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*

By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.
Benchmarking ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Glycyrrhiza ; Quality Control

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

OBJECTIVE: To investigate the relationship between hypoxia inducible factor 1 (HIF1α) and Wilms' tumor 1associating protein (WTAP) expression level in t(8;21) acute myeloid leukemia cells. METHODS: The t(8;21) acute myeloid leukemia cell lines, including SKNO-1 and Kasumi-1 were treated by Echinomycin for 24 h, RT-qPCR and Western blot were used to detect the expression levels of WTAP mRNA and the protein. The CoCl RESULTS: The expression level of WTAP mRNA and the protein in the echinomycin treated group was significantly lower than those in the control group (P<0.01). The expression level of WTAP protein in the CoCl CONCLUSION The inhibition of HIF1-α could down-regulates the expression of WTAP, while the up-regulation of HIF1α could up-regulates the expression of WTAP, which shows that there is a positive correlation of HIF1α and WTAP expression. This result suggesting that HIF1α may be involves in the expression regulation of WTAP gene.
Cell Cycle Proteins ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Leukemia, Myeloid, Acute/genetics* ; Nuclear Proteins ; RNA Splicing Factors ; RNA, Messenger

In the field of forensic medicine, diagnosis of sudden cardiac death is limited by subjective factors and manual measurement methods, so some parameters may have estimation deviation or measurement deviation. As postmortem CT imaging plays a more and more important role in the appraisal of cause of death and cardiopathology research, the application of deep learning such as artificial intelligence technology to analyze vast amounts of cardiac imaging data has provided a possibility for forensic identification and scientific research workers to conduct precise diagnosis and quantitative analysis of cardiac diseases. This article summarizes the main researches on deep learning in the field of cardiac imaging in recent years, and proposes a feasible development direction for the application of deep learning in the virtual anatomy of sudden cardiac death at present.
Artificial Intelligence ; Autopsy ; Death, Sudden, Cardiac/etiology* ; Deep Learning ; Forensic Medicine ; Humans

Objective To investigate the effect of the endoscopic surveillance system in irrigating fluid absorption and bleeding during transurethral resection of the prostate.Methods In vitro trials,we simulated the fluid absorption and bleeding in the operation by using self-developed endoscopic surveillance system from January 2013 to June 2013.Continuous irrigation of 5 ％ mannitol solution,we extracted 5 times irrigating fluid (each time 100 ml and a total of 500 ml) in the process of irrigation and recorded absorption measurements of every time extraction rinses.At the same time,we dripped human whole blood 5 times(each time 5 ml and a total of 25 ml) in the process of irrigation and recorded the bleeding measurements.The above process was repeated three times to detect the accuracy and consistency of the endoscopic surveillance system.In clinical trials,50 cases of BPH were monitored in surgery and the biochemical index,hemodynamics,irrigating fluid absorption and bleeding were compared from October 2016 to April 2017.The included criteria contained as follow:the age of patients should be more than 50 years.The transabdominal ultrasound showed that the volume of prostate should be more than 60 ml.The maximal uroflowmetry should be less than 15ml/s.The IPSS scores should be more than 8.Based on the operative time,two groups (＜60 min and ≥ 60 min) were classified.Results We developed the endoscopic surveillance system which is original in the world.In vitro trials,the average irrigating fluid were (100.60 ± 2.07) ml,(201.00±3.39) ml,(302.00±4.67) ml,(403.60±4.39) ml and (502.40 ±7.57) ml;and the average bleeding were (5.06 ± 0.11) ml,(10.10 ± 0.16) ml,(15.04 ± 0.15) ml,(20.06 ± 0.11) ml and (25.10 ± 0.16) ml.No significant difference was observed in all groups (P ＞ 0.05).In clinical trials,we compared some preoperative and postoperative indexes.The average blood oxygen saturation were (94.46 ± 2.49) ％ and (92.39 ± 2.77) ％ (P ＜ 0.01),the average Serum sodium ion concentration were (141.05 ± 2.52) mmol/L and (138.06 ± 4.27) mmol/L(P ＜ 0.01),the average HGB were (143.50 ± 13.43) g/L and (137.04 ± 14.25) g/L(P ＜ 0.01).The average HCT were (42.05 ± 4.09) ％ and (137.04 ± 14.25) ％ (P ＜ 0.01).The average HR were (77.9 ± 7.6) beats per minute and (77.93 ± 6.93) beats per minute (P＞0.05).The MAP were (90.32 ± 9.75) mmHg and (91.07±8.96)mmHg(P＞0.05).The average serum potassium ion concentration were (4.13 ± 0.53) mmol/L and (4.09 ± 0.37) mmol/L (P ＞ 0.05).The average irrigating fluid absorption of the group less than 60 minutes and the group equal or more than 60 minutes were (401.83 ± 279.23) ml and (885.25 ± 367.68) ml (P ＜ 0.01).The average blood loss were (64.10 ±47.47) ml and (158.40 ± 65.22) ml(P ＜0.01).The preoperative and postoperative hemodynamic,blood biochemical and hematology showed difference in our trials.Irrigating fluid absorption and blood loss were positively associated with operation time.Conclusions The endoscopic surveillance system was safety and accuracy.It can offer real-time monitoring data and alarm mechanism for the surgeons that possibly improve operation safety.

OBJECTIVESTo investigate the resistance and virulence profiles of uropathogenic Escherichia coli (UPEC) and its treatment by Chinese medicine (CM) Fuzheng Qingre Lishi Formula (, FQLF).

METHODSUPEC strains were isolated from recurrent urinary tract infections (UTIs) patients. Patient sensitivities to 17 antibiotics were tested by the disk diffusion method. Virulence genes were screened by plolymerase chain reaction. A mouse model was constructed using a multi-drug resistant and virulent UPEC strain and treated with FQLF or the antibiotic imipenem. The treatment efficacy was evaluated by bacterial clearance from urine and the urinary organs.

RESULTSA total of 90 UPEC strains were collected, and 94.4% of the isolates were resistant to at least 1 antibiotic. Approximately 66.7% of the UPEC strains were multi-drug resistant. More than one virulence gene was found in 85.6% of the isolates. The extended-spectrum β-lactamases (ESBL)-positive strains were more resistant than the negative ones. The virulence gene number was positively correlated with the resistance number (P<0.05). A mouse model was successfully constructed using UPEC10. Treatment with either FQLF or antibiotics significantly cleared bacteria from the mouse urine after 14 days. In the untreated control, the bacteria lasted for 28 days. FQLF treatment of the UTI mouse model greatly reduced the bacterial number in the kidney and bladder, but could not completely clear the bacteria.

CONCLUSIONSMulti-drug resistance is common among UPEC isolates, and the resistance is positively related with virulence. FQLF could treat UPEC UTIs, but could not completely clear the bacteria from the host.

Objective To compare the curative effect and short-term benefits of laparoscopic liver resection with open liver resection in elderly patients with malignant liver tumors and medical comorbidities.Methods Patients aged 70 and over who received liver resections for malignant liver tumors between January and October 2015 were enrolled.The perioperative outcomes of 17 patients with laparoscopic approach were matched and compared with those of 34 patients with conventional open approach in a 1:2 ratio.Results There was no significant difference found between the two groups with regard to age,gender,incidence of comorbid illness,hepatitis B positivity,and Child-Pugh grading of liver function.The median tumor size was 3 cm for both groups.The types of liver resection were similar between the two groups with no significant difference in the duration of operation (laparoscopic: 195 min vs.open: 210 min,P=0.436).The perioperative blood loss was 150 mL in the laparoscopic group and 330 mL in the open group (P=0.046) with no significant difference in the number of patients with blood transfusion.The duration of hospital stay was 6 days (3-15 days) for the laparoscopic group and 8 days (5-105 days) for the open group (P=0.005).Conclusion Laparoscopic liver resection is safe and feasible for elderly patients.The short-term benefits of laparoscopic approach proves to be evident for geriatric oncological liver surgery.

OBJECTIVETo observe the effect of solar infrared ray (IR) radiation on the expressions of c-Jun and collagens I and III in cultured human skin fibroblasts (HSFs) and explore the molecular mechanism by which IR radiation causes aging of the skin.

METHODSPrimarily cultured HSFs exposed to IR radiation were examined for changes of the cell viability with MTT assay. The mRNA and protein expressions of c-Jun and collagens I and III was detected with real-time quantitative PCR and immunocytochemistry.

RESULTSMTT assay showed that IR irradiation caused inhibition of cell proliferation compared with the control cells. The mRNA and protein expression of collagen I was decreased significantly by IR irradiation with the increase of the irradiation dose (P<0.01). HSFs irradiated by IR for 12 h showed a dose-dependent reduction of the expression of collagen type III mRNA and protein (P<0.05, P<0.01), but the expression increased dose-dependently in response to IR exposure for 24 h (P<0.05 or 0.01). IR irradiation enhanced the mRNA and protein expression of c-Jun in a dose-dependence manner (P<0.05 or 0.01).

CONCLUSIONSIR irradiation can increase the expression of c-Jun, inhibit the expression of collagen I, and cause disturbance in collagen III expression in human skin fibroblasts, which may be one of the mechanism of IR radiation to initiate and promote skin photoaging.

Cell Proliferation ; Cell Survival ; Cells, Cultured ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Fibroblasts ; metabolism ; radiation effects ; Humans ; Infrared Rays ; Proto-Oncogene Proteins c-jun ; metabolism ; RNA, Messenger ; metabolism ; Skin ; cytology ; Skin Aging ; Ultraviolet Rays

BACKGROUNDMicroRNA-206 (miR-206) and connexin 43 (Cx43) are related with the distant metastasis of breast cancer. It remains unclear whether the regulatory effect of miR-206 on Cx43 is involved in metastasis of breast cancer.

METHODSUsing quantitative real-time polymerase chain reaction and Western blot, the expressions of miR-206 and Cx43 were determined in breast cancer tissues, hepatic and pulmonary metastasis (PM), and cell lines (MCF-10A, MCF-7, and MDA-MB-231). MCF-7/MDA-M-231 cells were transfected with lentivirus-shRNA vectors to enhance/inhibit miR-206, and then Cx43 expression was observed. Cell counting kit-8 assay and Transwell method were used to detect their changes in proliferation, migration, and invasion activity. The mutant plasmids of Cx43-3' untranslated region (3'UTR) at position 478-484 and position 1609-1615 were constructed. Luciferase reporter assay was performed to observe the effects of miR-206 on luciferase expression of different mutant plasmids and to confirm the potential binding sites of Cx43.

RESULTSCx43 protein expression in hepatic and PM was significantly higher than that in the primary tumor, while no significant difference was showed in messenger RNA (mRNA) expression. MiR-206 mRNA expression in hepatic and PM was significantly lower than that in the primary tumor. Cx43 mRNA and protein levels, as well as cell proliferation, migration, and invasion capabilities, were all significantly improved in MDA-MB-231 cells after reducing miR-206 expression but decreased in MCF-7 cells after elevating miR-206 expression, which demonstrated a significantly negative correlation between miR-206 and Cx43 expression (P = 0.03). MiR-206 can drastically decrease Cx43 expression of MCF-7 cells but exerts no effects on Cx43 expression in 293 cells transfected with the Cx43 coding region but the lack of Cx43-3'UTR, suggesting that Cx43-3'UTR may be the key in Cx43 regulated by miR-206. Luciferase expression showed that the inhibition efficiency was reduced by 46.80% in position 478-484 mutant, 16.72% in position 1609-1615 mutant; the inhibition was totally disappeared in double mutant (P = 0.02).

CONCLUSIONSMiR-206 can regulate the expression of Cx43, the cytobiological activity, and the metastasis of breast cancer through binding to the two binding sites in Cx43-3'UTR: position 478-484 and position 1609-1615.

Breast Neoplasms ; pathology ; Cell Movement ; Cell Proliferation ; Connexin 43 ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; MicroRNAs ; genetics ; physiology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; RNA, Messenger ; analysis