Hepatic fibrosis is a complex dynamic process caused by multiple chronic pathogenic factors， characterized by excessive accumulation of liver extracellular matrix and abnormal liver structure and function. If anti-fibrotic treatment is not performed in time， it can progress to liver cirrhosis and even liver cancer. Hepatic fibrosis has a complex pathogenesis， and previous studies mainly focused on the activation of hepatic stellate cells. Recent studies have shown that myeloid cells have the potential of multi-directional differentiation and can also participate in the development and progression of hepatic fibrosis. This article systematically reviews the role and regulatory mechanism of myeloid cells in hepatic fibrosis， in order to provide a reference for clinical diagnosis and targeted therapy.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

OBJECTIVE To explore the effects of limonin on renal lesions， glucose metabolism， inflammation， and oxidative stress in gestational diabetic rats and its possible mechanisms. METHODS The model of gestational diabetic rats was established by intraperitoneal injection of streptozotocin. The diabetic rats were divided into the model group （intragastrical administration and tail vein injection of equal volume of normal saline）， limonin low-， medium-， and high-dose groups （intragastrical administration of limonin， at doses of 12.5， 25.0 and 50.0 mg/kg， and equal volume of normal saline into the tail vein）， and combination group [intragastrical administration of limonin 50.0 mg/kg + tail vein injection of c-Jun N-terminal kinase （JNK） activator Anisomycin 2 mg/kg ]， with 12 rats in each group. In addition， 12 pregnant rats were selected as the control group （intragastrical administration and tail vein injection of equal volume of normal saline）. They were given relevant medicine， once a day， for 14 consecutive days. After the last administration， fasting blood glucose （FBG）， the levels of fasting insulin （FINS）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum were detected； the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， blood urea nitrogen （BUN）， and creatinine （Cr） in the renal tissue were detected； the pathological changes of renal tissue were observed； the expressions of proteins related to the JNK/nuclear factor-κB （NF-κB） signaling pathway in the renal tissue were detected. RESULTS Compared with control group， in model group， the rats showed pathological injuries in the kidney tissue， such as glomerular atrophy， edema of renal tubular epithelial cells； the levels of FBG， FINS， IL-1β， IL-6， TNF-α， MDA， BUN and Cr， HOMA-IR， as well as the phosphorylation levels of JNK and NF-κB 0453-6602005。E-mail：mcvi45@163.com p65 proteins were increased significantly （P＜0.05）， while the levels of SOD and GSH-Px were decreased significantly （P＜0.05）. Compared with model group， in each dose group of limonin， the degree of renal tissue lesions in rats was alleviated， and the above-mentioned indicators were significantly improved （P＜0.05）， showing an obvious dose-effect relationship （P＜0.05）. Compared with high-dose limonin group， in the combination group， the degree of renal tissue lesions in rats was relatively aggravated， and the changes in the above-mentioned indicators were significantly reversed （P＜0.05）. CONCLUSIONS Limonin has a certain improvement effect on renal lesions， glucose metabolism， inflammation， and oxidative stress in pregnant rats with gestational diabetes. Its mechanism may be related to the inhibition of the JNK/NF-κB signaling pathway.

ObjectiveTo analyze the drug resistance and the molecular typing characteristics through pulsed field gel electrophoresis (PFGE) of Campylobacter spp. isolated from patients with infectious diarrhea in Baoshan District of Shanghai, and to provide a basis for Campylobacter spp. prevention and control and clinical medication. MethodsCampylobacter spp. was isolated, cultured and identified from stool samples of diarrheal patients collected from medical institutions at two monitoring sites in Baoshan District from 2019 to 2022. Antimicrobial susceptibility testing for 12 antibiotics was conducted on the isolated Campylobacter jejuni (C. jejuni) and Campylobacter. Coli (C. coli), and molecular typing was performed using PFGE. ResultsA total of 179 strains of Campylobacter spp. were isolated from 1 786 samples of diarrheal patients, with a positive rate of 10.02%. The highest resistance rate of C. jejuni was to ciprofloxacin (98.63%), followed by tetracycline (97.26%) and nalidixic acid (89.73%). C. coli was completely resistant to ciprofloxacin and nalidixic acid (100.00%), followed by tetracycline (90.91%). The multidrug resistance rates of C. jejuni and C. coli were 89.73% and 100.00%, respectively. 142 strains of C. jejuni produced 122 PFGE bands, while 33 strains of C. coli produced 33 PFGE bands, and the distribution of the bands was relatively dispersed. ConclusionFrom 2019 to 2022, the detection rate of Campylobacter in diarrheal patients was relatively high in Baoshan District of Shanghai, the multidrug resistance rate of Campylobacter isolates from diarrheal patients was relatively serious, in addition, the drug resistance pattern was complex, and the PFGE band pattern displayed a polymorphic distribution.

This paper primarily investigated the protective effects and potential mechanisms of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma in alleviating isoprenaline(ISO)-induced hypertrophy and damage in H9c2 cardiomyocytes. Initially, H9c2 cardiomyocytes were used as the research subject to analyze the effects of ISO at different concentrations on cell hypertrophy and damage. On this basis, the H9c2 cardiomyocytes were divided into blank, model, and high-dose(200 μg·mL~(-1)), medium-dose(100 μg·mL~(-1)), and low-dose(50 μg·mL~(-1)) groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma. Cell hypertrophy and damage models were induced by treating cells with 400 μmol·L~(-1) ISO for 24 hours. The Incucyte live-cell analysis system was utilized to observe the status, size changes, and confluence of the cells in each group. Cell viability was detected by using the CCK-8 assay. Western blot analysis was employed to detect the expression of Ras-associated protein 7A(RAB7A), sequestosome 1(SQSTM1/p62), autophagy-related protein Beclin1, and microtubule-associated protein 1 light chain 3(LC3). Immunofluorescence was used to detect the expression level of the autophagy marker Beclin1 in H9c2 cells. The results demonstrated that compared with the blank group, the model group showed a significant reduction in cell viability(P<0.01) and a marked increase in cell hypertrophy, with an average cell length growth of 13.53%. Compared with the model group, the high-dose, medium-dose, and low-dose groups of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma exhibited reduced hypertrophy, with respective growths of 6.89%, 8.30%, and 8.49% and a significant decrease in growth rates(P<0.01). Cell viability in the high-dose of total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma was also significantly increased(P<0.01). Western blot and immunofluorescence results indicated that compared with the blank group, the model group showed changes in Beclin1, RAB7A, and p62 expression, as well as the LC3Ⅱ/LC3Ⅰ ratio, although most changes were not statistically significant. In the groups treated with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma, the expression of autophagy-related proteins Beclin1 and RAB7A and the LC3Ⅱ/LC3Ⅰ ratio were significantly increased(P<0.05), while p62 expression significantly decreased(P<0.05). These findings collectively suggested that pretreatment of cells with total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma significantly enhanced autophagy activity in cells. In summary, total saponins from Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma inhibit ISO-induced hypertrophy and damage in H9c2 cells by promoting autophagy, demonstrating potential cardioprotective effects and providing new insights and scientific evidence for their preventive and therapeutic use in cardiovascular diseases.
Autophagy/drug effects* ; Saponins/pharmacology* ; Panax notoginseng/chemistry* ; Panax/chemistry* ; Animals ; Rats ; Cell Line ; Drugs, Chinese Herbal/pharmacology* ; Rhizome/chemistry* ; Isoproterenol/adverse effects* ; Myocytes, Cardiac/cytology* ; Hypertrophy/drug therapy*

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

OBJECTIVE: To explore the efficacy and safety of venetoclax combined with demethylating drugs and intense chemotherapy in the treatment of acute myeloid leukemia (AML). METHODS: The clinical data of 76 patients with AML treated in Qilu Hospital of Shandong University Dezhou Hospital from January 2019 to March 2024 were retrospectively analyzed. Patients were divided into observation group and control group. 38 patients in the observation group received venetoclax combined with demethylating drugs (decitabine or azacytidine) and 38 patients in the control group with the "3+7" intensive chemotherapy regimen. The primary endpoints of clinical observation were complete remission (CR), CR with incomplete hematologic recovery (CRi), partial remission (PR), non remission (NR), and overall response rate (ORR). Secondary endpoints were overall survival (OS) and drug safety. RESULTS: After 2 courses of treatment, the CR+CRi rate in observation group and control group was 71.05% and 65.79%, respectively, and the ORR was 81.58% and 78.95%, respectively. After all courses of treatment, CR+CRi rate in the observation group and the control group was 73.68% and 78.95%, respectively, and the ORR was 81.58% and 84.21%, respectively, with no statistical significance between the two groups (P >0.05). After 1 course of treatment, there were statistically significant differences in the proportion and degree of myelosuppression, the duration of neutropenia and the duration of thrombocytopenia between the two groups (P < 0.05), while there were no statistically significant differences in the occurrence of neutropenia with fever between the two groups (P >0.05). The incidence of non-hematological adverse reactions was highest in infection (mainly pulmonary infection) and gastrointestinal reaction. Among the many adverse reactions, there were statistically significant differences in the infection and hypokalemia between the two groups (P < 0.05), the incidence of hypokalemia in observation group and control group was 42.11% and 15.79%, respectively, and the infection rate in observation group and control group was 73.68% and 94.74%, respectively. The median OS was 13.13(1.67-53.63) months in the observation group and 16.60(0.57-59.67) months in the control group. CONCLUSION The combination of venetoclax and demethylating drugs has a low degree of myelosuppression, but a long recovery time, a response rate as good as that of intensive chemotherapy, and a lower infection rate. However, the incidence of hypokalemia is low in the intensive chemotherapy regimen, and the regimen significantly improves the long-term outcome of patients.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Sulfonamides/therapeutic use* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Decitabine/therapeutic use* ; Azacitidine/therapeutic use* ; Middle Aged ; Treatment Outcome ; Adult ; Aged ; Remission Induction

Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide. Among its histological subtypes, non-small cell lung cancer (NSCLC) accounts for the majority of cases, representing the predominant pathological type. Notably, in the elderly population, NSCLC continues to be a major contributor to cancer-related deaths. With the global ageing population, immunosenescence has emerged as a key factor influencing the occurrence, progression, and the efficacy of immunotherapy of NSCLC. Immunosenescence refers to the age-related decline in immune system function, which manifests as alterations in both the quantity and functionality of immune cells. These include thymic involution, T cell exhaustion, epigenetic modifications, weakened immune responses, and a chronic low-grade inflammatory state. This review comprehensively analyzes the role of immunosenescence in elderly patients with advanced NSCLC and proposes potential therapeutic strategies to intervene in the immunosenescence process. By targeting immunosenescence, these strategies aim to inhibit the progression of NSCLC and improve the effectiveness of immunotherapy.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Immunotherapy ; Lung Neoplasms/genetics* ; Immunosenescence ; Aged

Objective To investigate the efficacy of Fumai Zhuyu Decoction combined with radial shock wave therapy(RSWT)in treating convalescent stroke patients with lower limb spasm,and to observe its effect on serum neuron-specific enolase(NSE)and transforming growth factor-β1(TGF-β1).Methods From January 2022 to January 2024,a total of 111 convalescent stroke patients with lower limb spasm of qi deficiency and blood stasis syndrome were selected from the First Affiliated Hospital of Hebei North University.According to the treatment method,the patients were divided into two groups.The 55 patients in the western medicine(WM)group were treated with RSWT,and 56 patients in the traditional Chinese medicine(TCM)group were treated with Fumai Zhuyu Decoction orally and RSWT.The course of treatment for the two groups covered 6 months.Before and after treatment,the two groups were observed in the changes of modified Ashworth Scale(MAS)score for the evaluation of muscle tone of hemiplegic limbs,Clinical Spasticity Index(CSI)score,Barthel Index(BI)score for the evaluation of activities of daily living,three-dimensional gait parameters(velocity,cadence,step length),serum levels of NSE and TGF-β1,and hemorheological indicators of plasma viscosity(PV),low-shear blood viscosity(LBV),high-shear blood viscosity(HBV)and platelet aggregation rate(PAR).After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate of the TCM group was 94.64%(53/56),and that of the WM group was 76.36%(42/55).The intergroup comparison(tested by chi-square test)showed that the efficacy of the TCM group was significantly superior to that of the WM group(P＜0.01).(2)After treatment,the MAS and CSI scores of the two groups were lowered(P＜0.05)and the BI scores were increased compared with those before treatment(P＜0.05).The decrease of MAS and CSI scores and the increase of BI scores in the TCM group were significantly superior to those in the WM group(P＜0.01).(3)After treatment,the three-dimensional gait parameters of velocity,cadence,and step length in the two groups were increased compared with those before treatment(P＜0.05),and the increase of gait parameters in the TCM group was significantly superior to that in the WM group(P＜0.01).(4)After treatment,the serum NSE level of the two groups was significantly decreased that before treatment(P＜0.05),and the serum TGF-β1 level was significantly increased compared with that before treatment(P＜0.05).The decrease of serum NSE level and the increase of serum TGF-β1 level in the TCM group were significantly superior to those in the WM group(P＜0.01).(5)After treatment,the hemorheological indexes such as PV,LBV,HBV and PAR in the two groups were significantly lowered compared with those before treatment(P＜0.05),and the decrease in the TCM group was significantly superior to that in the WM group(P＜0.01).Conclusion Fumai Zhuyu Decoction combined with RSWT can effectively improve the limb spasm degree and walking function,reduce serum NSE level,increase serum TGF-β1 level,and correct the abnormal blood hemorheology in convalescent stroke patients with lower limb spasm of qi deficiency and blood stasis syndrome.The curative effect of the combined treatment is significantly superior to that of RSWT alone.

Objective To evaluate the effects of Qitan Decoction(QTD)combined with radial shockwave therapy(RSWT)on walking ability,balance function,and neural injury markers in stroke patients with lower limb spasticity during convalescence.Methods A retrospective study was conducted on 100 stroke patients with lower limb spasticity of qi deficiency and blood stasis type treated at the First Affiliated Hospital of Hebei North University from December 2021 to December 2023.Patients were divided into a conventional group(n=49,receiving RSWT alone)and an trial group(n=51,receiving RSWT plus QTD)based on treatment protocols.Both groups received standard stroke care(including cerebral metabolism improvement,neurotrophic support,and antiplatelet therapy).The intervention lasted 6 months.The changes in Modified Ashworth Scale(MAS)scores,Functional Gait Assessment(FGA)scores,Berg Balance Scale(BBS)scores,Stroke-Specific Quality of Life(SS-QOL)scores,serum neural injury markers[gama-aminobutyric acid(GABA),brain-derived neurotrophic factor(BDNF)],and kinematic parameters(peak knee flexion,peak hip flexion)were observed,and the clinical efficacy was compared between groups.Results(1)After 6 months of treatment,the total effective rate of the trial group was 94.12％(48/51),and that of the conventional group was 75.51％(37/49),and the intergroup(by chi-square test)comparison showed that the efficacy of the trial group was significantly superior to that of the conventional group(P＜0.01).(2)After treatment,the MAS scores of patients in the two groups were lower than before treatment(P＜0.05),and the FGA,BBS,and SS-QOL scores were higher than before treatment(P＜0.05),and the reduction of the MAS scores and the increase of the FGA,BBS,and SS-QOL scores of the trial group were significantly superior to those of the conventional group(P＜0.01).(3)After treatment,the serum GABA and BDNF levels of patients in the two groups were higher than those before treatment(P＜0.05),and the increase in serum GABA and BDNF levels in the trial group was significantly superior to that in the conventional group(P＜0.01).(4)After treatment,the peak knee flexion and peak hip flexion of patients in the two groups were elevated compared with those before treatment(P＜0.05),and the trial group's elevation of peak knee flexion and peak hip flexion was significantly superior to that of the conventional group(P＜0.01).Conclusion QTD combined with RSWT effectively alleviates spasticity,enhances walking/balance function,mitigates neural injury,and improves quality of life in stroke patients with lower limb spasticity of qi deficiency and blood stasis syndrome during convalescence.