Objective To explore the effects of plantamajoside on the proliferation and invasion of human gastric cancer cell line BGC823.Methods BGC823 cells were randomly separated into a control group,a plantamajoside group,an AAV-NC(transfection of empty plasmids packaged with lentivirus)group and a plantamajoside+AAV-HIF-1α(transfection of HIF-1α overexpression plasmid packaged with lentivirus)group.Cell proliferation,inva-sion,apoptosis,the numbers of vascular mimicry(VM)lumens and vascular branches,the expression of prolifera-tion,apoptosis,epithelial mesenchymal transition(EMT)related proteins,HIF-1α/VEGF pathway proteins of cells were all examined.Results Compared with control group,the BGC823 cell viability,colony formation num-ber,invasion number,VM lumen number,vascular branch number,and expression of Ki-67,PCNA,vimentin,MMP9,Snail,VEGFA,VE-cadhering,HIF-1α and VEGF protein were all lower in plantamajoside group(P＜0.05).The apoptosis rate,the cleaved Caspase-3,Bax,and E-cadherin protein expression were significantly increased(P＜0.05).Compared with plantamajoside group,the BGC823 cell viability,colony formation number,invasion number,VM lumen number,vascular branch number,and expression of Ki-67,PCNA,vimentin,MMP9,Snail,VEGFA,VE-cadherin,HIF-1α and VEGF protein were higher in the plantamajoside+AAV-HIF-1α group(P＜0.05).The apoptosis rate,the cleaved caspase-3,Bax,and E-cadherin protein expression were lower(P＜0.05).Conclusions Plantamajoside inhibits proliferation,EMT,invasion,and VM of human gastric cancer cell line and induce its apoptosis.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To explore the factors affecting the use of medical sutures in medical institutions based on the autore-gressive integrated moving average(ARIMA)model so as to provide basis and optimization strategy for the rational use of medical sutures in medical institutions.Methods The monthly usage amount of medical sutures in some hospital from January 2014 to November 2023 was used as the research subject.An ARIMA model was established by R language,with the data on medical suture usage amount from January 2014 to December 2018 used as the training set;the reliability of the ARIMA model was verified with the data on medical suture usage amount from January to December 2019 as the validation set.The monthly usage amount of medical sutures from January 2021 to November 2023 was predicted with the validated ARIMA model,then the predictive value was compared with the actual one to evaluate the benefits of implementing the medical suture optimization policy in January 2021.Results The established ARIMA model passed the white noise test(P＞0.05),and the difference between the predicted and actual values for the whole year of 2019 was not statistically significant(P＞0.05);after the implementation of the medical suture optimization policy,the actual usage amount of medical sutures in some hospital decreased.The actual value from January 2021 to November 2023 was much lower than the predicted value,and the difference was statistically significant(P＜0.05).Conclusion The ARIMA model-based medical suture usage data prediction and configuration optimization scheme contributes to clarifying the law of medical suture usage in some hospital,and provides references for optimization and precision managment of medical suture configuration.[Chinese Medical Equipment Journal,2024,45(8):73-77]

In recent years,the isolation rate of carbapenem-resistant Klebsiella pneunoniae(CRKP)in China has increased year by year.Due to its multidrug resistance and high mortality in patients,CRKP brings severe challen-ges to the clinical treatment.The major mechanism of drug resistance in CRKP is the production of carbapenemases,with Ambler A,B,and D being the common types while Ambler type C comparativly rare.Klebsiella pneumoniae carbapenemase(KPC)is the most common carbapenemase,which belongs to type A.KPC-producing Klebsiella pneumoniae(KPC-KP)widely spreads in the world,with very limited number of effective clinical drugs.In this re-view,advances in the treatment KPC-KP were summarized to provide reference for clinical treatment.

Objective:To explore the application effect of biofeedback functional electrical stimulation (BF-FES) combined with vaginal hysterectomy (TVH) in elderly patients with pelvic organ prolapse (POP) .Methods:A prospective study was conducted on 92 elderly POP patients admitted to the hospital from Jul. 2020 to Dec. 2022. They were divided into a study group (45 cases) and a control group (47 cases) using a random number table method. The control group received TVH treatment and underwent routine pelvic floor rehabilitation training after surgery; The research group received BF-FES treatment on the basis of the control group. All patients were treated continuously for 4 weeks and followed up for 6 months. The surface electromyographic values, three-dimensional pelvic floor ultrasound parameters, and urodynamic indicators between the two groups were compared before treatment and at 4 weeks of treatment. The results of the 1-hour urinary pad test before treatment, at 4 weeks of treatment, and at 3 and 6 months of follow-up were compared.Results:The surface electromyographic values of the two groups of patients at each stage of treatment for 4 weeks were higher than those before treatment. The surface electromyographic values of the study group at rest, rapid contraction, tense contraction, endurance contraction, and post rest stages were higher than those of the control group ( P<0.05). After 4 weeks of treatment, the mobility of the bladder neck in both groups was higher than those before treatment, while the posterior angle and rotation angle of the urethra and bladder were lower than those before treatment; The mobility of the bladder neck in the study group was higher than that in the control group, while the posterior angle of the urethra and bladder, as well as the rotation angle of the urethra were lower than those of the control group ( P<0.05). The maximum urine flow rate, maximum bladder volume, and average urine flow rate of the two groups after 4 weeks of treatment were higher than those before treatment, while residual urine volume was lower than that before treatment; The maximum urine flow rate, maximum bladder volume, and average urine flow rate in the study group were were higher than those in the control group. The residual urine volume in the observation group was lower than that in the control group ( P<0.05). After 4 weeks of treatment, 3 months of follow-up, and 6 months of follow-up, the increase in 1-hour urine pad weight of patients in the two groups gradually decreased compared to that before treatment, and the study group was lower than the control group ( P<0.05) . Conclusion:BF-FES combined with TVH can significantly enhance pelvic muscle strength, improve pelvic floor ultrasound parameters and urodynamic indicators in elderly POP patients, and have a significant effect on treating urinary incontinence in patients.

Objective:To explore the application effect of biofeedback functional electrical stimulation (BF-FES) combined with vaginal hysterectomy (TVH) in elderly patients with pelvic organ prolapse (POP) .Methods:A prospective study was conducted on 92 elderly POP patients admitted to the hospital from Jul. 2020 to Dec. 2022. They were divided into a study group (45 cases) and a control group (47 cases) using a random number table method. The control group received TVH treatment and underwent routine pelvic floor rehabilitation training after surgery; The research group received BF-FES treatment on the basis of the control group. All patients were treated continuously for 4 weeks and followed up for 6 months. The surface electromyographic values, three-dimensional pelvic floor ultrasound parameters, and urodynamic indicators between the two groups were compared before treatment and at 4 weeks of treatment. The results of the 1-hour urinary pad test before treatment, at 4 weeks of treatment, and at 3 and 6 months of follow-up were compared.Results:The surface electromyographic values of the two groups of patients at each stage of treatment for 4 weeks were higher than those before treatment. The surface electromyographic values of the study group at rest, rapid contraction, tense contraction, endurance contraction, and post rest stages were higher than those of the control group ( P<0.05). After 4 weeks of treatment, the mobility of the bladder neck in both groups was higher than those before treatment, while the posterior angle and rotation angle of the urethra and bladder were lower than those before treatment; The mobility of the bladder neck in the study group was higher than that in the control group, while the posterior angle of the urethra and bladder, as well as the rotation angle of the urethra were lower than those of the control group ( P<0.05). The maximum urine flow rate, maximum bladder volume, and average urine flow rate of the two groups after 4 weeks of treatment were higher than those before treatment, while residual urine volume was lower than that before treatment; The maximum urine flow rate, maximum bladder volume, and average urine flow rate in the study group were were higher than those in the control group. The residual urine volume in the observation group was lower than that in the control group ( P<0.05). After 4 weeks of treatment, 3 months of follow-up, and 6 months of follow-up, the increase in 1-hour urine pad weight of patients in the two groups gradually decreased compared to that before treatment, and the study group was lower than the control group ( P<0.05) . Conclusion:BF-FES combined with TVH can significantly enhance pelvic muscle strength, improve pelvic floor ultrasound parameters and urodynamic indicators in elderly POP patients, and have a significant effect on treating urinary incontinence in patients.

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 investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Objective:To construct a prognosis associated micro RNA(miRNA) prediction model based on bioinformatics analysis and evaluate its application value in pancreatic cancer patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 171 pancreatic cancer patients from the Cancer Genome Atlas (TCGA) (https: //cancergenome.nih.gov/) between establishment of database and September 2017 were collected. There were 93 males and 78 females, aged from 35 to 88 years, with a median age of 65 years. Of the 171 patients, 64 had complete clinicopathological data. Patients were allocated into training dataset consisting of 123 patients and validation dataset consisting of 48 patients using the random sampling method, with a ratio of 7∶3. The training dataset was used to construct a prediction model, and the validation dataset was used to evaluate performance of the prediction model. Nine pairs of miRNA sequencing data (GSE41372) of pancreatic cancer and adjacent tissues were downloaded from Gene Expression Omnibus database. The candidate miRNAs were selected from differentially expressed miRNAs in pancreatic cancer and adjacent tissues for LASSO-COX regression analysis based on the patients of training dataset. A prognosis associated miRNA prediction model was constructed upon survival associated miRNAs which were selected from candidate differentially expressed miRNAs. The performance of prognosis associated miRNA prediction model was validated in training dataset and validation dataset, the accuracy of model was evaluated using the area under curve (AUC) of the receiver operating characteristic curves and the efficiency was evaluated using the consistency index (C-index). Observation indicarors: (1) survival of patients; (2) screening results of differentially expressed miRNAs; (3) construction of prognosis associated miRNA model; (4) validation of prognosis associated miRNA model; (5) comparison of clinicopathological factors in pancreatic cancer patients; (6) analysis of factors for prognosis of pancreatic cancer patients; (7) comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging. Measurement data with normal distribution were represented as Mean± SD, comparison between groups was analyzed by the student- t test, and comparison between multiple groups was analyzed by the AVONA. Measurement data with skewed data were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Ordinal data were analyzed using the rank sum test. Correlation analysis was conducted based on count data to mine the correlation between prognosis associated miRNA model and clinicopathological factors. COX univariate analysis and multivariate analysis were applied to evaluate correlation with the results described as hazard ratio ( HR) and 95% confidence interval ( CI). HR<1 indicated the factor as a protective factor, HR>1 indicated the factor as a risk factor, and HR equal to 1 indicated no influence on survival. The Kaplan-Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Survival of patients: 123 patients in the training dataset were followed up for 31-2 141 days, with a median follow-up time of 449 days. The 3- and 5-year survival rates were 16.67% and 8.06%. Forty-eight patients in the validation dataset were followed up for 41-2 182 days, with a median follow-up time of 457 days. The 3- and 5-year survival rates were 15.63% and 9.68%. There was no significant difference in the 3- or 5-year survival rates between the two groups ( χ2=0.017, 0.068, P>0.05). (2) Screening results of differentially expressed miRNAs. Results of bioinformatics analysis showed that 102 candidate differentially expressed miRNAs were selected, of which 63 were up-regulated in tumor tissues while 39 were down-regulated. (3) Construction of prognosis associated miRNA model: of the 102 candidate differentially expressed miRNAs, 5 survival associated miRNAs were selected, including miR-21, miR-125a-5p, miR-744, miR-374b, miR-664. The differential expression patterns of pancreatic cancer to adjacent tissues were up-regulation, up-regulation, down-regulation, up-regulation, and down-regulation, respectively, with the fold change of 4.00, 3.43, 3.85, 2.62, and 2.35. A prognostic expression equation constructed based on 5 survival associated miRNAs = 0.454×miR-21 expression level-0.492×miR-125a-5p expression level-0.49×miR-744 expression level-0.419×miR-374b expression level-0.036×miR-664 expression level. (4) Validation of prognosis associated miRNA model: The C-index of prognosis associated miRNA model was 0.643 and 0.642 for the training dataset and validation dataset, respectively. (5) Comparison of clinicopathological factors in pancreatic cancer patients: results of COX analysis showed that the prognosis associated miRNA model was highly related with pathological T stage and location of pancreatic cancer ( Z=45.481, χ2=10.176, P<0.05). (6) Analysis of factors for prognosis of pancreatic cancer patients: results of univariate analysis showed that pathological N stage, radiotherapy, molecular targeted therapy, score of prognosis associated miRNA model were related factors for prognosis pf pancreatic cancer patients ( HR=2.471, 0.290, 0.172, 2.001, 95% CI: 1.012-6.032, 0.101-0.833, 0.082-0.364, 1.371-2.922, P<0.05). Results of multivariate analysis showed that molecular targeted therapy was an independent protective factor for prognosis of pancreatic cancer patients ( HR=0.261, 95% CI: 0.116-0.588, P<0.05) and score of prognosis associated miRNA model≥1.16 was an independent risk factor for prognosis of pancreatic cancer patients ( HR=1.608, 95% CI: 1.091-2.369, P<0.05). (7) Comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging: in the training dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.671, -1.867, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging for 3- and 5-year survival prediction was 0.797, 0.935 and 0.737 , 0.703, with the 95% CI of 0.622-0.972, 0.828-1.042 and 0.571-0.904 , 0.456-0.951. The C-index was 0.643 and 0.534. In the validation dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.729, -1.923, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging was 0.750, 0.873 and 0.721 , 0.703, with the 95% CI of 0.553-0.948, 0.720-1.025 and 0.553-0.889, 0.456-0.950, respectively. The C-index was 0.642 and 0.544. Conclusions:A prognosis associated miRNA prediction model can be constructed based on 5 survival associated miRNAs in pancreatic cancer patients, as a complementation to current TNM staging and other clinicopathological parameters, which provides individual and accurate prediction of survival for reference in the clinical treatment.