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*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVES: To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora. METHODS: Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy. RESULTS: The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05). CONCLUSIONS The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.
Bacteria/genetics* ; Bifidobacterium ; Child ; Feces/microbiology* ; Gastrointestinal Microbiome ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Aim To explore the anti-inflammatory effect of taurolithocholic acid (TLCA) through network pharmacology-based analyses, to verify with in vitro macrophage study and to reveal the possible mechanisms. Methods The potential targets of TLCA were acquired from public database, and then the protein-protein interaction (PPI) networks against inflammation were constructed and visualized by using Cytoscape. Gene ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. The binding activity of TLCA and its target (TGR5) was evaluated through molecular docking analysis. Lastly, the results of the network analysis were confirmed by lipopolysaccharide and interferon-γ induced RAW264.7 cells. Results There were 87 anti-inflammatory potential targets were screened. GO analysis revealed gene functions were mainly involved in regulation of inflammatory response, membrane raft and protein tyrosine kinase. The results of KEGG pathway analysis suggested that PI3K-Akt signaling pathway, human cytomegalovirus infection might be the critical pathways of TLCA against inflammation. The results of in vitro experiments showed that TLCA decreased the LPS and IFN-γ induced inflammatory response in RAW 264.7 macrophages. Furthermore, the expression of TGR5 protein increased after TLCA treatment. Conclusions The potential therapeutic targets of TLCA against inflammation are revealed through network pharmacology analysis. Our results indicate that TLCA might regulate key inflammatory markers through the membrane receptor TGR5.

Objective To analyze the protective effect of luteolin on the pancreas of mice with severe acute pancreatitis and to explore its possible molecular mechanism. Methods Sixty healthy male C57/ BL mice of SPF grade were divided into three groups according to the random number table method, the control group, the severe acute pancreatitis (SAP) model group and the treatment group, 20 cases in each group. The model was established by the caerulein method. The levels of lipase, amylase, heme oxygenase (HO)-1, tumor necrosis factor (TNF)-α, malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by ELASA method . The protein and mRNA levels of nuclear factor(NF)-κB, P38 and p-P38 in each group were determined by Western blotting and Real-time PCR. Results Compared with the control group, the pancreas dry-wet weight ratio, lipase and amylase, inflammatory factors HO-1, TNF-α levels, oxidative stress index MDA levels increased significantly, while SOD levels were significantly lower in the model group and the treatment group (P<0. 05). Compared with the model group, the pancreas dry-wet weight ratio, lipase and amylase, TNF-α and MDA levels in the treated group decreased significantly, while HO-1 and SOD levels increased significantly (P<0. 05). Compared with the control group, the levels of NF-κB and p-P38 protein and mRNA in the model group and the treatment group increased significantly (P<0. 05), and there was no significant change in P38 mRNA protein and expression level (P>0. 05). Compared with the model mice, the levels of NF-κB, p-P38 protein and mRNA in the treated group decreased significantly (P<0. 05). Conclusion Luteolin has a protective effect on SAP mice. Its possible molecular mechanism is to relieve inflammatory stress and oxidative stress, and down-regulate the expression of NF-κB and p-P38 protein.

Objective To evaluate the value of the three-dimensional visualization technology for the preoperative assessment of liver autotransplantation for end-stage hepatic alveolar echinococcosis. Methods A total of 8 patients with end-stage hepatic alveolar echinococcosis undergoing liver autotransplantation in Qinghai Provincial People’s Hospital from May 2013 to July 2017 were collected. All cases received preoperative abdominal CT scanning and dynamic three-phase enhanced CT scanning, and the original CT data were transferred to the human 3D visualization virtual surgical planning system. The volumes of Echinococcus multilocularis and pre-resected liver were measured using the 3D visualization reconstruction, and the relationship between the lesion and the neighboring tissues was observed. The value of the 3D visualization technology for the preoperative assessment of liver autotransplantation for end-stage hepatic alveolar echinococcosis was assessed by comparing with the intraoperative findings. Results The 3D visualization reconstruction model clearly displayed the adjacent relationship between the lesions of end-stage hepatic alveolar echinococcosis and the neighboring tissues, and no significant difference was seen between the pre-resected liver volume in 3D visualization reconstruction model and the actually resected liver volume (t = 1.083, P > 0.05). Conclusions 3D visualization technology is feasible to develop a reasonable scheme for liver resection and vascular anastomosis for end-stage hepatic alveolar echinococcosis prior to liver autotransplantation, which may increase the success of surgery and improve the prognosis.

Objective To develop an infusion joint of the two-cavity catheter used for deep vein thrombolysis and explore its clinical application.Methods The joint was composed of a perfusion tube,a perfusion tube tee,two connecting hoses,two connecting hard tubes,two Luer tapers,a liquid inlet connected with the tee,No.1 and No.2 liquid outlets.The liquid medicine was driven to flow through the tube and inlet by gravity,and then came into No.1 and No.2 liquid outlets respectively.Results There were no significant differences between the joint and the traditional way when used for deep vein thrombolysis with a two-cavity catheter (P＞0.05),while the joint had patient satisfaction increased significantly and the time consumed decreased obviously when compared with the traditional way (P＜0.05).Conclusion The joint executes deep vein thrombolysis with a two-cavity catheter and only a set of infusion set,gains advantages in simple structure,low cost and easy operation,and thus is worthy promoting clinically.

Objective To investigate the clinical characteristics and antimicrobial resistance of Acinetobacter baumannii(A.baumannii) in neonatal intensive care units (NICUs).Methods The clinical isolation and antimicrobial resistance of A.baumannii causing healthcare-associated infection(HAD in 4 NICUs of a hospital from October 2012 to October 2014 were analyzed statistically.Results A total of 11 640 neonates were admitted in 4 NICUs,500(4.3 ％) developed HAI,51 (10.2 ％) developed 52 cases of A.baumannii infection.Distribution of A.baumannii infection was as follows:NICU of extremely premature infants,premature infants,full-term infants,and surgical NICU were 42,1,4,and 5 cases respectively.Incidences of A.baumannii HAI in 4 seasons were compared,difference was statistically significant(x2 =16.05,P＜0.05),infection mainly occurred in the spring and summer.A.baumannii had high resistance rates to β-1actam antibiotics (such as piperacillin/sulbactam,cefepime,imipenem)and gentamycin(＞90 ％),resistance rate to amikacin was the lowest (51.9 ％).Among 52 strains of A.baumannii,46 were multidrug-resistant strains,and 3 were extensively drug-resistant strains.Conclusion A.baumannii HAI is most serious in NICU of extremely premature infants,resistance rates to commonly used antimicrobial agents are high.