Objective To investigate the role and regulatory mechanism of stress-inducing protein 1(SESN1)in liver gluconeogenesis of fasting mice.Methods RT-qPCR was used to detect mRNA expression of SESN1 in liver tissues of C57BL/6J mice and primary mouse hepatocytes treated with forskolin(Fsk)and dexamethasone(Dex).HepG2 cells were transfected with plasmids and the effects of SESN1 overexpression on mRNA expression of gluconeogenesis related genes PGC-1α,PEPCK and G6Pase was detected by RT-qPCR.The effect of SESN1 on the promoter activity of PGC-1α in HepG2 cells was studied using a dual luciferase reporter system.The effect of SESN1 on PGC-1α deacetylation was detected by overexpression of SESN1 and inhibition of SIRT1 expression.By knocking down SIRT1 expression,we detected whether it mediated the changes in mRNA levels of SESN1 in-duced gluconeogenesis related genes.Results The mRNA expression of SESN1 was significantly increased in liver tissues of starved C57BL/6J mice and in primary hepatocytes treated with Fsk and Dex(P<0.001).Over-expression of SESN1 in HepG2 cells promoted mRNA expression of PGC-1α,PEPCK and G6Pase(P<0.001)and promoter activity of PGC-1α(P<0.001).Over-expression of SESN1 decreased the acetylation level of PGC-1α in primary hepatocytes.Sirt family inhibitors NAM and shRNA adenovirus interfered with SIRT1 expression respective-ly,and antagonized the deacetylation effect of SESN1 on PGC-1α.The expression of PGC-1α,PEPCK and G6Pase induced by SIRT1 was also significantly impaired(P<0.000 1).Conclusions SESN1 regulates liver gluconeogene-sis in mice with a SIRT1-dependent mechanism.

Objective To investigate the effect of Nutlin-3a,a mouse double minute 2 homolog(MDM2)inhibitor,on lipid metabolism of mouse adipose.Methods High-fat diet-induced obesity(DIO)C57BL/6J mice were randomly divided into a control group injected with DMSO and an experimental group injected with Nutlin-3a.Then we conducted glucose tolerance(GTT)and insulin tolerance(ITT)tests.The epididymal white adipose tissue(eWAT),inguinal white adipose tissue(iWAT)and brown adipose tissue(BAT)of animals were isolated and microscopy of WATs with hematoxylin-eosin(HE)staining was performed to observe the morphological changes of adipocytes.The expression of lipid metabolism related gene cell death-inducing DFF45-like effector C(CIDEC)in eWAT were detected by qPCR and Western blot.Results Compared with the control group,Nutlin-3a was found to promote the body weight(P＜0.001),but no effect on glucose tolerance and insulin sensitivity in DIO mice.Nutlin-3a treatment decreased the size of adipocytes and fat deposition in adipose tissue and downregulated the mRNA and protein levels of CIDEC in eWAT.Conclusions Nutlin-3a inhibits the formation of lipid droplets by downregulating expression of CIDEC in white adipose tissue.

Objective:The evidence on the use of bedside ultrasound to assess muscle mass in critically ill adults was retrieved and screened, and the best evidence was summarized.Methods:A computer search was conducted for relevant literature on ultrasound measurement of muscle mass in critically ill adults in domestic and foreign databases such as BMJ Best Clinical Practice, UpToDate, PubMed, CNKI, and guide website and professional association website. The search time limit was from the establishment of the database to August 30, 2023. Literature quality was evaluated by four researchers trained in systematic evidence-based courses according to literature type.Results:A total of 15 literatures were included, including 2 guideline, 4 expert consensus, 5 systematic reviews and 4 randomized controlled studies. A total of 22 pieces of evidence were summarized, including 6 aspects: position and patient preparation, feasibility of implementation by nursing staff, selection of probe and matters needing attention, muscle positioning, evaluation of muscle structure by ultrasound and the guiding significance of ultrasound evaluation of muscle mass.Conclusions:The best evidence summary of bedside ultrasound assessment of muscle mass in critically ill adults summarized in this study is scientific and systematic, and provides evidence-based basis for establishing standardized ultrasound assessment procedures in clinic.

Objective:To investigate gender differences in arterial velocity pulse index(AVI), which is an indicator of vascular stiffness, across various age groups.Additionally, the study will also examine the risk factors associated with AVI.Methods:This cross-sectional study enrolled 4311 patients with an average age of 57.8±12.8 years at Jiading Branch of Shanghai First People's Hospital between August 2020 and September 2021.Patients were divided into three groups based on age: young(<45 years old, n=755), middle-aged(45-59 years old, n=1260), and elderly(≥60 years old, n=2 296). The AVI of the subject was obtained using the cuff oscillation wave method.The subject's AVI was acquired using the cuff oscillation wave.High AVI, indicating arteriosclerosis, was defined as AVI≥33.The subjects were then divided into two groups: the high AVI group(122 cases)and the normal AVI group(4 189 cases).Results:The ankle-brachial index(AVI)was found to be 12.8±3.7, 17.5±5.7, and 19.8±6.5 in the young, middle-aged, and elderly groups, respectively.The study revealed that AVI increased with age( Ftrend=767.819, P<0.01). Additionally, the incidence of high AVI in middle-aged women was found to be(2.8% or 20/722), which was higher than that in men 0.9%(5/538)in the same age group.This difference was statistically significant( χ2=5.371, P<0.05). The results of the multivariate logistic regression analysis indicate that being overweight, having a higher height, and a pulse rate greater than 80 BPM are protective factors in preventing a high incidence of AVI.The odds ratios( OR)with 95% confidence intervals( CI)for these factors were 0.468(0.317-0.690), 0.926(0.895-0.958), and 0.143(1.026-2.432), respectively, all with a P-value less than 0.01.On the other hand, old age, systolic blood pressure of 140 mmHg or higher, and diastolic blood pressure of 90 mmHg or higher were identified as risk factors for AVI.The ORs with 95% CIs for these factors were 2.119(1.322-3.396), 6.652(4.136-10.699), and 1.580(1.026-2.432), respectively, all with a P- value less than 0.05l. Conclusions:Arterial stiffness, as measured by the ankle-brachial index(ABI), tends to increase with age.In middle-aged subjects, women have a higher incidence of high ABI than men.Independent risk factors for high ABI include age and increased blood pressure, while factors such as overweight and height may affect the measured value of ABI.

Objective:Analysis of influencing factors of enteral nutrition interruption in critically ill patients in general surgery department and its impact on prognosis.Methods:A total of 91 cases of critically ill patients in general surgery department were selected who were admitted to the general surgery of General Hospital of Eastern Theater Command of the Chinese People′s Liberation Army in Nanjing from June 2021 to March 2022 by convenient sampling method, demographic and enteral nutrition interruption data were collected,and patients were divided into enteral nutrition interruption group and enteral nutrition uninterrupted group to investigate the analysis of the factors of affecting enteral nutrition interruption and its impact on prognosis by Logistic regression analysis.Results:There were 59 cases in the enteral nutrition interruption group and 32 cases in the enteral nutrition uninterrupted group. There were statistically significant differences in gender, analgesic and sedatives, Gastro-kinetic agent and feeding intolerance between both groups ( χ2 values were 4.51-9.97, all P<0.05). Logistic regression analysis results showed that gender ( OR=4.566, 95%CI 1.332-15.657, P<0.05), analgesic and sedatives ( OR=3.437, 95%CI 1.112-10.621, P<0.05), and feeding intolerance ( OR=4.116, 95%CI 1.257-13.479, P<0.05) were the factors of enteral nutrition interruption. There were statistically significant differences between the two groups in the number of days of enteral nutrition up to goal in 3 days, 3-7 days and 7 days, albumin,length of stay in intensive care unit, total length of stay and hospitalization expenses between both groups ( Z values were -2.80 - -0.73, all P<0.05). Conclusions:Female, analgesic and sedatives and feeding intolerance are the risk factors of enteral nutrition interruption in critically ill patients in general surgery department, and enteral nutrition interruption has an adverse impact on the prognosis.Medical staff should avoid excessive use of analgesic and sedatives, and do well in feeding tolerance management to reduce the occurrence of enteral nutrition interruption.

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC

Objective:To investigate the clinical significance and correlation between blood glucose variability and cognitive impairment in elderly patients with metabolic syndrome.Methods:A total of 80 elderly metabolic syndrome patients and 50 healthy controls in Chinese People′s Armed Police Corps Hospital in Sichuan Province from December 2017 to March 2019 were selected as study group and control group respectively, and the difference of general data and biochemical indicators between two groups were compared. The cognitive function of the metabolic syndrome patients was measured by Montreal cognitive assessment scale (MoCA) at admission. The patients were divided into cognitive dysfunction group and normal cognition group according to MoCA score. The glycemic variability was detected by 72-h dynamic monitoring of blood glucose started within 24 h after admission, and the difference of average blood glucose (Glu Ave), standard deviation of glucose (Glu SD), mean amplitude of glycemic excursions in 24 h (MAGE), glycemic index (GLI), glucose variability (Glu CV) and other indicators between cognitive dysfunction group and normal cognition group were also compared. Results:The levels of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterin (LDL-C), glycated hemoglobin (HbA 1c) were significantly increased in the study group [(25.48 ± 3.86) kg/m 2 vs. (22.83 ± 4.60) kg/m 2, (139.09 ± 10.17) mmHg (1 mmHg = 0.133 kPa) vs. (128.12 ± 7.8) mmHg, (73.00 ± 6.65) mmHg vs. (69.90 ± 5.99) mmHg, (9.12 ± 1.54) mmol/L vs. (4.92 ± 0.63) mmol/L, (2.17 ± 0.49) mmol/L vs. (1.70 ± 0.48) mmol/L, (5.32 ± 0.62) mmol/L vs. (4.61 ± 0.45) mmol/L, (3.05 ± 0.79) mmol/L vs. (2.31 ± 0.53) mmol/L, (7.89 ± 1.92)% vs. (5.30 ± 0.56)%], high density lipoprotein cholesterol (HDL-C) were significantly decreased in the study group [(0.98 ± 0.25) mmol/L vs. (1.19 ± 0.43) mmol/L] compared to the control group, and the differences were statistically significant ( P<0.05). The disease course, HbA 1c, Glu Ave, Glu SD, MAGE, GLI, Glu CV were markedly increased in the cognitive dysfunction group compared to those in the normal cognition group [(7.39 ± 1.87) years vs. (6.50 ± 1.52) years, (8.52 ± 2.21)% vs. (7.32 ± 1.21)%, (11.6 ± 3.35) mmol/L vs. (9.84 ± 2.19) mmol/L, (2.98 ± 0.54) mmol/L vs. (2.17 ± 0.47) mmol/L, (1.19 ± 0.46) mmol/L vs. (0.71 ± 0.28) mmol/L, 95.83 ± 19.77 vs. 86.94 ± 15.22, (27.96 ± 10.38)% vs. (23.02 ± 8.16)%]( P<0.05). Logistic regression model showed that disease course, HbA 1c, Glu Ave, Glu SD, MAGE, GLI, Glu CV were independent risk factors for the cognitive impairment in elderly patients with metabolic syndrome.In addition, there were positive correlation between MoCA score and disease course, HbA 1c, Glu Ave, Glu SD, MAGE, GLI, Glu CV ( P<0.05). Receiver operating characteristic curve demonstrated that GluSD>2.56 mmol/L [area under the curve (AUC)=0.897] or (and) MAGE>1.11 mmol/L (AUC = 0.821) may indicated the occurrence of cognitive impairment. Conclusions:Glu Ave, Glu SD, MAGE, GLI and Glu CV are all correlated with cognitive dysfunction in elderly patients with metabolic syndrome, and Glu SD and MAGE may be considered as a potential maker for prediction of cognitive dysfunction.

Objective: To detect the expression of nuclear transcription factor OCT-4 in laryngeal squamous cell carcinoma (LSCC) and its relationship with CD44, and to explore the relationship between OCT-4 and the cancer stem cells and its significance in tumors. Methods: Sixty-nine specimens of laryngeal surgical resection were selected from LSCC patients from January 2008 to December 2012 in Lanzhou General Hospital of Lanzhou Military Region. Another 18 cases of normal laryngeal mucosa tissues were selected as control. OCT-4, CD44 and OCT-4⁺ CD44⁺ cells were observed by using tissue microarray, immunohistochemistry staining and immunohistochemical double staining techniques, and the relationship between their pathological features, such as expression intensity, distribution, cell morphology and clinical parameters were analyzed to explore the clinicopathological significance of CD44⁺ OCT-4⁺ cells. Results: The percentage of CD44-positive cells in LSCC was significantly higher than that in normal laryngeal mucosa tissues [(63.62±8.76)% vs. (13.61±5.81)%, P < 0.001]. The percentage of OCT-4-positive cells in LSCC was (50.44±10.84)%, while it was not expressed in normal laryngeal mucosa tissues (P < 0.001). In LSCC, the expression of OCT-4 was significantly lower than that of CD44 (P < 0.001); the coexpression rate of these two molecules was (5.07±2.90)%. The percentage of CD44-positive cells in poorly differentiated LSCC was significantly higher than that in the well-differentiated group [62.78% (8.22%) vs. 28.62% (30.45%), P < 0.05]. The percentage of OCT-4-positive cells in poorly differentiated LSCC was significantly higher than that in the well-differentiated group [49.89% (13.12%) vs. 33.00% (20.00%), P < 0.05]. In the cancer stem cells, the percentage of OCT-4⁺ CD44⁺ cells in poorly differentiated carcinoma group was also significantly higher than that in the well-differentiated carcinoma group (P < 0.01), the lower the degree of differentiation, the higher the expression level of OCT-4. In LSCC poorly differentiated group, the expressions of OCT-4 and CD44 showed no significant difference between different T stages, but the percentage of OCT-4⁺ CD44⁺ cells elevated with T stage increasing (P < 0.05). The expression of OCT-4 in patients with lymph node metastasis was significantly higher than that in patients without lymph node metastasis (P < 0.01). Conclusions The expressions of OCT-4 and CD44 are associated with the malignant biological behaviors of LSCC closely. OCT-4 may be a valuable marker of tumor stem cells of LSCC.

This study aimed to investigate the protective effects of Baibu Tang on bleomycin-induced pulmonary fibrosis in mice. After intratracheally giving bleomycin(3. 5 mg/kg), mice were orally administered Baibu Tang once a day for 14 consecutive days, takingnintedanib as a positive control. The anti-fibrotic effects were assessed by the hydroxyproline level and the histopathological changes in H&E or Masson stained lung tissues. The results revealed that the lung coefficient, hydroxyproline content, inflammation and collagen deposition were increased significantly in the lung tissue of the model mice. Both ethanol and water extracts of Baibu Tang significantly improved all the pathological indexes in mice, but the effect of the ethanol extract was better than that of the water extract. Baibu Tang with Baibu(root of Stemona tuberosa)containing different components(neotuberostemonine, tuberostemonine and stemoninine, respectively)could significantly reduce hydroxyproline level and collagen deposition in the lung tissue of bleomycin-induced mice, and there was no significant difference in their activity. This result showed that the changes in the chemical composition of Stemona tuberosa(Baibu, monarch drug for Baibu Tang)have little effect on the anti-fibrosis activity of Baibu Tang, and its mechanism and material basis need further investigation.

Objective To compare the values of peripheral blood and tumor tissue Annexin A3 protein expressions for predictinge platinum resistance in ovarian epithelial cancer. Methods A total of 72 cases of newly treated ovarian epithelial cancer and undergoing platinum based chemotherapy after surgery,and completely followed up in this hospital from February 2010 to February 2012 were selected and divided into the platinum-sensitive group(54 cases) and platinum-resistant group(18 cases) according to the platinum resistance evaluation criteria. Peripheral blood Annexin A3 level was detected by chemiluminescence immunoassay. Tumor tissue Annexin A3 level was detected by adopting the immunohistochemical staining. The predictive value of peripheral blood and tumor tissue Annexin A3 for predicting platinum resistance was analyzed by drawing the ROC curve. Results The peripheral blood Annexin A3 level in the platinum-sensitive group was significantly lower than that in the platinum-resistant group,the difference was statistically significant(P<0.05), the positive rate of tumor tissue Annexin A3 expression in the platinum sensitivity group was significantly lower than that of platinum-resistant group(P<0.05). The median survival time in peripheral blood Annexin A3 low concentration group was significantly higher than that of high concentration group(31.2 months vs. 20.4 months, P<0.05). The median survival time in tissue Annexin A3 low expression group was significantly higher than that in the high expression group (35.2 months vs. 23.1 months P<0.05). The multivariate analysis showed that the level of Annexin A3 expression in serum and tumor tissue were the independent risk factor for affecting platinum resistance (all P<0.05). The area of curve (AUC) of peripheral blood Annexin A3 in predicting platinum resistance was 0. 821, which of tissue Annexin A3 in predicting platinum was 0. 763, peripheral blood Annexin A3 for predicting platinum resistance was significantly higher than tissue Annexin A3 (P< 0.05). Conclusion The expression levels of Annexin A3 protein in peripheral blood and tumor tissue are significantly increased in the patients with platinum resistant ovarian cancer,the predictive value of Annexin A3 protein in peripheral blood for platinum resistance is better than that of tissue Annexin A3 protein.