Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

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*

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-β-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-β-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) μmol·L~(-1).
Fruit/chemistry* ; Morinda/chemistry* ; Synoviocytes ; Cell Proliferation ; Arthritis

Lung cancer, as one of the malignant tumors with the fastest increasing morbidity and mortality in the world, has a serious impact on people's health. With the continuous advancement of medical technology, more and more medical methods are applied to lung cancer screening, which has gradually increased the detection rate of early lung cancer. At present, the standard operation for the treatment of early non-small cell lung cancer (NSCLC) is still lobectomy and mediastinal lymph node dissection. There is a growing trend to use segmentectomy for the treatment of early stage lung cancer. Anatomical segmentectomy not only removes the lesions to the maximum extent, but also preserves the lung function to the greatest extent, and its advantages are also obvious. This article reviews the progress of anatomical segmentectomy in the treatment of early NSCLC.

Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Doxorubicin/therapeutic use* ; Etoposide ; Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prednisone/therapeutic use* ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Vincristine/therapeutic use*

Objective: To assess the level and trend of varicella-zoster virus (VZV) antibody among healthy population in Beijing in 2017, after the five-year implementation of the two doses varicella vaccination strategy in 2012, and to provide evidence for scientific evaluation of immunization strategy. Methods: A total of 2 144 subjects in ten age groups from 8 districts of Beijing city were recruited in this study using cross-sectional survey based on multi-stage cluster random sampling method. Serum samples were collected and VZV antibody was detected by ELISA. The influencing factors of antibody concentration and positive rate were analyzed and compared with the study in 2012. The antibody concentration and antibody positive rate were analyzed by nonparametric test and χ² test respectively. Results: The ratio of subjects with registered residence in Beijing city to other provinces was 1∶1. The ratio of male to female was 1∶1.08. The median concentration of VZV antibody was 341.4 (78.6, 1 497.8) mIU/ml, and the total antibody positive rate was 71.1% (1 524/2 144). There were significant differences in antibody positive rate (χ²=736.39, P<0.01) and antibody concentration (χ²=740.34, P<0.01) among different age groups. The antibody positive rate generally increased with age (χ²_trend=7.32, P_trend<0.01). Among 862 children under 14 years old, the antibody positive rate of two doses vaccination 72.8% (182/250) was significantly higher than that of one dose vaccination 51.9% (154/297) (χ²=25.14, P<0.01). There was significant difference between 1-4 years old group (χ²=11.71, P<0.01) and 10-14 years old group (χ²=5.95, P=0.02), but not in 5-9 years old group (χ²=3.00, P=0.07). Compared with the study in 2012, the antibody positive rate increased in 5-9 years old group (χ²=14.35, P<0.01) and decreased in 1-4 years old group (χ²=11.51, P=0.01) in 2017. Conclusion: The recommended varicella booster vaccination has significantly improved the VZV antibody level of children in Beijing city. In the future, it is necessary to explore a more optimized two doses varicella vaccination schedule for children in combination with epidemiological evidence.
Adolescent ; Antibodies, Viral ; Chickenpox/prevention & control* ; Chickenpox Vaccine ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Herpesvirus 3, Human ; Humans ; Infant ; Male ; Vaccination

The chemical constituents from the branches and leaves of Artocarpus incisus were isolated and purified via silica gel, ODS, and Sephadex LH-20 column chromatography as well as preparative HPLC. The chemical structures of all isolated compounds were identified in the light of their physicochemical properties, spectroscopic analyses, and comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 20 compounds were isolated and characterized from the 90% ethanol extract of the branches and leaves of A. incisus, which were identified as tephrosin(1), 6-hydroxy-6 a, 12 a-dehydrodeguelin(2), sarcolobin(3), lupiwighteone(4), 12-deoxo-12α-methoxyelliptone(5), 6 aα,12 aα-12 a-hydroxyelliptone(6), homopterocarpin(7), 3-hydroxy-8,9-dimethoxypterocarpan(8), pterocarpin(9), maackiain(10), medicarpin(11), calycosin(12), genistein(13), formononetin(14), 5-hydroxy-4',7-dimethoxy isoflavone(15), liquiritigenin(16), 4(15)-eudesmene-1β,7α-diol(17), ent-4(15)-eudesmene-1β,6α-diol(18), 1α-hydroxyisodauc-4-en-15-al(19), and guaianediol(20). Except compounds 13 and 16, all other compounds were isolated from the Artocarpus plants for the first time. Additionally, using MTS assay, compounds 1-20 were eva-luated for their anti-rheumatoid arthritis activities by measuring their anti-proliferative effects on synoviocytes in vitro. As a consequence, compounds 1-16 showed notable anti-rheumatoid arthritis activities, which displayed inhibitory effects on the proliferation of MH7 A synovial fibroblast cells, with the IC_(50) values in range of(9.86±0.09)-(218.07±1.96) μmol·L~(-1).
Arthritis ; Artocarpus ; Cell Proliferation ; Ethanol ; Genistein ; Plant Extracts/pharmacology* ; Silica Gel ; Synoviocytes

The placement of the flexible ureteroscopic sheath during lithotripsy may injure the ureter. We have developed a double-tube flexible ureteral access sheath. Thirteen patients with renal calculi were treated with double-tube and flexible sheath in one stage. CT examination of 13 cases showed that the ureter was normal. The double-tube flexible ureteral access sheath makes the operation of sheathing easy, safe and effective.