OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

Objective:To investigate the correlation between the evidence-based practice competence of undergraduate nursing interns and hospital evidence-based culture, and to provide a reference for the design of evidence-based practice activities in the internship program for undergraduate nursing interns in the future.Methods:From December 2021 to February 2022, the nursing interns in Hunan province of China were selected as subjects, and the evidence-based practice competence scale for nursing interns and the hospital evidence-based practice culture scale were used to investigate the evidence-based practice ability of nursing interns and hospital evidence-based practice culture. SPSS 26.0 was used for statistical analysis and inference.Results:The total score of evidence-based practice competence was 84.67±27.17 among the nursing interns, and the total score of hospital evidence-based practice culture was 79.65±15.92. Evidence-based practice competence was positively correlated with the total score of hospital evidence-based practice culture and the scores of each dimension ( r=0.635-0.813, P<0.01). Conclusions:The evidence-based practice competence of undergraduate nursing interns needs to be improved, which is positively correlated with hospital evidence-based practice culture. Schools should cooperate with teaching hospitals to create a good hospital evidence-based practice culture, systematically optimize the clinical practice arrangements of nursing interns, and promote the development of the evidence-based practice competence of nursing interns.

Objective:To investigate the association between different dietary patterns and subtypes of metabolic associated fatty liver disease(MAFLD).Methods:A total of 6 022 check-ups at the health management center of the Second Hospital of Dalian Medical University from January 2022 to March 2023 were selected as study subjects. MAFLD was categorised into three subtypes: overweight/obese type, metabolic disorder type, and diabetic type. Factor analysis was used to extract dietary patterns. Logistic regression was used to assess the impact of dietary patterns on MAFLD occurrence, constructing interaction models between dietary patterns intake and age, gender, and physical exercise levels. Results:Four dietary patterns were extracted based on feature sorting after factor analysis and were named as the high-quality protein pattern, the fruit-vegetable pattern, egg-aquatic pattern, and the processed meat pattern. Regression analysis of the unadjusted model showed that overweight/obese and diabetic types of MAFLD were negatively associated with the high-quality protein mode, while model-adjusted regression analysis showed that the processed meat pattern was positively associated with the risk of MAFLD, and fruit-vegetable pattern was positively associated with overweight/obese MAFLD( P<0.05). The results of subgroup analyses suggested that female( OR=1.55, 95% CI 1.14-2.15) with a high intake of pickle pattern had a higher risk of overweight/obese MAFLD than male( OR=1.18, 95% CI 1.02-1.49). Conclusion:High-quality protein pattern was negatively correlated with MAFLD, whereas fruit-vegetable pattern and processed meat pattern were positively correlated with MAFLD. Female with high consumption of processed meat pattern are more likely to develop overweight/obesity MAFLD compared with male. It is recommended that people with MAFLD reduce their intake of processed products and high-fructose food, and consume adequate amounts of high-quality protein food to maintain a balanced diet.

Objective:To investigate the relationship between obesity and incident chronic kidney disease(CKD) in a population undergoing health check-ups.Methods:This is a retrospective cohort study. A total of 31 251 participants who had at least 2 health physical examinations in the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2017 to December 2022 and met the inclusion criteria were selected. The participants were divided into normal body weight group, overweight group, and obese group according to baseline body mass index. Cox proportional hazard regression model was used to analyze the relationship between obesity and new-onset CKD, and the dose-response relationship between body mass index and CKD was analyzed with restricted cubic splines.Results:Multivariate Cox regression analysis showed that the risk of developing CKD increased by 13%( HR=1.13, 95% CI 1.01-1.25) and 55%( HR=1.55, 95% CI 1.36-1.76) in the overweight and obese group compared to the normal weight group. Subgroup analysis indicated that obese women had a higher risk of developing CKD compared to men. There was a " U-shaped" correlation between body mass index and CKD in male population, with the lowest risk of CKD occurring at body mass index of 19.6-24.2 kg/m 2. In women, the relationship between body mass index and CKD was approximately linear, with the risk of CKD gradually increasing when body mass index exceeded 22.5 kg/m 2. Conclusions:Obesity is an independent risk factor for new-onset CKD, and obese women have a higher risk of developing CKD than men. Regarding CKD prevention, men are advised to maintain a higher level of body weight within the normal range of body mass index, while women are encouraged to control their weight to a lower level within the normal body mass index range.

Objective:To explore the correlation between systemic immunity-inflammation index(SII) and hyperuricemia(HUA).Methods:Participants who had at least 3 health checkups in the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2022 were selected to construct a dynamic cohort. The SII, reflecting the inflammatory state of the body, was constructed using neutrophil, platelet, and lymphocyte counts. A Cox proportional hazard regression model was used to explore the association between SII and HUA in the overall population and different subgroups of the population, and sensitivity analysis was performed twice. Results:A total of 20 022 subjects were included, and the mean follow-up time was 3.67 years. After adjusting for confounding factors, each unit increase in the natural logarithm of SII(lnSII) was associated with a 24% increased risk of hyperuricemia( HR=1.24, 95% CI 1.16-1.32, P<0.001). As a categorical variable, compared with the lowest quartile array( Q1), the risk of HUA in the total population increased by 12%( HR=1.12, 95% CI 1.03-1.21, P=0.006), 14%( HR=1.14, 95% CI 1.06-1.24, P=0.001), 27%( HR=1.27, 95% CI 1.17-1.37, P<0.001) in Q2, Q3 and Q4 groups within the general population, respectively. All subgroup analysis and sensitivity analysis showed that SII was positively correlated with HUA. Conclusions:Elevated levels of SII significantly increase the risk of HUA. Assessing the body′s inflammatory status using SII can aid in risk screening and preventive management for individuals at high risk of HUA.

AIM To establish the HPLC fingerprints for freeze-dried powder of Yinhuo Decoction,and to determine the contents of rehmannitin D,methylophiopogonanone A,verbascoside,protocatechuic acid,catalpol,schisandrol A,schisandrin B,schisandrin A.METHODS The fingerprint esablishment was performed on a 30℃thermostatic Supersil AQ18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 230 nm.The UPLC-MS/MS content determination was performed on a 30℃thermostatic Alphasil VC-C18 column(2.1 mm×100 mm,2.5 μm),with the mobile phase comprising of acetonitrile-0.1%formic acid flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS There were 17 common peaks in the fingerprints for 10 batches of freeze-dried powder with the similarities of more than 0.90.and piloside,crystal blue glycoside,deacetylated caryoside schisandrin A were identified.Eight constituents showed good linear relationships within their own ranges(R2＞0.990 6),whose average recoveries were 98.7%-101.1%with the RSDs of 2.0%-5.2%.CONCLUSION The combination of fingerprints and content determination can completely characterize the quality of Yinhuo Decoction reference sample,thus provide a reference for the quality evaluation of its key chemical properties.

Objective To explore the development and validation of a prediction model for severe communi-ty-acquired pneumonia in adults based on peripheral blood inflammatory indicators.Methods Venous blood samples of 204 community-acquired pneumonia in adults patients admitted to 7 hospitals in Chongqing area from April 2021 to August 2022 were collected to detect C-reactive protein(CRP),peripheral white blood cell count(WBC),neutrophil to lymphocyte ratio(NLR),cytokines,lymphocyte subgroups and neutrophil CD64 index.All of patients were divided into a training group and a validation group according to the time of admis-sion.Univariate and multivariate Logistic regression were used to analyze the data of the training group,the characteristic factors of severe progression for pneumonia were selected to construct the nomogram model,and the data of the validation group was used to verify the model.The receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the prediction ability of the model for severe community-acquired pneumonia in adults.Results Logistic regression analysis showed that age,CRP,WBC,interleukin(IL)-4/interferon gamma ratio and IL-6/IL-10 ratio were independent risk factors for severe community-acquired pneumonia in adults.The area under the ROC curve of the nomogram model in the training group and the validation group was 0.893 and 0.880,respectively.The calibration curve and DCA results shown that the model had a good prediction effect for severe community-acquired pneumonia in adults.Conclusion The inflammatory indicators included in this model are simple and easy to obtain clinically.This model with good differentiation and accuracy,it can be used as a practical tool to predict severe community-ac-quired pneumonia in adults,and has certain clinical application value.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Liver is the main organ of glucose and lipid metabolism, and persistent hyperglycemia is a common cause of liver injury. Panax notoginsenosides (PNS) is the main active ingredient in Panax notoginseng, which have anti-inflammatory and antioxidant effects. In this study, quantitative proteomics combined with experimental verification was used to explore the protective effect of PNS on liver injury in type 2 diabetes mellitus (T2DM) mice and its potential mechanism. All experiments were approved by the Ethical Committee Experimental Animal Center of North Sichuan Medical College (NSMC2022023). Hematoxylin-eosin (H&E) staining and transmission electron microscopy were used to observe the effect of PNS on the histopathological changes of liver in T2DM mice. TdT-mediated dUTP Nick-end labeling (TUNEL) staining was used to analyze the effect of PNS on hepatocyte apoptosis in T2DM mice. Reactive oxygen species (ROS) and malonaldehyde (MDA) kits were used to detect the effect of PNS on oxidative damage of liver in T2DM mice. Subsequently, proteomics profiling of mice in T2DM and T2DM+PNS groups were investigated based on quantitative proteomics. Differentially expressed proteins were screened out according to fold change and significance level in T2DM and T2DM+PNS groups, respectively. Pathway enrichment analysis of these differential proteins was done using GeneAnalytics database. Gene ontology analysis was conducted by Metascape database. Protein-protein interaction networks were constructed based on STRING database. Western blot was used to detect protein expression. These results showed that PNS could improve liver abnormalities, inhibit hepatocyte apoptosis, and improve the morphology of mitochondria and endoplasmic reticulum in T2DM mice. Proteome data demonstrated that 489 genes expression changed significantly in liver of T2DM mice compared with normal, and 42 ones were significantly reversed after PNS treatment and returned to normal levels. Pathway analysis showed that sterol hormone biosynthesis, adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling pathway, oxidative stress, insulin signaling, phosphatidylinositol pathway, tumor necrosis factor-α (TNF-α) mediated inflammation, insulin resistance, and mTOR signaling pathway exhibited notable changes based on pathway enrichment ratio and significance level. It is worth noting that PNS could improve the abnormal changes of AMPK, TNF-α, apoptosis and insulin pathways. Western blot manifested that PNS inhibit the expression of Bax, Grp78 and Chop, reduce ratio of cleaved casp6/casp6, increase the levels of pAMPKα, HO-1 and Nu-Nrf2 in the liver of T2DM mice. These results suggested that PNS may play protective roles in the liver of T2DM mice by inhibiting apoptosis via activating AMPK/Nrf2/HO-1 signaling pathway, alleviating oxidative stress and endoplasmic reticulum stress.