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 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*

Humans ; DNA, Mitochondrial ; Cross-Sectional Studies ; East Asian People ; DNA Methylation ; Hypertension/epidemiology* ; China/epidemiology*

RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat diet-fed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.

Objective: To analyze the association of stored autologous blood transfusion (SABT) with tumor recurrence in PCa patients after radical prostatectomy and explore the application of SABT in this surgical procedure. METHODS: Forty-five PCa patients underwent radical prostatectomy in our hospital in recent five years, of whom, 20 received SABT (group A) and the other 25 allogeneic blood transfusion (group B) intraoperatively. After surgery, we followed up the patients regularly for 3－66 months by examination of the levels of total PSA (tPSA) and free PSA (fPSA), digital rectal examination (DRE), and MRI to observe the biochemical recurrence of the tumor. We compared the data obtained between the two groups of patients. RESULTS: In group A, 8 cases were in stages T1a－T1b and 12 in stages T2a－T2c, and in group B, 14 cases were in stages T1a－T1b and 11 in stages T2a－T2c. The volume of transfused blood was 800 ml in group A and 400－1 200 ml in group B. No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss or postoperative Gleason scores (P > 0.05), nor in the tPSA level or the results of DRE and MRI at 12, 24, 36, 48 and over 48 months (P > 0.05). CONCLUSIONS SABT is safe for PCa patients undergoing radical prostatectomy and does not increase the tumor recurrence rate after surgery.

AIM:To investigate the regulatory effect of NADPH oxidase-4 (NOX-4) on PI3K signaling path-way in transforming growth factor-β1 (TGF-β1)-induced collagen type Ⅰ (collagen Ⅰ) synthesis from lung cancer cells and the mechanisms. METHODS:Human lung cancer A549 cells were cultured in vitro and stimulated with TGF-β1. The ex-pression of NOX family and collagen family at mRNA and protein levels as well as the PI3K class Ⅰ catalytic subunits and the activation of PI3K signaling pathway was measured. A549 cells were pre-treated with NOX-4 inhibitor diphenyleneiodo-nium (DPI), and the expression of collagen Ⅰ at mRNA level as well as the PI3K class Ⅰ catalytic subunits and the activa-tion of PI3K signaling pathway was measured upon TGF-β1 stimulation. RESULTS:TGF-β1 stimulated the expression of NOX-4 and collagen Ⅰ at mRNA and protein levels as well as the expression of PIK3CD and the activation of PI3K signaling pathway at a dose- and time-dependent manner. NOX-4 inhibitor DPI partly reversed TGF-β1-induced collagen Ⅰ expres-sion. Inhibition of NOX-4 down-regulated the degree of TGF-β1-stimulated activation of PI3K signaling pathway without effect on the expression of PIK3CD. CONCLUSION:NOX-4 participates in TGF-β1-induced collagen Ⅰ synthesis from lung cancer cells via regulating the activation of PI3K signaling pathway. TGF-β1/NOX-4/PI3K signaling pathway axis acts as a regulatory role in collagen Ⅰ synthesis from lung cancer cells.

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 study and establish the UPLC fingerprints of Lianhua Qingwen Capsules. Methods The samples were separated with a Waters ACQUITY UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) by linear gradient elution. The wavelength for detection was set at 239 nm; mobile phase was set at a flow rate of 0.3 mL/min;the column temperature was set at 30 ℃. Results UPLC fingerprints of Lianhua Qingwen Capsules were established with 32 common peaks. 9 of 32 common peaks were identified, including neochlorogenic acid (peak No.4, source from Lonicerae Japonicae Flos and Houttuyniae Herba), chlorogenic acid (peak No.6, source from Forsythiae Fructus, Lonicerae Japonicae Flos and Houttuyniae Herba), cryptochlorogenic acid (peak No.8, source from Lonicerae Japonicae Flos and Houttuyniae Herba), isoforsythiaside A (peak No.15, source from Forsythiae Fructus), forsythoside A (peak No.20, source from Forsythiae Fructus), quercitrin (peak No.23, source from Houttuyniae Herba), isochlorogenic acid C (peak No.24, source from Lonicerae Japonicae Flos), phillyrin (peak No.26, source from Forsythiae Fructus), glycyrrhizic acid (peak No.31, source from Glycyrrhizae Radix et Rhizoma). The similarities in 10 batches of Lianhua Qingwen Capsules samples were all above 0.96. Conclusion The method is with good precision, repeatability and stability, which can be used as a new means for the quality control of Lianhua Qingwen Capsules.

OBJECTIVE: To explore the effect of automotive paint volatile on the learning and memory ability and its influence mechanism of the amino acid neurotransmitters in the brain tissue of mice. METHODS: Thirty specific pathogen free healthy male Kunming mice were randomly divided into control group,primer group and topcoat group,10 mice in each group. By static inhalation intoxication method,the primer group and topcoat group were exposed to corresponding paint volatile 600 and 580 mg / m3 respectively every day for 4 weeks,6 days per week,one time a day,2 hours each time.The mice of the control group were kept in the exposure cabinet without any paint volatile. After the exposure,the neuroethology examination was carried out by Morris water maze test. The amino acid levels of glutamic acid( GLU),aspartic acid( ASP),γ-aminobutyric acid( GABA) and glycine( GLY) in brain tissue of mice were detected by high performance liquid chromatography. RESULTS: Compared with the control group,the escape latency and the first crossing platform time were longer( P < 0. 05),target quadrant staying time and platform crossing times were decreased( P <0. 05),and the levels of GLU,ASP,GABA and GLY in brain tissues were decreased in the primer group and the topcoat group( P < 0. 05). There was no significant difference between the primer group and the topcoat group in the above indexes( P > 0. 05). CONCLUSION: Automotive paint volatiles exposure may lower the learning and memory abilities of mice,and could reduce the secretion of amino acid neurotransmitters in the brain tissue of mice.

BACKGROUNDOocyte vitrification is widely used throughout the world, but its clinical efficacy is inconsistent and depends on the vitrification media. This study compared the developmental potential and clinical results of in vivo matured oocytes cryopreserved with different vitrification media.

METHODSThis retrospective study involved vitrified-warmed oocytes at one in vitro fertilization laboratory. Vitrification media kits comprised the MC kit (ethylene glycol [EG] plus 1,2-propanediol [PROH]), the KT kit (EG plus dimethyl sulphoxide [DMSO]), and the Modified kit (EG plus DMSO and PROH kit). Rates of oocyte survival and subsequent developmental potential were recorded and analyzed. The t-test and the Chi-square test were used to evaluate each method's efficacy.

RESULTSOocyte survival rate was significantly higher for the Modified kit (92.0%) than for the MC kit (88.2%) (P < 0.05) and the KT kit (77.3%) (P < 0.001). The rate of high-quality embryo development in the Modified kit group (35.8%) was significantly higher than in the MC kit group (29.0%) and the KT kit group (28.3%) (P < 0.001). No significant differences were observed in the clinical pregnancy and implantation rates among the MC, KT, and Modified kit groups (37.2% vs. 30.2% vs. 39.6%; 21.9% vs. 18.8% vs. 27.4%, respectively) (P > 0.05). The high-quality embryo rate per warmed oocyte was significantly higher (23.4%) in the Modified kit group than in the other groups (P < 0.001). The embryo utilization and live birth rates per warmed oocyte were the highest in the Modified kit group, but not significantly (P > 0.05).

CONCLUSIONSModified vitrification media are efficient for oocyte vitrification and, with further verification, may be able to replace commercially available media in future clinical applications.

Adult ; Cryopreservation ; methods ; Female ; Fertilization in Vitro ; methods ; Humans ; In Vitro Oocyte Maturation Techniques ; methods ; Oocytes ; cytology ; Pregnancy ; Retrospective Studies ; Vitrification