Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro. METHODS: The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1. RESULTS: Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01). CONCLUSION Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.
Male ; Humans ; Mice ; Animals ; NF-kappa B/metabolism* ; Mice, Nude ; Cell Line, Tumor ; Signal Transduction ; Prostatic Neoplasms/drug therapy* ; RNA, Messenger

In order to learn from the advanced experience of postgraduate education in foreign first-class universities, Harvard University, Johns Hopkins University and London School of Hygiene and Tropical Medicine were selected as the objects in this study to analyze and compare the advantages and characteristics of their postgraduate training model, curriculum setting and teaching resources, thereby providing suggestions for the reform and development in the cultivation of master of public health and preventive medicine in China.

This study aims to explore the electrophysiological properties and changes in gene expression of basket cells, a unique population of GABAergic interneurons expressing parvalbumin (PV), during the postnatal development of mouse prefrontal cortex (PFC). Toward this goal, we took use of the G42 transgenic mouse line which specifically expresses enhanced green fluorescent protein (EGFP) in basket cells. The brain slices of PFC were prepared from the postnatal 7 (P7), 14 (P14) and 21 days (P42) G42 mice and whole-cell patch clamp recording was performed in basket cells. In addition, we sorted the basket cells by flow cytometry and analyzed their transcription profiling on P7, P14, and P21 using RNA-seq technology. The results showed that the resting membrane potential and membrane input resistance decreased gradually from P7 to P21. The amplitude and duration of action potential of basket cells increased and decreased from P7 to P21, respectively. In contrast, the threshold of action potential of basket cells did not have a significant change from P7 to P21. The frequency of spontaneous excitatory postsynaptic currents (sEPSCs) of basket cells increased gradually, while the amplitudes of sEPSCs of basket cells remained constant from P7 to P21. RNA sequencing from basket cells revealed that the expression of 22 and 660 genes was upregulated and downregulated from P7 to P14, respectively. By contrast, the expression of 107 and 69 genes was upregulated and downregulated from P14 to P21, respectively. The differentially expressed genes in basket cells from P7 to P21 were significantly enriched in pathways such as neuron apoptotic process, mRNA processing, Golgi vesicle transport and axon guidance. Altogether, we characterized electrophysiological properties and changes in gene expression of basket cells during the postnatal development in mouse PFC. These results provide insight into the mechanisms underlying the development of basket cells in mouse cortex.
Animals ; Gene Expression ; Interneurons/metabolism* ; Mice ; Mice, Transgenic ; Parvalbumins/metabolism* ; Prefrontal Cortex/metabolism*

Objective To investigate the effects of heat shock protein Gp96 on alcoholic liver fibrosis in mice. Methods A total of 220 male healthy C57BL/6 J mice were randomly divided into four groups; normal control group (n = 10), saline+alcohol induced liver fibrosis group (n = 70), the injection of CRISPR expression Gp96-sgRNA3 by tail vein+ alcohol induced liver fibrosis group (n = 70), the intraperitoneal injection of nuclear factor kappa B(NF-κB) inhibitors PDTC+alcohol induced liver fibrosis group (n = 70). The blood was got from eyeballs and the mice were killed after 8 weeks of ethanol induction. We detected the activity of serum aspartate aminotransferase (AST) in mice of different groups. The pathological changes were detected by HE staining, sirius red staining and periodic acid-Schiff (PAS) staining in the liver of mice. The expression of Gp96 and transforming growth factor βl ( TGF-βl ) were detected by Western blotting. Results Compared with the normal control group, the AST enzyme activity and liver fibrosis increased significantly, glycogen decreased significantly in other three groups (P<0.01). Compared with the saline+alcohol group, the AST enzyme activity and liver fibrosis increased more significantly, glycogen decreased more significantly, Gp96 expression decreased significantly and TGF-βl expression increased significantly in Gp96-sgRNA3+ alcohol group and NF-κB inhibitors PDTC+ alcohol group (P<0.01 or P<0.05). Conclusion The injection of CRISPR expression plasmid Gp96-sgRNA3 by tail vein significantly inhibited the Gp96 expression, promoted the degree of alcoholic liver fibrosis in mice, and NF-κB signaling pathway played a certain role in regulating the expression of Gp96.

Objective::To observe the clinical efficacy of Dahuang Zhuyu decoction for oral administration and enema on severe acute pancreatitis with syndromes of blood stasis and toxin and its effect on serum inflammatory factors. Method::Sixty eight patients with severe acute pancreatitis with syndromes of blood stasis and toxin who were admitted in Henan Provincial People's Hospital from September 2017 to December 2018 were randomly divided into treatment group (34 cases) and control group (34 cases). The control group was treated with western medicine. The treatment group was treated with Dahuang Zhuyu decoction for oral administattion and enema in addition to the therapy of the control group. Both groups were treated for 7 days. Before and after treatment, abdominal pain, bloating, nausea and vomiting were scored separately, serum amylase (AMS), lipase (LPS), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were detected, and abdominal pain disappearance time, bloating disappearance time and exhaust recovery time were recorded. Result::After treatment, the abdominal pain score, abdominal distension score, nausea and vomiting score, serum AMS, LPS, IL-6 and TNF-α were lower than those before treatment (P<0.05), and those in treatment group was lower than those in control group (P<0.05). After treatment, IL-10 level in both groups was higher than those before treatment (P<0.05), and that in treatment group was higher than that in control group (P<0.05). The disappearance time of abdominal pain, the disappearance time of abdominal distension and the recovery time of exhaust were shorter in treatment group than in control group (P<0.05). The total effective rate of the treatment group was higher than that of the control group (P<0.05). Conclusion::Dahuang Zhuyu decoction for oral administration and enema for severe acute pancreatitis with syndromes of blood stasis and toxin can alleviate clinical symptoms, reduce amylase and lipase levels, inhibit the expression of pro-inflammatory factors, promote the expression of anti-inflammatory factors, restore intestinal function, and improve clinical efficacy.