ObjectiveExploring the role of microRNA126 （miRNA126） in chronic kidney disease combined with atherosclerosis （CKD AS） by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group， model group， losartan group， and low， medium， and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low， medium， and high dose groups （6.0， 12.0， 24.0 g·kg^-1·d^-1） of Shenshuai Xiezhuo decoction and the losartan group （20 mg·kg^-1·d^-1） were gavaged， and the corresponding intervention was carried out for eight weeks. Then， the rats were killed， and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats： blood creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） and Masson staining of aortic tissue and pathological observation under a light microscope were carried out， and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA levels of miRNA126， PI3K， Akt， and mTOR in rats， and Western blot was used to determine the protein expression levels of phosphorylated （p）-PI3K， PI3K， p-Akt， Akt， p -mTOR， mTOR， benzyl chloride 1 （Beclin-1）， and microtubule-associated protein light chain 3Ⅱ/Ⅰ （LC3Ⅱ/LC3Ⅰ）. ResultCompared with the sham operation group， the serum SCr， BUN， TC， TG， and LDL-C in the model group were significantly increased （P<0.01）. Compared with the model group， the SCr， BUN， TC， TG， and LDL-C were decreased in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction （P<0.05）. Compared with the sham operation group， thickening plaques， infiltration of mononuclear macrophages， a small number of foam cells， disordered arrangement of smooth muscle fibers in the tunica media， and increased collagen fibers were observed in the model group， and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group， the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group， the expression of miRNA126 in the aortic tissue of the model group was significantly decreased （P<0.01）， and the mRNA expressions of PI3K， Akt， and mTOR were significantly increased （P<0.01）. Compared with the model group， the expression of miRNA126 in the aortic tissue of rats in high， medium， and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased （P<0.01）， while the mRNA expressions of PI3K， Akt， and mTOR were significantly decreased （P<0.01）. Compared with the sham operation group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the model group were significantly increased （P<0.01）， while the protein levels of Beclin-1， LC3Ⅰ， and LC3Ⅱ were significantly decreased （P<0.01）. Compared with the model group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction were decreased （P<0.05）， while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased （P<0.05）. ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats， and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126， restores the autophagy of aortic endothelial cells， protects the damage of CKD vessels， reduces the formation of As plaques， and slows the development of cardiovascular complications.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective To investigate the value of transient elastography (TE) in the staging of hepatic fibrosis in patients with autoimmune liver disease (ALD). Methods PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP databases were searched for English and Chinese articles on TE in the staging of hepatic fibrosis in ALD published from January 2000 to January 2021. Two reviewers independently performed data extraction for the articles included, and QUADAS2 was used for quality assessment. The bivariate mixed effects model in Stata 15.0 software was used to perform the Meta-analysis. Results A total of 11 articles were included, with 1041 patients in total. In the diagnosis of significant hepatic fibrosis (F≥2), TE had a pooled sensitivity of 0.81 (95% CI : 0.75-0.86), a specificity of 0.87(95% CI 0.79-0.92), and an area under the receiver operating characteristic curve (AUC) of 0.91(95% CI 0.88-0.93); in the diagnosis of advanced hepatic fibrosis (F≥3), TE had a pooled sensitivity of 0.81(95% CI 0.74-0.87), a sensitivity of 0.90(95% CI 0.85-0.93), and an AUC of 0.92(95% CI 0.90-0.94); in the diagnosis of early-stage liver cirrhosis (F4), TE had a pooled sensitivity of 0.87(95% CI 0.74-0.93), a specificity of 0.93(95% CI 0.87-0.97), and an AUC of 0.96(95% CI 0.94-0.97). Conclusion TE has a good diagnostic value in evaluating significant liver fibrosis, advanced liver fibrosis, and early-stage liver cirrhosis in patients with ALD, especially with a relatively high diagnostic accuracy for early-stage liver cirrhosis.

Objective:To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B.Methods:98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks.Results:During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log 10IU/ml vs. (0.73 ± 0.81) log 10IU/ml, P = 0.017; (1.54 ± 1.27) log 10IU/ml vs. (0.57 ± 0.56) log 10IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion:Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

Objective To explore the joint toxic effect of formaldehyde and benzene on testicles of the mice. Methods 78 Kunming male mice were divided into groups, in the formaldehyde treatment groups were exposed at dosage of 0.2 mg/kg,2 mg/kg,20 mg/kg, in the benzene treatment groups were exposed at dosage of 100.0 mg/kg,200.0 mg/kg,400.0 mg/kg and the in formaldehyde and benzene combined treatment groups were exposed at dosage of 0.1+50.0 mg/kg,1+100.0 mg/kg,10+200.0 mg/kg respectively. The treatments were conducted by peritoneal injection for five consecutive days,once a day,then killed on 6th day. The activity of superoxide dismutase(SOD),the contents of maleic dialdehyde(MDA),the contents of copper(Cu),zinc(Zn) in testicles of the mice were determined. Results Compared with those in the negative control groups,the activity of SOD and the contents of Cu, Zn in the testicles of the mice in each treatment group significantly decreased, while the contents of MDA significantly increased (P

Objectives:To study the soft tissue profile characteristic in the early permanent dentition with Class Ⅲ malocclusion, and then to analyze the relationship between hard and soft tissue. Methods: 50 normal occlusion and 50 Class Ⅲ malocclusion children were examined cephalometrially with the lip at rest. Results:Compared with the normal occlusion group, All measurement except 9 soft tissue variables and 1 hard tissue variables was statistically significant with t-test in the Class Ⅲ malocclusion group (P

Objective To research the indoor air pollution in offices induced by decoration and its health effects. Methods According to the completed time, the offices were divided into 6 groups (2 month group, 2-4 month group, 5-8 month group, 9-11 month group, 12-18 month group, over 5 year group). The concentration of indoor air pollutants was determined and 617 people from the decorated offices were randomly selected to finish the questionnaires on health. Results The over standard rate of formaldehyde, benzene and ammonia in indoor air was the highest in 2 month group, 100%, 87.3%, 83.9% respectively. The concentration of indoor air pollutants decreased as the time went on, about one year after decoration, the concentrations were lower than the standard limits (GB/T 18883-2002). The adverse response rate of the staff members in offices decorated group (76.4%) was significantly higher than that in the control group (30.9%) (P

Objective To study the effect of inhaling formaldehyde on learning and memory in mice. Methods 24 KM mice were randomly divided into four groups: the control group (clean air),the low dose group (1 mg/m3),the moderate dose group (3 mg/m3) and the high dose group (5 mg/m3). The mice were exposed to different concentrations of gaseity formaldehyde,2 h/day,for 14 consecutive days. Then their behavior of learning and memory were tested by step-down test,passive avoidance test and Morris water maze experiment. Results Step-down test showed that the mice in the moderate dose group and the high dose group made notable errors compared with the control group (P

Objective To explore the genotoxicity of formaldehyde to mice.Methods Mice were exposed to formaldehyde of several concentrations(1.25,0.50,and 5.00 mg/m3) in the toxicant exposure chamber,2 h/d for 15 consecutive days.Bone marrow micronuclei test and single cell gel electrophoresis were employed to test the genotoxicity.Results Compared with the control group,a significant increase in the rate of micronuclei and the DNA damage of peripheral lymphocytes in experimental groups were found.As to the rate of micronuclei and DNA damage,an obvious dose-effect relationship was showed.Conclusion Formaldehyde has a genotoxic effect for mice,much more attention should be paid in this research field.