objective To analyze the precision and stability of optical surface imaging system for patients who received radiotherapy with active breath control. Methods Eighteen radiotherapy patients with lung metastasis were managed by active breath control (ABC).The difference error detected by optical surface imaging system and CBCT were defined as the precision of optical surface imaging system. The variation among the error of optical surface imaging positioning the value of correction of treatment position and the error detected by optical surface imaging again were defined as the stability of optical surface imaging system. Intrafractional errors were analyzed by optical surface imaging system through whole treatment process (including breath hold and free breath). Results The optical surface imaging system had precision (systematic (Σ) and random errors (σ)) of 1.78/3.42 mm 2.54/6.57 mm and 2.79/3.22 mm respectively and stability of2.12/2.54 mm 3. 09/4.02 mm and 1.37/3.55 mm respectively in lateral-medial superior-inferior and anterior-posterior directions. The intrafractional errors (Σ and σ) were 0.42/0.85 mm 0.41/1.47 mm and 0.41/1.47 mm respectively for breath hold duration and 4.76/4.16 mm 6.54/7.78 mm and 3.13/5.92 mm for free breath duration in lateral-medial superior-inferior and anterior-posterior directions. Conclusions As an effective method for validate breath hold;Optical surface imaging system can improve the precision and safety of active breath control. However,the factors that affect the accuracy and stability of the optical surface imaging system in patients undergoing radiotherapy with ABC are not clear;it cannot replace the CBCT for positioning verification.

Objective To explore the diagnostic value of DWI after secretin stimulation for the diagnosis of mild chronic pancreatitis (CP). Methods This was a prospective study. Ninety-nine consecutive individuals including 23 healthy volunteers, 11 risk volunteers, 15 mild CP patients, 14 moderate CP patients and 36 severe CP patients underwent secretin DWI and faecal elastase 1(FE-1) testing. The subjects were grouped by Cambridge classification about endoscopic retrograde cholangiography (ERCP), CT and ultrasonography. Secretin stimulated diffusion weighted imaging(S-DWI), the ADCs, time to peak ADCs and FE-1 were performed on all subjects. The changes of pancreatic ADC values were observed before and after the injection of secretin. All ADCs and FE-1 were compared between groups with single factor analysis of variance, and the correlation between ADCs and FE-1 was determined with Pearson analysis. ROC curves were performed to identify the diagnostic efficacy of DWI related measures. Results Eight patients with severe CP were excluded because the significant atrophy of the pancreatic parenchyma prohibited the evaluation of ADC measurement. Ninety-one individuals were divided into five groups including 23 healthy volunteers, 11 risk volunteers, 15 mild CP patients, 14 moderate CP patients and 28 severe CP patients. The mean baseline and peak ADCs were higher in the healthy volunteers than in other groups, with significant differences (P<0.05). There was no ADC peak in severe CP patients. There were significant differences between the mean baseline ADCs and the peak ADCs in the other groups (P<0.05). The mild and moderate CP groups showed a delayed peak. The area under curve (AUC) of the mean baseline and peak ADCs, time to peak ADCs for differentiating mild CP was 0.818, 0.912 and 0.965, respectively. Using 4.67 min as the cutoff value, time to peak ADCs were most accurate for differentiating healthy from risk patients and those with evident pancreatitis, yielding a sensitivity of 80.0%and a specificity of 100.0%. Good correlations between baseline and peak ADCs, time to peak ADCs, and FE-1 were shown(r=0.57, 0.72 and-0.84, P<0.01). Conclusions Using the peak and time to peak ADCs may improve the detection of risk and mild CP. Secretin-enhanced DWI is a noninvasive, convenient and accurate method.

Objective To analyze the displacement of titanium clips for tumor bed localization after breast-conserving surgery for breast cancer and its influential factors.Methods A retrospective analysis was performed on the cone-beam computed tomography (CT) images of 14 patients with breast cancer who received radiotherapy after breast-conserving surgery from April to October,2016.The relative position of the chest wall and the errors of the titanium clips in radiotherapy were measured.A Pearson correlation analysis was used to analyze the correlation of the displacement of titanium clips with the relative position of titanium clips,the breast volume,the vertical distance between the titanium clips and the tangential line of the chest wall,and the maximum thickness of the breast.Results The system errors of the chest wall in left-right,superior-inferior,and anterior-posterior directions were 4.42,3.44,and 5.13 mm,respectively,and the random errors were 3.55,3.07,and 4.54 mm,respectively.The titanium clips had a large displacement relative to the chest wall,mainly in the left-right direction.The maximum system error was 4.39 mm and the random error was 2.42 mm.The displacement of titanium clips was not significantly correlated with the breast volume and the maximum thickness of the breast (P>0.05).However,the relative position of titanium clips in superior-inferior direction was significantly correlated with the displacement of the lowest,the most lateral,the most anterior,and the most posterior titanium clips (P<0.05).As to the uppermost clips,there was a significant difference in displacement between the clips close to the chest wall and the clips far from the chest wall (P=0.02).Conclusions Due to large setup error and displacement of titanium clips during radiotherapy,simultaneous integrated boost is not suitable for patients with breast cancer who are immobilized by vacuum cushion and received radiotherapy.The unstable immobilization may be the major influential factor for the displacement of titanium clips.

This article is aimed to study the optimal process of preparation of Golden water-soluble gel, and to establish its quality control method. Taking the gel forming properties, stability, water loss rate, pH as investigation index, the best extraction process was screened by single factor and orthogonal test design. TLC method was used to identify the product of trichosanthin, rhubarb, and the content of paeoniflorin was determined by HPLC method. The optimal condition of preparation process is to use 1% carbomer as gel matrix, 10% glycerol as humectants, and 0.5%triethanolamine as pH modulators; trichosanthes and rhubarb could be detected by TLC method, with pH range 5.00 - 5.15. The linear range of paeoniflorin was 29.04-945.20μg·mL-1, the average recovery was 98.80%, and RSD was 2.91% (n=9). Golden gel forming process is simple and quality controllable with reliability and good stability.

OBJECTIVE: To investigate the safety, efficacy and long-term patency of parallel shunts (PS) in the management of the transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. MATERIALS AND METHODS: Between March 2007 and October 2010, 18 patients (13 men and 5 women) who underwent TIPS revision with the creation of PS were evaluated retrospectively. In the first 10 patients, a 10-mm-diameter Wallgraft endoprosthesis was deployed; in the latter 8 patients, an 8-mm-diameter Fluency endoprosthesis was deployed. RESULTS: The creation of PS was technically successful in all patients. The mean +/- standard deviation portosystemic pressure gradient before and after the procedure was 25.5 +/- 7.3 mm Hg (range, 16-37 mm Hg) and 10.9 +/- 2.3 mm Hg (range, 7-16 mm Hg), respectively. The duration of follow-up was 16.7 +/- 10.8 months (range, 6-42 months). The primary shunt patency rates at 12 months after the creation of PS was 70% with Wallgraft endoprostheses and 87.5% with Fluency endoprostheses. CONCLUSION: TIPS revision with the creation of PS is a safe, effective and durable method for treating shunt dysfunction.
Adult ; Aged ; Blood Pressure Determination ; Female ; Humans ; Male ; Middle Aged ; Polytetrafluoroethylene ; Portasystemic Shunt, Transjugular Intrahepatic/adverse effects/*methods ; Prosthesis Design ; Reoperation/methods ; Retrospective Studies ; Stents

Objective To summarize the features of signs of digital subtraction angiography (DSA) of small intestinal stromal tumor (SIST) with different invasion risk degrees.Methods The clinical data of 15 patients with SIST who were admitted to the West China Hospital of Sichuan University from September 2008 to June 2010 were retrospectively analyzed.The signs of DSA of SIST with different invasion risk degrees were analyzed.Results The result of DSA showed that 1 patient with low-invasive SIST presented draining veins and clear edge with homogeneously stained tumor in arterial phase.Enlarged tumors vessels,sharp edges and uniform tumor staining were observed in 4 patients with low-invasive risks.Enlarged and disordered tumor vessels and irregular shape were observed in 4 patients with moderate-invasive risks,and 3 of them showed heterogeneity stained tumor.Obvious enlarged and disordered tumor vessels,unclear edge and uniform tumor staining were showed in 6 patients with high-invasive risks.Conclusions The higher invasive risks correlates with more irregular and disorder tumor vessels.The tumors with lower-invasive risks have more regular and trim blood vessels.