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.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVE: To observe the awakening effect and safety of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on consciousness disorder in children with early severe traumatic brain injury (STBI) based on western medicine treatment. METHODS: A total of 62 children with STBI were randomly divided into an observation group (31 cases,1 case dropped off) and a control group (31 cases, 1 case dropped off). The control group was treated with routine rehabilitation therapy (6 times a week for 30 days), and intravenous drip of cattle encephalon glycoside and ignotin injection (once a day for 28 days). On the basis of the treatment in the control group, the observation group was treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), Yintang (GV 24⁺), Baihui (GV 20), Sanyinjiao (SP 6), Zusanli (ST 36), etc., and supplementary acupoints according to clinical symptoms, once a day, 6 times a week for 30 days. The scores of Glasgow coma scale (GCS), coma recovery scale-revised (CRS-R) and modified Barthel index (MBI) were observed before treatment and 10, 20 and 30 d into treatment. Electroencephalogram (EEG) grading before and after treatment was observed in the two groups, and safety was evaluated. RESULTS: After 10, 20 and 30 days of treatment, the scores of GCS, CRS-R and MBI in the two groups were increased compared before treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). After treatment, EEG grading of both groups was improved compared with that before treatment (P<0.05), and the observation group was better than the control group (P<0.05). There were no adverse events or adverse reactions in the two groups during treatment. CONCLUSION On the basis of western medicine treatment, Xingnao Kaiqiao acupuncture plays a remarkable role in wakening the early STBI children, can improve the level of consciousness disorder and daily living ability, and it is safe and effective.
Acupuncture Points ; Acupuncture Therapy ; Brain ; Brain Injuries, Traumatic/therapy* ; Consciousness Disorders/therapy* ; Humans ; Child

To investigate the effect of the interval between neoadjuvant chemoradiotherapy (nCRT) and surgery on the clinical outcome of esophageal cancer. Methods    PubMed and EMbase databases from inception to March 2018 were retrieved by computer. A random-effect model was used for all meta-analyses irrespective of heterogeneity. The meta-analysis was performed by RevMan5.3 software. The primary outcomes were operative mortality, incidence of anastomotic leakage, and overall survival; secondary outcomes were pathologic complete remission rate, R0 resection rate, and positive resection margin rate. Results    A total of 17 studies with 18 173 patients were included. Among them, 13 were original studies with 2 950 patients, and 4 were database-based studies with a total of 15 223 patients. The results showed a significant positive correlation between the interval and operative mortality (Spearman coefficient=0.360, P=0.027). Dose-response meta-analysis revealed that there was a relatively better time window for  surgery after nCRT. Further analysis for primary outcomes at different time cut-offs found the following results: (1) when the time cut-off point within 30-70 days, the shorter interval was associated with a reduced operative mortality (7-8 weeks: RR=0.67, 95% CI 0.55-0.81, P<0.05; 30-46 days: RR=0.63, 95%CI 0.47-0.85, P<0.05; 60-70 days: RR=0.64, 95%CI 0.48-0.85, P<0.05); (2) when the time cut-off point within 30-46 days, the shorter interval correlated with a reduced incidence of anastomotic leakage (RR=0.39, 95%CI 0.21-0.72, P<0.05); when the time cut-off point within 7-8 weeks, the shorter interval could achieve a critical-level effect of reducing the incidence of anastomotic leakage (RR=0.73, 95%CI 0.52-1.03, P>0.05); (3) when the time cut-off point within 7-8 weeks, increased interval significantly was associated with the poor overall survival (HR=1.17, 95% CI 1.00-1.36, P<0.05). Secondary outcomes found that the shorter interval could significantly reduce the positive resection margin rate (RR=0.53, 95% CI 0.38-0.75, P<0.05) when time cut-off point within 56-60 days. Conclusion    Shortening the interval between nCRT and surgery can reduce the operative mortality, the incidence of anastomotic leakage, long-term mortality risk, and positive resection margin rate. It is recommended that surgery should be performed as soon as possible after the patient's physical recovery, preferably no more than 7-8 weeks, which supports the current study recommendation (within 3-8 weeks after nCRT).

Objective To investigate the value of CT guided 125 I seed implantation combined with chemotherapy in the treat-ment of unresectable non-small cell lung cancer .Methods The related data of 42 cases of middle and advanced non-small cell lung cancer treated in this hospital from January 2012 to December 2016 were retrospectively analyzed .The group A (23 cases) received the 125I seed implantation combined with chemotherapy ,while the group B(19 cases) adopted the simple chemotherapy .All cases conducted the chest CT re-examination at 1 ,2 ,6 months after treatment .The curative effects and complications were compared be-tween the two groups .Results The total effect rate (RR) at 1 ,2 ,6 months had statistical difference between the two groups (P<0 .05) .The adverse reactions in the group A were small ,large amounts of pneumothorax (26 .1% ,6/23) ,bone marrow suppression (26 .1% ,6/23) ,nausea and vomiting(30 .4% ,7/23) ,which in the group B were d 5 .3% (1/19) in the group B were bone marrow suppression (36 .8% ,7/19) ,nausea and vomiting (26 .3% ,5/19) .No severe complications were observed .The occurrence rate of adverse reactions had no statistical difference between the two groups (P>0 .05) .The adverse reactions were improved after symp-tomatic treatment .Conclusion CT guided 125 I seed implantation combined with chemotherapy has higher effective rate and more significant effect in treating unresectable non-small cell lung cancer .

BACKGROUND: Human olfactory mucosa mesenchymal stem cells (hOM-MSCs) not only have the basic characteristics of mesenchymal stem cells, but also originate from the ectoderm and are prone to differentiate into neurons, which are a kind of ideal seed cells for nerve repair and regeneration. Cells are conventionally cultured in about 21% in vitro, while only 3%-9% oxygen is found in the human body and tissue space. There is still no report on the effect of hypoxia on the proliferation and activity of hOM-MSCs.OBJECTIVE: To explore whether hypoxic microenvironment can promote hOM-MSCs proliferation and activity and the related mechanism. METHODS: hOM-MSCs were isolated, cultured and identified by flow cytometry and immunofluorescence. The passage 4 hOM-MSCs were divided into three groups: 21% O2 group, 3% O2 group and 3% O2+20 μmol/L YC-1 (HIF-1α inhibitors) group. Proliferation and apoptosis of hOM-MSCs was detected by flow cytometry after 72 hours of culture. The proliferating cell nuclear antigen protein expression was detected by western blot. The mRNA and protein expression of HIF-1α and TWIST were detected by Q-PCR and western blot. RESULTS AND CONCLUSION: The purity of hOM-MSCs was up to 97%, as defined by flow cytometry. The proliferation index of 3% O2 group was higher than the 21% O2 group (P < 0.05), and cell survival and apoptosis ratio (apoptotic cells included mechanical death + early apoptosis + late apoptosis) between the two groups had no significant difference (P > 0.05). Western blot results showed that the proliferating cell nuclear antigen protein expression in the 3% O2 group was significantly higher than that in the other groups (P < 0.05). The HIF-1α and TWIST expressions at mRNA and protein levels in the 3% O2 group were significantly higher than those in the other groups (P < 0.05). To conclude, hypoxic microenvironment can promote the hOM-MSCs proliferation and has no effect on the apoptosis, and the HIF-TWIST signal pathway plays an important role in this progress.

BACKGROUND:Stem cells have been widely used in the treatment of spinal cord injury,but the clinical application is limited by immune rejection,difficulty in cell harvesting and purification.However,human nasal mucosa mesenchymal stem cells (hNM-MSCs) have no such problems,and its clinical application in the treatment of spinal cord injury has been not reported yet.OBJECTIVE:To observe the biological characteristics of autologous hNM-MSCs and its clinical efficacy in the treatment of advanced incomplete spinal cord injury.METHODS:NM-MSCs were isolated from the human nasal mucosa,cultured and identified in vitro.The ultrastructure of NM-MSCs was observed by transmission electron microscope and scanning electron microscope.Then the NM-MSCs were induced to differentiate into osteocytes,adipocytes,stem cell spheres,or neurons in vitro.Totally eight patients with incomplete spinal cord injury were enrolled and subjected to hNM-MSCs transplantation via lumbar puncture for 1-3 sessions of about 5× 107 cells each,with an interval of 5-7 days,after the approval of the medical ethics committee.All the patients were followed up for 6 months.Preoperative and postoperative therapeutic effect evaluations were performed on the basis of American Spinal Injury Association (ASIA) scores.RESULTS AND CONCLUSION:Under light microscope,the NM-MSCs were mainly spindle-shaped,positive for STRO-1 and exhibited a radial arrangement.NM-MSCs highly expressed CD73,CD90 and CD105,but did not express CD34 and CD45,with the purity of over 97％.And lots of podgy microvilli were seen on the surface of NM-MSCs under the scanning electron microscope,and two kinds of cell morphologies were seen under the transmission electron microscope.Moreover,hNM-MSCs had the ability to differentiate into osteocytes,adipocytes,stem cell spheres and neurons.During the 6-month follow-up,seven patients achieved neurological function recovery to different extents except for one patient,and no side effects were found.It is concluded that hNM-MSCs can become the ideal seed cells for tissue-engineered cell repair.Autologous NM-MSCs transplantation for the treatment of spinal cord injury can achieve the ideal effect,with the value of clinical application.

To study the variation of six ester-type alkaloids and characteristic fingerprints in the process from Radix Aconite Lateralis to Heishunpian and lay a foundation for the study of the processing principle of Heishunpian, HPLC. analysis was performed on a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) with acetonitrile and 40 mmol x L(-1) ammonium acetate (adjusted to pH 10 with concentrated ammonia water) as mobile phase. The detection wavelength was set at 235 nm. The flow rate was set at 0.8 mL x min(-1) and the injection volume was 10-20 microL. Six ester-type alkaloids were determined and characteristic fingerprints of the process were established. As the process continues, the contents of diester diterpene alkaloids were decreased step by step, while the contents varia tion of monoester diterpene alkaloids were not obvious. Each sample showed significant difference in characteristic fingerprints. With the exception of 6 known monoester diterpene alkaloids and diester diterpene alkaloids, 13 peaks were marked in the characteristic fingerprints, of which the total change rule of the other 7 unknown peaks were similar with 3 diester diterpene alkaloids. The established method is accurate, reliable and repeatable, and can provide reference for revealing change rule of index components and illuminating processing principle in the process of Heishunpian.
Aconitine ; chemistry ; Aconitum ; chemistry ; Alkaloids ; chemistry ; Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Esters ; chemistry ; Molecular Structure

Objective To detect the level of nitric oxide (NO) and amino acids in cerebrospinal fluid and serum of epilepsy children in different time. Methods The level of NO and amino acids in cerebrospinal fluid and serum of epilepsy children in different time were determined with nitrate reductase and high performance liquid chromatography (HPLC) with fluorimetric detection. Results The level of NO2 - increased 30 min, 60 min, 120 min after seizures (P<0.01), but dropped to normal 180 min after seizures (P>0.05). The level of glutamate (Glu) significantly increased in all epilepsy groups (P<0.05). The level of glycine (Gly) dropped gradually in all epilepsy groups (P<0.05).Conclusion NO may participate in the generation of seizures and the injury process to brain. The imbalance between excitatory and inhibitory amino acids may play an important role in the pathogenesis of epilepsy. The toxicity of excitatory amino acids may be the main injury to the brain.

Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Drug-Eluting Stents ; Humans ; Paclitaxel ; therapeutic use