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*

Aim To analyze the effects of berberine on the apoptosis of colon epithelial cells and polymorpho-nuclear neutrophils ( PMNs) in mice with ulcerative colitis ( UC ) by regulating JAK/STAT signaling pathway. Methods The UC mouse models were established by dextran sulfate sodium ( DSS) method and were randomly divided into control group, UC group, low-dose, middle-dose and high-dose berberine groups and positive drug group ( mesalazine enteric-coated tablet group) . In addition, the mice were randomly di¬vided into UC group, high-dose berberine group, AG490 group, and high-dose berberine + AG490 group. Levels of serum tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6) and colon epithelial cell apoptosis and PMN apoptosis were compared among the groups. Western blot was used to detect the expres¬sions of colon tissue apoptosis-related and JAK/STAT signaling pathway-related proteins. Results The lev¬els of serum TNF-α and IL-6, apoptosis rate of colon epithelial cell and protein expressions of Fas, FasL, Bax, caspase-3, p-JAK2/JAK2 and p-STAT3/STAT3 in each dose berberine group and positive drug group were significantly lower than those in UC group (P < 0.05), and the above indicators in berberine groups were reduced gradually (P <0.05) . The PMN apoptosis rate and Bcl-2 protein expression were significantly higher in each dose berberine group and positive drug group than those in UC group (P <0. 05) , and the two indicators increased gradually in berberine groups ( P < 0.05). AG490 could reverse the above effects of berberine ( P < 0. 05 ). Conclusions Berberine can inhibit the apoptosis of colon epithelial cell and promote the apoptosis of PMN in UC mice by regulating the JAK/STAT signaling pathway, and then play a role in the treatment of UC.

Objective: To explore the association between chronic hepatitis B virus infection and diabetes among adults. Methods: The baseline data of China Kadoorie Biobank ( CKB ) study from Tongxiang of Zhejiang Province was used for analysis. Community residents were investigated in the study from August 2004 to May 2008, including questionnaire survey, physical measurement and biological sample test. Univariate and multivariate logistic regression models were used to estimate the association of chronic hepatitis B virus infection with diabetes. Results: Totally 52 888 participants were included in the final analysis. The overall prevalence of HBsAg-positive was 3.55% ( N=1 877 ). The overall prevalence of diabetes was 5.17% ( N=2 733 ). The prevalence of HBsAg-positive in diabetic patients was 3.51% ( N=96 ). Both univariate and multivariate logistic regression models indicated that there was no association between chronic hepatitis B virus infection and diabetes（ P>0.05 ）. Conclusion No significant association has been found between chronic hepatitis B virus infection and diabetes among adults.

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
Bortezomib/therapeutic use* ; Chromosome Aberrations ; Humans ; Multiple Myeloma/drug therapy* ; Prognosis ; Retrospective Studies

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

Objective: To explore the clinical significance of transcranial Doppler flow grades for patients with acute cerebral infarction combined with H type hypertension. Methods: 92 patients with acute cerebral infarction combined with H type hypertension were divided into observation group, and 78 patients with acute cerebral infarction were divided into control group during the same period. The differences of the two groups were compared and researched. The correlation between transcranial Doppler flow grade of acute cerebral infarction combined with H type hypertension and the score of NIHSS was compared and analyzed. Results: As the results of transcranial Doppler flow grades, the ratio of the patients in 0 grade was 10.87% in observation group, and it was significantly higher than that of control group (1.28%) (x2=4.925, P<0.05). The ratio of the patients in 5 grade was 6.52% in observation group, and it was significantly lower than that of control group (21.79%) (x2=8.417, P<0.05). The blood flow velocities of systole and diastole of observation group were significantly lower than that of control group (t=3.645, t=5.251, P<0.05), respectively. The cerebral infarct size of observation group was significantly larger than that of control (t=4.405, P<0.05). The score of NIHSS of observation group was significantly higher than that of control group (t=2.688, P<0.05). The results of Pearson linear correlation analysis indicated that there was a significantly negative correlation between transcranial Doppler flow grades and NIHSS (r=-0.284, P<0.05). Conclusion: The transcranial Doppler flow grades can identify the order of severity for patients with acute cerebral infarction combined with H type hypertension.

Follicle-stimulating hormone (FSH) is synthesized and secreted by the anterior pituitary, which binds to its receptors expressed on the membrane of Sertoli cells in the testis to bring about spermatogenesis. With the development of DNA sequencing technology, FSH SNPs rs10835638 and FSHR SNPs rs6165, rs6166, and rs1394205 were detected, which might directly affect the expression of FSH and activity of FSHR, resulting in male spermatogenic dysfunction. This review focuses on the relationship of FSH and FSHR gene polymorphisms with male infertility.
Follicle Stimulating Hormone ; genetics ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Single Nucleotide ; Receptors, FSH ; genetics ; Sertoli Cells ; Spermatogenesis ; Testis

A phytochemical investigation on the aerial parts of a Tibetan medicine Meconopsis horridula, by solvent extraction, repeated chromatographies on silica gel, Sephadex LH-20, and preparative TLC techniques, led to the isolation of 9 compounds. By spectroscopic analysis and comparison of its 1H and 13C-NMR data with those in literatures, their structures were identified as oleracein E(1), N-( trans-p-coumaroyl) tyramine (2), chrysoeriol (3), apigenin (4), hydnocarpin (5), p-coumaric acid glucosyl ester (6), stigmast-5-ene-3beta-ylformate (7), 3beta-hydroxy-7alpha-ethoxy-24beta-ethylcholest-5-ene (8), and beta-sitosterol (9), respectively, among which compounds 6-8 were isolated from the genus for the first time,and 1,3 were isolated from the species for the first time. A MTT method was applied to evaluate the cytotoxic activity of compounds 14 against the human hepatocellular liver carcinoma cell line (HepG2), and compound 1 showed significant cytotoxicity against HepG2,with its inhibitory rate of 52.2% at 10 micromol x L(-1).
Medicine, Tibetan Traditional ; Molecular Structure ; Papaveraceae ; chemistry ; Plant Extracts ; chemistry ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo investigate the effect of propofol at doses for different anesthesia depths on γ-aminobutyric acid (GABA) in different cerebral regions at propofol uptake equilibrium in dogs.

METHODSTwelve 12-18-month-old healthy hybrid dogs weighing 10-12 kg were randomly divided into light anesthesia group (n=6) and deep anesthesia group (n=6) with a single bolus dose of propofol (5.5 and 7.0 mg/kg, respectively) completed in 15 s followed by intravenous propofol infusion at a constant rate (55 and 70 mg·kg(-1)·h(-1), respectively). Blood samples (2 ml) were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations 50 min after the start of the infusion. The dogs were then sacrificed and tissues were taken from different brain regions and the cervical cord to measure GABA concentrations using high-pressure liquid chromatography (HPLC).

RESULTSThe plasma propofol concentrations in internal carotid artery and jugular vein were similar in both light anesthesia group (3.00 ± 0.31 and 3.10 ± 0.51 µg/ml, respectively, P>0.05) and deep anesthesia group (6.41 ± 0.05 and 6.40 ± 0.11 µg/ml, respectively, P>0.05). GABA concentrations in the brain regions were significantly higher in deep anesthesia group than in light anesthesia group (P<0.05). The dorsal thalamus and hypothalamus showed greater GABA variations [(83.83 ± 2.230%) and (85.83 ± 1.72)%] compared to other brain regions at different anesthesia depths (P<0.05).

CONCLUSIONSIn both groups, plasma propofol concentrations in the internal carotid artery and internal jugular vein reach equilibrium at 50 min of propofol infusion. The variation of GABA is associated with the anesthesia depth of propofol, and GABA variation in the dorsal thalamus and hypothalamus plays an important role in propofol anesthesia.

Anesthetics, Intravenous ; pharmacokinetics ; Animals ; Brain ; metabolism ; Dogs ; Female ; Male ; Propofol ; blood ; pharmacokinetics ; gamma-Aminobutyric Acid ; metabolism