ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

Objective To explore the independent risk factors for long-term adverse prognosis after percutaneous renal artery angioplasty in patients with transplant renal artery stenosis(TRAS).Methods We retrospectively collected medical records and surgery details of TRAS patients who underwent renal artery angioplasty at the Department of Peripheral Vascular Diseases,The First Affiliated Hospital of Xi'an Jiaotong University,from January 2017 to June 2021.All patients were followed up for 3 years post-operation.Multivariate Cox regression analyses were performed to find the independent predictive factors for long-term adverse prognosis after renal artery angioplasty in the TRAS patients.Results A total of 45 TRAS patients who underwent percutaneous renal artery angioplasty were included in this study.During the five-year follow-up period,10 patients(22.2％)experienced long-term adverse events.These consisted of 3 patients(6.7％)who died from any cause,1 patient(2.2％)who developed transplant renal artery dissection,6 patients(13.3％)who had restenosis of the transplant renal artery,and 1 patient(2.2％)who lost the transplant kidney and received dialysis again.Multivariate Cox regression analysis showed that male gender(HR=4.915,95％CI:1.036-23.328,P=0.045)and balloon angioplasty alone(HR=8.594,95％CI:2.191-33.710,P=0.002)were independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.Conclusion Male gender and balloon angioplasty alone are independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.

Objective:To carry out evidence-based practice in the management of exercise rehabilitation for kinesiophobia patients after degenerative lumbar spine disease surgery, construct review indicators, analyze barriers and facilitators to evidence-based practice, and develop strategies for action change.Methods:Using the integrated-promoting action on research implementation in health services model (i-PARIHS model) as a theoretical framework, clinical nursing problems were identified, the evidence-based practice group was built, evidence was systematically retrieved, evaluated, and summarized, and review indicators were developed and review methodology was clarified. An evidence-based baseline review of 36 healthcare professionals in the Department of Orthopedics of the First Affiliated Hospital of Bengbu Medical University was conducted from October 2023 to January 2024 using the Evidence-based Readiness Scale. Barriers and facilitators to the evidence-based practice were analyzed based on the results of the baseline review, strategies for action were developed accordingly.Results:A total of 23 pieces of best evidence were included and 32 review indicators were developed. In the baseline review, 25 of the review indicators had an accurate implementation rate of < 60% and 14 had an implementation rate of 0. The main barriers of evidence-based practice were lack of effective feedback systems, lack of kinesiophobia mentoring programs, and lack of management processes and educational materials. The main facilitators were active support from organizational leadership and high motivation of patients and their families to participate. A total of 15 action strategies were eventually developed.Conclusions:This study constructed review indicators for the management of exercise rehabilitation in kinesiophobia patients after degenerative lumbar spine disease surgery based on the best evidence. There are several barriers in clinical practice. The action change strategy developed is scientifically sound and feasible.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To investigate the correlation between frailty and immune markers in elderly patients diagnosed with heart failure with preserved ejection fraction(HFpEF).Methods:A total of 416 elderly patients with HFpEF, who were hospitalized in the Department of Geriatrics at Henan Provincial People's Hospital from March 2021 to December 2023, were selected as research subjects.The Fried frailty phenotype was employed to assess frailty.Fasting venous blood samples were collected to measure levels of CD4+ T lymphocytes, CD8+ T lymphocytes, the CD4+ /CD8+ ratio, and immunoglobulins A, M, and G. Spearman correlation analysis and multiple linear regression analysis were conducted to evaluate the relationship between frailty scores and immune markers.Results:Spearman correlation analysis revealed a significant association between frailty score and the CD4+ /CD8+ ratio( r=-0.659, P<0.001), immunoglobulin A( r=-0.454, P<0.001), immunoglobulin M( r=-0.522, P<0.001), and immunoglobulin G( r=-0.802, P<0.001).Furthermore, multiple linear regression analysis indicated that, after adjusting for confounding factors, frailty score served as a significant negative predictor of the CD4+ /CD8+ ratio( β=-0.562, P<0.001), immunoglobulin A( β=-0.366, P<0.001), immunoglobulin M( β=-0.445, P<0.001), and immunoglobulin G( β=-0.772, P<0.001).In comparison to the non-frail group, the frail group exhibited significantly lower values for the CD4+ /CD8+ ratio( β=-0.666, P<0.001)and levels of immunoglobulin A( β=-0.514, P<0.001), immunoglobulin M( β=-0.526, P<0.001), and immunoglobulin G( β=-0.814, P<0.001). Conclusions:In hospitalized elderly patients with heart failure with HFpEF, frailty serves as an independent risk factor for the reduction of the CD4+ /CD8+ ratio, as well as levels of immunoglobulin A, immunoglobulin M, and immunoglobulin G. Furthermore, the frailty score demonstrates a significant negative predictive value for these immunological markers.Therefore, it is essential to enhance our understanding of frailty and to prioritize its prevention and treatment, as this may help mitigate immune dysfunction and promote recovery in elderly patients.

Objective To explore the independent risk factors for long-term adverse prognosis after percutaneous renal artery angioplasty in patients with transplant renal artery stenosis(TRAS).Methods We retrospectively collected medical records and surgery details of TRAS patients who underwent renal artery angioplasty at the Department of Peripheral Vascular Diseases,The First Affiliated Hospital of Xi'an Jiaotong University,from January 2017 to June 2021.All patients were followed up for 3 years post-operation.Multivariate Cox regression analyses were performed to find the independent predictive factors for long-term adverse prognosis after renal artery angioplasty in the TRAS patients.Results A total of 45 TRAS patients who underwent percutaneous renal artery angioplasty were included in this study.During the five-year follow-up period,10 patients(22.2％)experienced long-term adverse events.These consisted of 3 patients(6.7％)who died from any cause,1 patient(2.2％)who developed transplant renal artery dissection,6 patients(13.3％)who had restenosis of the transplant renal artery,and 1 patient(2.2％)who lost the transplant kidney and received dialysis again.Multivariate Cox regression analysis showed that male gender(HR=4.915,95％CI:1.036-23.328,P=0.045)and balloon angioplasty alone(HR=8.594,95％CI:2.191-33.710,P=0.002)were independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.Conclusion Male gender and balloon angioplasty alone are independent risk factors for long-term adverse prognosis after renal artery angioplasty in TRAS patients.

Objective The pathophysiological process of acute high-altitude hypoxia-induced lung injury affects protein expression levels,which are mainly evaluated by Western blot.No systematic study has investigated changes in internal control proteins as calibration loading amounts.Methods Lung injury at an altitude of 6000 m was induced in a low-pressure,low-oxygen chamber for 8,24,and 72 h using C57BL/6J mice.Establishment of the model was confirmed by hematoxylin and eosin staining.Expression levels of various internal control proteins,including vinculin,α-tubulin,eukaryotic translation initiation factor 5(EIF5),β-actin,and glyceraldehyde 3-phosphate dehydrogenase(GAPDH)were detected by Western blot,and total protein expression was detected by Coomassie blue staining.Furthermore,the lung injury model in vitro was establised by using,Bronchial epithelial cell(BZAS-2B)andhunman umbilical vein endothelial cells(HUVECS)confirmed by TUNEL staining.Expression levels of internal control proteins were detected by Western blot,and total protein expression was detected by Coomassie Blue staining.Results Acute 8,24,and 72 h hypoxic models were successfully established in lung tissue,demonstrating consistent total protein expression and stable levels of the internal reference proteins vinculin,α-tubulin,EIF5,andβ-actin.GAPDH expression was elevated in the HH8 h,HH24 h,and HH72 h groups compared with the normoxia(Nor)group,but only the increase at HH72 h groups was significant.Similarly,8,24,and 48 h hypoxic models were successfully established in BEAS-2B cells and HUVECs,with consistent total protein expression.In BEAS-2B cells,expression levels of the internal reference proteins β-actin and GAPDH were consistent with the normoxic control(NC)group,while vinculin,α-tubulin,and EIF5 expression levels were significantly reduced under hypoxic conditions for up to 24 h.In HUVECs,vinculin and α-tubulin expression levels were also consistent with the NC group,while EIF5,β-actin,and GAPDH expression levels were significantly reduced at 8 h and increased at 48 h.Conclusions Acute hypoxia induces lung tissue injury,and protein expression levels of the internal reference proteins vinculin,α-tubulin,EIF5,and β-actin are stable,making them suitable internal references for Western blot.Additionally,Western blot detected differential expression levels of the internal reference proteins vinculin,α-tubulin,EIF5,β-actin,and GAPDH in BEAS-2B cells and HUVECs,as the most important in vitro lung tissue models of hypoxia-induced injury.

Objective To predict the current and future ecological suitability distribution areas of Scutellariae Radix in Shandong Province at present and in the future;To screen the main environmental factors affecting its suitable distribution;To provide a reference for the protection of wild resources and the site selection artificial planting of Scutellariae Radix.Methods Taking Scutellariae Radix as the research object,based on the MaxEnt model,the potential suitable habitats were predicted using 84 distribution points of and 48 environmental factors of Scutellariae Radix,and the main environmental factors affecting the distribution of Scutellariae Radix were explored.Its potential suitable habitat areas were predicted under four greenhouse gas emission concentration scenarios(SSP126,SSP245,SSP370,and SSP585)for the years 2021-2040,2041-2060,2061-2080 and 2081-2100.Results The MaxEnt model was optimized through feature combination and regularization constant parameters,and its predictive ability was good(AUC value of 0.871).The primary driving environmental factors affecting its distribution were the maximum temperature in the warmest month(bio_05),soil gravel content(cf05)and altitude(elev).Under the current climate conditions,Scutellariae Radix is mainly distributed in the hilly areas of central and southern Shandong and some areas of in the hilly areas of Jiaodong.Under the future climate conditions of SSP126,SSP245,SSP370 and SSP585,the areas of suitable habitat of Scutellariae Radix in Shandong will show a decreasing trend.Except for the SSP126,the medium and high adaptation areas of Scutellariae Radix will disappear in the other three modes.Conclusion The results of this study can provide an important reference for the protection,rational utilization and planting layout of Scutellariae Radix in Shandong Province.

Objective To predict the current and future ecological suitability distribution areas of Scutellariae Radix in Shandong Province at present and in the future;To screen the main environmental factors affecting its suitable distribution;To provide a reference for the protection of wild resources and the site selection artificial planting of Scutellariae Radix.Methods Taking Scutellariae Radix as the research object,based on the MaxEnt model,the potential suitable habitats were predicted using 84 distribution points of and 48 environmental factors of Scutellariae Radix,and the main environmental factors affecting the distribution of Scutellariae Radix were explored.Its potential suitable habitat areas were predicted under four greenhouse gas emission concentration scenarios(SSP126,SSP245,SSP370,and SSP585)for the years 2021-2040,2041-2060,2061-2080 and 2081-2100.Results The MaxEnt model was optimized through feature combination and regularization constant parameters,and its predictive ability was good(AUC value of 0.871).The primary driving environmental factors affecting its distribution were the maximum temperature in the warmest month(bio_05),soil gravel content(cf05)and altitude(elev).Under the current climate conditions,Scutellariae Radix is mainly distributed in the hilly areas of central and southern Shandong and some areas of in the hilly areas of Jiaodong.Under the future climate conditions of SSP126,SSP245,SSP370 and SSP585,the areas of suitable habitat of Scutellariae Radix in Shandong will show a decreasing trend.Except for the SSP126,the medium and high adaptation areas of Scutellariae Radix will disappear in the other three modes.Conclusion The results of this study can provide an important reference for the protection,rational utilization and planting layout of Scutellariae Radix in Shandong Province.