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 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 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 investigate the relationship between glycemic variability and glycosylated hemoglobin (HbA1c) level during follow-up in elderly male patients with type 2 diabetes.Methods:Retrospective cohort study. A total of 200 elderly male patients who received continuous glucose monitoring from January 2007 to January 2011 were recruited in the Second Medical Center of PLA General Hospital. The subjects were divided into two groups according to baseline mean amplitude of glycaemic excursion (MAGE) level, including MAGE <3.9 mmol/L group ( n=114) and MAGE ≥3.9 mmol/L group ( n=86). The correlation between baseline MAGE and mean HbA1c during follow-up were evaluated by univariate Pearson correlation analysis and multivariate linear regression analysis. Results:Baseline characteristics including age, body mass index, waist circumference, smoking, drinking, fasting blood glucose, blood lipid and blood pressure were comparable between MAGE <3.9 mmol/L group and MAGE ≥3.9 mmol/L group. The average follow-up period was 12.5 years. The mean HbA1c during follow-up in MAGE ≥3.9 mmol/L group was significantly higher than that in MAGE <3.9 mmol/L group (7.23%±0.72% vs. 6.91%±0.77%, t=-2.94, P=0.004). The proportion of mean HbA1c <7.0% during follow-up in MAGE ≥3.9 mmol/L group was 44.2% (38/86), which was significantly lower than that in MAGE <3.9 mmol/L group [60.5% (69/114), χ 2=5.26, P=0.022]. In univariate analysis, MAGE at baseline was correlated with the mean HbA1c during follow-up ( r=0.306, P<0.001). Multivariate linear regression analysis suggested that the baseline MAGE remained an independent influential factor of mean HbA1c ( β=0.09, 95% CI: 0.03 to 0.15, P=0.006, R2=0.31) after several confounding factors were adjusted. Conclusions:With the increased glycemic variability at baseline, mean HbA1c level during follow-up is accordingly elevated. The glycemic variability at baseline is independently related to mean HbA1c level during follow-up in elderly male patients with type 2 diabetes.

Objective:To summarize the clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach (TOETSLVA).Methods:We retrospectively reviewed the medical record of patients who underwent TOETSLVA in our department from November 2011 to May 2020, including 3 males and 95 females, aged from 18 to 57 years old. Initial 81 cases were categorized in "Period A (November 2011-November 2015)" and subsequent 17 cases in "Period B (August 2019-May 2020)" . Data about demographics, operation time and complications were collected. SPSS 22.0 software was used for statistical analysis.Results:In Period A, the average age of patients was (34.2±9.4) years old; the mean tumor diameter was (2.33±0.80) cm; postoperative pathology showed benign nodules in 76 cases and malignant carcinoma in 5 cases; there were 65 cases of unilateral subtotal thyroid lobectomy, 6 cases of isthmus lobectomy, and 5 cases of bilateral subtotal thyroid lobectomy, with the mean operation time of (132.70±47.22) min; in 5 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (185.4±31.40) min; postoperative neck infections occurred in 6 cases; temporary vocal cord paralysis occurred in 1 case, which it recovered within two months; and CO 2 gas embolism occurred in 2 cases. In Period B, the average age of patients was (35.1±8.5) years old; mean tumor diameter was (1.32±0.67) cm; postoperative pathology indicated malignant nodules in 15 cases and benign nodules in 2 cases; in 2 cases of unilateral thyroid lobectomy, the mean operation time was (153.5±34.64) min; in 15 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (123.73±14.26) min; and none of patients developed postoperative neck infections or CO 2 gas embolism. All patients had different degree of cutaneous numbness in the submandibular region after surgery, which recovered within 1-2 weeks. There were no complications such as postoperative secondary hemorrhage, permanent vocal cord paralysis, hypoparathyroidism in both the periods. The median follow-up time was 86 months (57-105 months) in Peroid A and 5 months (3-12 months) in Peroid B. During the follow-up periods, there were no obvious abnormalities in swallowing, chewing, oral sensory function and neck activity, and also no tumor recurrence or metastasis. Conclusions:TOETSLVA is a safe and feasible surgery method, with a good cosmetic result. This approach will not lead to a postoperative cutaneous numbness of the submandibular region for a long time.

Objective To detect the expression levels of cytokines in peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL), and to explore their clinical significances. Methods The levels of interleukin-1β (IL-1β), IL-2R, IL-6, IL-8, tumor necrosis factor (TNF) and IL-10 in peripheral blood of 38 newly diagnosed patients with DLBCL and 20 healthy adults in Anqing Municipal Hospital from April 2013 to January 2017 were detected and analyzed by immunofluorescence method. Results The levels of IL-2R, IL-6, IL-8, TNF and IL-10 in DLBCL group were significantly higher than those in healthy control group (all P< 0.05). The levels of IL-2R and TNF in stage Ⅲ-Ⅳ group [(5985±26) U/ml and (42.2±5.8) pg/ml)] were higher than those in stageⅠ-Ⅱ group [(3672 ±28) U/ml and (30.4 ±2.6) pg/ml] (t values were 34.861 and 28.451; P values were 0.023 and 0.038 respectively). The levels of IL-2R and IL-10 in the high-risk group (IPI 4-5) [(6322±36) U/ml and (77±7) pg/ml] were higher than those in the low-risk group (IPI 0-1) [(2567± 32) U/ml and (50±5) pg/ml)] (t values were 58.327 and 24.264; P values were 0.001 and 0.041 respectively). IL-2R, IL-6 and IL-10 levels in patients with B symptom group [(6234±26) U/ml, (38.1±2.3) pg/ml, (90± 10) pg/ml] were higher than those in patients without B symptom group [(6234 ±26) U/ml, (38.1 ±2.3) pg/ml, (90±10) pg/ml) (t values were 32.263,24.321, 36.529; P values were 0.027, 0.043, 0.020). Conclusion The levels of IL-2R, IL-6, IL-8, TNF and IL-10 in DLBCL patients are higher than those in healthy controls, and the levels of cytokines are correlated with the clinical characteristics of DLBCL patients.

Objective To evaluate the accuracy of different noninvasive methods for the diagnosis of nonalcoholic steatohepatitis(NASH) and hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with type 2 diabetes mellitus(T2DM). Method A prospective comparative study was performed for 91 patients with T2DM and NAFLD, which were diagnosed by glucose tolerance test and liver biopsy. The height and body mass of the patient were measured, and the body mass index(BMI) was calculated. The fasting venous blood of the patient was collected, and then the blood routine, liver function and ferritin were measured. NPS, neutrophil lymphocyte ratio(NLR), BARD score, FIB-4 index, APRI, and NAFLD fibrosis score(NFS) were calculated. All patients underwent transient elastography (Fibrotouch) to evaluate the degree of liver stiffness measurement (LSM) and controlled attenuation parameter. All the liver biopsy specimens were categorized by SAF as the gold standard for evaluating NASH and liver fibrosis NASH. Correlation analysis was applied to compare the correlation between the noninvasive methods and SAF. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the diagnostic value of the noninvasive methods for NASH and liver fibrosis NASH. Results In T2DM combine with NAFLD patients, NPS, LSM, NFS, APRI, FIB4 and BMI scores were positively correlated with SAF (r value was 0.509, 0.508, 0.252, 0.396, 0.313 and 0.213, respectively; P value was <0.001, <0.001, 0.016,<0.001, 0.003 and 0.043, respectively). LSM, NPS, NFS and FIB4 scores were positively correlated with liver fibrosis (r value was 0.535, 0.337, 0.315 and 0.315, respectively; P value was <0.001, 0.001, 0.002, 0.002, respectively). The ROC curve shows that the area under the curve of NPS, LSM, APRI, FIB4 and BMI for diagnosing NASH was 0.838, 0.760, 0.734, 0.623 and 0.682, respectively, and P value was 0.000, 0.000, 0.000, 0.044 and 0.003, respectively. For the diagnosis of fibrotic NASH, that value of LSM, NFS, FIB4 and NPS was 0.795, 0.765, 0.686 and 0.623, respectively, and P value was 0.000, 0.001, 0.020 and 0.123, respectively. Conclusions NPS, LSM and APRI have good clinical diagnostic value for NASH. LSM and NFS have good diagnostic value for fibrotic NASH.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.

Objective: To investigate the effect of dietary control combined with different exercise modes on plasma vaspin, irisin, and metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD) through a randomized open parallel-controlled study. Methods: The patients aged 30-65 years who visited Tianjin Third Central Hospital from January 2013 to December 2014 and were diagnosed with NAFLD by liver ultrasound and fat content determination were screening, and 474 patients were enrolled in this randomized controlled trial and divided into aerobic exercise group, resistance exercise group, and control group. All patients received dietary intervention. The three groups were compared in terms of biochemical parameters, fat content, NFS score, energy metabolic parameters, body composition index, and levels of vaspin and irisin at baseline and after 6 months of intervention. SPSS 19.0 was used for statistical analysis. The t-test, the Mann-Whitney U test, the chi-square test, and an analysis of variance were used for comparison between groups. The multiple imputation method was used for missing data, and the results were included in the intention-to-treat analysis. Results: There were no significant differences in age, sex, anthropometrical parameters, and biochemical parameters between the three groups at baseline. Compared with dietary control alone, aerobic exercise and resistance exercise helped to achieve significant reductions in waist circumference, diastolic pressure, percentage of body fat, volatile fatty acid, fasting blood glucose, homeostasis model assessment of insulin resistance, triglyceride, low-density lipoprotein cholesterol, free fatty acid, uric acid, alanine aminotransferase, and liver fat content after 6 months of intervention (P < 0.05). The aerobic exercise group had a significant increase in non-protein respiratory quotient and significant reductions in body mass index and aspartate aminotransferase after intervention, as well as a significant increase in resting energy expenditure and significant reductions in abdominal fat ratio and total cholesterol after 6 months of resistance exercise (P < 0.05). The aerobic exercise group and the resistance exercise group had a significant reduction in vaspin and a significant increase in irisin after intervention (P < 0.05), and the resistance exercise group had significantly greater changes in these two adipokines than the aerobic exercise group (P < 0.05). Conclusion Exercise therapy is an effective method for the treatment of metabolism-associated diseases, and a combination of resistance and aerobic exercises is more reasonable and effective in clinical practice. As a relatively safe exercise mode, resistance exercise can also effectively improve the metabolic state of NAFLD patients.

Objective To evaluate the feasibility and results of laparoscopic thyroidectomy by oral and breast approach for the treatment of papillary throid carcinoma.Methods Thyoidectomy was performed in 26 cases,including 24 females and 2 males with the average age of 34 years (range 20-53 years).All patients were diagnosed throid carcinoma confirmed by FNA or B-mode ultrasound examination,a thyroid lobe or total thyroidectomy and central compartment dissection was performed by breast approach,then additional dissection of central compartment was completed through oral approach.Results Laparoscopic thyroidectomy via oral in combination with brest approach was performed successfully in all 26 cases.The mean operative time was (164 ± 13) min,including average time of oral approach of (40 ± 7) min.The mean number of lymph node dissection in central compartment was 7.42 ± 4.88,oral approach achieved additional 1.23 ± 2.21,with metastatic lymph nodes diseccted by oral approach in 3 cases.Conclusions Laparoscopic thyroidectomy via oral in combination with breast approach for the treament of papillary throid carcinoma is better than breast approach alone in central compartment dissection.