ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective:To discuss the role of angiopoietin-like protein 6(ANGPTL6)in liver fibrosis,and to analyze the improving effect of engineered exosome(Exo)-delivered ANGPTL6 mRNA on liver fibrosis.Methods:A total of 12 C57BL/6 mice were randomly divided into olive oil group(OIL group)(intraperitoneally injected with olive oil)and carbon tetrachloride(CCl4)group(intraperitoneally injected with a mixture of olive oil and CCl?),with 6 mice in each group;another 12 C57BL/6 mice were randomly divided into control group(fed a with methionine-choline sufficient diet)and methionine-choline deficient(MCD)group(fed a with MCD diet),and two kinds of mouse liver fibrosis models were established.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in various groups.A total of 30 mice were randomly divided into olive oil+phosphate buffered saline(PBS)group(OIL+PBS group)(intraperitoneally injected with olive oil twice a week for 8 weeks,then injected with PBS buffer by tail vein twice a week for 6 weeks),CCl4+Exo-green fluorescent protein(GFP)mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with GFP mRNA for 6 weeks),and CCl?+Exo-ANGPTL6 mRNA group(established liver fibrosis model by intraperitoneal injection of CCl4 mixture and were injected by tail vein with engineered Exo loaded with ANGPTL6 mRNA for 6 weeks),with 10 mice in each group.The mice in CCl4+Exo-GFP mRNA group and CCl4+Exo-ANGPTL6 mRNA group were injected with engineered Exo twice a week,20 μg per mouse each time(volume 100 μL).ELISA method was used to detect the serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities in the mice in various groups;Masson staining and Sirius red staining were used to observe the collagen deposition in liver tissue of the mice in various groups;immunohistochemistry method was used to detect the α-smooth muscle actin(α-SMA)expression levels in liver tissue of the mice in various groups;RT-qPCR method was used to detect the expression levels of α-SMA,collagen type Ⅰ alpha 1 chain(Col1a1),transforming growth factor β1(TGF-β1),and tissue inhibitor of metalloproteinase 1(TIMP-1)mRNA in liver tissue of the mice in various groups.Results:The bioinformatics analysis results showed that ANGPTL6 expression was significantly down-regulated in activated hepatic stellate cell(aHSC).The ultrasound examination results showed that the liver surface of the mice in OIL group was fine and smooth;compared with OIL group,the liver section of the mice in CCl? group was rough and uneven.The RT-qPCR and Western blotting results showed that compared with OIL group,the ANGPTL6 mRNA and protein expression levels in liver tissue of the mice in CCl? group were significantly decreased(P<0.05).The engineered Exo extracted from the supernatant of HEK293T cells had intact structure and could be largely enriched in the fibrotic liver after tail vein injection,with GFP protein being largely expressed in the liver.The ELISA assay results showed that compared with OIL+PBS group,the ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-ANGPTL6 mRNA group,the serum ALT and AST activities in CCl4+Exo-GFP mRNA group were significantly decreased(P<0.05).The Masson staining and Sirius red staining results showed that compared with OIL+PBS group,the collagen deposition in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased,and the relative collagen area was increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the collagen deposition in tissue liver of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased,and the relative collagen area was decreased(P<0.05).The immunohistochemistry results showed that compared with OIL+PBS group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-GFP mRNA group was significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the α-SMA protein expression level in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group was significantly decreased(P<0.05).The RT-qPCR results showed that compared with OIL+PBS group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-GFP mRNA group were significantly increased(P<0.05);compared with CCl4+Exo-GFP mRNA group,the expression levels of Col1a1,α-SMA,TGF-β1,and TIMP-1 mRNA in liver tissue of the mice in CCl?+Exo-ANGPTL6 mRNA group were significantly decreased(P<0.05).Conclusion:Engineered Exo-delivered ANGPTL6 mRNA injected via the tail vein in the mice is mainly enriched in the liver,and engineered Exo delivery of ANGPTL6 mRNA has an improving effect on liver fibrosis in the mice.

Objective:To evaluate the clinical utility of an intelligent endoscope transportation system in the digestive endoscopy center.Methods:A parallel-group controlled trial was conducted at Digestive Endoscopy Center of Qilu Hospital of Shandong University from June 1st to December 31st 2024, comparing robotic intelligent endoscope transport (experimental group) versus manual transport (control group). Performance metrics, including response time, transportation speed, labor efficiency, contamination prevention, closed-loop traceability, and nursing staff satisfaction, were statistically analyzed. Full-time equivalent (FTE) was introduced to quantify the operational efficiency of the experimental group.Results:The study included a total of 60 206 instances of intelligent endoscope transportation and 60 485 instances of manual transportation data. The robotic group demonstrated significantly shorter response times versus manual group for initial dispatch (51.08±14.97 seconds VS 54.44±13.61 seconds, t=35.8, P<0.001) and recovery response time (32.52±11.26 seconds VS 40.20±11.40 seconds, t=103.93, P<0.001). During the 148 days operational period, the success rate was 99.83% (60 104/60 206) and the failure rate was 0.17% (102/60 206) for robotic transports. Primary failure causes were wireless disconnection, pathfinding errors, and mechanical faults, averaging 1.05 malfunctions/month with no adverse events. The success and failure rate was 99.26% (60 043/60 485) and 0.74% (442/60 485) respectively for manual transports. Staff satisfaction was significantly higher for robotic transport in endoscopic transportation (4.65±0.55 scores VS 3.97±0.98 scores, t=96.5, P<0.001) and delivery process (4.71±0.59 scores VS 3.90±1.04 scores, t=210.3, P<0.001). and workload intensity was significantly lower (4.06±0.77 scores VS 4.48±0.63 scores, t=59.9, P=0.025). The system reduced labor requirements by 3.68 FTE, yielding annual savings of ￥657 000. Conclusion:The robotic intelligent endoscope transport system improves work efficiency, reduces nursing labor costs and physical workload, enhances job experience and satisfaction, and enables full-process smart traceability, providing a validated solution for endoscopy center logistics.

Fasting plasma glucose(FPG)has been widely used in the diagnosis of diabetes mellitus(DM)for its advantages of rapidity,economy,simplicity and acceptability.Hemoglobin A1c(HbA1c)has the advantages of being simple,stable,accurate and unaffected by related factors,and has been used in the diagnosis of DM since it was standardized.However,the value of FPG and HbA1c in the early diagnosis of diabetes have been controversial.The purpose of this paper is to explore the value of the two in the early diagnosis of diabetes.

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Objective To investigate the effect of lifestyle on cognitive decline in rural people aged 40 years and older in Xi'an.Methods This was a prospective cohort study.People aged 40 years and older in two villages in Huyi District were selected as the study population.They completed the baseline survey from October 2014 to March 2015 as well as two follow-up visits in 2016 and 2018,respectively.A comprehensive score of lifestyle was calculated based on factors including smoking,drinking,exercise,and diet collected at the baseline.The Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function at both baseline and follow-up;a≥4-point decrease in MMSE score from the baseline was defined as marked cognitive decline.Multivariable Logistic regression,propensity score correction,and propensity score matching were used to investigate the relationship between lifestyle and cognitive decline.Results A total of 1 348 participants were ultimately enrolled and 56(4.2％)of them met the criteria for marked cognitive decline(△MMSE≥4-points).Among them,386(28.6％)people had smoking history,184(13.6％)were drinkers,214(15.9％)lacked physical activity,and 400(29.7％)ate a diet high in oil and salt.Generally,304(22.6％)met the definition of the unhealthy lifestyle(comprehensive score＜6),which means more than one of the four subscales was unhealthy or more than two were relatively unhealthy.Multivariable Logistic regression analysis showed that unhealthy lifestyle was positively associated with marked cognitive decline(OR=2.838,95％CI:1.302-5.525,P=0.005).Propensity-score adjusted model yielded very similar results(OR=2.786,95％CI:1.371-5.661,P=0.005).Propensity score matching was performed to further balance the differences in covariates between the two groups.Multivariate Logistic regression analysis conducted in the matched population revealed that the risk of marked cognitive decline was still higher in those with unhealthy lifestyle(OR=3.994,95％CI:1.582-12.176,P=0.006).Conclusion Unhealthy lifestyle is associated with an increased risk of cognitive decline in cognitively normal people aged 40 years and older.

Objective:To explore the gaze characteristics towards emotional portraits in children with attention deficit hyperactivity disorder(ADHD),in order to reveal their potential unique patterns of emotional cognition.Methods:A case-control design was employed,including 81 children diagnosed with the DSM-5 ADHD and 57 normal control(NC)children.Emotional images from the Chinese Children's Emotional Image Library were used as stimuli.The Tobii Pro X3-120 eye-tracking device was utilized to record fixation count(FC)and fixation duration percentage(FDP)under a free-viewing paradigm.Mixed-effects ANOVA was applied to explore the effects of group,gaze region(eyes and mouth),and emotional attributes on gaze characteristics,controlling for gen-der and age.Results:The FC and FDP of ADHD children were lower than those of NC children,particularly in the eye region of non-negative emotional images(P＜0.05).However,no significant differences were observed be-tween the two groups when viewing negative emotional images(sadness and anger)(P＞0.05).NC children ex-hibited a significant emotional bias effect in their gaze behavior towards emotional portraits(P＜0.05),whereas ADHD group showed only slight differences between non-negative emotional images(adjusted P＜0.05),indica-ting a weaker overall emotional attention bias.Conclusion:Children with ADHD display reduced attention to non-negative emotional expressions and a diminished emotional attention bias,suggesting potential deficits in emotional processing during face perception.

Objective To share our experience of laparoscopic papillary ureterovesical replantation,so as to provide reference for the treatment of patients with lower ureteral lesions.Methods A retrospective analysis was conducted on 22 patients treated in our hospital during 2019 and 2024,including 12 cases of lower ureteral stenosis,3 cases of congenital macroureter,2 cases of terminal ureteral tumor,3 cases of bladder diverticulum,and 2 cases of ureterovaginal fistula.The operation time,intraoperative blood loss,drainage tube removal time,urinary catheter removal time,postoperative hospital stay,DJ tube removal time and occurrence of postoperative complications were statistically analyzed.Results All operations were successfully completed.The operation time(156.73±36.73)minutes,the intraoperative blood loss(35.64±11.47)mL,the drainage tube removal time(7.14±1.77)days,the catheter removal time(10.05±2.73)days,the postoperative hospital stay(13.04±3.79)days,and the DJ tube removal time(69.91±9.35)days.During the follow-up of 3 to 24 months,re-examinations such as B ultrasound and urography indicated no obvious ureterovesical anastomotic stenosis;cystography showed one patient had ureteral reflux.After long-term follow-up,no renal function impairment or ureteral reflux was observed.Conclusion The papillary ureterovesical replantation is safe,effective,simple and easy to operate in the treatment of lower ureteral lesions.It also has characteristics of short operation time and good anti-reflux effect,which is worthy of clinical recommendation.

Based on network pharmacology,through molecular docking and experimental validation,the study explored the mechanism of the Hypericum japonicum-Rehmannia glutinosa-Salvia ple-beian compound(HRS)in the treatment of liver injury.Mice were randomly divided into a control group(CON group),a model group(CCL4 group),a high-dose drug group(HRS-H group),and a low-dose group(HRS-L group).A mouse liver injury model was established using CCL4 induction,liver tissue pathological morphology was observed,and the relative expression levels of liver in-flammatory cytokine genes was measured.Active ingredients of traditional Chinese medicine and targets related to Chinese medicine and diseases were obtained from databases such as Herb,TCM-SP,PubChem,Swiss Target Prediction,Gene Cards and DisGeNET.The intersection of targets was used to obtain potential drug targets.The potential targets were analyzed for protein-protein inter-action(PPI)using the string database and a network diagram of"drug-active component-intersec-tion target"was constructed using Cytoscape.DAVID database was used for GO and KEGG path-way analysis,and Auto Dock Tools software was used for molecular docking.Finally,the results of molecular docking by examining the expression of key target genes and downstream genes such as those related to the PI3K-AKT pathway and the autophagy pathway were experimentally valida-ted.Results:Animal experiment results showed that compared to the CON group,the CCL4 group of mice exhibited disrupted liver architecture,hepatocyte steatosis,vacuolization,and extensive in-flammatory cell infiltration.These characteristics were ameliorated by drug treatment groups with the HRS-H group demonstrating superior effects compared to the HRS-L group.RT-qPCR results from mouse livers showed significantly increased relative expression of TNF-α and INOS mRNA compared to the CON group in the CCL4 group(P＜0.01),and significantly increased IL-1β mR-NA relative expression(P＜0.05).Compared to the CCL4 group,the HRS-H group showed signifi-cantly decreased TNF-α,INOS,and IL-1β mRNA relative expressions(P＜0.01).155 potential tar-gets for HRS in alleviating liver damage were identified through network pharmacology,with top-ranked key target points including STAT3,SRC,PIK3R1,PIK3CA,AKT1,HSP90A11,EGFR,and ESR.Key active ingredients included Tetramethoxyluteolin,Hispidulin,Eupafolin,Kaempferol,and Eupaformonin.GO enrichment analysis yielded 940 entries,and KEGG enrichment analysis yielded 177 biological pathways.Molecular docking results showed a strong binding ability between the main components of HRS and key target points.RT-qPCR results showed increasing trends for EGFR,PI3KCA,HSP90A11,and NF-κB mRNA compared to the CON group in the CCL4 group,significantly increased AKT1 mRNA relative expression(P＜0.05),significant decreases in ULK1,ATG5,LC3B,and ATG7 mRNA relative expressions(P＜0.05),and extremely significant decreases in PTEN,ATG13,BECLIN-1,ATG16L1,ATG12,ATG4B,and ATG3 mRNA relative expressions(P＜0.01).Compared to the CCL4 group,the HRS-H group showed significantly de-creased PI3KCA,HSP90A11,and NF-κB mRNA relative expressions(P＜0.05),extremely signif-icantly decreased EGFR,AKT1,and mTOR mRNA relative expressions(P＜0.01),increased ULK1 relative expression trends,significantly increased PTEN,ATG16L1,ATG5,LC3B,and ATG7 mRNA relative expressions(P＜0.05),extremely significantly increased ATG13,BECLIN-1,ATG12,ATG4B,and ATG3 mRNA relative expressions(P＜0.01).Conclusion:The HRS ex-erts hepatoprotective effects through multi-component,multi-pathway approaches,with alleviating inflammation and promoting hepatocyte autophagy through PI3K-AKT pathway likely being im-portant mechanisms for its protective effects.