Kupffer cells(KC),the hepatic resident macrophages,are located in the sinusoids,and play a crucial role in clearing intestinal-derived pathogens and damaged red blood cells,regulating iron and fat metabolism,and maintaining immune toler-ance.In acute and chronic hepatopathy,KC are implicated in liver injury and repair by crosstalk between other hepatocellular popula-tions such as hepatocytes,endothelial cells,hepatic stellate cells and so on,by which maintain liver homeostasis.KC are highly plas-tic,and different liver disease models and different hepatic microenvironmental signals can induce changes in the phenotype and func-tion of hepatic macrophages.In this review,we summarize the subsets of KC and their functions in specific liver disease models based on cell origin,cell polarization,cell surface markers,and gene expression profiles identified by single-cell sequencing techniques.We are aiming to target specific KC subsets to prevent or treat related liver diseases,and promote the progress of precision medicine for liver diseases.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective:To observe the effect of acupuncture synchronized exercise therapy on sensory and motor functions of lower limbs in stroke patients,and to provide scientific basis for the optimization of rehabilitation program for stroke patients.Method:Seventy stroke patients hospitalized in the Rehabilitation Department of the Affiliated Hospital of Shan-dong University of Traditional Chinese Medicine from March 2022 to July 2022 were selected and randomly di-vided into synchronous group and control group,35 patients in each group.The patients in the synchronous group received routine exercise therapy and synchronized acupuncture treatment,while the patients in the con-trol group received acupuncture and subsequent exercise therapy continuously.Before and after treatment,the revised Nottingham sensory assessment scale(reNSA),Fugl-Meyer sensory rating scale,Fugl-Meyer motor function assessment(FMA),Berg rating scale,modified Barthel index rating scale(MBI)and modified Ash-worth spasm rating scale(MAS)were used to evaluate the curative effects.Result:After treatment,the scores of reNSA deep sensation,reNSA compound sensation and Fugl sensation in two groups were significantly increased(P<0.05).The scores of deep and shallow sensation in the synchro-nous group were significantly higher than those in the control group,while there was no significant difference between the two groups in the scores of compound sensation and Fugl sensation(P>0.05).After treatment,the FMA-UE score,Berg score and MBI score in the two groups were significantly increased(P<0.05),and the FMA-UE score,Berg score and MBI score of the synchronous group were also significantly higher than those of the control group(P<0.05).The composition of MAS scores in both groups also improved significant-ly after treatment,but there was no significant difference between the two groups before or after treatment(χ2=2.469,P=0.650;χ2=1.651,P=0.648).Conclusion:Acupuncture synchronized exercise therapy can effectively improve the sensory and motor functions of the lower limbs after stroke,and its effect is better than that of exercise therapy and acupuncture sequen-tial therapy.

Objective:To observe the effect of acupuncture synchronized exercise therapy on sensory and motor functions of lower limbs in stroke patients,and to provide scientific basis for the optimization of rehabilitation program for stroke patients.Method:Seventy stroke patients hospitalized in the Rehabilitation Department of the Affiliated Hospital of Shan-dong University of Traditional Chinese Medicine from March 2022 to July 2022 were selected and randomly di-vided into synchronous group and control group,35 patients in each group.The patients in the synchronous group received routine exercise therapy and synchronized acupuncture treatment,while the patients in the con-trol group received acupuncture and subsequent exercise therapy continuously.Before and after treatment,the revised Nottingham sensory assessment scale(reNSA),Fugl-Meyer sensory rating scale,Fugl-Meyer motor function assessment(FMA),Berg rating scale,modified Barthel index rating scale(MBI)and modified Ash-worth spasm rating scale(MAS)were used to evaluate the curative effects.Result:After treatment,the scores of reNSA deep sensation,reNSA compound sensation and Fugl sensation in two groups were significantly increased(P<0.05).The scores of deep and shallow sensation in the synchro-nous group were significantly higher than those in the control group,while there was no significant difference between the two groups in the scores of compound sensation and Fugl sensation(P>0.05).After treatment,the FMA-UE score,Berg score and MBI score in the two groups were significantly increased(P<0.05),and the FMA-UE score,Berg score and MBI score of the synchronous group were also significantly higher than those of the control group(P<0.05).The composition of MAS scores in both groups also improved significant-ly after treatment,but there was no significant difference between the two groups before or after treatment(χ2=2.469,P=0.650;χ2=1.651,P=0.648).Conclusion:Acupuncture synchronized exercise therapy can effectively improve the sensory and motor functions of the lower limbs after stroke,and its effect is better than that of exercise therapy and acupuncture sequen-tial therapy.

Kupffer cells(KC),the hepatic resident macrophages,are located in the sinusoids,and play a crucial role in clearing intestinal-derived pathogens and damaged red blood cells,regulating iron and fat metabolism,and maintaining immune toler-ance.In acute and chronic hepatopathy,KC are implicated in liver injury and repair by crosstalk between other hepatocellular popula-tions such as hepatocytes,endothelial cells,hepatic stellate cells and so on,by which maintain liver homeostasis.KC are highly plas-tic,and different liver disease models and different hepatic microenvironmental signals can induce changes in the phenotype and func-tion of hepatic macrophages.In this review,we summarize the subsets of KC and their functions in specific liver disease models based on cell origin,cell polarization,cell surface markers,and gene expression profiles identified by single-cell sequencing techniques.We are aiming to target specific KC subsets to prevent or treat related liver diseases,and promote the progress of precision medicine for liver diseases.

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.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.