Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.

Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.

Objectives: . Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system. Methods: . We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables. Results: . The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16–2.57); were older (MD, 5.47 years, 95% CI, 2.44–8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33–2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56–3.44 cm); exhibited limited mouth opening (MD, −0.52 cm; 95% CI, −0.88 to −0.15 cm); had limited neck flexibility (MD, −10.05 cm; 95% CI, −14.10 to −6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07–5.48). Conclusion . We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (

Objective: To evaluate the association of long-term ambient fine particulate matters (PM_2.5) exposure with elevated blood pressure in children. Methods: From April 2012 to June 2013, we used cluster randomized sampling method to investigate 9 354 children aged 5-17 years old from 68 primary and middle schools in the seven Northeastern Cities (Shenyang, Dalian, Fushun, Anshan, Benxi, Liaoyang and Dandong) in Liaoning Province, and measured their blood pressure (BP). A spatial statistical model nested by aerosol optical depth (AOD) was used to inverse PM_2.5 concentrations. Generalized additive model was used to quantify the association between PM_2.5 exposure and blood pressure in children. To examine the associations, two-level regression model was used to evaluate individual characteristics′ modifying effect on the health influence of PM_2.5. Results: The prevalence of hypertension in children was 13.78% (1 289/9 354). The results showed that there was an associations between hypertension and pollutants, and the multivariable regression analysis indicated that the increase in mean systolic blood pressure (SBP), diastolic blood pressure (DBP), and the OR of hypertension associated with a 10 μg/m³ increase for PM₂.5 were 3.12 (95%CI: 2.71-3.54) mmHg (1 mmHg=0.133 kPa), 1.45 (95%CI:1.12-1.78) mmHg, and 1.55 (95%CI: 1.10-2.19), respectively. Compared with non-breastfeeding children (OR=2.10, 95%CI: 1.39-3.17), children who were breastfeeding (OR=1.49, 95%CI: 1.00-2.20) exhibited consistently weaker effects, and the interaction effect of P value was 0.002. Conclusion Study findings indicate that long-term exposure to PM_2.5 is associated with increased arterial BP and hypertension among the children. Breastfeeding may reduce this association.

Objective To explore the changes of left ventricular torsion function in patients with latent obstructive hypertrophic cardiomyopathy ( HCM ) ,and provide quantitative informations for clinical evaluation of cardiac function . Methods A total of 49 consecutive patients with HCM without left ventricular outflow tract obstruction at rest were enrolled . All subjects underwent exercise stress echocardiography . After exercise left ventricular outflow tract pressure gradient ( LVO T‐PG ) ≥30 mm Hg was positive for exercise stress test ( latent obstruction) ,w hile LVO T‐PG＜ 30 mm Hg was negative for exercise stress test ( non‐obstruction) . An ultrasound system obtained two‐dimensional ultrasound images of resting and moving peaks . The global longitudinal strain ( GLS ) ,global circumferential strain ( GCS ) , global radial strain ( GRS) of the left ventricle 16 segments and left ventricular rotation ,twist were analysis using off‐line EchoPAC software . T he differences of the above parameters were compared between the two groups . Results T here were no significant differences in GLS ,GRS ,GCS and Rotation‐B between the two groups in resting and peak period of exercise ( all P ＞ 0 .05 ) ,GRS in both groups were significantly increased compared with that before exercise ( all P ＜ 0 .05 ) . Compared with the negative exercise stress group ,the left ventricular twist and Rotation‐A were significantly increased in resting and peak period of exercise in the positive exercise stress test group( all P ＜0 .05) . Compared with before exercise ,Rotation‐A and left ventricular twist were significantly decreased in the positive exercise stress test group ( all P ＜0 .05) ,while no significantly difference was found in the negative exercise stress group ( all P ＞ 0 .05 ) . Conclusions Left ventricular torsion function is significantly changed in rest and after exercise in latent obstructive HCM patients ,providing valuable quantitative information for clinical comprehensive evaluation of cardiac function .

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

Objective To explore the improvement of cognitive impairment in patients with mild and moderate vascular cognitive impairment( VCI) treated with cerebralcare granule ( CG) and basic treat-ment.Methods From October in 2014 to December in 2016 year,143 cases of VCI patients were admitted from six hospitals in some areas of Hebei Province as the research objects,and divided into CG treatment group (experimental group,n=98) and conventional treatment group (control group,n=66).Three months and six months after treatment,the score of mental state examination ( MMSE) ,the Montreal cognitive assess-ment scale ( MoCA) and the daily living capacity scale( ADL) of the two groups were compared after 3 and 6 moths of treatment.Results ①The total score of MMSE in the experimental group was higher than that of the control group for six months after treatment, and the difference was statistically significant ( ( 23. 76 ± 4.02) vs (21.52±5.13),P<0.05).②Six months after treatment,the total score of MoCA ((21.06±4.66) vs (18.32±5.20)) and visual spatial/executive function((3.05±1.37) vs (2.42±1.66)),calculation force ((2.24±0.84) vs (1.83±1.05)) and orientation ability((5.20±1.12) vs (4.06±1.35)) scores in the ex-perimental group were significantly higher than those in the control group (P<0.05) .③Six months after treat-ment,the ADL score in the experimental group was lower than that before treatment,and the difference was statistically significant((24.96±8.74) vs (29.20±11.55),P<0.05);while there was no significant difference in the ADL score between the experimental group and the control group after 6 months (P>0.05).Conclusion CG can improve cognitive function in mild to moderate VCI patients,mainly in visual space/execution func-tion,calculation ability and orientation ability,and with the extension of treatment time,the curative effect is more obvious.

Objective To evaluate left ventriclular systolic function in patients with obstructive hypertrophic cardiomyopathy (HOCM) after modified Morrow surgery using two-dimensional speckle tracking imaging (2D-STI).Methods Twenty three HOCM patients were recruited in this study.Echocardiographic data from HOCM patients during pre-operation,1-month and 3-month post-operation were analyzed by Qlab software to compare the variation in systolic function indicators 1-month and 3-month post-operation including global and 16 segmental longitudinal strain,circumferential strain and conventional echocardiographic parameters of left ventricle.Results Compared with preoperative data of HOCM patients,postoperative LVOT diameter and pressure gradient,left atrial diameter and volume index were significantly decreased(P<0.05),but there was no significant difference in left ventricular ejection fraction(P<0.05).Compared with the preoperative case,global and segmental longitudinal strain showed significant reduction after 1 week and gradually recovered after 3 months,without significant variation.The longitudinal strain of the anteroseptum reduced significantly and the longitudinal strain of the free wall increased after 3 months,however,the circumferential strain reduced significantly.The circumferential strain of basal and middle segment after 3 months had improved significantly than those of postoperative 1 week.The circumferential strain of surgical site is no obvious change and the strain of free wall was improved after 3 months.Conclusions 2D-STI can effectively evaluate global and regional systolic function of left ventricle for HOCM patients after modified Morrow surgery.