Longitudinal perioperative patient-reported outcomes in open compared with minimally invasive hysterectomy.

BACKGROUND: There are few prospective studies in the gynecologic surgical literature that compared patient-reported outcomes between open and minimally invasive hysterectomies within enhanced recovery after surgery pathways. OBJECTIVE: This study aimed to compare prospectively collected perioperative patient-reported symptom burden and interference measures in open compared with minimally invasive hysterectomy cohorts within enhanced recovery after surgery pathways. STUDY DESIGN: We compared patient-reported symptom burden and functional interference in 646 patients who underwent a hysterectomy (254 underwent open surgery and 392 underwent minimally invasive surgery) for benign and malignant indications under enhanced recovery after surgery protocols. Outcomes were prospectively measured using the validated MD Anderson Symptom Inventory, which was administered perioperatively up to 8 weeks after surgery. Cohorts were compared using Fisher exact and chi-squared tests, adjusted longitudinal generalized linear mixed modeling, and Kaplan Meier curves to model return to no or mild symptoms. RESULTS: The open cohort had significantly worse preoperative physical functional interference (P=.001). At the time of hospital discharge postoperatively, the open cohort reported significantly higher mean symptom severity scores and more moderate or severe scores for overall (P<.001) and abdominal pain (P<.001), fatigue (P=.001), lack of appetite (P<.001), bloating (P=.041), and constipation (P<.001) when compared with the minimally invasive cohort. The open cohort also had significantly higher interference in physical functioning (score 5.0 vs 2.7; P<.001) than the minimally invasive cohort at the time of discharge with no differences in affective interference between the 2 groups. In mixed modeling analysis of the first 7 postoperative days, both cohorts reported improved symptom burden and functional interference over time with generally slower recovery in the open cohort. From 1 to 8 postoperative weeks, the open cohort had worse mean scores for all evaluated symptoms and interference measures except for pain with urination, although scores indicated mild symptomatic burden and interference in both cohorts. The time to return to no or mild symptoms was significantly longer in the open cohort for overall pain (14 vs 4 days; P<.001), fatigue (8 vs 4 days; P<.001), disturbed sleep (2 vs 2 days; P<.001), and appetite (1.5 vs 1 days; P<.001) but was significantly longer in the minimally invasive cohort for abdominal pain (42 vs 28 days; P<.001) and bloating (42 vs 8 days; P<.001). The median time to return to no or mild functional interference was longer in the open than in the minimally invasive hysterectomy cohort for physical functioning (36 vs 32 days; P<.001) with no difference in compositive affective functioning (5 vs 5 days; P=.07) between the groups. CONCLUSION: Open hysterectomy was associated with increased symptom burden in the immediate postoperative period and longer time to return to no or mild symptom burden and interference with physical functioning. However, all patient-reported measures improved within days to weeks of both open and minimally invasive surgery and differences were not always clinically significant.

[ABC prognostic classification and MELD 3.0 and COSSH-ACLF â ¡ prognostic evaluation in acute-on-chronic liver failure].

Objective: To investigate the ABC prognostic classification and the updated version of Model for End-stage Liver Disease (MELD) score 3.0 and Chinese Group on the Study of Severe Hepatitis B ACLF Ⅱ score (COSSH-ACLF Ⅱ score) to evaluate the prognostic value in acute-on-chronic liver failure (ACLF). Methods: ABC classification was performed on a 1 409 follow-up cohorts. The area under the receiver operating characteristic curve (AUROC) was used to analyze MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ score after 3 days of hospitalization (COSSH-Ⅱ-3d). The prognostic predictive ability of patients were evaluated for 360 days, and the prediction differences of different classifications and different etiologies on the prognosis of ACLF were compared. Results: The survival curve of 1 409 cases with ACLF showed that the difference between class A, B, and C was statistically significant, Log Rank (Mantel-Cox) χ2=80.133, P<0.01. Compared with class A and C, χ2=76.198, P<0.01, the difference between class B and C, was not statistically significant χ2=3.717, P>0.05. AUROC [95% confidence interval (CI)] analyzed MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ-3d were 0.644, 0.655, 0.817 and 0.839, respectively (P<0.01). COSSH-Ⅱ had better prognostic predictive ability with class A ACLF and HBV-related ACLF (HBV-ACLF) for 360-days, and AUROC (95% CI) were 0.877 and 0.881, respectively (P<0.01), while MELD 3.0 prognostic predictive value was not better than MELD. Conclusion: ACLF prognosis is closely related to ABC classification. COSSH-Ⅱ score has a high predictive value for the prognostic evaluation of class A ACLF and HBV-ACLF. COSSH-Ⅱ score has a better prognostic evaluation value after 3 days of hospitalization, suggesting that attention should be paid to the treatment of ACLF in the early stage of admission.

Tenuivirus utilizes its glycoprotein as a helper component to overcome insect midgut barriers for its circulative and propagative transmission.

Many persistent transmitted plant viruses, including rice stripe virus (RSV), cause serious damage to crop production worldwide. Although many reports have indicated that a successful insect-mediated virus transmission depends on a proper interaction between the virus and its insect vector, the mechanism(s) controlling this interaction remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanisms underlying the entrance of RSV virions into SBPH midgut cells for virus circulative and propagative transmission. We have determined that this non-enveloped tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to overcome the midgut barrier(s) for RSV replication and transmission. In the absence of this glycoprotein, purified RSV virions were unable to enter SBPH midgut cells. In the RSV-infected cells, this glycoprotein was processed into two mature proteins: an amino-terminal protein (NSvc2-N) and a carboxyl-terminal protein (NSvc2-C). Both NSvc2-N and NSvc2-C interact with RSV virions. Our results showed that the NSvc2-N could bind directly to the surface of midgut lumen via its N-glycosylation sites. Upon recognition, the midgut cells underwent endocytosis followed by compartmentalization of RSV virions and NSvc2 into early and then late endosomes. The NSvc2-C triggered cell membrane fusion via its highly conserved fusion loop motifs under the acidic condition inside the late endosomes, leading to the release of RSV virions from endosomes into cytosol. In summary, our results showed for the first time that a rice tenuivirus utilized its glycoprotein NSvc2 as a helper component to ensure a proper interaction between its virions and SBPH midgut cells for its circulative and propagative transmission.

[Efficacy and safety of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome treated with glycoprotein â ¡b/â ¢a receptor antagonist].

Objective: To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI). Methods: The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization. Results: A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI (OR=0.881, 95%CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group (OR=1.401, 95%CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group (OR=0.919, 95%CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group (OR=1.559, 95%CI 1.130-2.150; P=0.007). Conclusion: In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.

[Advances in early warning and treatment of pre-hepatic failure].

Liver function of patients with pre-hepatic failure deteriorates rapidly, and with this there exists a risk of liver failure and high rates of mortality. This paper summarizes the concept of pre-hepatic failure, particularly the advances in early warning and treatment of pre-hepatic failure developing into hepatic failure, with a view to enhance clinicians' concerns to pre-hepatic failure for promoting the advancement of liver failure prevention and treatment, and improving the success rate of liver failure treatment.

[Clinical analysis of 2 820 cases of drug-induced liver injury].

Objective: To investigate the clinical characteristics, incidence trend, underlying diseases, causative drug and prognosis of drug-induced liver injury (DILI), so as to provide basis for its prevention and treatment. Methods: A retrospective study was conducted on 2 820 DILI cases who were admitted to our hospital from January 2002 to December 2015, and their clinical characteristics, incidence trends, underlying related diseases, causative drug, treatment and outcome were analyzed. Results: Among 2 820 DILI cases, the ratio of male to female was 1:1.44, and the age was (44.00±16.32) years old. According to the clinical classification of DILI, there were 2 353 cases (83.43%) of hepatocyte injury, 353 cases (12.51%) of cholestatic type and 114 cases (4.04%) of mixed type. In the three clinical classification of DILI, there was no statistically significant difference in the ratio of male to female (χ(2) = 3.032, P > 0.05). However, the difference in the ratio of male to female between different age groups was statistically significant (χ(2) = 48.367, P < 0.001). Among the patients with liver disease and acute liver disease admitted to our hospital from January 2002 to December 2015, the proportion of DILI and acute DILI showed an overall upward trend. The main underlying related diseases of 2 820 DILI cases were fever (15.14%), skin diseases (11.84%), cardiovascular and cerebrovascular diseases (11.17%). Chinese herbal patent medicines (37.49%), antibiotics (15.85%), antipyretic-analgesics (14.37%), and so on were the main causative drugs involved, and the prognostic differences among the three clinical classifications of DILI in terms of cure, improvement, ineffectiveness, and death were statistically significant (H = 61.300, P < 0.001). Conclusion: In recent years, among the patients with liver disease in our hospital, the proportion of DILI has shown an obvious upward trend, involving a variety of underlying diseases and causative drugs, and thus it needs clinical attention.

[Establishment of clinical features and prognostic scoring model in early-stage hepatitis B-related acute-on-chronic liver failure].

Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

[Clinical observation of drug-coated balloon in the treatment of lower extremity arterial long segment lesions].

Objective: To observe the efficacy of drug -coated balloon (DCB) in the treatment of long -segment arterial stenosis in lower extremity. Methods: Were retrospectively analyzed in February 2017 to January 2018,the First Hospital Affiliated to China Medical University of vascular surgical treated 80 patients with lower limb sclerosis of arterial congee appearance (lesion length>10 cm), accept the DCB and stents (BMS) treatment, compared two groups of patients with preoperative and postoperative issue patency rate of target lesion, ABI, Rutherford, amputation rate and the change of clinical symptoms and quality of life. Results: There were 60 cases in DCB group,20 cases in BMS group and 80 cases in BMS group. The patency rate of DCB group was 83.33% and 75.00% at 6 and 12 months after operation. The patency rate was 85.00% and 65.00% in the BMS group at 6 and 12 months after surgery. ABI, walking distance, Rutherford grade and clinical symptoms were significantly improved in the two groups compared with those before surgery. During the operation, 1 patient in the DCB group presented flow limiting interlayer and 1 patient still had>50% stenosis after predilation, and then underwent stent implantation for remediation. Conclusion: The treatment of lower limb arterial stenosis with DCB can obtain better near -and medium-term clinical efficacy.

Imatinib-induced ophthalmological side-effects in GIST patients are associated with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1.

Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021 for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1 rs2235040 were protective factors to periorbital oedema with OR of 0.313 (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253 (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the incidence of Imatinib-induced ophthalmological toxicities, and polymorphism analyses in associated genes might be beneficial to optimize Imatinib treatment.

Acupuncture for reduction of symptom burden in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation: a randomized sham-controlled trial.

PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy. Patients and clinical evaluators, but not acupuncturists, were blinded to group assignment. Symptom burden, the primary outcome was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days post transplantation. RESULTS: Among 60 participants, true acupuncture produced nonsignificant reductions in overall MDASI core symptom scores and symptom interference scores during transplantation (P = .4 and .3, respectively), at 15 days (P = .10 and .3), and at 30 days posttransplantation (P = .2 and .4) relative to sham. However, true acupuncture was significantly more efficacious in reducing nausea, lack of appetite, and drowsiness at 15 days (P = .042, .025, and .010, respectively). Patients receiving sham acupuncture were more likely to increase pain medication use posttransplantation (odds ratio 5.31, P = .017). CONCLUSIONS: Acupuncture was well tolerated with few attributable adverse events. True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing AHCT, and reduce the use of pain medications. These findings need to be confirmed in a future definitive study. TRIAL REGISTRATION: NCT01811862.

Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2.

DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.

Determinants of Gefitinib toxicity in advanced non-small cell lung cancer (NSCLC): a pharmacogenomic study of metabolic enzymes and transporters.

Skin rash, diarrhea and hepatotoxicity are the most common toxicities of Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The present study investigated the effects of genetic polymorphisms of drug target, metabolizing enzymes and transporters on Gefitinib toxicities. Thirty single-nucleotide polymorphisms, including EGFR, cytochromes P450 and ATP-binding cassette (ABC), were genotyped by matrix-assisted laser desorption/ionization time-of-flight platform in 59 non-small cell lung cancer patients treated with Gefitinib. Correlation analyses were performed to evaluate their effects on Gefitinib-induced toxicities. ABCB1 rs1128503 TT genotype was a significant high-risk determinant of both skin rash and diarrhea, with 15.78- and 10.78-fold of incident risk increased, respectively. (odds ratio (OR)=15.78, 95% confidence interval (CI) 2.01-124.1, P=0.0087; OR=10.78, 95% CI 1.54-75.40, P=0.0166 vs non-TT genotypes). Patients with ABCB1 rs1128503 TT genotype had greater risk of skin rash and diarrhea. Therefore, polymorphism analyses of ABCB1 might be beneficial to optimize Gefitinib treatment.

[Process of the degradation in vivo and biosafety of biodegradable magnesium alloy stent].

Objective: To observe the degradation process of biodegradable magnesium alloy stent (BMAS) in vivo in order to evaluate its degradation time and biological safety. Methods: Twenty-four male New Zealand white rabbits were divided into two groups: group A (n=12) and group B (n=12). The BMAS (a total of 12) was implanted in the infrarenal aorta of each rabbit in group A, while group B was the control group, without treatment. Color Doppler ultrasound was used at the 1, 2, 3, 4 months postoperatively to observe the degradation process of stents in group A. The arterial blood samples and main organs of two groups were also collected for biochemical examination and biosafety. Degradation assessment included transmission X-ray tomography (XRT), scanning electron microscope (SEM) and energy dispersion spectrum (EDS). Results: The XRT showed that the morphology of the stent was basically intact at 1 month after implantation, then scaffold composites were gradually degraded and absorbed. Degradation was basically completed at 4 months after operation. The early degradation products were Mg(2+) , then gradually replaced by Ca(2+) , P and other inorganic composition. There was no obvious adverse reactions in group A during the 4 months follow-up period. There was no statistical difference between the two groups in blood biochemical and pathological results (all P>0.05). Conclusion: BMAS can be degraded within 4 months in the abdominal aorta of rabbit, and the main degradation products are Ca(2+) and P, with good biosafety.

[Clinical and pathological differences between papillary thyroid carcinoma with Graves' disease and papillary thyroid carcinoma with Hashimoto's thyroiditis].

Objective: To explore the clinical and pathological differences between papillary thyroid carcinoma (PTC) with Graves' disease (GD) and PTC with Hashimoto's thyroiditis (HT). Methods: A total of 33 PTC patients with GD and 132 PTC patients with HT in the First Affiliated Hospital of China Medical University from January 2009 to December 2015 were enrolled. The clinical and histopathological data were analyzed. Results: The average serum concentration of thyroid stimulating hormone (TSH) of PTCs with GD was significantly lower than PTCs with HT [0.01 (0, 0.10) mU/L vs 2.28(1.51, 3.14) mU/L, P<0.001]. However, there was no significant difference between the two groups in nodule diameter [(15.7±7.0) mm vs (13.5±7.8)mm, P=0.14], percentage of lymph node metastasis (LNM) [33.3%(11/33) vs 39.4%(52/132), P=0.52], TNM stage Ⅲ-Ⅳ disease [12.1%(4/33) vs 11.4% (15/132), P=1.00], papillary thyroid micro-carcinoma (PTMC) [60.6% (20/33) vs 60.6%(80/132), P=1.00]and classic PTC in all its variant patterns [81.8%(27/33) vs 75.0%(99/132), P=0.36]. The age (P<0.01, OR=0.95, 95%CI: 0.92-0.98) and PTMC (P<0.01, OR=0.30, 95%CI: 0.13-0.67), rather than TSH (P=0.08) were independently correlated with LNM. Recurrence rate of PTC with GD was significantly lower than PTC with HT (log-rank test, P=0.03). In Cox proportional hazards regression model, variant pattern of PTC was independently correlated with recurrence rate (P<0.05). Conclusions: GD with PTC wasn't different from HT concomitant with PTC, except for thyroid function test. In addition, recurrence rate of PTC with GD was lower than that of PTC with HT after controlling TSH in the same level.

[Clinical effect and safety of 144-week treatment with entecavir capsules in treatment-naïve HBeAg-positive patients with chronic hepatitis B].

Objective: To investigate the clinical effect and safety of entecavir capsules in the treatment of treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). Methods: A total of 158 HBeAg-positive CHB patients were given oral entecavir capsules at a dose of 0.5 mg/time once a day for 144 weeks. Clinical outcome and safety were evaluated at baseline and at 24, 48, 72, 96, 120, and 144 weeks of treatment respectively. The Fisher's exact test was used for the analysis of categorical data. Results: After 144 weeks of treatment, 90.91% of all patients achieved virologic response (< 69 IU/ml), the normalization rate of alanine aminotransferase was 88.18%, the clearance rate of HBeAg was 33.33%, and the seroconversion rate of HBeAg was 24.07%. Of all patients, 2 dropped out due to adverse events and 5 experienced serious adverse reactions. Conclusion: Entecavir capsules can inhibit viral replication and have good safety in treatment-naïve HBeAg-positive CHB patients.

The Colicin E1 TolC-Binding Conformer: Pillar or Pore Function of TolC in Colicin Import?

The mechanism by which the drug export protein TolC is utilized for import of the cytotoxin colicin E1 across the outer membrane and periplasmic space is addressed. Studies of the initial binding of colicin E1 with TolC, occlusion of membrane-incorporated TolC ion channels, and the structure underlying the colicin-TolC complex were based on the interactions with TolC of individual colicin translocation domain (T-domain) peptides from a set of 19 that span different segments of the T-domain. These studies led to identification of a short 20-residue segment 101-120, a "TolC box", located near the center of the colicin T-domain, which is necessary for binding of colicin to TolC. Omission of this segment eliminated the ability of the T-domain to occlude TolC channels and to co-elute with TolC on a size-exclusion column. Far-ultraviolet circular dichroism spectral and thermal stability analysis of the structure of T-domain peptides implies (i) a helical hairpin conformation of the T-domain, (ii) the overlap of the TolC-binding site with a hinge of the helical hairpin, and (iii) a TolC-dependent stage of colicin import in which a central segment of the T-domain in a helical hairpin conformation binds to the TolC entry port following initial binding to the BtuB receptor. These studies provide the first structure-based information about the interaction of colicin E1 with the unique TolC protein. The model inferred for binding of the T-domain to TolC implies reservations about the traditional model for colicin import in which TolC functions to provide a channel for translocation of the colicin in an unfolded state across the bacterial outer membrane and a large part of the periplasmic space.

The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer.

BACKGROUND: MiR-214 is aberrantly regulated in several tumours, but its underlying mechanisms in colorectal cancer (CRC) metastasis remain largely unknown. This study aimed to demonstrate the function and potential mechanism of miR-214 in regulating invasion and metastasis of CRC. METHODS: The transcription factor and targets of miR-214 were predicted by bioinformatics and validated using ChIP and dual-luciferase reporter assay. DNA methylation status was explored using bisulphite sequencing PCR. The in vitro and in vivo function of miR-214 in CRC was evaluated using MTT, plate colony formation, Matrigel invasion and animal models. Real-time PCR or western blotting was performed to detect FOXD3, miR-214 and MED19 expressions in CRC cells and clinical specimens. RESULTS: MiR-214 was downregulated in CRC and was significantly correlated with lymphatic metastasis. Downregulation of miR-214 might due to promoter hypermethylation in CRC. FOXD3 was validated as a transcription factor of miR-214 by ChIP assay. Dual-luciferase assay identified MED19 as a target of miR-214 in CRC. In vitro and in vivo experiments showed that miR-214 mediated the inhibiting effect of FOXD3 on proliferation, invasion and metastasis by targeting MED19. Spearman's correlation analysis showed a positive correlation between FOXD3 and miR-214, and negative correlations between FOXD3 and MED19, miR-214 and MED19 in CRC cells and clinical specimens. CONCLUSIONS: FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of CRC. Targeting the miR-214-mediated axis might be helpful for the treatment of CRC.

[Risk factors for short-term outcome of patients with HBV-related acute-on-chronic liver failure].

OBJECTIVE: To investigate the risk factors for the short-term outcome of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and to establish a risk model for predicting the short-term outcome of these patients. METHODS: A total of 338 patients with HBV-related ACLF who were admitted to 30 Lod hospital of PLA hospital from January 2010 to January 2014 were enrolled, and a prospective clinical follow-up was performed for them. Multivariate logistic regression was used to determine the risk factors for short-term (12 weeks) outcome, the predictive model with logistic regression equation was established, and the predictive value of this model was evaluated. RESULTS: The multivariate logistic regression analysis showed that age, a family history of hepatitis B, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), white blood cell (WBC), platelet (PLT), international normalized ratio (INR), total bilirubin (TBil), total bile acid (TBA), creatinine, Na, HBV DNA, and HBeAg were the independent risk factors for the short-term outcome of these patients. Logistic(p) = -4.466 + 1.192 age + 1.631 family history of hepatitis B + 1.091 HE + 1.631 HRS + 1.208 WBC -1.487 PLT + 1.092 INR + 1.446 TBil + 1.608 TBA -1.101 CHE + 1.279 CRE -1.713 Na + 1.032 HBV DNA + 0.833 HBeAg. The area under the receiver operating characteristic curve of the model for the prediction of short-term outcome was 0.930, the cut-off value was 3.16, the sensitivity was 0.860, and the specificity was 0.871. With the increasing scores of the equation, the mortality of patients tended to increase gradually. CONCLUSION: Age, a family history of hepatitis B, HE, HRS, WBC, PLT, INR, TBil, TBA, CHE, CRE, Na, HBV DNA, and HBeAg are the independent risk factors for the short-term outcome of patients with HBV-related ACLF. The model for predicting short-term outcome established on the basis of independent risk factors has a better clinical value in guiding clinical therapy.

The rtA181S mutation of hepatitis B virus primarily confers resistance to adefovir dipivoxil.

The study aimed to clarify clinical significance of hepatitis B virus (HBV) rtA181S mutation in Chinese HBV-infected patients. A total of 18 419 patients with chronic HBV infection from Beijing 302 Hospital were investigated. HBV complete reverse transcriptase region of polymerase was screened by direct sequencing, and the results were verified by clonal sequencing. Replication-competent mutant and wild-type HBV genomic amplicons were constructed and transfected into the HepG2 cells and cultured in the presence or absence of serially diluted nucleos(t)ide analogues. Intracellular HBV replicative intermediates were quantitated for calculating the 50% effective concentration of the drug (EC(50)). The rtA181S was detected in 98 patients with 12 kinds of mutational patterns. Genotype C and genotype B HBV infection occupied 91.8% and 8.2% in rtA181S-positive patients, in contrast to 84.6% and 15.4% in rtA181S-negative patients (P < 0.01). All rtA181S-positive patients had received nucleos(t)ide analogues. rtA181S was detected in multiple patients with virologic breakthrough. Phenotypic analysis of patient-derived viral strains showed that rtA181S, rtA181S+N236T, rtN236T and rtA181V strains had 68.5%, 49.9%, 71.4% and 66.2% of natural replication capacity of wild-type strain, and 3.7-fold, 9.8-fold, 7.9-fold and 5.6-fold increased EC(50) to adefovir dipivoxil (ADV). The rtA181S strain remained susceptible to lamivudine, entecavir and tenofovir, and ADV susceptibility was restored after the mutation was eliminated through site-directed mutagenesis. Rescue therapy with entecavir or combination therapy was effective in rtA181S-related ADV-refractory patients. The rtA181S mutation confers moderate resistance to ADV. It could be induced by either lamivudine or ADV and contribute ADV treatment failure.

Setup errors in cone-beam computed tomography and their effects on acute radiation toxicity in cervical cancer radiotherapy.

This study aimed to evaluate cone-beam computed tomography setup errors during cervical cancer treatment and the effects of these errors on acute radiation toxicity and treatment efficacy. A total of 170 cervical cancer patients were randomly divided into image-guided radiation therapy (IGRT; 86 patients) and intensity-modulated radiation therapy (IMRT; 84 patients) groups to receive IGRT and IMRT, respectively. After correcting setup errors for the 86 patients in the IGRT group, the X-, Y- and Z-axis errors were smaller than the corresponding errors before correction (P < 0.01, P < 0.05, and P < 0.05, respectively). The setup errors unevenly influenced the affected organs and dosage distributions in the targeted regions. The frequencies of patients with grade 0 or I urinary toxicity were 86.0% (74/86) and 44.0% (37/84) in the IGRT and IMRT groups, respectively (P < 0.01), whereas the frequencies of patients with grade 0 or I gastrointestinal toxicity were 83.7% (72/86) and 53.6% (45/84) in the IGRT and IMRT groups, respectively (P < 0.01). The two groups had similar response rates (P > 0.05). IGRT significantly corrected and reduced setup errors during cervical cancer treatment and enhanced the dosage distribution accuracy within the affected organs and targeted regions. IGRT can reduce the adverse effect of radiotherapy, thereby achieving improved efficacy during cervical cancer treatment.