ObjectiveTo investigate the anti‑pancreatic fibrosis mechanism of Klotho‑derived peptide 7 （KL7） by observing its effect on a mouse model of chronic pancreatitis （CP） induced by cerulean， and to provide a basis for clinical medication. MethodsA total of 40 male BALB/c mice were randomly divided into control group， model group， low-dose KL7 group （2 mg/kg）， and high-dose KL7 group （4 mg/kg）， with 10 mice in each group. All mice except those in the control group were given intraperitoneal injection of cerulean （50 μg/kg） 6 times a day at an interval of 1 hour， twice a week for 4 consecutive weeks to establish a model of CP. The mice in the low-dose KL7 group and the high-dose KL7 group were treated with different doses of KL7 once a day for 4 consecutive weeks. In vivo imaging was used to observe the accumulation of KL7 in the pancreas； molecular docking was used to detect the binding of KL7 to transforming growth factor-β type Ⅱ receptor （TβRⅡ）； the mice were measured in terms of body weight and pancreatic weight； HE staining was used to observe the pathological changes of pancreatic tissue； Masson staining was used to observe the degree of pancreatic fibrosis； immunohistochemical staining was used to measure the expression of α-smooth muscle actin （α-SMA） and type Ⅰ collagen （COL1A1）； Western blotting was used to measure the protein expression levels of α-SMA， TβRII， and phosphorylated small mothers against decapentaplegic homolog 2/3 （p-Smad2/3） in pancreatic tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test and the Dunnett’s-T3 test were used for further comparison between two groups. ResultsKL7 was significantly enriched in the pancreatic tissue of CP mice， and there was a strong binding activity between KL7 and TβRⅡ. Compared with the control group， the model group had significant reductions in pancreatic mass and relative pancreatic mass （P<0.000 1）， with disordered structure of pancreatic tissue， an increase in inflammatory cell infiltration， and significant increases in fibrosis degree， the positive areas of α-SMA and COL1A1 （P<0.000 1）， and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.05）. Compared with the model group， the high-dose KL7 group had significant increases in pancreatic mass and relative pancreatic mass （P<0.01）， with alleviation of structural damage of pancreatic tissue and inflammatory cell infiltration， a significant reduction in fibrosis degree， and significant reductions in the positive areas of α-SMA and COL1A1 （P<0.001） and the protein expression levels of α-SMA， TβRⅡ， and p-Smad2/3 （P<0.01）. ConclusionKL7 has a significant targeted therapeutic effect on pancreatic fibrosis in CP mice through specific binding of KL7 to TβRⅡ， thereby inhibiting the activation of the TGF-β/Smad signaling pathway.

ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp^-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp^-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp^-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp^-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp^-/- mice through the MAPK signaling pathway.

Objective To explore the relationships between social support,positive coping,caregiver burden and family resilience of primary caregivers of first-stroke patients.Methods A questionnaire survey was conducted among 307 primary caregivers of first-stroke patients in 2 tertiary hospitals in Shanghai by convenience sampling method.Social support rating scale,simplified coping style questionnaire,Zarit caregiver burden interview,and family resilience assessment scale were used for questionnaire survey.Pearson correlation analysis and structural equation models were used for data analysis.Results A total of 288 valid questionnaires were collected,and the effective recovery rate was 93.81％.Pearson correlation analysis showed that there was a positive correlation between family resilience and social support,family resilience and positive coping,and social support and positive coping(r=0.375,0.627,and 0.277;all P＜0.01),while caregiver burden and social support,caregiver burden and positive coping,and family resilience and caregiver burden were all negatively correlated(r=-0.203,-0.343,and-0.444;all P＜0.01).The mediating effect model was constructed with positive coping and caregiver burden as mediating variables,social support as independent variables,and family resilience as dependent variables.The results showed that social support could mediate family resilience through positive coping,with a mediating effect of 0.164,accounting for 26.1％of the total effect;social support could also affect the family resilience of the primary caregivers of first-stroke patients through the partial chain mediating effect of positive coping and caregiver burden,with a mediating effect value of 0.032,accounting for 5.1％of the total effect.Conclusion Social support can predict family resilience among primary caregivers of first-stroke patients,and positive coping and caregiver burden play chain mediating roles in the impact of social support on family resilience.

Bronchial asthma(hereinafter referred to as asthma)is a common chronic respiratory disease characterized by airway inflammation,airway hyperresponsiveness,and airway remodeling.Its pathogenesis is highly complex and heterogeneous,involving multiple factors such as genetics,immunity,and environmental exposure.Currently,therapeutic options for asthma remain relatively limited,making it an urgent priority to explore its underlying mechanisms,identify effective treatment strategies,and develop new drugs.In this context,the establishment of animal models for asthma plays an irreplaceable and crucial role.However,to date,no single ideal animal model has been able to fully and accurately replicate all the features of the onset and progression of human asthma.This study systematically reviews the research progress over the past five years in the establishment methods of asthma animal models.It provides a detailed overview of commonly used experimental animals(such as mice,rats,and guinea pigs),frequently used sensitizing agents(including ovalbumin,house dust mite,lipopolysaccharide,and toluene diisocyanate),and the methods for establishing asthma models using these animals and sensitizers.This study also presents an objective evaluation of the advantages,limitations,and applicability of each model.Evaluation criteria for asthma models are summarized across multiple dimensions,including behavioral assessments,pulmonary function,histopathology,immunological indicators,and pharmacodynamics.Although methods for establishing refractory asthma models remain underdeveloped,several strategies for modeling refractory asthma have been summarized through a review of relevant literature,aiming to provide useful references for related research.Based on current scientific and technological advancements,it is anticipated that future research on asthma animal models will focus more on clinical relevance,technological innovation,and multidisciplinary integration.Specifically,future models are expected to adopt multi-sensitizer induction protocols,apply cutting-edge tools such as gene editing,enhance clinical relevance and promote diversification and personalization of models.Furthermore,advanced technologies such as bioimaging and biosensing are anticipated to enable dynamic monitoring of airway inflammation and remodeling.Organ-on-a-chip platforms may also be explored as potential alternatives to traditional animal models.The ultimate goal is to develop multifactorial,composite models that better simulate the complexity and heterogeneity of human asthma.

Bronchial asthma(hereinafter referred to as asthma)is a common chronic respiratory disease characterized by airway inflammation,airway hyperresponsiveness,and airway remodeling.Its pathogenesis is highly complex and heterogeneous,involving multiple factors such as genetics,immunity,and environmental exposure.Currently,therapeutic options for asthma remain relatively limited,making it an urgent priority to explore its underlying mechanisms,identify effective treatment strategies,and develop new drugs.In this context,the establishment of animal models for asthma plays an irreplaceable and crucial role.However,to date,no single ideal animal model has been able to fully and accurately replicate all the features of the onset and progression of human asthma.This study systematically reviews the research progress over the past five years in the establishment methods of asthma animal models.It provides a detailed overview of commonly used experimental animals(such as mice,rats,and guinea pigs),frequently used sensitizing agents(including ovalbumin,house dust mite,lipopolysaccharide,and toluene diisocyanate),and the methods for establishing asthma models using these animals and sensitizers.This study also presents an objective evaluation of the advantages,limitations,and applicability of each model.Evaluation criteria for asthma models are summarized across multiple dimensions,including behavioral assessments,pulmonary function,histopathology,immunological indicators,and pharmacodynamics.Although methods for establishing refractory asthma models remain underdeveloped,several strategies for modeling refractory asthma have been summarized through a review of relevant literature,aiming to provide useful references for related research.Based on current scientific and technological advancements,it is anticipated that future research on asthma animal models will focus more on clinical relevance,technological innovation,and multidisciplinary integration.Specifically,future models are expected to adopt multi-sensitizer induction protocols,apply cutting-edge tools such as gene editing,enhance clinical relevance and promote diversification and personalization of models.Furthermore,advanced technologies such as bioimaging and biosensing are anticipated to enable dynamic monitoring of airway inflammation and remodeling.Organ-on-a-chip platforms may also be explored as potential alternatives to traditional animal models.The ultimate goal is to develop multifactorial,composite models that better simulate the complexity and heterogeneity of human asthma.

Objective To investigate the effect of ClearInfinity deep learning reconstruction algorithm on image quality and radiation dose of abdominal computed tomography angiography(CTA)at low kV and low contrast medium.Methods One hundred patients who underwent abdominal CTA were selected and randomly divided into group A and group B.Group A:tube voltage 70 kV,con-trast medium 30-35 mL,divided into A1 and A2 subgroups according to reconstruction algorithm,group A1 50%ClearInfinity,group A2 50%ClearView iterative algorithm;group B:tube voltage 100 kV,contrast medium 60-70 mL,50%ClearView.CT values and standard deviation(SD)values of region of interest(ROI)of abdominal aorta,proper hepatic artery,superior mesenteric artery,renal artery and common iliac artery were evaluated objectively,while signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated;subjective scores were evaluated by two physicians;radiation doses of groups A and B were analyzed.Results Volume CT dose index(CTDIvol),dose length product(DLP)and effective dose(ED)in group A were significantly lower than those in group B(P<0.05),subjective scores in group A1 and group B were higher than those in group A2(P<0.05),and there was no difference between group A1 and group B(P>0.05).Compared with group A1,SNR and CNR of all vessels in group A2 were significantly decreased.CT values of abdominal aorta and common iliac artery,CNR of common iliac artery and supe-rior mesenteric artery in group B were significantly increased,SNR of renal artery was significantly decreased(P<0.05).Conclusion ClearInfinity deep learning reconstruction algorithm combined with 70 kV scanning technology can obtain better abdom-inal CTA image quality,and effectively reduce the radiation dose and contrast medium of patients,which has high clinical application value.

Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3％(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10％,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

Objective To investigate whether ginsenoside Rh1(G-Rh1)can alleviate liver fibrosis induced by a choline-deficient,L-amino acid-defined,high-fat diet(CDAHFD)and to explore its underlying mechanisms.Methods Male C57BL/6J mice were randomly divided into 6 groups(n=8 in each group),including a standard diet group(or the control group),a high-fat diet group(or the CDAHFD group),a silymarin group(given silymarin at 5 mg/kg),a low-dose G-Rh1 group(given G-Rh1at 5 mg/kg),a medium-dose G-Rh1 group(given G-Rh1at 10 mg/kg),and a high-dose G-Rh1 group(given G-Rh1 at 20 mg/kg).The control group was given a standard feed,while the other groups were fed CDAHFD for 7 weeks to establish the mouse model of liver fibrosis.Starting from the first week,the mice in the treatment groups were administered the corresponding drugs by intragastric gavage once daily for 7 weeks in succession.After the administration of the final drug treatment,the body mass and organ mass of the mice in different groups were measured,and the organ index was obtained according.Liver tissues were examined using HE staining,Sirius red staining,and immunohistochemistry(IHC)staining.Western blot was performed to measure α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1),two liver fibrosis-related proteins,and fibroblast growth factor 12(FGF-12),a pathway-related protein.The serum biochemical indicators,including aspartate transferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),and direct bilirubin(DBIL),were measured.Additionally,RAW246.7 cells were randomly divided into 5 groups,including a control group,a lipopolysaccharide(LPS)group,and 3 G-Rh1 treatment groups.The control group had only RAW246.7 cells in the culture medium.The other groups were given LPS(500 ng/mL),and the 3 treatment groups received G-Rh1 at 10,20,and 40 μmol/L in addition.The supernatants from the 5 groups of RAW246.7 cells were collected and cocultured with HSC-T6 cells for 24 hours to observe and compare the effects of G-Rh1 and LPS on the expression of fibrosis-related proteins,including α-SMA,Col1a1,etc,in HSC-T6 cells and on the expression of fibrotic signaling pathway-related proteins,including fibroblast growth factor 12(FGF-12)and signal transducer and activator of transcription 3(STAT3)/phosphorylated STAT3(p-STAT3),in RAW264.7 cells.Flow cytometry was conducted to analyze the phenotypes of RAW246.7 cells,and ELISA was performed to measure fibrosis-related factors,including monocyte chemoattractant protein-1(MCP-1)and transforming growth factor-β(TGF-β).Results Compared with the control mice,the mice in the CDAHFD group exhibited obvious liver fibrosis.Compared with CDAHFD mice,mice in the G-Rh1 treatment groups all showed alleviation of liver fibrosis of was alleviated to some extent in a dose-dependent manner,and the improvement effect was superior to that of silymarin,a reference drug.G-Rh1 also alleviated CDAHFD-induced body mass loss(P＜0.01),reduced the liver index(P＜0.01),and significantly decreased the serum levels of AST,ALT,DBIL,and TBIL(P＜0.0001).Significant differences in the protein expression ofα-SMA,TGF-β1,and FGF-12 in the liver were observed(P＜0.01).Compared with the LPS group,the LPS+G-Rh,groups exhibited significant differences in the expression of FGF-12 and p-STAT3/STAT3 in RAW246.7 cells,and α-SMA and Col1a1 in HSC-T6 cells(P＜0.001).In the LPS+G-Rh,groups(the 20 μmol/L and 40 μmol/L treatment groups),the conversion ratio of Ly6C-low expressing RAW246.7 cells into Ly6C-high expressing RAW246.7 cells decreased significantly(P＜0.0001),while the secretion of fibrosis-related factors MCP-1 and TGF-β decreased(P＜0.0001),which was consistent with the trend of the activation levels of HSC-T6 cells.Conclusions G-Rh1 can prevent and improve CDAHFD-induced liver fibrosis in mice,potentially through mechanisms involving the reduction of RAW264.7 phenotype transformation mediated by FGF-12 overexpression.

Objective To observe the effect of acupuncture synchronized with speech training on speech function of patients with post-stroke motor aphasia.Methods Sixty inpatients with post-stroke motor aphasia were selected from the Affiliated Hospital of Shandong Univer-sity of Traditional Chinese Medicine,from January to August,2023.They were randomly divided into control group(n=30)and synchronous group(n=30).Both groups received acupuncture and speech training;the con-trol group received acupuncture in the morning and speech training in the afternoon,while the synchronous group received acupuncture and speech training synchronously,for three weeks.They were assessed with Chi-nese Rehabilitation Research Center Standard Aphasia Examination(CRRCAE),Non-Language-Based Cognitive Assessment(NLCA)and Communication Activities of Daily Living(CADL)before and after treatment.Results The subscores of CRRCAE and NLCA,and score of CADL increased in both groups(|t|>2.081,P<0.05)after treatment,and they were better in the synchronous group than in the control group(|t|>2.680,P<0.05).Conclusion Synchronous mode of acupuncture and speech training is more effective on post-stroke motor aphasia than time-sequence mode.