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 analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections.

OBJECTIVE: To explore biomechanical characteristics of minimally invasive different screw fixations in treating Sanders typeⅡcalcaneal fractures. METHODS: Dicom data of calcaneus by CT scan were input into Mimics 21.0 software and Ansys15.0 software to construct three-dimensional finite element digital model of calcaneus;this model was input into UG NX 10.0 software, and calcaneus was cut according to Sanders classification to establish Sanders typeⅡ calcaneus model with posterior articular surface collapse;then simulated minimally invasive screw internal fixation after calcaneal fracture:a screw from posterior articular surface was used to outside-in fix sustentaculum tali, other 4 screws were used to fix calcaneus by different methods through calcaneal tuberosity, and 4 different calcaneal models were obtained. Under the same conditions, 4 types of internal fixation models were loaded respectively, and nonlinear finite element analysis was performed to calculate the stress distribution of different internal fixation models. RESULTS: Under the same condition of loading, the model 3 had smaller displacement value, maximum calcaneus displacement value and maximum equivalent stress value of the screw than other three internal fixation models, and the stress was more dispersed. CONCLUSION In minimally invasive screw internal fixation of calcaneus fracture, after 1 sustentaculum tali screw fixation, 2 screws crossed fix posterior articular surface from calcaneal tuberosity, 2 screws fix parallelly calcaneocuboid joint from calcaneal tuberosity are more suitable for biomechanical requirements, and could provide basic theory for clinical treatment.
Bone Screws ; Calcaneus/surgery* ; Finite Element Analysis ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Humans ; Treatment Outcome

OBJECTIVE: To investigate the therapeutic effect of gene silencing peptidyl arginine deaminase 4 (PAD4) on pulmonary interstitial lesions induced by collagen-induced arthritis (CIA) mice, and possible mechanisms. METHODS: A CIA mouse model was established in DBA/1 mice, followed by a tail vein injection of the virus solution prepared by the PAD4-siRNA expression vector once a week for 8 times. The mice were sacrificed at the end of the experiment. The expression of PAD4 mRNA in lungs was detected by real-time quantitative PCR (qRT-PCR). The expression of PAD4 protein was detected by tissue immunohistochemistry. Cell culture was performed by spleen tissue. Flow cytometry changes in the ratio of Tfh cells to Tfr cells were examined; lung staining was performed in the lungs to observe changes in lung pathology. RESULTS: (1) Compared with the blank group, the expression of PAD4 mRNA in the lung tissue of the model group increased, the difference was statistically significant (P < 0.05). PAD4 mRNA in the lung tissue of the CIA mice after PAD4-siRNA treatment. The expression level was significantly lower than that of the model group and the negative control group, and the difference was statistically significant (P < 0.05). (2) Red fluorescence was less in the lung tissue of the blank group, while more red fluorescence was observed in the inflammatory cell infiltration area and trachea around the lung tissue of the model group and the negative control group, and the red fluorescence of the three groups after PAD4-siRNA treatment was significantly reduced; (3) Compared with the blank group, the proportion of Tfh cells in the model group increased, the difference was statistically significant (P < 0.05), the proportion of Tfh cells in spleen cells of the CIA mice after PAD4-siRNA treatment was significantly lower than that of the model group and the negative control group, the difference was statistically significant (P < 0.05); compared with the blank group, in the mouse spleen cells in the model group the proportion of Tfr cells was slightly decreased, but the difference was not statistically signifi-cant. The proportion of Tfr cells in the spleen cells of the mice increased after PAD4-siRNA treatment, but the difference was statistically significant only in the PAD4-siRNA2 group compared with the model group and the negative control group (P < 0.05); (4) The proportion of Tfh/Tfr in the spleen cells of the model group was increased, compared with the blank group, the difference was statistically significant (P < 0.05); the ratio of Tfh/Tfr in the three groups after PAD4-siRNA treatment all decreased, the difference was statistically significant (P < 0.05); (5) Compared with the blank group, the alveolar wall of the lung tissue of the model group was thickened, the inflammatory cell infiltration was increased, and the lung tissue destruction and inflammatory infiltration of the CIA mice were decreased after PAD4-siRNA treatment. The degree of reduction was reduced. CONCLUSION Gene silencing of PAD4 can reduce the proportion of Tfh cells, increase the proportion of Tfr cells, reverse the proportion of Tfh/Tfr, and reduce the degree of interstitial lesions and inflammatory infiltration of lung tissue.
Animals ; Arginine ; Arthritis, Experimental/therapy* ; Gene Silencing ; Lung ; Mice ; Mice, Inbred DBA

With the discussion on the origins and the evolution of Star Twelve Points, combined with ancient astronomical stellar map, it is realized that the three-dimensional spatial diagram of Star Twelve Points can be approximately regarded as a Big Dipper map from the side view. Under the direction of image thinking, the function of Big Dipper was compared with the function of Star Twelve Points. Furthermore, according to "the opening-closing-pivoting" theory in and the theory of " cycle in round" proposed by , the mechanisms of Star Twelve Points on adjusting functional activities of and the movement of viscera-meridian--blood is elaborated, providing a new idea for acupuncture clinical treatment of miscellaneous diseases.

BACKGROUND:Collagen-bioglass-polycaprolacton (COL-BG-PCL) composites have good biocompatibility, mechanical properties and biodegradability that are beneficial to cell adhesion, proliferation and angiogenesis. OBJECTIVE:To study the effect of COL-BG-PCL bioactive scaffold on the proliferation, migration and differentiation of human dental pulp cells (hDPCs). METHODS:hDPCs were isolated and cultured on the COL-BG-PCL bioactive scaffold. MTT, cell scratch test and enzyme-linked immunosorbent assay (ELISA) assay were used to detect the proliferation, migration and differentiation abilities of hDPCs before and at 1, 3, 7, 14, 24 days after inoculation onto the COL-BG-PCL bioactive scaffold. RESULTS AND CONCLUSION:Compared with the cells without inoculation onto the COL-BG-PCL bioactive scaffold, (1) the proliferation ability of the cells cultured on the COL-BG-PCL scaffold was significantly enhanced (P<0.01), and with the prolongation of the inoculation time, the cell proliferation ability was gradually increased; (2) the cell migration ability of the cells cultured on the COL-BG-PCL scaffold was significantly enhanced (P<0.01), and with the prolongation of the inoculation time, the migration ability of the cells cultured on the COL-BG-PCL scaffold was gradually increased; (3) the level of alkaline phosphatase in the supernatant of the cells cultured on the COL-BG-PCL scaffold was significantly increased (P<0.01), and with the prolongation of the inoculation time, the level of alkaline phosphatase in the supernatant was gradually increased. In summary, the COL-BG-PCL scaffold can promote the proliferation, migration and differentiation of hDPCs.

Animals ; Carrier Proteins ; genetics ; Immunohistochemistry ; Lacrimal Apparatus ; metabolism ; Lung ; metabolism ; Mice ; Mice, Inbred NOD ; Microfilament Proteins ; genetics ; RNA, Small Interfering ; genetics ; physiology ; Random Allocation ; Sjogren's Syndrome ; genetics ; immunology ; therapy