Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

The articles on alarm management of clinical medical equipment from January 2000 to January 2023 were collected with common databases in the world as search sources.CiteSpace software was used for trend drawing of annual publication distribution,author cooperation network mapping,country/institution cooperation network mapping and keyword knowledge mapping,and for analyzing related issues in depth.The annual publication of medical equipment alarm management research showed a fluctuating upward trend,the authors had good cooperative relationship with the organizations,the hotspots included ventilator,alarm and alarm fatigue in Chinese and alarm fatigue,intensive care unit and patient safety in English,and the research frontier involved in alarm fatigue,false alarm and alarm management.References were provided for conducting related research in China.

Ultra-high performance liquid chromatography coupled with quadrupole/time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS/MS) has been used to detect the metabolites of schaftoside in plasma, bile, urine and feces of mice after oral administration. The study was approved by the Experimental Animal Ethics Committee from Xuzhou Medical University (No. XZMULL201612024). Compounds were identified by analyzing their high-resolution mass spectrometry data, mass spectra, and comparison with reference substances and the literatures. The parent compound and 29 metabolites were detected in the plasma, bile, urine and feces samples of mice. The main metabolic pathways of schaftoside in mice include deglycosylation/glycosylation, hydroxylation/dehydroxylation, hydrogenation, methylation, acetylation, sulfation, and glucuronidation. This study provides references for the material basis of schaftoside in vivo.

Objective To study the effect of velvet antler polypeptides (VAP) on antioxidant in Alzheimer' s disease model mice. Methods Eight months old male amyloid precursor protein (APP)/presenilin-l (PS1) double transgenic mice were selected as Alzheimer' s disease (AD) model and divided into the model group and the VAP intervention group, 12 in each group. Besides, normal mice of the same brood (with no transgene) were recruited as a control group (n= 12).After 6 months of intragastric administration, behavior, morphology and oxidative stress related indicators were detected.SH-SY5 cells were used to establish AD model of damaged by Ap2535. The expression levels of APP and p-secreatase-l(BACE1) protein in mouse hippocampus were detected by Western blotting. VAP intervention group SH-SY5Y cells was cultured with VAP (500 g/L) and amyloid P(Ap) 2535(25 ixmol/L) for 24 hours. Control group cells were normally cultured by DMEM medium. Cell apoptosis, membrane potential, reactive oxygen species (ROS) levels and oxidative stress related indexes were detected. Results In animal models, compared with the model group, the escape latency of mice in the VAP intervention group was shortened (P<0. 05). The neuronal cells in the CA1 region of the hippocampus of the model group were reduced and arranged disorderly. The arrangement of the VAP intervention group was relatively regular, and the morphology was significantly improved. Compared with the model group, senile plaques were decreased in the VAP intervention group. Compared with the model group, the malondialdehyde (MDA) content ol the VAP intervention group increased, and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content increased, the difference was statistically significant. Compared with the control group, the APP and BACE1 content in the model group increased. Compared with the model group, the contents of APP and BACE1 in the VAP intervention group decreased, and the difference was statistically significant (P<0. 05). In the cell model, the apoptosis rates of the VAP intervention group decreased. Compared with the model group, the mitochondrial membrane potential of the VAP intervention group increased, the content ol ROS decreased, the content of MDA decreased, and the content of SOD and GSH-Px increased. The difference were statistically significant (P<0. 05). Conclusion VAP has a protective effect on oxidative stress damage caused by Alzheimer' s disease model animals and cells, which may be achieved by reducing ROS production and increasing the activity of antioxidant enzymes to reduce Ap deposition.

Objective To study the effect of velvet antler polypeptides (VAP) on Rho/ROCK pathway in APP/ PSl double transgenic mice. Methods APP/PSl double transgenic mice were randomly divided into model group and velvet antler polypeptide group, 20 mice in each group, and control group consisting of 20 mice of the same litter and the same gender negative. The mice in VAP group were given velvet antler polypeptide 100 mg/kg by intragastric administration once a day for 28 days. After treatment, the water maze experiment was detected and recorded the escape latency and the number of crossing platforms of the mice; the ultrastructures of the synapse were observed by transmission electron microscopy; the expression of Rhs homolog gene family member A(RhoA) and Rho associated coiled-coil forming protein kinase II(ROCKII) in the hippocampal CAI area were observed by immunofluorescence. The expression levels of RhoA and ROCKII protein in the hippocampus were detected by Western blotting. The contents of hippocampus amyloid (3-protein(A(3),

Objective To investigate the effects of up-regulation of zinc finger and BTB domain containing 20 (A20) expression on learning and memory and apoptosis of hippocampal neurons in APP

Objective To observe the effect of epigallocatechin gallate (EGCG) on the spatial learning memory deficit in amyloid procursor protein (APP) / presenilin-1 (PS1) double transgenic mice, synaptic ultrastructure and expression of neural cell adhesion molecule in hippocampal CA1 region. Methods Eight weeks old male APP / PS1 double transgenic mice were selected as Alzheimer’s disease (AD) model and divided into the model group, the EGCG group and the donepezil hydrochloride group, 12 in each group.Besides,normal mice of the same brood (with no transgene) were recruited as a normal group (n = 12). Related indices were detected after 6 months continuous gastrogavage. The spatial learning-memory deficit of APP / PS1 double transgenic mice was detected by Morris water maze test. The synaptic ultrastructure of hippocampal CA1 region was observed by transmission electron microscopy. The expression levels of neural cell adhesion molecule (NCAM) and polysialyltranseferase α2,8-polysialic acid (ST8Sia Ⅱ) protein in hippocampal CA1 region of APP / PS1 transgenic mice were detected by immunofluorescence and Western blotting. Results Compared with the normal group, the mean value of escape latency in the model group was extended, and compared with the model group, the mean value of escape latency in the EGCG group and donepezil hydrochloride group were increased (P < 0. 05) . The result of electron microscope showed that the changes of synaptic interface curvature of EGCG group and donepezil hydrochloride group were not obvious. Compared with the model group, the width of the synaptic gap becomes narrower and the thickness of the post-synaptic compact were increases (P < 0. 05) . Immunofluorescence showed that the expression of NCAM and ST8Sia Ⅱ proteins in the hippocampus CA1 region was expressed in the cytoplasm of neurons, the expressions of NCAM and ST8Sia Ⅱ in hippocampal CA1 region were significantly increased in EGCG group and donepezil hydrochloride group (P< 0. 05) . Their contents also showed higher levels of expression in Western blotting (P < 0. 05) . Conclusion EGCG shows improvement on the spatial learning-memory deficit in APP / PS1 double transgenic mice,which may be associated with affecting the synaptic structure of hippocampus and improving the expressions of neural cell adhesion molecule.

Background:The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma;therefore,the use of morcellation is limited in the USA.A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy.Methods:A national multicenter study was performed in China.From 2002 to 2014,33,723 cases were retrospectively selected.We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application.A total of 62 cases were finally pathologically confirmed as malignant postoperatively.Additionally,the medical records of the 62 patients were analyzed in details.Results:The proportion of postoperative malignancy after morcellation application was 0.18％ (62/33,723) for patients who underwent laparoscopic myomectomy.Nearly 62.9％ (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery.And,23 (37.1％) patients showed rapid growth at the final preoperative ultrasound.With respect to the pathological types,38 (61.3％) patients had detectable endometrial stromal sarcoma,13 (21.0％) had detectable uterine leiomyosarcoma,only 3 (3.2％) had detectable carcinosarcoma,and 5 (8.1％) patients with leiomyoma had an undetermined malignant potential.Conclusions:The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy.Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential,and morcellation should be avoided.

OBJECTIVETo observe the effects of Compound Zhebei Granule (, CZBG) combined with chemotherapy on surface markers of leukemia stem cell (LSC) in the bone marrow of patients with acute myeloid leukemia (AML).

METHODSSeventy-eight patients with AML received bone marrow aspiration and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were tested using flow cytometry method. A total of 24 refractory or relapsed AML patients were enrolled and treated with one cycle of standard chemotherapy combined with CZBG. Bone marrow samples were obtained before and after treatment, and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were examined by flflow cytometry.

RESULTSCompared with refractory or relapsed AML patients, patients achieved remission had a significant lower percentage of CD34(+) CD123(+) cells(P<0.01) and CD33(+) CD123(+) cells (P<0.01), indicating that controlling the LSC percentage may be important for patients with AML to achieve sustainable remission. Compared with those before treatment, the expression levels of CD34(+) CD123(+) were significantly decreased after CZBG combined with chemotherapy treatment (P<0.01). The percentages of CD34(+) CD123(+) cells and CD33(+) CD123(+) in patients achieving complete remission after CZBG combined with chemotherapy treatment were both significantly lower than those in patients with nonremission (P<0.01).

CONCLUSIONCZBG combining chemotherapy could reduce the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) LSC, which might improve the clinical efficacy of refractory or relapsed AML.

Antigens, CD ; metabolism ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Bone Marrow Cells ; drug effects ; metabolism ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplastic Stem Cells ; metabolism ; pathology ; Remission Induction