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.

Objective:To explore the material basis and mechanism of Sangjiang Ganmao injection （SG） in the treatment of common cold by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） and network pharmacology. Method:UPLC-Q-Orbitrap HRMS was used to identify the chemical components of SG with mobile phase of acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-10 min， 4%-15%A； 10-35 min， 15%-30%A； 35-45 min， 30%-33%A； 45-55 min， 33%-60%A； 55-58 min， 60%A）， flow rate of 0.2 mL·min^-1， electrospray ionization （ESI） and scanning range of m/z 100-1 500 under positive and negative ion modes. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and GeneCards 5.0 database were used to screen and predict the potential targets of chemical components in SG， STRING 11.0 database and Cytoscape 3.7.2 software were used to construct protein-protein interaction （PPI） network model， gene ontology （GO） analysis and pathway analysis were performed on potential targets by Metascape 3.5， Reactome database and Kyoto Encyclopedia of Genes and Genomes （KEGG）， Cytoscape 3.7.2 software was used to build the network of "herbs-ingredients-key targets". Result:A total of 54 components in SG were identified， and 80 potential targets of SG for treatment of common cold were predicted and screened based on this. SG exerted therapeutic effects by acting on targets such as interleukin （IL）-6， tumor necrosis factor （TNF） and IL-10， and signaling pathways such as IL-17 signaling pathway， TNF signaling pathway and interaction of cytokine receptors. Conclusion:SG may interfere with the expression of inflammatory cytokines by acting on related targets and pathways such as inflammation and immune system， and regulate the immune function of the body as a whole， thereby exerting a therapeutic effect.

Metformin is currently the first-line drug for the treatment of type 2 diabetes, and it is the most widely used oral hypoglycemic drug in the world. In addition to its significant hypoglycemic effect, metformin also has potential therapeutic effects on diseases such as tumors, obesity, thyroid diseases, polycystic ovarian diseases and cardiovascular diseases. However, the specific mechanism of action of metformin is still unclear. A large number of studies have shown that the regulation of energy metabolism by metformin is not only the core of its mechanism of action in the treatment of type 2 diabetes, but also an important mechanism for its therapeutic effects in diseases such as tumors and cardiovascular diseases. In this paper, the clinical application and related drug mechanisms of metformin in the treatment of non-diabetic diseases were summarized, so as to provide reference for the majority of medical workers, and look forward to a more in-depth exploration of its drug mechanism and clinical application in the future.

According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.
Aconitum ; chemistry ; Alkaloids ; administration & dosage ; chemistry ; toxicity ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; toxicity ; Arthritis, Rheumatoid ; drug therapy ; Chromatography, High Pressure Liquid ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Female ; Humans ; Male ; Mice ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Tandem Mass Spectrometry

Objective To establish standardized traceable management procedure for implanted high-value consumables in operating room.Methods The management model combining information-based system operation process and quality control process was designed,and management results before and after implementation were compared.Results There were statistically significant differences in error rates of information recording,bar code sticking and charging of implantable high-value consumables after the implementation of the process management mode (P＜0.05).At the same time,there were statistically significant differences in improvement of traceability of high-value consumables,adverse event reporting and patient satisfaction(P＜0.05).Conclusion Establishment of management model in operating room for implanted high-value consumables can ensure medical safety and increase medical quality.It was proved to improve the level of hospital management.

BACKGROUND: Previous studies have confirmed that rabbit bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts under osteogenic induction in vitro, stably express the specific phenotype of osteoblasts and have osteogenic ability. Calf cortical bone scaffold with partial cancellous bone has good biocompatibility and degradability, which can be used as a carrier material of bone marrow mesenchymal stem cells. OBJECTIVE: To combine rabbit BMSCs with calf bone composite according to the basic principles of bone tissue engineering and to observe the osteogenesis in the New Zealand white rabbits after implantation of BMSCs/calf bone composite into the ilium, thereby providing a direct evidence for preliminary clinical application of tissue-engineered bone products.METHODS: BMSCs/calf cortical bone scaffold with partial cancellous bone (tissue-engineered bone group), simple calf heterogeneous bone (heterogeneous bone group) or autologous iliac bone (autologous iliac bone group) was randomly implanted into the rabbit ilium. The changes of implant surface and tissue reactions around the implant were observed.X-ray examination was performed to observe osteogenic changes at 4, 8, 12, 24 weeks after implantation. Immunohistochemistry staining was used to observe the expression of bone morphogenetic protein 2.RESULTS AND CONCLUSION: After heterogeneous bone implantation, the wound healed well, and there were no systemic or local inflammation and toxicity reactions in all groups. The X-ray results showed that at postoperative 24 weeks, the implant was basically fused with the host bone in the tissue-engineered bone group, but the fusion was unsatisfactory in the heterogeneous bone group. The process of ossifications from cartilages was observed in all groups by hematoxylin-eosin staining, and bone morphogenetic protein 2 was positive for immunohistochemical staining. Findings from in vivo experiments indicate that rabbit BMSCs seeded onto the calf cortical bone scaffold with partial cancellous bone could construct tissue-engineered bone by osteoinductation in vitro in the rabbits.

Atropa belladonna is a medicinal plant and main commercial source of tropane alkaloids (TAs) including scopolamine and hyoscyamine, which are anticholine drugs widely used clinically. Based on the high throughput transcriptome sequencing results, the digital expression patterns of UniGenes representing 9 structural genes (ODC, ADC, AIH, CPA, SPDS, PMT, CYP80F1, H6H, TRII) involved in TAs biosynthesis were constructed, and simultaneously expression analysis of 4 released genes in NCBI (PMT, CYP80F1, H6H, TRII) for verification was performed using qPCR, as well as the TAs contents detection in 8 different tissues. Digital expression patterns results suggested that the 4 genes including ODC, ADC, AIH and CPA involved in the upstream pathway of TAs, and the 2 branch pathway genes including SPDS and TRII were found to be expressed in all the detected tissues with high expression level in secondary root. While the 3 TAs-pathway-specific genes including PMT, CYP80F1, H6H were only expressed in secondary roots and primary roots, mainly in secondary roots. The qPCR detection results of PMT, CYP80F1 and H6H were consistent with the digital expression patterns, but their expression levels in primary root were too low to be detected. The highest content of hyoscyamine was found in tender stems (3.364 mg x g(-1)), followed by tender leaves (1.526 mg x g(-1)), roots (1.598 mg x g(-1)), young fruits (1.271 mg x g(-1)) and fruit sepals (1.413 mg x g(-1)). The highest content of scopolamine was detected in fruit sepals (1.003 mg x g(-1)), then followed by tender stems (0.600 mg x g(-1)) and tender leaves (0.601 mg x g(-1)). Both old stems and old leaves had the lowest content of hyoscyamine and scopolamine. The gene expression profile and TAs accumulation indicated that TAs in Atropa belladonna were mainly biosynthesized in secondary root, and then transported and deposited in tender aerial parts. Screening Atropa belladonna secondary root transcriptome database will facilitate unveiling the unknown enzymatic reactions and the mechanisms of transcriptional control.
Alkaloids ; biosynthesis ; genetics ; metabolism ; Atropa belladonna ; genetics ; metabolism ; Gene Expression Regulation, Plant ; genetics ; Hyoscyamine ; genetics ; metabolism ; Plants, Medicinal ; genetics ; metabolism ; Scopolamine Hydrobromide ; metabolism ; Tropanes ; metabolism

OBJECTIVETo investigate the method and efficacy of reduction mammaplasty with central gland pedicle based on Würinger' s horizontal septum in the treatment of female breast hypertrophy.

METHODSFrom Mar. 2009 to Sept. 2011, a series of 21 consecutive patients with mild and moderate hypermastia underwent reduction mammaplasty with central gland pedicle. Only the mammary gland located at cranial portion of septum was resected and the mammary gland located at caudal portion of septum was preserved.

RESULTSIn our series, the mean resection weight per breast was (327.8 +/- 148.6) g, the mean nipple-to clavicle midpoint was 20.0 cm (range, 18.0-22.0 cm) and the mean nipple-to-sternal-notch distance was 21.0 cm (range, 19.5-22.5 cm) postoperatively. Nipple was moved upward 6.5 cm on average (range, 4.0-10.0 cm). There was no hematoma and nipple-areolar complex (NAC) necrosis. Minimal wound dehiscence occurred in one case and healed by dressing change. 17 cases were followed up for 3 months to 2 years. Satisfactory breast shape was achieved with good NAC sensibility.

CONCLUSIONSThe reduction mammaplasty with central gland pedicle based on Würinger' s horizontal septum is a safe and reliable technique for mild and moderate hypermastia. Satisfactory breast contour, as well as NAC viability and sensibility, could be achieved with lower occurrence of hematoma or seroma.

Adult ; Breast ; pathology ; surgery ; Female ; Humans ; Hypertrophy ; surgery ; Mammaplasty ; methods ; Middle Aged ; Young Adult

OBJECTIVETo investigate the therapeutic effect of glandular flap combined with dermal flap suspension for correction of mild and moderate breast ptosis.

METHODSThe dermal flap was formed according to the breast ptosis and dissection was performed between the skin and gland. The superior-lateral gland was partially resected or cut vertically only to form the lateral glandular flap. Then the glandular flap was rotated medially and fixed to shrink the glandular base area. Then the breast was up-positioned and fixed with dermal flap to remodel the breast shape.

RESULTSFrom Mar. 2006 to Mar. 2010, 46 cases were treated with satisfactory result. There was no severe complication, except for 2 cases of unilateral hematoma. 40 cases were followed up for 6 months to 4 years with good breast shape. No secondary ptosis, breast flatten and NAC sensation disorder was happened.

CONCLUSIONSGlandular flap combined with dermal flap suspension is a good method for mild and moderate breast ptosis with reliable long-term results. The breasts have busty appearance and good projection with inconspicuous scar.

Adult ; Breast ; surgery ; Breast Diseases ; surgery ; Female ; Humans ; Mammaplasty ; methods ; Middle Aged ; Surgical Flaps

OBJECTIVETo explore the management strategies and outcome of treatment for multi-focal esophageal carcinoma.

METHODSTwenty two patients with multi-focal esophageal carcinoma who underwent esophagectomy by a single surgeon team from March 2000 to March 2011 at the Beijing Cancer Hospital were reviewed retrospectively. The clinical and pathological characters were analyzed, and the outcome was compared with that of 471 patients with single esophageal carcinoma who received esophagectomy by the same surgeon team during the same period.

RESULTSEighteen out of 22 patients with multi-focal esophageal cancer underwent esophagectomy via transthoracic approach while 4 patients via transhiatal. Eight patients received neoadjuvant chemotherapy and 15 patients received adjuvant chemotherapy. Four hundred and seventy-one out of 471 patients with single esophageal cancer underwent esophagectomy via transthoracic approach while 60 patients via transhiatal. One hundred and fourty-eight patients received neoadjuvant chemotherapy and 267 patients received adjuvant chemotherapy. The 3-year survival of the 22 patients with multi-focal esophageal carcinoma was 41.9%, and the median survival time was 29.2 months. The 3-year survival of the 471 patients with single esophageal carcinoma was 54.7%, and the median survival time was 46.8 months. There was no significant difference in survival between the two groups(P=0.051).

CONCLUSIONSThe prognosis of patients with multi-focal occurrence esophageal carcinoma was poor. Extended esophageal resection may be beneficial to these patients with concurrent systemic chemotherapy.

Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Esophageal Neoplasms ; surgery ; therapy ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; surgery ; therapy ; Retrospective Studies ; Treatment Outcome