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.

The quality management system verification of 67 medical device manufacturers in some region was introduced generally.The common defects during the quality management system verification of medical device manufacturerswere summarized from 11 aspects of organization and personnel,plant and facility,equipment,document management,design and development,procurement,production management,quality control and etc.The causes for the common defects were analyzed.Some countermeasures were proposed including strengthening the training and education of related personnel,continuously promoting quality management system,enhancing managment and execution mechanism and improving the mechanism of personnel participation and encouragement.References were provided for establishing and running the quality management system of medical device manufacturers.[Chinese Medical Equipment Journal,2024,45(8):83-90]

Abstract: Objective　In order to explore the application prospects of the phenyl pyrazole insecticide fipronil for mosquito control and identify potential target genes involved in the resistance of Aedes aegypti to fipronil, and lay the foundation for an in-depth study of the resistance mechanism of Aedes aegypti to fipronil. Methods　Using Aedes aegypti sensitive strains as experimental materials, Aedes aegypti larvae were treated with fipronil, and the differences in gene expression of Aedes aegypti larvae before and after drug administration were compared at the transcriptome level using transcriptome sequencing combined with bioinformatics analysis, and the differential genes were analyzed. Results　A total of 757 differentially expressed genes were identified between the fipronil-treated group and control group, including 217 and 540 up- and down-regulated genes, respectively. Among these, the expression of glutamate-gated chloride channel (GluCls) genes varied significantly before and after treatment. Gene ontology analysis revealed that differentially expressed genes were enriched in catalytic activity, binding, metabolic processes, and membrane-related functions, while KEGG pathway analysis indicated enrichment in biosynthesis, metabolism, and life regulation processes, while the glutathione metabolic pathway was enriched in 15 differentially expressed genes. Conclusions The transcriptome results revealed that GST gene expression was significantly upregulated in fipronil-treated Aedes aegypti larvae, indicating that GST gene is involved in the development of fipronil resistance in Aedes aegypti larvae. In addition, GluCls gene expression was also significantly different before and after treatment, suggesting that GluCls migh be a potential target receptor for fipronil resistance in Aedes aegypti. As GluCls is an ideal target receptor found only in invertebrates, this discovery provides a reference and basis for further exploration of the toxicological mechanism of fipronil on Aedes aegypti.

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*

This study was to investigate the protective effect of paeoniflorin (PF) on hydrogen peroxide-induced injury. Firstly, "SMILES" of PF was searched in Pubchem and further was used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Injury-related molecules were obtained from GeenCards database, and the predicted targets of PF for injury treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, and the KEGG analysis was conducted in Webgestalt. Then, cell viability and cytotoxicity assay were established by CCK8 assay. Also, the experimental cells were allocated to control, model (200 μmol·L

Objective:To reveal the effective components， targets and possible mechanisms of Qinggan Huayu granules in the treatment of non-alcoholic fatty liver disease （NAFLD） and liver cancer based on network pharmacology and experimental verification， and to provide a basis for its rational interpretation of treating different diseases with same method for NAFLD and liver cancer. Method:Based on databases of traditional Chinese medicine and disease， the network pharmacology was used to screen main active compounds and potential targets of Qinggan Huayu granules for NAFLD and liver cancer. STRING 11.0 was used to analyze the interaction between potential targets. The core targets were selected from the interaction targets by cytoHubba plug-in. The gene ontology （GO） function and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed on the target by Metascape database. At the same time， in vitro experiments were conducted to validate the effect of kaempferol， one of the main active ingredients of Qinggan Huayu granules， on hepatocellular carcinoma cell model and NAFLD cell model. Result:A total of 43 potential targets of Qinggan Huayu granules for for NAFLD and liver cancer were screened， corresponding to 136 active ingredients in 8 herbal medicines. Through enrichment analysis of potential targets， there were 20 biological processes， 13 molecular functions， 9 cellular components and 15 signaling pathways. Qinggan Huayu granules regulated biological behaviors of tumors related to liver cancer and NAFLD （such as apoptosis inhibition and oxidative stress） mainly through kaempferol， quercetin， luteolin and other active ingredients for Caspase-3 （CASP3）， tumor protein p53 （TP53）， vascular endothelial growth factor A （VEGFA） and other hub genes. In vitro experiments revealed that kaempferol could inhibit cell proliferation in a dose-dependent manner in hepatocellular carcinoma cell model. And kaempferol could modulate the levels of malondialdehyde （MDA） and glutathione peroxidase （GPx）， which were the molecular markers of oxidative stress of NAFLD cell model. Kaempfero also regulated the expression level of CASP3 in hepatocellular carcinoma cell model and NAFLD cell model. Conclusion:The main mechanism of Qinggan Huayu granules in treating liver cancer and NAFLD with concept of treating different diseases with same method is related to systematic synergy effect of multiple compounds （represented by quercetin， luteolin and kaempferol）， multiple targets （represented by VEGFA， TP53 and CASP3） and multiple signaling pathways （represented by oxidative stress and cell apoptosis）.

italic>Dendrobium officinale Kimura et Migo is a rare Chinese herbal medicine, while Dendrobium crepidatum Lindl is a local medicine in Yunnan, both of which have the function of nourishing yin and stomach. To reveal the differences in chemical composition between the two species, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to analyze the chemical composition of stems and leaves of D. officinale and D. crepidatum. Principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) were used to determine the differences in metabolites between species and parts of Dendrobium. Fifty-eight chemical compounds were identified in the two species. Analysis indicated that the side ring of alkaloids connected with nitrogen was readily cleaved during analysis. The results of PCA analysis showed that the stems and leaves of D. officinale and D. crepidatum could be easily differentiated, and the chemical constituents of D. officinale and D. crepidatum were significantly different. OPLS-DA analysis showed that there were 16 metabolite differences between the stems and 22 differences in metabolites between the leaves of D. officinale and D. crepidatum. The main metabolite differences in components between the two Dendrobium species were dendrocrepidine B, dendrocrepidine C and dendrocrepine. There were 14 differences in metabolites between the stems and leaves of D. crepidatum. In conclusion, the chemical compositions of D. officinale and D. crepidatum are quite different; the small molecular compounds of D. officinale are mainly terpenoids and flavonoids, and the content of alkaloids is low. There is no significant difference between stem and leaf. In contrast, D. crepidatum is mainly composed of alkaloids and terpenoids, with crepidamine and dendrocrepine as its unique components, and there are great differences in the components between stems and leaves. This study provides a theoretical basis for the development and utilization of Dendrobium resources.

Objective:To compare the curative efficacy in the treatment of humeral surgical neck fractures between open reduction and locking plating versus closed reduction and interlocking intramedullary nailing.Methods:From July 2018 to July 2020, 60 patients with humeral surgical neck fracture were treated at Department of Orthorpaedic Trauma, Jiangmen Wuyi Hospital of Traditional Chinese Medicine. They were 24 males and 36 females, aged from 40 to 70 years and injured at the left side in 35 cases and at the right side in 25 ones. Of them, 30 underwent open reduction and locking plating (open group) and the other 30 closed reduction and interlocking intramedullary nailing (closed group). The 2 groups were compared in terms of operation time, intraoperative blood loss, surgical incision length, fracture healing time, Neer shoulder function scoring 3 months after surgery, and postoperative complications.Results:There were no statistically significant differences between the open and closed groups in preoperative general data, showing they were comparable ( P>0.05). The length of surgical incision [(5.2±1.1) cm], operation time [(34.3±12.7) min], intraoperative blood loss [(52.5±7.3) mL] and fracture healing time [(9.2±1.5) weeks] in the closed group were significantly better than those in the open group [(11.1±2.5) cm, (69.4±21.4) min, (123.5±5.2) mL and (14.2±3.4) weeks)] ( P<0.05). The excellent and good rate by Neer shoulder function scoring at 3 months after operation in the closed group (93.3%, 28/30) was significantly higher than that in the open group (66.7%, 20/30) ( P<0.05). There were no postoperative complications in either group. Conclusion:In the treatment of humeral surgical neck fractures, the curative efficacy of closed reduction and interlocking intramedullary nailing is better than that of open reduction and locking plating.

Wound age estimation is one of the major tasks in forensic practice. However, relatively accurate estimation of the wound age is still a conundrum and research spotlight world-widely. Studies show that microRNAs (miRNAs) are involved in the whole process of the skin wound repair, and miRNAs, as biomarkers, might be used to estimate the time of skin injury owing to their characteristic advantage. This paper summarizes the miRNA fundamental function, properties, current research progress in the estimation of wound age, and its limitations, and put forward prospect of potential application and research based on miRNAs in estimation of wound age.
Biomarkers ; Humans ; MicroRNAs/genetics* ; Skin/injuries* ; Soft Tissue Injuries ; Wound Healing

Objective: The moisture content in the soil directly affects the yield and quality of Panax notoginseng, especially at the age of three years old. However, the suitable moisture for the growth of P. notoginseng is unknown. In this study, the effects of different soil moisture on the growth of P. notoginseng were studied. Methods: Four different water treatments (0.45 field capacity (FC), 0.60 FC, 0.70 FC, and 0.85 FC) were set up in Shilin County, Yunnan Province, China. The water consumption and daily dynamic of water consumption were determined daily (from April 21 to October 18, 2012), and the daily dynamic of water consumption under different weather conditions (sunny and rainy) was determined. The transpiration coefficient and water use efficiency were calculated through dry matter accumulation and total water consumption. Accumulation of saponins of roots of P. notoginseng were analyzed by HPLC after treated, and the soil moisture content suitable for the growth of P. notoginseng was estimated by regression fitting of the active ingredient accumulation and the soil moisture content. Results: The water consumption of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.89, 3.68, 3.37 and 2.73 kg/plant per day, respectively. The water consumption of P. notoginseng from June to August was greater than other months. The daily dynamic of water consumption on sunny days and sunny days after rain showed a “double peak” feature, and it showed a “single peak” feature on rainy days. The water uses efficiency (WUE) of 0.85 FC, 0.70 FC, 0.60 FC and 0.45 FC were 2.51, 3.32, 4.59, 3.39 gDW/kg H