Objective To investigate the characteristics of menopause-related symptoms and cognition status of menopausal hormone therapy(MHT)among menopausal women.Methods A total of 619 menopausal women with menopause-related symptoms who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University were selected as the study subjects.Data were collected by questionnaire to analyze the characteristics of menopause-related symptoms,and the menopausal women's cognitive status of MHT and therapeutic effects were explored.Results Among 371 perimenopausal women,the menopause-related symptoms with the top three rates were fatigue(69.81％),insomnia(66.85％),and hot flush-sweating(58.22％).Among 248 postmenopausal women,the menopause-related symptoms with the top three rates were hot flashes and sweating(64.11％),bone and joint pain(60.89％),and fatigue(56.85％).The incidence of insomnia and fatigue in postmenopausal women was significantly lower than that in perimenopausal women(P＜0.01),while the incidence of bone and arthralgia,urinary system infection,vaginal dryness and painful intercourse was significantly higher than that in perimenopausal women(P＜0.01).There was no significant difference in Kupperman score between perimenopausal and postmenopausal women(P＞0.05),but score degree distribution differed significantly(P＜0.05).Perimenopausal women had the highest proportion of mild score while postmenopausal women had the highest proportion of moderate score.There were significant differences in Kupperman score among postmenopausal women with different menopause ages,menopause years and menopause mode(P＜0.05).The earlier menopause age and shorter menopause years,the higher Kupperman score was;the Kupperman score was significantly higher in surgical menopause than in natural menopause(P＜0.05).Multivariate Logistic regression analysis showed that age of 45-54 years old,retirement or unemployment,spouse's disease or death,abnormal sexual life,and high education level were the risk factors for the occurrence of menopausal symptoms(P＜0.05);high family income and＞3 times/week exercise were the protective factors for the occurrence of menopausal symptoms(P＜0.05).The Internet was the way that accounted for the highest proportion of menopausal women's understanding of MHT(39.92％),and the tumor accounted for the highest proportion of menopausal women's concern about MHT(33.67％).There were 465 menopausal women without MHT contraindications(89.77％)who used MHT under the guidance of professional doctors,and their symptoms improved significantly after treatment(P＜0.05).Conclusion Menopausal women have obvious menopause-related symptoms,and the earlier the age,the shorter the menopause years and the more severe symptoms in the surgical menopause.Therefore,it is necessary to pay attention to the impact of menopause on the health of menopausal women and increase the use rate of MHT to improve the quality of life of menopausal women.

OBJECTIVE: To study the effect of gradient shear stress on platelet aggregation by microfluidic chip Technology. METHODS: Microfluidic chip was used to simulate 80% fixed stenotic microchannel, and the hydrodynamic behavior of the stenotic microchannel model was analyzed by the finite element analysis module of sollidwork software. Microfluidic chip was used to analyze the adhesion and aggregation behavior of platelets in patients with different diseases, and flow cytometry was used to detect expression of the platelet activation marker CD62p. Aspirin, Tirofiban and protocatechuic acid were used to treat the blood, and the adhesion and aggregation of platelets were observed by fluorescence microscope. RESULTS: The gradient fluid shear rate produced by the stenosis model of microfluidic chip could induce platelet aggregation, and the degree of platelet adhesion and aggregation increased with the increase of shear rate within a certain range of shear rate. The effect of platelet aggregation in patients with arterial thrombotic diseases were significantly higher than normal group (P<0.05), and the effect of platelet aggregation in patients with myelodysplastic disease was lower than normal group (P<0.05). CONCLUSION The microfluidic chip analysis technology can accurately analyze and evaluate the platelet adhesion and aggregation effects of various thrombotic diseases unde the environment of the shear rate, and is helpful for auxiliary diagnosis of clinical thrombotic diseases.
Humans ; Microfluidics ; Platelet Adhesiveness ; Platelet Aggregation ; Blood Platelets/metabolism* ; Platelet Aggregation Inhibitors/pharmacology* ; Platelet Activation/physiology* ; Thrombosis

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(C_min) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole C_min were analyzed, and the changes of voriconazole C_min after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole C_min and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole C_min was negatively correlated with albumin level (r=-2.673). Voriconazole C_min in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole C_min showed that compared with voriconazole C_min 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole C_min> 5.0 mg/L group was increased (χ²=4.318, P=0.038). CONCLUSION The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole C_min, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole C_min of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Humans ; Male ; Female ; Voriconazole/therapeutic use* ; Antifungal Agents/therapeutic use* ; C-Reactive Protein ; Creatinine ; Glucocorticoids ; Retrospective Studies ; Drug Monitoring ; Hematologic Diseases

OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR _PFS=2.047, P =0.039; HR _OS=4.854, P =0.001). CONCLUSION Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.
Humans ; Prognosis ; Fibrinogen ; Disease-Free Survival ; Albumins/therapeutic use* ; Hemostatics/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation. METHODS: Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed. RESULTS: Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05). CONCLUSION Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.
Mice ; Animals ; Bone Marrow ; Reactive Oxygen Species ; Mice, Inbred C57BL ; Hematopoietic Stem Cells ; Whole-Body Irradiation ; Radiation, Ionizing ; Bone Marrow Cells

OBJECTIVE: To investigate the diagnostic efficacy of seven glomerular filtration rate (GFR) evaluation formulas Schwartz2009, Schwartz1976, Counahan-Barratt, Filler, CKD-EPI_scysc, Cockrofi-Gault, CKD-EPI_ScysC-Scr in high concentration of methotrexate (HDMTX) chemotherapy dose adjusted cut-off point (GFR ≤85 ml/min) in children with acute lymphoblastic leukemia (ALL). METHODS: One hundred and twenty-four children with ALL were included in the study. GFR determined by renal dynamic imaging (sGFR) was used as the standard to evaluate the accuracy, consistency of eGFR calculated by seven formulas and sGFR, and the diagnostic efficacy of each formula when the sGFR ≤85 ml/min boundary. RESULTS: All of the accuracy of eGFR estimated by Schwartz2009 were greater than 70% in the 0-3, >4 and ≤6, >6 and ≤9, >9 and ≤16 years old group and male group, and the consistency exceeded the professional threshold. When the sensitivity of the ROC curve sGFR ≤85 ml/min was 100% of CKD-EPI_scysc in the 0-3, >3 and ≤4 years old group, Filler in the >3 and ≤4 years old group, and Cockrofi-Gault in the >6 and ≤9 years old group, the specificity was 73.02%, 78.95%, 78.95%, 69.32%, respectively, and the AUC under the ROC curve was the largest (P<0.05). CONCLUSION Schwartz2009 formula predicts the highest accuracy of eGFR in the 7 glomerular filtration rate. CKD-EPI_scysc, Filler, and Cockrofi-Gault formulas have more guiding signi-ficance for the adjustment of HDMTX chemotherapy in pre-adolescence in children with ALL when sGFR ≤85 ml/min.
Adolescent ; Humans ; Male ; Child ; Child, Preschool ; Glomerular Filtration Rate ; Methotrexate ; Creatinine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Renal Insufficiency, Chronic/diagnosis*

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

OBJECTIVE: To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms. METHODS: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo. RESULTS: The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01). CONCLUSION Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.
Animals ; Mice ; NF-kappa B/metabolism* ; Lipopolysaccharides ; RAW 264.7 Cells ; Zebrafish ; NF-KappaB Inhibitor alpha/metabolism* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; STAT3 Transcription Factor/metabolism* ; Inflammation/metabolism* ; Anti-Inflammatory Agents/therapeutic use*

OBJECTIVE: To investigate the down-regulation of ANRIL (Antisense non-coding RNA in the INK4 Locus) effects on proliferation and apoptosis of Kasumi-1 cells and its related molecular mechanism. METHODS: Recombinant lentivirus was used to construct ANRIL down-regulation Kasumi-1 cells (sh-ANRIL group) and its control cells (sh-NC group). A fluorescence microscope was used to observe the transfection efficiency, RT-qPCR was used to detect knockdown efficiency and ANRIL expression in PBMCs and MBMCs of patients with acute myeloid leukemia (AML). Proliferation and apoptosis of Kasumi-1 cells were assayed by CCK-8 method and flow cytometry. Western blot was employed to detect the expression of PI3K, AKT, p-AKT, and relevant protein after down-regulation of ANRIL in Kasumi-1 cells. RESULTS: ANRIL overexpressed significantly in PBMCs and MBMCs of patients with AML, the transfection efficiency of recombinant lentivirus carrying sh-ANRIL and sh-NC on Kasumi-1 cells exceeded 90%, and the knockdown efficiency was 70%. When DNR was administrated for 24, 48, and 72 hours, the cell inhibition rate of the sh-ANRIL group was (47.40±1.49)%, (69.11±0.51)% and (91.82±1.10)%, which were significantly higher than those of the sh-NC group, respectively (P<0.05). The apoptotic rate in the sh-ANRIL group was (10.29±0.58)%, which was significantly higher than (5.42±0.67)% of the sh-NC group (P<0.01). After DNR treatment for 24 hours, the apoptotic rate of the sh-ANRIL group was (54.41±1.69)%, which was significantly higher than (38.28±1.42)% of sh-NC group (P<0.001). Western blot revealed that the protein levels of PI3K, p-AKT, PCNA, and BCL-2 in the sh-ANRIL group were reduced significantly than those in the sh-NC group, while the BAX protein expression increased. CONCLUSION ANRIL may affect the proliferation and apoptosis of Kasumi-1 cells through PI3K/AKT signaling pathway. ANRIL is a potential therapeutic target for AML.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; RNA, Long Noncoding/genetics*

OBJECTIVE: To investigate the potential antitumor effect and its mechanism of dihydroartemisinin (DHA) on diffuse large B-cell lymphoma (DLBCL). METHODS: OCI-Ly7 cells were respectively treated with different concentrations of DHA (0, 12.5, 25, 50 and 100 μmol/L) , CCK-8 was used to detect the cells viability. Subsequently, OCI-Ly7 cells were divided into 5 groups : DHA 0,25,50,100 μmol / L and DHA (100 μmol / L) + Colivelin (STAT3 activator). Aldehyde dehydrogenase (ALDH) positive cells were sorted by flow cytometry, the sphere-forming ability of stem cells was detected. Transwell assay and scratch test were used to analyze the invasion and migration of cells. Western blot was used to detect the expression of migration and invasion-related proteins, as well as the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3(STAT3). RESULTS: DHA induced obvious cytotoxicity to OCI-Ly7 cells. Compared with the control group, the stem cell-like properties, invasion and migration of OCI-Ly7 were significantly inhibited in DHA 50 μmol/L group and 100 μmol/L group, while the phosphorylation levels of JAK2 and STAT3 were significantly reduced. There was no significant difference in DHA 25 μmol/L group compared with the control group. Treated with Colivelin, the inhibition of DHA on OCI-Ly7 stem cell-like properties, invasion and migration was significantly reversed, and the expression of p-STAT3 was significantly up-regulated. CONCLUSION DHA has antitumor effect on DLBCL, and its mechanism may be through inhibiting the activation of JAK2/STAT3 pathway to inhibit the stem cell-like properties, invasion and migration of DLBCL cells.
Aldehyde Dehydrogenase/pharmacology* ; Antineoplastic Agents/therapeutic use* ; Artemisinins/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Janus Kinase 2 ; Lymphoma, Large B-Cell, Diffuse/pathology* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction ; Sincalide/pharmacology*