A piecewise constitutive model for collagen fiber tissues.

Inspired by Meyers et al. (Science, 2013), a piecewise model is established so as to individually predict both the heel region and the linear region of stress-strain curve. When the piecewise model satisfactorily predicts the experimental data, the constitutive parameters are precisely identified with definite physical significances. Along with this piecewise guideline, a complete constitutive model can be established for the whole stress-strain curve of collagen fiber tissues with the failure region as well. Graphical abstract.

Unstable Non-isthmic Spondylolisthesis Following Unilateral Biportal Endoscopy Assisted Unilateral Laminotomy for Bilateral Decompression: A Case Report.

Lumbar decompressive laminectomy is a standard treatment for degenerative lumbar spinal stenosis, but in some cases, can lead to iatrogenic spondylolysis and delayed segmental instability. Iatrogenic spondylolysis occurs in most cases in pars interarticularis, but rare cases have also been reported, pediculolysis in pedicle and laminolysis in lamina. Minimally invasive spine surgery (MIS) is known to have a low risk of developing these iatrogenic spondylolyses, and unilateral biportal endoscopy is the MIS that has been drawing attention. We present a case of a 72-year-old female who was diagnosed with L4-5 unstable non-isthmic spondylolisthesis and severe right central disc extrusion 10 weeks after UBE assisted unilateral laminotomy for bilateral decompression (ULBD) at the consecutive segments of L3-4 and L4-5. Pre-operative imaging studies revealed severe central stenosis without spondylolisthesis at L3-L4 and L4-L5 along with L4-L5 facet tropism. She was managed by anterior lumbar interbody fusion and cement augmented pedicle screw fixation, which resulted in the complete resolution of her clinical and neurologic symptoms.

[The influence of cachexia on the immunotherapy efficacy of Sintilimab for non-small cell lung cancer].

Objective: To investigate whether cachexia affects the treatment effect of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC). Methods: The prognosis of 62 patients with advanced NSCLC who received anti-programmed cell death-1 (PD-1) in Henan Provincial People's Hospital from 2019 to 2021 were retrospectively analyzed. The cachexia was evaluated before and after the second course of immunotherapy. Kaplan-Meier and Log rank methods were used for survival analysis, Cox regression model was used for multivariate analysis, and Spearman's correlation analysis was used for correlation analysis. Results: After the second course of immunotherapy, psoas major muscle area (PMMA) values of the cachexia group and the control group were (14.10±4.09) and (11.66±3.22) cm(2) respectively, with statistics significance (P=0.001). The level of Prealbumin and body weight were correlated with cachexia (P<0.05). The 6-month and 1-year survival rates of 62 cases in the whole group were 58.6% and 42.5%, respectively. The progression-free survival (PFS) in the control group (7.6 months) was higher than that in the cachexia group (3.8 months, P=0.006). The PFS in patients with high expression of PD-L1 (7.1 months) was longer than that of patients with low expression (3.8 months, P=0.009). The overall survival (OS) in the cachexia group (6.3 months) was lower than that in the control group (18.2 months, P=0.006). The OS in patients with high expression of PD-L1 (14.5 months) was longer than that of patients with low expression (1 months, P=0.038). The level of Prealbumin, the level of PD-L1 expression and the change rate of PMMA were related to the OS of the patients (P<0.05). The level of Prealbumin and the change rate of PMMA were the independent influencing factors of the OS (P<0.05). The PMMA and the level of Prealbumin were negatively correlated (r=-0.003 8, P<0.05). Conclusion: Cachexia has a negative impact on the outcomes of patients who received anti-PD-1 immune checkpoint inhibitor therapy.

Hypocomplementemia (C3) as an independent predictor for children with acute post-streptococcal glomerulonephritis: a long-term observation.

OBJECTIVE: The aim of this study was to examine the altering patterns in clinical characteristics and severity of acute post-streptococcal glomerulonephritis (APSGN) in children. PATIENTS AND METHODS: We analyzed the medical records of 119 children who were diagnosed with APSGN from 1987 to 2018, retrospectively. The patients were divided into two groups: Group I (n=72, before 1998) and Group II (n=47, after 1998). Clinical, radiologic, and laboratory findings were compared between the two groups. RESULTS: The clinical manifestations, including vomiting (20.8% vs. 4.3%, p=0.014), oliguria (40.3% vs. 19.1%, p=0.016), and generalized edema (86.1% vs. 63.8%, p=0.005), were statistically less frequent since 1998. Pulmonary edema on chest X-ray (22.7% vs. 4.4%, p=0.014) was less frequent in Group II than in Group I. The level of BUN (23.3±19.3 vs. 18.8±11.2, p=0.009) was lower in Group II than in Group I, while that of creatinine was not significantly different between the two groups. C3 level was an independent factor for predicting the development of edema (odds ratio [OR]: 1.034, 95% CI: 1.010-1.060, p=0.006) and acute nephritic symptoms (≥2) (OR: 0.974, 95% CI: 0.952-0996, p=0.020). It was also negatively correlated with an increasing number of acute nephritic symptoms, including oliguria and edema, in patients with APSGN (R=-0.182, p=0.048). CONCLUSIONS: This study demonstrated that APSGN had favorable clinical manifestations and severity over the past 30 years. The monitoring of C3 levels can be used to assess the disease severity and risk of complications, including edema and oliguria, which are decreasing in South Korean children.

[Insulin-like growth factor-1 alleviates hepatocyte senescence by regulating intranuclear p53-progerin pathway].

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H(2)O(2)). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-ß-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-ß-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.

[A new analysis method for 24-hour intraocular pressure data].

The study aimed to introduce a new analysis method of 24-hour intraocular pressure (IOP) and to propose the concept of overall IOP. Data of 24-hour IOP of a patient with a confirmed diagnosis of normal tension glaucoma was selected. Based on the present indexes including peak IOP, trough IOP, maximum difference, and mean IOP, new indexes were proposed, which included main IOP, duration of main IOP, and rate of IOP increase. A radar chart was drawn, and overall IOP was calculated. Overall IOP value = IOP distribution (sum of IOP value multiplied by the corresponding duration) × IOP fluctuation (standard deviation) × rate of IOP increase/100. By comparing two series of IOP data, the advantages of the new IOP indexes were demonstrated. The introduction of the concept of overall IOP expands the description of IOP from a single static state to a comprehensive dynamic state, which enables us to analyze the results of 24-hour IOP monitoring more thoroughly. (Chin J Ophthalmol, 2021, 57: 228-231).

[Association between serum vitamin D level and immune imbalance in advanced schistosomiasis patients with liver fibrosis].

OBJECTIVE: To examine the relationship between serum vitamin D level and immune imbalance in advanced schistosomiasis patients with liver fibrosis. METHODS: A total of 120 advanced schistosomiasis patients with liver fibrosis that were admitted to the Department of Schistosomiasis of The First Hospital of Jiaxing City from May 2016 to September 2018 were recruited as the observation group, and 50 healthy volunteers randomly sampled from the hospital during the same period served as the control group. The serum IgG antibody, IgA antibody, C3 complement, C4 complement, CD4+ cell proportion, CD8+ cell proportion, 25-hydroxyvitamin D [25(OH)D] levels were compared between the two groups. Liver fibrosis was classified into grade I, II and III according to the classification criteria of liver fibrosis by ultrasonography, and the serum IgG antibody, IgA antibody, C3 complement, C4 complement, CD4+ proportion, CD8+ proportion, 25(OH)D levels were compared among patients with grade I, II and III liver fibrosis. In addition, all patients were classified into the sufficient group, the insufficient group and the deficient group according to the serum vitamin D level, and the serum IgG antibody, IgA antibody, C3 complement, C4 complement, CD4+ proportion, CD8+ proportion, 25(OH)D levels were compared among these three groups. Moreover, the associations of the serum vitamin D level with these immune indicators were examined. RESULTS: The 120 advanced schistosomiasis patients with liver fibrosis included 58 men and 62 women, and had a mean age of (72.00 ± 3.00) years. There were 32 cases with grade I liver fibrosis, 46 cases with grade II liver fibrosis, and 42 cases with grade III liver fibrosis. There were no significant differences between the observation group and the control group in terms of serum D-dimer, total cholesterol (TC), triglyceride (TG), C3 complement or C4 complement levels (t = 2.467, 0.322, 0.790, -2.432 and -2.630, all P values > 0.05); however, there were significant differences seen in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood calcium, blood phosphorus, IgG antibody, IgA antibody, CD4+ proportion, CD8+ proportion, and 25(OH)D levels (t = 5.130, 6.382, -1.341, 2.361, 8.708, 11.783, -2.995, -6.543 and -3.022, all P values < 0.05). In addition, there were significant differences in AST, ALT, blood phosphorus, IgA antibody, C3 complement, CD8+ cell proportion and 25(OH)D levels among patients with grades I, II and III liver fibrosis (F = 19.704, 16.254, 62.669, 49.347, 5.430, 5.434 and 5.783, all P values < 0.05). There were significant differences in ALT, blood phosphorus, IgA antibody, CD8+ cell proportion and 25(OH)D levels between patients with grades I and III liver fibrosis (all P values < 0.05), and significant differences were seen between patients with grades II and III liver fibrosis in terms of blood phosphorus, IgA antibody and CD8+ cell proportion (all P values < 0.05), while there was a significant difference in the CD8+ cell proportion between patients with grades I and II liver fibrosis (P < 0.05). Moreover, there were significant differences among the sufficient, insufficient and deficient groups in terms of IgG antibody, IgA antibody, C3 complement, CD4+ cell proportion and CD8+ cell proportion (F = 13.303, 59.623, 8.698, 9.969 and 12.805, all P values < 0.05), and there was a significant difference in the CD8+ cell proportion between the insufficient and deficient groups (P < 0.05). Pearson correlation analysis revealed that serum 25(OH)D level were negatively associated with IgG and IgA antibody levels (r = -0.754 and -0.773, both P values < 0.05), and positively associated with C3 complement, CD4+ cell proportion and CD8+ cell proportion in advanced schistosomiasis patients with liver fibrosis (r = 0.827, 0.850 and 0.830, all P values < 0.05). CONCLUSIONS: Immune imbalance occurs in advanced schistosomiasis patients with liver fibrosis, and serum vitamin D level may correlate with immune imbalance in advanced schistosomiasis patients with liver fibrosis.

LINC01605 regulates proliferation, migration and invasion of colorectal cancer cells via targeting miR-3960/SOX11.

OBJECTIVE: We aimed to determine the expression level of long intergenic non-coding ribonucleic acid 1605 (LINC01605) in colorectal cancer (CRC), and to explore the effects of the LINC01605/microRNA (miR)-3960/sex-determining region Y-box 11 (SOX11) regulatory axis on the biological behaviors of CRC cells and the molecular mechanism therein. PATIENTS AND METHODS: Tissue specimens were collected from 38 patients with CRC, and the relative expression level of LINC01605 in the CRC tissues and CRC cells was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, the effects of LINC01605 on the proliferation, apoptosis, invasion and metastasis of CRC cells were observed via in vitro assays [cell counting kit (CCK)-8 assay, flow cytometry and transwell assay]. Besides, the possible miRNAs binding to LINC01605 were predicted by the bioinformatics method, and they were screened and verified using qRT-PCR and Dual-Luciferase reporter gene assay. Finally, the downstream target genes of miR-3960 were predicted by means of bioinformatics, and they were also screened and confirmed via qRT-PCR and Dual-Luciferase reporter gene assay. RESULTS: According to the results of qRT-PCR, the expression of LINC01605 was up-regulated in 31 out of 38 cases of CRC tissue specimens, and its expression in CRC cells was higher than that in normal colorectal cells. The results of in vitro assays revealed that the proliferation, migration and invasion abilities of CRC cells were weakened, with an increased apoptosis rate after interference with LINC01605 expression. Based on the results of qRT-PCR and Dual-Luciferase reporter gene assay, miR-3960 was the target of LINC01605, while SOX11 was the target of miR-3960. Moreover, the expression of miR-3960 rose, but that of SOX11 declined after interference with LINC01605 expression. It was found through Western blotting that the protein expression of SOX11 was lowered after interference with LINC01605 expression. CONCLUSIONS: LINC01605 has an up-regulated expression in CRC, and accelerates the proliferation, migration and metastasis of CRC cells by the miR-3960/SOX11 regulatory axis.

Dissociable dopaminergic and pavlovian influences in goal-trackers and sign-trackers on a model of compulsive checking in OCD.

RATIONALE: Checking is a functional behaviour that provides information to guide behaviour. However, in obsessive-compulsive disorder (OCD), checking may escalate to dysfunctional levels. The processes underpinning the transition from functional to dysfunctional checking are unclear but may be associated with individual differences that support the development of maladaptive behaviour. We examined one such predisposition, sign-tracking to a pavlovian conditioned stimulus, which we previously found associated with dysfunctional checking. How sign-tracking interacts with another treatment with emerging translational validity for OCD-like checking, chronic administration of the dopamine D2 receptor agonist quinpirole, is unknown. OBJECTIVES: We tested how functional and dysfunctional checking in the rat observing response task (ORT) was affected by chronic quinpirole administration in non-autoshaped controls and autoshaped animals classified as sign-trackers or goal-trackers. METHODS: Sign-trackers or goal-trackers were trained on the ORT before the effects of chronic quinpirole administration on checking were assessed. Subsequently, the effects on checking of different behavioural challenges, including reward omission and the use of unpredictable reinforcement schedules, were tested. RESULTS: Prior autoshaping increased checking. Sign-trackers and goal-trackers responded differently to quinpirole sensitization, reward omission and reinforcement uncertainty. Sign-trackers showed greater elevations in dysfunctional checking, particularly during uncertainty. By contrast, goal-trackers predominantly increased functional checking responses, possibly in response to reduced discrimination accuracy in the absence of cues signalling which lever was currently active. CONCLUSIONS: The results are discussed in terms of how pavlovian associations influence behaviour that becomes compulsive in OCD and how this may be dependent on striatal dopamine D2 receptors.

Randomized, Open-Label, Phase IV, Korean Study of Kidney Transplant Patients Converting From Cyclosporine to Prolonged-Release Tacrolimus Plus Standard- or Reduced-Dose Corticosteroids.

BACKGROUND: This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. METHODS: At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. RESULTS: Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. CONCLUSION: Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.

[Genetic Polymorphisms of 19 STR Loci in Populations of Three Culture Region in Shandong].

OBJECTIVES: To analyse the genetic polymorphisms of 19 autosomal STR loci in Han population of east, middle-northwest and southwest-south Shandong and to explore its genetic relationships among the population of these three regions. METHODS: STR loci of 1 044 unrelated Han individuals in three Shandong regions were typed with a Goldeneye® DNA ID System 20A kit. The allele frequency and population genetics parameters of 19 autosomal STR loci were statistically analysed by Modified-Powerstates software. The genetic distances among the population in three regions were calculated by Arlequin v3.5 software. The phylogenetic tree was conducted using MEGA v4.0 software. RESULTS: Fifteen of 19 autosomal STR loci were detected with the H values greater than 0.7, PIC values greater than 0.7, and DP values greater than 0.9 in the populations of all three Shandong regions. Among the populations in these three regions, the genetic distance between the populations in middle-northwest and southwest-south Shandong was closest （Fst=0.000 16）, followed by east and southwest-south Shandong （Fst=0.0003 6）. The genetic distance between the populations in east and middle-northwest Shandong was the farthest （Fst=0.000 66, P<0.05）. CONCLUSIONS: The 19 autosomal STR loci show good genetic polymorphisms in Han population of three Shandong regions, and 15 of them are high. There are genetic differences between the populations in east and middle-northwest Shandong.

Effect of Changes in Body Mass Index on Cardiovascular Outcomes in Kidney Transplant Recipients.

BACKGROUND: A higher body mass index (BMI) before kidney transplantation (KT) is associated with increased mortality and allograft loss in kidney transplant recipients (KTRs). However, the effect of changes in BMI after KT on these outcomes remains uncertain. The aim of this study was to investigate the effect of baseline BMI and changes in BMI on clinical outcomes in KTRs. METHODS: A total of 869 KTRs were enrolled from a multicenter observational cohort study from 2012 to 2015. Patients were divided into low and high BMI groups before KT based on a BMI cutoff point of 23 kg/m2. Differences in acute rejection and cardiovascular disease (CVD) between the 2 groups were analyzed. In addition, clinical outcomes across the 4 BMI groups divided by BMI change 1 year after KT were compared. Associations between BMI change and laboratory findings were also evaluated. RESULTS: Patients with a higher BMI before KT showed significantly increased CVD after KT (P = .027) compared with patients with a lower BMI. However, among the KTRs with a higher baseline BMI, only persistently higher BMI was associated with increased CVD during the follow-up period (P = .003). Patients with persistently higher BMI had significantly decreased high-density lipoprotein cholesterol and increased hemoglobin, triglyceride, and hemoglobin A1c levels. Baseline BMI and post-transplantation change in BMI were not related to acute rejection in KTRs. CONCLUSIONS: BMI in the 1st year after KT as well as baseline BMI were associated with CVD in KTRs. More careful monitoring of obese KTRs who do not undergo a reduction in BMI after KT is required.

Expression of bovine rotavirus VP8 and preparation of IgY antibodies against recombinant VP8.

Group A rotavirus is the leading cause of acute gastroenteritis in cattle and swine. Although, vaccination against this virus is an effective strategy for prevention, additional strategy to control disease is necessary. Egg yolk immunoglobulin (IgY)-based passive immunization could be a better option in preventing this disease. Bovine rotavirus (BRV) is group A rotavirus and possesses a genome of 11 segments of double-stranded RNA. The outer layer of capsid is composed of two proteins (VP7 and VP4), which induce virus neutralizing antibodies. Trypsin cleavage of VP4 produces VP8 (28 kDa) and VP5 (60 kDa) fragments. Since a number of studies have demonstrated the induction of neutralizing antibodies using VP8 subunit vaccines, we have produced IgY against the recombinant VP8. The cDNA spanning the VP8 subunit was amplified from bovine rotavirus-infected cells and cloned into pET21d(+) expression vector to generate recombinant VP8. The resulting carboxy-terminal His-tagged VP8 proteins were expressed in Escherichia coli strain BL21(DE3) by isopropyl ß-D-1-thiogalactopyranoside (IPTG) induction. The recombinant proteins were purified using Ni-NTA agarose beads, and the purified protein was used as the immunizing agent to produce polyclonal antibodies in chicken. The resulting polyclonal antisera specifically recognized VP8 in Western blot assay and were able to neutralize BRV replication in cell cultures. These results demonstrate that IgY can be used in immunological assays and, in addition, in passive immunization of newborn calves against BRV.

Analysis of the 19 Y-STR and 16 X-STR loci system in the Han population of Shandong province, China.

The sex-linked short tandem repeats (STR), Y-STR and X-STR, are important for autosomal STRs in forensic paternity testing. We evaluated the forensic parameters of 19 Y-STRs and 16 X-STRs in the Han population of Shandong province, China. A Goldeneye 20Y kit (DYS391, DYS389I, DYS390, DYS389II, DYS348, DYS456, Y-GATA-H4, DYS447, DYS19, DYS392, DYS393, DYS388, DYS439, DYS635, DYS448, DYS460, DYS458, DYS437, DYS385 a/b) was used to analyze the forensic parameters of 534 unrelated males. A Goldeneye17X system (DXS6795, DXS9902, DXS8378, HPRTB, GATA165B12, DXS7132, DXS7424, DXS6807, DXS6803, GATA172D05, DXS6800, DXS10134, GATA31E08, DXS10159, DXS6789, DXS6810, amelogenin) was used to analyze 97 unrelated males and 214 females. In addition, we used the kits to examine 5 cases with abnormal amelogenin test results, as well as a male child with agenosomia typed by autosomal STR. We found 203 Y-STR haplotypes with allele frequencies ranging from 0.0019 to 0.7959, and GD ranging from 0.3429 to 0.9667. Expect in DXS6803, the allele frequencies of the other 15 X-STR loci showed no differences between females and males. PDF ranged from 0.5504 to 0.9638, while PDM ranged from 0.3176 to 0.8377. With the exception of DXS6803 and DXS6810, the allele frequencies of other X-STR loci were in accordance with Hardy-Weinberg equilibrium in females. One amelogenin negative case was characterized as a deletion of Y-DYS458. This paper provided data regarding the genetic polymorphism of Y-STRs and X-STRs in the Han population, and demonstrated the importance of Y-STR and X-STR in forensic autosomal STR analysis.

Mouse tetherin enhances moloney murine leukemia virus-induced syncytium formation.

Tetherin (also referred to as BST-2 or CD317) is an antiviral cellular restriction factor that inhibits the release of many enveloped viruses. It is a 30-36 kDa type II transmembrane protein, expression of which is induced by type I interferon. Mouse tetherin inhibits nascent cell-free particle release. However, it is unclear whether mouse tetherin restricts cell-to-cell spread of moloney murine leukemia virus (Mo-MLV) or whether is the mouse tetherin involved in syncytium formation. To examine cell-to-cell spread and syncytium formation of Mo-MLV in the presence or absence of mouse tetherin, R peptide (the cytoplasmic tail of the transmembrane protein (TM); 16 amino acids) truncated Env expressing vector was constructed. It contained enhanced green fluorescent protein (EGFP) in the proline rich region (PRR) of Env. This R(-)Env full-length molecular clone could rule out virus-cell transmission due to the slightly reduced R(-)Env protein incorporation into the viral particles. When NIH3T3 cells stably expressing mouse tetherin were transfected with R(-)Env full-length molecular clone, syncytium formation was significantly enhanced in the tetherin-expressing cells. These data suggest that tetherin-mediated retention of R-defective virions on the cell surface could enhance syncytium formation. In addition, we found that the R(-)Env full-length molecular clone containing EGFP in the PRR of Env to be a useful tool allowing fast and convenient detection of syncytia by fluorescence microscopy.

Circulating miR-199a-3p in plasma and its potential diagnostic and prognostic value in glioma.

OBJECTIVE: The present study aimed to examine the possibility of using plasma miR-199a-3p as a biomarker for glioma. PATIENTS AND METHODS: Plasma miR-199a-3p expression glioma patients and normal healthy controls were quantified by Quantitative reverse transcription PCR. Then, the associations of serum miR-199a-3p level with clinicopathological factors or survival of glioma patients were further evaluated. Receiver operating characteristics (ROC) and area under the ROC curve (AUC) were used to validate the diagnostic value of miR-199a-3p. Univariate and multivariate Cox regression analyses were finally performed to analyze the independent factors for overall survival. RESULTS: The qRT-PCR results showed that the miR-199a-3p expression was significantly downregulated in glioma tissues compared with the adjacent non-tumor tissues (p<0.01). Furthermore, plasma miR-199a-3p level was significantly lower in glioma patients when compared with healthy controls (p<0.01). ROC curve analysis showed that plasma miR-199a-3p was a useful marker for discriminating cases from healthy controls, with an area under the ROC curve (AUC) of 0.8466 (95% confidence interval (CI) 0.772 to 0.9211, p<0.001). Moreover, miR-199a-3p expression was associated with various clinicopathological parameters, including WHO grade (p=0.001) and KPS score (p=0.008). We found that glioma patients with low miR-199a-3p expression level had distinctly shorter overall survival than patients with high miR-199a-3p expression level (p=0.0067). Univariate and multivariate analysis suggested that miR-199a-3p expression was an independent predictor of poor prognosis. CONCLUSIONS: These findings indicated that the circulating miR-199a-3p could be used as a promising novel biomarker for the diagnosis and prognosis of glioma.

Evidence for miR-17-92 and miR-134 gene cluster regulation of ovarian cancer drug resistance.

OBJECTIVE: Ovarian cancer treatments are often impeded by drug resistance. It has been proposed that microRNA (miRNA) expression patterns may play a role in drug resistance among ovarian cancers. The present study investigated the relationship between resistance to the cancer drug paclitaxel and miRNA expression. MATERIALS AND METHODS: We compared the expression patterns of miRNA genes in paclitaxel-sensitive (SKOV3) and paclitaxel-resistant (SKOV3-TR30) cell lines. RESULTS: Expression of the miR-134 gene cluster was found to be significantly lower in the paclitaxel-resistant cell line than in the paclitaxel-sensitive cell line, while the expression of the miR-17-92 gene cluster was significantly higher in the paclitaxel-resistant cells. An analysis of miRNA target gene protein expression revealed that several targets of miR-17-92 were significantly altered between the two cell types. CONCLUSIONS: The higher expression of miR-17-92 and lower expression of mi-134 and the associated alterations of target gene expression may be associated with the drug-resistant nature of some ovarian cancers.

A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus.

In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer: a meta-analysis of published studies.

The aim of this meta-analysis was to clarify whether a longer interval between the end of neoadjuvant chemoradiotherapy (nCRT) and surgery is associated with better outcomes in esophageal cancer. nCRT followed by surgery is the most common approach for patients with resectable esophageal cancer. Operations are performed within 2-8 weeks after nCRT; however, the optimal interval between nCRT and surgery for esophageal cancer is unknown. We performed a systematic literature search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Clinical Trials database for studies published between January 2000 and December 2014. Eligible studies were prospective or retrospective studies of esophageal cancer that assessed the effects of intervals longer or shorter than 7-8 weeks between the end of nCRT and surgery. The primary end-points were the overall survival (OS) and pathologic complete response (pCR). Secondary end-points were anastomotic leak, R0 resection, and postoperative mortality rate. A meta-analysis was performed to estimate odds ratios (ORs) using fixed-effect and random-effect models, with Review Manager 5.2. The five studies that met the eligibility requirements included 1,016 patients: 520 in the shorter interval group (≤7-8 weeks) and 496 in the longer interval group (>7-8 weeks). The results of our meta-analysis indicate that a longer interval between nCRT and surgery may be disadvantageous for 2-year OS (OR = 1.40, 95% confidence interval [CI]: 1.09-1.80, P = 0.010) and R0 resection rate (OR = 1.71, 95% CI: 1.14-2.22, P = 0.009). The pCR, anastomotic leak rate, and postoperative morbidity were similar in the two groups. A longer interval (more than the standard 7-8 weeks) from the end of preoperative nCRT to surgery did not increase the rate of pCR in esophageal cancer, and the different intervals had similar effects on anastomotic leak rate and postoperative mortality rates. However, the longer interval between nCRT and surgery may be disadvantageous for long-term OS. These results should be validated prospectively in a randomized trial.