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.

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

Intravenous immunoglobulin (IVIG) is used to treat various diseases and has anticancer effects that suppress metastases in animal models of sarcoma and melanoma. However, these effects have been observed in a limited number of clinical cases. We report the case of a patient with metastatic breast cancer in which long-term IVIG treatment stopped disease progression in the absence of salvage chemotherapy. The patient was treated with IVIG for the treatment of immune thrombocytopenia. Surprisingly, the lung and brain metastases were stabilized, and the patient achieved a progression-free interval of 29 months. More cases are needed to investigate and confirm the efficacy of IVIG in solid tumors in the future.

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.
Biopsy/adverse effects* ; Cardiomegaly/pathology* ; Cardiomyopathy, Hypertrophic/diagnosis* ; Eosine Yellowish-(YS) ; Fibrosis ; Heart Defects, Congenital ; Hematoxylin ; Humans ; Lipofuscin ; Male ; Myocardium/pathology* ; Retrospective Studies

Purpose: To assess characteristics the application of mobile medication system and medication administration error (MAE) alerts in a general hospital. Methods: The subject hospital adopted a mobile medication system in 2016. All medication administrations in the general wards and ICUs were automatically recorded in real-time using identification barcodes, drug barcodes, and hand-held point-of-care devices. MAE alert logs were recorded from April 1st 2017 to March 31st 2018. For this study analysis was done using Pearson’s chi-squared test for potentially related factors of MAE alerts included administration time, order type, medication route, and length of nurse’s employment. Results: The total number of medications during the period of this study was 3,227,990. Among them, 2,698,317 medication doses were recorded, resulting in the system application rate of 83.6%. The system application rate was significantly correlated with all factors related to potential MAE alters. In this study 23,314 MAE alerts(0.9% of the total medication doses) were identified. The MAE alerts were related to new (OR=2.26, p<.001) and emergency (OR=2.25, p<.001) orders, and administration at a non-standard time (OR=2.032, p<.001). Medication route (p<.001), and nurse’s employment duration(p<.001) were also related. Conclusion A mobile medication system contributes to improving patient safety by preventing potential MAEs. The MAE alerts were related to administration time, order type, medication route, and duration of nurse’s employment. In order to prevent medication administration errors, it is necessary to standardize the process of medication and create an environment in which medication administration can be performed in a planned situation.

Objective To investigate the estimation of early and mid-term wound age by a combination of four mRNAs, the DNA polymerase delta-interacting protein 3 （POLDIP3） mRNA, regulator of chromosome condensation 1 like （RCC1L） mRNA, proline-rich 5 （PRR5） mRNA, and ribonucleic acid export 1 （RAE1） mRNA in rats skeletal muscles. Methods The model of rat skeletal muscle contusion was established, and then contusion area muscle tissue was extracted 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 h after injury. Histomorphological changes during the repair process after rat skeletal muscle contusion were observed. The relative expressions of Poldip3, Rcc1l, Prr5 and Rae1 mRNAs were detected by reverse transcription real-time quantitative polymerase chain reaction （RT-qPCR）. Different stages of wound age were classified by using the expression patterns of four genes at various time points after injury. The accuracy of the results was verified by Fisher discriminant analysis. Results Histomorphological results showed that the repair process after skeletal muscle contusion occurred with the prolonging of time. Through combination of the expression trends of the four kinds of mRNAs, the 48 h after injury could be divided into three periods, 4-12 h, 16-28 h and 32-48 h. The Fisher discrimination method showed that the classification accuracy rates of the three periods were 83.3%, 75.0% and 73.3%, respectively. Conclusion The classification discrimination based on the relative expression of every gene has a higher accuracy, and the accuracy of wound age estimation with combination of mRNA relative expressions is higher than that with a single indicator. By combining with Fisher discrimination method, this method can be used for early and mid-term wound age estimation.
Animals ; Contusions/metabolism* ; Muscle, Skeletal/metabolism* ; RNA, Messenger/genetics* ; Rats ; Rats, Sprague-Dawley ; Time Factors

Objective To elucidate the difference between methicillin-resistant Staphylococcus aureus (MRSA)and methicillin-sensitive S.aureus (MSSA)in terms of genotypes and distribution of virulence genes with the clinical strains isolated from Hohhot,and explore the relationship between the changing resistance of S.aureus and the virulence transition.Methods Pulsed field gel electrophoresis (PFGE)and multi locus sequence typing (MLST)methods were employed to do molecular typing for 30 MRSA strains and 30 MSSA strains isolated from inpatients in Hohhot,Inner Mongolia.PCR method was used to profile the distribution of virulence genes among these strains.Results PFGE typing results showed that 60 S.aureus strains were classified into 19 major types.MSSA strains belonged to 16 types,mainly types I and H.MRSA strains mainly belonged to types of K and M.Among the 20 strains with different PFGE types,MRSA strains were mainly identified as ST-239 type.but the prevalence of sec ,seg ,sei,sem,sen,seo,fnbB ,ebpS and cap 5 was higher in MSSA strains than in MRSA strains (P<0.05).Conclusions The clinical strains of S .aureus isolated from Hohhot showed diverse genotyping features.ST-239 was the major PFGE type of MRSA strains.The prevalence of virulence genes was higher in MSSA strains than in MRSA strains. Characteristic cluster is found for specific virulence genes.The results also suggest that acquisition of specific antibiotic resistance may be associated with change of specific virulence feature in S.aureus.

Objective To investigate the study of acute toxicity of mon-golian medicine Meng gen wu sen ri le, to understand the dose of acute toxicity and distribution and death of acute toxicity after the administra-tion, to determine lethal dose 50 ( LD50 ) of Meng gen wu sen ri le. Methods According to the results of preliminary experiments, using Conn synthesis method ( modified Karber method ) , divided into six groups dosage are 14.30, 9.28, 6.04, 3.92, 2.55, 1.66 g? kg-1 , af-ter experiments observing 14 day, to record the change of the weight and adverse reaction.Results LD50 of Meng gen wu sen ri le is 5.1597 g? kg-1 ( 95%CI:3.6652-7.2637 g? kg -1 ).In 14 days, it does not appear obvious symptoms of adverse reaction and body weight has growth trends.Conclusion According to the results of experiments, LD50 of Meng gen wu sen ri le is 100 times of the clinical dosage, tip single oral is safer.

Objective To observe the therapeutic effect of Deduhonghua-7 powder on liver fibrosis and its correlation with matrix metalloproteinases ( MMPs) and transforming growth factor β1 ( TGF-β1 ) .Methods The rats were divided into 4 groups, blank group, model group, control group, experiment group, 8 rats each group.The CCl4 was used to induce rat liver fibrosis.The control group was given colchicine pill, CMC sodium cellulosate was used to prepare 2% of colchicine suspen-sion, once time per day, 0.2 mL · kg-1 each time.The experiment group was given Deduhonghua-7 powder, CMC sodium cellulosate was used to prepare 3% of Deduhonghua-7 powder suspension, once time per day, 0.2 mL· kg -1 each time; blank group and model group were given same volume of pure water.All rats were sacrificed after 40 days of medication.Western blot was acted to detect the matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-13 (MMP-13),tissue inhibitor of metalloproteinases-1 (TIMP-1) protein expression.The PCR was used to detect the changesoftype Ⅰ, Ⅲ collagen, TGF -β1 mRNA gene expression.Results The MMP-1, MMP -13 protein expression in rats of model group was down -regulated compared with blank group ( P<0.05 ).The TIMP-1 protein expression was up-regulated compared with blank group ( P<0.05 ) . The mRNA expressions of typeⅠprocollagen, typeⅢprocollagen and TGF-β1 were increased compared with blank group(P<0.05).The MMP-1, MMP-13 protein expression of control group and experiment group were significant-ly up-regulated compared with model group.The TIMP-1 protein expression significantly down-regulated compared with model group.The mRNA gene expression of type I procollagen, typeⅢprocollagen and TGF-β1 were down-regulated compared with model group ( P<0.05 ).Conclusion Deduhonghua-7 powder regulate and maintain the stabilization of MMP/TIMP to block the expression of TGF-βand inhibit the transcription of type I,Ⅲ collagen and TGF-β1 mRNA to reach the purpose of detention of occurrence and development of liver fibrosis.

Objective To investigate the efficacy and mechanism of mongolian medicine Menggenwusenrile in the treatment of imiquimod -induced psoriasiform skin inflammation in mice.Methods Fifty cases of BALB/c female mice were randomly divided into normal control group, model group, Menggenwusenrile low, middle and high dose groups, 10 cases in each group.Normal control group was given 0.3% sodium car-boxyl methyl cellulose(CMCNa) 2 mL/100 g, once a day intragastric administration for consecutive 21 days.Modal group was given 0.3%CMCNa 2 mL/100 g, once a day intragastric administration for consecu-tive 21 days.Menggenwusenrile low, middle and high dose groups were given 0.33, 0.66, 1.32 g? kg-1 , once a day intragastric administration for consecutive 21 days.The expression of proliferating cell nuclear anti-gen ( PCNA) , transforming growth factor-α( TGF-α) , tumor necrosis factor-α( TNF-α) , platelet endothelial cell adhesion molecule-1/CD31 (CD31), vascular endothelial growth factor (VEGF)and Toll -like receptors-2 ( TLR-2 ) were detected by immunohistochemical stai-ning.Results Six kinds of immunohistochemical analysis showed the each drug dose group was higher than the model group, high dose is bet-ter than middle dose group, the middle dose group is better than low dose.Conclusion Menggenwusenrile have a better therapeutic effect in imiquimod-induced psoriasiform skin inflam-mation in mice.