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.

ObjectiveTo construct ¹³¹Ⅰ-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma. MethodsThree short nucleic acid chains self-assembled to a long nucleic acid chain after being annealed， and ¹³¹Ⅰ-NT was obtained by radioiodine labeling using chloramine T method. The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography. The stability of the labeled products in vitro at different temperatures and different storage solvents was detected. The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy， and the radioactive uptake ratio of ¹³¹Ⅰ-NT combined with human hepatocellular carcinoma cell HepG2 and normal hepatocyte L02 was measured. The biodistribution of ¹³¹Ⅰ-NT was obtained through injecting ¹³¹Ⅰ-NT into HepG2 tumor-bearing mice via tail vein. ResultsThe labeling rate of ¹³¹Ⅰ-NT was （93.05±0.74） %， and the radiochemical purity post purification was （98.35±0.32） %. Its radiochemical purity in PBS and pure serum at 4℃ for 24 h was （92.77±0.04） % and （89.43±0.2） %， respectively. The radioactivity uptake rate of HepG2 cells was higher than that of L02 cells after ¹³¹Ⅰ-NT was incubated with two kinds of cells for 2 h significantly. After injection of ¹³¹Ⅰ-NT through tail vein， the radioactive uptake per gram of tumor tissue were （4.9±0.55）%ID/g， （10.12±0.32）%ID/g and （4.25±0.31）%ID/g at 30 min， 1 h and 2 h， respectively. The T/M ratio was 7.33±2.04， 36.54±12.72 and 44.93±7.90 respectively. ConclusionsThe ¹³¹Ⅰ-labeled long chain nucleic acid nanotrain was constructed successfully， which possesses relatively high stability in vitro ， and high targeting ability to HepG2 cells in vitro and HepG2 tumor-bearing mouse model. Our study demonstrated that ¹³¹Ⅰ-NT may be a potential radionuclide carrier targeting human liver cancer， which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinoma.

Aim To evaluate the protective effect of α-asarone on microglials with cerebral ischemia/reperfusion injury by measuring the expression of polar transformation and related inflammatory proteins in BV2 cells in vitro and its mechanisms.Methods The cerebral ischemia/reperfusion injury BV2 cells were pretreated by α-asarone in vitro and simulated by OGD/R model.The effect of α-asarone on the viability of damaged cells in OGD/R model was determined by CCK-8; the morphological changes of cells were observed to analyze the general morphology of cells; the levels of proinflammatory factor IL-1β, IL-18 and anti-inflammatory factor IL-10, IL-4, and ROS activity secreted by BV2 cells were detected by ELISA; the protein expressions of TGF-β, TNF-α and inflammatory related protein NLRP3, caspase 1, p-NF-κB were detected by Western blot.Results The results of in vitro experiments were as follows: the activity of damaged cells in OGD/R model was significantly increased by α-asarone, with the increase of administration dose, the cells in the low, medium and high dose groups of α-asarone decreased, and the "amoeba-like" cells and the cell body were gradually became stereoscopic and full.From the results of cell morphology, it could be seen that α-asarone had a certain proliferative effect on normal cells; the release was significantly reduced of proinflammatory factor IL-1β, IL-18 and TNF-α in OGD/R injured BV2 cells pretreated with α-asarone, also increased the release of IL-10, IL-4 and TGF-β, with a dose-effect relationship, and the high dose(16 μmol·L-1)was the best; the expressions of inflammatory related protein NLRP3, caspase 1, NF-κB and ROS activity in injured cells of OGD/R model were significantly reduced after pretreatment with α-asarone.Conclusions α-asarone has a significant protective effect on cerebral ischemia/reperfusion injury, mainly by regulating ROS activity and inhibiting phosphorylation of NF-κB, in order to reduce the excessive activation of NLRP3 inflammatory corpuscles reducing the secretion of proinflammatory factor IL-1β and IL-18, promoting the secretion of anti-inflammatory factor IL-10 and IL-4, so as to protect cerebral ischemia/reperfusion injury by anti-inflammatory reaction.

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

OBJECTIVE: To investigate the efficacy and safety of total spine endoscopy in the treatment of lumbar disc herniation combined with posterior apophyseal ring separation. METHODS: From January 2015 to January 2018, a total of 21 patients with lumbar disc herniation complicated with posterior apophyseal ring separation were treated with total spine endoscopy via interlamina approach. There were 17 males and 4 females. The age ranged from 18 to 48 years old and the median age was 27 years old. All were single segment unilateral disc herniation, interlaminar approach was adopted, and the herniated disc was removed unilaterally at the symptomatic side under the microscope, and all or part of the broken bonewas removed. RESULTS: There were no complications such as incision infection, intervertebral space infection, intestinal injury, dural injury and cerebrospinal fluid leakage. The operation time ranged from 32 to 92 minutes and the median time was 57 minutes. Postoperative imaging examination showed that 2 patients had complete resection of osteotomy of posterior edge of vertebral body, 16 patients had partially resection and 3 patients had no resection. All intervertebral discs were completely removed. All 21 patients were followed up, and the duration ranged from 12 to 36 months, with a median of 15 months. The VAS of lumbago was 7.10±1.20 before surgery, 3.46±0.23 on the 3rd day after surgery, 2.36±0.19 on the 6th month after surgery; and the VAS of leg pain was 8.80±0.55 before surgery, 3.54±0.28 on the 3rd day after surgery, and 2.59±0.26 on the 6th month after surgery. The Oswestry Disability Index score was (69.71±9.37)% before surgery, (32.19±6.95)% on the 6th month after surgery, and (20.95± 6.16)% at the latest follow up. Onthe 1st year after operation, 16 patients got an excellent result, 4 good and 1 fair according to Macnab evaluation system. CONCLUSION Total spine endoscopy via interlaminal approach can be used as an option in the treatment of lumbar disc herniation combined with vertebral posterior margin dissociation, which can reduce trauma and injury to the lumbar dorsal muscle and achieve similar decompression effect as open surgery. The long term efficacy needs to be further proved by prospective randomized controlled studies with larger sample size.
Adolescent ; Adult ; Diskectomy, Percutaneous ; Female ; Humans ; Intervertebral Disc Displacement ; Lumbar Vertebrae ; Male ; Middle Aged ; Neuroendoscopy ; Prospective Studies ; Retrospective Studies ; Treatment Outcome ; Young Adult

In ischemic stroke, increased level of neuronal complex of nitric oxide synthase (nNOS)-postsynaptic density protein-95 (PSD-95) plays an important role in neuronal damage. We aimed to establish a screening model to identify compounds capable of uncoupling nNOS interaction with PSD-95. In this model, human embryonic kidney-293T (HEK-293T) cells were transfected with either pCDH-Flag-nNOS or pcDNA3.1-PSD-95 plasmid to obtain the protein of Flag-nNOS or PSD-95. Incubating Flag-nNOS with PSD-95 causes formation of the nNOS-PSD-95 complex. ZL006, a known uncoupler of nNOS-PSD-95 interaction, can disturb the interaction between Flag-nNOS and PSD-95, serving as a positive control. The method coupling antibodies to magnetic beads with glutaraldehyde was used to decrease the cost and increase the efficiency. To establish that our model is suitable for selecting nNOS-PSD-95 uncouplers, we evaluated the ability of IC87201, another reported uncoupler of nNOS-PSD-95 interaction, and structural analogs of ZL006. IC87201 and one structure analog of ZL006 showed uncoupling effect, supporting that our model can be used to select different types uncoupler blocking nNOS-PSD-95 interaction.

Volatile organic compounds (VOCs) in ambient air can participate in photochemical reactions, which lead to the generation of secondary pollutants such as ozone and aerosol. So real-time and accurate monitoring of atmospheric VOCs plays an important role in the study of the causes of air pollution. On the basis of proton transfer reaction mass spectrometry (PTR-MS) research, a novel dipolar proton transfer reaction mass spectrometer (DP-PTR-MS) for real-time and on-line monitoring atmospheric VOCs was developed. Compared with the conventional PTR-MS with one kind of reagent ion H3O+, DP-PTR-MS had three kinds of reagent ions H3O+, OH-, (CH)2COH+, which could be switched according to the actual detection need. So DP-PTR-MS can improve the qualitative ability and expand the detection range effectively. The reagent ion H3O+can be used for detecting VOCs whose proton affinities are greater than that of H2O. The reagent ion OH-can be used to identify VOCs cooperating with the reagent ion H3O+,and can also be used for detecting some inorganic substances such as CO2. The reagent ion (CH3)2COH+can be used for accurately detecting NH3under interference elimination circumstances. The limit of detection (LOD) and sensitivity of DP-PTR-MS were measured by using six kinds of standard gases. The results showed that the LOD for detecting toluene was 7×10-12(V/V) and the sensitivity for detecting ammonia has reached 126 cps/10-9 (V/V). The ambient air in Hefei city was on-line and real-time monitored for continuous 78 hours with DP-PTR-MS. The results showed that the newly developed DP-PTR-MS could be used for long-term and real-time monitoring atmospheric VOCs with the concentration of 10-12(V/V) level. DP-PTR-MS is an important tool for the study of the causes of atmospheric pollution and the monitoring of trace VOCs emissions.

AIM To investigate the effects of Shuxuening Injection (Ginkgo biloba leaf extract) on serum lactic acid (Lac),soluble CD14-st (Presepsin) and nitric oxide synthase (NOS) levels in sepsis patients.METHODS One hundred and eight patients with sepsis treated by routine treatment in our hospital from Jan.2014 to Oct.2016 were randomly divided into two groups,control group and Shuxuening group (therapy group).Two weeks were one therapeutic course.Before the treatment (the onset of patients within 3 hours),at 6 hours and 5 days after the treatment,Lac and Presepsin levels were detected,and the changes of nitric oxide (NO),NOS,inducible nitric oxide synthase (iNOS) and sequential organ failure assessment (SOFA) score were observed.Incidence of major adverse cardiac events (MACE) and 28-day survival were recorded at the same time.RESULTS Before the treatment,there were no significant differences in SOFA score and the levels of Lac,Presepsin,NO,NOS and iNOS between the two groups (P ＞ 0.05).Six hours after the treatment,the levels of Lac and Presepsin in the therapy group were lower than those in the control group (P ＜ 0.05),both the two groups had lower levels of Lac and Presepsin than those before the treatment (P ＜ 0.05);five days after the treatment,the levels of Lac and Presepsin in the two groups were lower than those at 6 hours after the treatment (P ＜ 0.05),the levels of Lac and Presepsin in the therapy group were lower than those in the control group (P ＜ 0.05).The SOFA score,NO,NOS and iNOS levels after the treatment in the therapy group were lower than those in the control group (P ＜ 0.05).The levels of Lac and Presepsin in sepsis patients were positively correlated with SOFA score (r =0.245,0.261,P =0.011,0.006).The patients in the therapy group had lower incidence of MACE and 28-day mortality rate than those in the control group (P ＜ 0.05).CONCLUSION The therapeutic effect of Shuxuening Injection combined with routine treatment on sepsis patients is superior to that of routine treatment,which can improve the prognosis of patients to a certain extent.

BACKGROUNDTotal hip arthroplasty (THA) in developmental dysplasia of the hip (DDH) is more complex than the normal hip, with large replacement risks and many complications. Although nonosteotomy THA is convenient to perform, femoral osteotomy shortening can avoid blood vessel and nerve traction injuries. This study aimed to compare osteotomy THA with nonosteotomy to determine reasonable options for operative management of DDH.

METHODSData on 48 DDH patients who underwent THA were analyzed retrospectively. The patients were divided into two groups: Group A 29 cases (nonosteotomy), and group B 19 cases (osteotomy). Harris and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, limb length discrepancy (LLD), radiological data on the hip, and claudication were evaluated. Data were analyzed by using paired-sample Student's t-test, independent-sample Student's t-test, and Pearson's Chi-square test; the test level was α =0.05.

RESULTSPostoperative Harris (90.7 ± 5.1) and WOMAC scores (88.0 ± 10.6) were significantly improved compared with preoperative Harris (44.8 ± 5.7) and WOMAC scores (42.0 ± 5.3) in group A (P < 0.05). Postoperative Harris (90.4 ± 2.8) and WOMAC scores (88.2 ± 5.9) were significantly improved compared with preoperative Harris (44.4 ± 4.2) and WOMAC scores (43.2 ± 4.3) in group B (P < 0.05). One case of dislocation occurred in group A; after closed reduction, dislocation did not recur. In group A, 2 patients developed cutaneous branch injury of the femoral nerve, which spontaneously recovered without treatment. Postoperative LLD >2 cm was seen in one case in group A and five cases in group B. Postoperative claudication showed no significant difference between the two groups (P > 0.05). No patients developed infection; postoperative X-rays showed that the location of the prosthesis was satisfactory, and the surrounding bone was not dissolved.

CONCLUSIONSTHA is effective and safe for DDH. For unilateral high dislocation DDH patients with limb lengthening ≤4 cm and good tissue conditions, THA without femoral osteotomy may be considered.

Adult ; Arthroplasty, Replacement, Hip ; methods ; Female ; Hip Dislocation, Congenital ; surgery ; Humans ; Male ; Middle Aged ; Osteotomy ; methods ; Postoperative Period ; Range of Motion, Articular ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVESTo study the surgical techniques and clinical outcomes of the revision surgery to treat recurrent dislocation after total hip arthroplasty.

METHODSFrom March 1997 to November 2010, 12 patients (12 hips) with revision total hip arthroplasty for recurrent dislocation were reviewed. There were 5 male and 7 female, aged from 20 to 73 years (mean age 52.7 years), whose body mass index (BMI) were 14.8-30.0 kg/m2 (mean 23.6 kg/m2). The Harris score and WOMAC score were registered and analyzed before surgery and at the time of latest follow-up. Any episode of dislocation and other complications such as deep infection, deep vein thrombosis and pulmonary embolism (DVT-PE) events, periprosthetic fracture, or early aseptic loosening were recorded.

RESULTSTwelve patients were successfully followed for 1.0-12.7 years (mean 4.0 years). No further dislocation episodes reported and all the hips were stable at the time of follow-up. No one complicated as deep infection, DVT-PE events, periprosthetic fracture, or early aseptic loosening. The Harris score was greatly improved from 38±21 before surgery to 81±9 at the time of last follow-up with statistic significance (t=-8.616, P<0.05) accompany with the WOMAC score elevation from 54±21 to 82±12 significantly (t=-6.200, P<0.05).

CONCLUSIONWith a reasonable algorithmic approach, the recurrent dislocated total hip arthroplasty can be treated with a relatively high success rate.

Adult ; Aged ; Arthroplasty, Replacement, Hip ; Female ; Follow-Up Studies ; Hip Dislocation ; surgery ; Humans ; Male ; Middle Aged ; Prosthesis Failure ; Recurrence ; Reoperation ; Retrospective Studies ; Young Adult