Objective:To explore the effects and mechanisms of chidamide on the osteogenic differentiation of bone marrow mesenchymal stromal cells(MSC)from myelodysplastic syndromes(MDS).Methods:MSC were isolated and cultured from bone marrow of MDS patients and healthy donors.CCK-8 assay was used to detect the effects of chidamide on the proliferation of MSC.The effects of chidamide on the activity of histone deacetylase(HD AC)in MSC was measured by a fluorescence assay kit and Western blot.Alkaline phosphatase(ALP)activity was detected on day 3 and calcium nodule formation was observed by Alizarin Red staining on day 21 after osteogenic differentiation.The expression of early and late osteogenic genes was detected on day 7 and day 21,respectively.RT-PCR and Western blot were used to detect the effects of chidamide on mRNA and protein expression of RUNX2 which is the key transcription factor during osteogenesis.Results:As the concentration of chidamide increased,the proliferation of MSC was inhibited.However,at a low concentration(1 μmol/L),chidamide had no significant inhibitory effect on MSC proliferation but significantly inhibited HD AC activity.In MSC from both MDS patients and healthy donors,chidamide(1 μmol/L)significantly increased ALP activity,calcium nodule formation,thereby mRNA expression of osteogenic genes,and restored the reduced osteogenic differentiation ability of MDS-MSC compared to normal MSC.Mechanistic studies showed that the osteogenic-promoting effect of chidamide may be related to the upregulation of RUNX2.Conclusion:Chidamide can inhibit HD AC activity in MSC,upregulate the expression of the osteogenic transcription factor RUNX2,and promote the osteogenic differentiation of MDS-MSC.

Objective:To explore the characteristics of the immunophenotypic expression of bone marrow monocytes (M ) and its clinical significance in patients with multiple myeloma (MM ). Methods:The monocyte immunophenotypes expression of 67 MM and 30 anemic patients (control group)were detected by flow cytometry.The immunophenotypes that exhibited statistical differences from the control group were screened out.Further univariate and multivariate regression was used analyze the risk factors affecting the prognosis. The effect of monocyte immunophenotype on the prognosis of MM was analyzed.The correlation of CD38+monocytes with clinical features was explored.Results:The percentages of CD138+monocytes (CD138+M％),CD27+monocytes (CD27+M％),and CD56+monocytes (CD56+M％)in the MM group were significantly higher than that in the control group(P<0.05),but the percentages of CD38+monocytes (CD38+M％)and HLA-DR+monocytes (HLA-DR+M％)were significantly lower than that in the control group (P<0.01 ).The median progression-free survival (PFS)was shorter in the low CD38+monocyte proportion (LCD38+M％)group compared to the high CD38+monocyte proportion (HCD38+M％) group.Additionally,the median overall survival (OS)was significantly shorter in the low CD138+monocyte proportion (LCD138+M％),low CD27+monocyte proportion (LCD27+M％),low CD38+monocyte proportion (LCD38+M％),and low HLA-DR+monocyte proportion (LHLA-DR+M％)groups.Cox regression analysis showed that the low CD38+M％ was an independent risk factor for OS.The LCD38+M％group had significantly higher proportions of involved/uninvolved free light chain ratios ≥100 and 1q21+compared to the HCD38+M％ group (P<0.05 ). Moreover,the proportion of CD38-myeloma cells was significantly higher in the LCD38+M％ group than that in the HCD38+M％ group (P<0.05).Conclusion:The expression of CD38+monocytes in bone marrow of MM patients is closely related to the prognosis and clinical characteristics.CD38+monocytes maybe used to predict prognosis and guide treatment decisions.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.
Ferritins ; Humans ; Iron ; Iron Overload ; Liver/metabolism* ; Myelodysplastic Syndromes/therapy* ; Primary Myelofibrosis ; Retrospective Studies ; Splenomegaly

Antiviral Oral Liquid is modified on the basis of Baihu Decoction in Treatise on Febrility Diseases by ZHANG Zhongjing and Qingwen Baidu Yin in Qing Dynasty, with effects in clearing toxic heat, repelling dampness and cooling blood. It is widely used in clinical treatment of common colds, influenza and upper respiratory tract infection, mumps, viral conjunctivitis and hand-foot-mouth disease, with a good clinical efficacy and safety. Based on a questionnaire survey of clinicians and a systematic review of study literatures on Antiviral Oral Liquid, the international clinical practice guidelines development method was adopted to analyze the optimal available evidences and expert experiences in the "evidence-based, consensus-based and experience-based" principles. The consensus was jointly reached by more than 30 multidisciplinary experts nationwide, including clinical experts of traditional Chinese and Western medicine in the field of respiratory diseases and infectious diseases, and methodological experts. In the study, literatures were retrieved based on clinical problems in the clinical survey as well as PICO clinical problems. The GRADE system was used for the classification and evaluation of evidence, and fully combined with clinical expert experience, so as to reach expert consensus by the nominal grouping method. This expert consensus recommended or suggested indications, usage and dosage, course of treatment, intervention time for treatment, and the safety and precautions of Antiviral Oral Liquid for treatment of influenza, and can provide reference for the rational use of this drug in clinical practice.
Antiviral Agents/therapeutic use* ; Consensus ; Hand, Foot and Mouth Disease ; Humans ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional

Liver cirrhosis is the leading cause of liver-related death globally, and the most common causes of liver cirrhosis are chronic hepatitis B and C, alcoholic liver disease, and nonalcoholic fatty liver disease. Recent studies have shown that despite an increase in the number of deaths due to liver cirrhosis around the world, there is a reduction in age-standardized death. In China, there are increases in number of patients with liver cirrhosis, prevalence rate of liver cirrhosis, number of deaths due to liver cirrhosis, and mortality rate of liver cirrhosis, while there are reductions in age-standardized prevalence rate and mortality rate; chronic hepatitis B remains the main cause of liver cirrhosis, with a gradual increase in the proportion of liver cirrhosis cases caused by alcoholic and nonalcoholic fatty liver diseases.

A LC-MS/MS method was developed for the rapid and simultaneous determination of genipin-1-β-D-gentiobioside,geniposide,naringin,hesperidin and neohesperidin in SD rat plasma.The linear relationships of these five constituents in rats were validated,and the specificity,accuracy,precision and stability met the requirements.Their pharmacokinetic parameters were calculated by DAS 3.2.2,and the results showed that the metabolic process in vivo of the five constituents accorded with the characteristics of noncompartmental model.Their main pharmacokinetic parameters were listed as follows:(1) genipin-1-β-D-gentiobioside:t_(1/2)(3.20±0.51)h,C_(max)(403.15±96.93)μg·L~(-1)and AUC_(0-t)(612.56±148.50)μg·L~(-1)·h for the model group,while t_(1/2)(3.07±0.75) h,C_(max)(229.50±60.63)μg·L~(-1)and AUC_(0-t)(413.14±76.37)μg·L~(-1)·h for the normal group;(2) geniposide:t_(1/2)(3.24±0.68) h,C_(max)(2 961.40±688.02)μg·L~(-1),and AUC_(0-t)(10 972.87±1 992.96)μg·L~(-1)·h for the model group,while t_(1/2)(4.56±0.96) h,C_(max)(1 833.27±558.13)μg·L~(-1),and AUC_(0-t)(8 996.27±3 053.48)μg·L~(-1)·h for the normal group;(3) naringin:t_(1/2)(1.64±0.59) h,C_(max)(415.13±259.54)μg·L~(-1),and AUC_(0-t)(608.62±289.05)μg·L~(-1)·h for the model group,while t_(1/2)(1.02±0.25) h,C_(max)(355.08±180.00)μg·L~(-1),and AUC_(0-t)(501.07±242.68)μg·L~(-1)·h for the normal group;(4) hesperidin:t_(1/2)(0.86±0.29) h,C_(max)(95.17±22.80)μg·L~(-1)and AUC_(0-t)(141.19±54.63)μg·L~(-1)·h for the model group,while t_(1/2)(0.95±0.31) h,C_(max)(46.48±18.33)μg·L~(-1)and AUC_(0-t)(69.51±14.73)μg·L~(-1)·h for the normal group;(5) neohesperidin:t_(1/2)(0.89±0.29) h,C_(max)(828.78±361.56)μg·L~(-1)and AUC_(0-t)(1 292.29±553.73)μg·L~(-1)·h for the model group,while t_(1/2)(0.90±0.31) h,C_(max)(314.68±172.45)μg·L~(-1)and AUC_(0-t)(385.99±138.55)μg·L~(-1)·h for the normal group.
Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Drugs, Chinese Herbal ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated β-amyloid (Aβ) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood. In the current study, we investigated the changes in key enzymes involved in β-amyloid precursor protein (APP) metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations. The results indicated that PB reduced Aβ secretion, which was caused by down-regulation of β-secretase (BACE1) expression, as indicated at both the protein and mRNA levels. Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1 (FoxO1) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of PB on BACE1 expression and Aβ secretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201. In conclusion, these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.
Alzheimer Disease ; Amyloid Precursor Protein Secretases/metabolism* ; Amyloid beta-Peptides/metabolism* ; Aspartic Acid Endopeptidases/metabolism* ; Down-Regulation ; Forkhead Box Protein O1/genetics* ; Humans ; Phosphorylation ; STAT3 Transcription Factor/metabolism* ; Secosteroids

OBJECTIVE: To detect the relationship between leukocytes derived microparticle (CD45 METHODS: The expression of CD45 RESULTS: The percentages of CD45 CONCLUSION High level of CD45
Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; Leukocytes ; Neoplasm, Residual ; Prognosis