Development of a standardized laparoscopic caecum resection model to simulate laparoscopic appendectomy in rats

Background

Laparoscopic appendectomy (LA) has become one of the most common surgical procedures to date. To improve and standardize this technique further, cost-effective and reliable animal models are needed.

Methods

In a pilot study, 30 Wistar rats underwent laparoscopic caecum resection (as rats do not have an appendix vermiformis), to optimize the instrumental and surgical parameters. A subsequent test study was performed in another 30 rats to compare three different techniques for caecum resection and bowel closure.

Results

Bipolar coagulation led to an insufficiency of caecal stump closure in all operated rats (Group 1, n = 10). Endoloop ligation followed by bipolar coagulation and resection (Group 2, n = 10) or resection with a LigaSure™ device (Group 3, n = 10) resulted in sufficient caecal stump closure.

Conclusions

We developed a LA model enabling us to compare three different caecum resection techniques in rats. In conclusion, only endoloop closure followed by bipolar coagulation proved to be a secure and cost-effective surgical approach.     

Genetic polymorphisms of glutathione S-transferase M1 and T1, and evaluation of oxidative stress in patients with non-small cell lung cancer

Background

Our objective is to investigate the genetic polymorphisms of the glutathione S-transferase M1 and T1 genes (GSTM1 and GSTT1) and evaluate oxidative damage in patients with non-small lung cancer (N-SCLC).

Methods

One hundred and ten patients with N-SCLC and 100 controls are included in this case-control study. Multiplex polymerase chain reaction (PCR) analyses were used to identify the genotypes. The activities of malondialdehyde (MDA) and nitric oxide (NO) and total antioxidant capacity (T-AOC) were detected by spectroscopic analysis.

Results

The frequencies of the GSTM1, T1, and GSTM1/T1 null genotypes in the patient group were significantly higher than that in the control group (OR = 2.071, P = 0.009; OR = 1.900, P = 0.024; OR = 3.258, P = 0.003). The activities of MDA and NO were significantly higher in the patient group than that in the control group (P <0.001), and T-AOC was significantly lower in patient group than that in control group (P <0.001). The activities of MDA, and NO were higher but the T-AOC was lower in patients with the GSTM1, T1 and M1/T1 null genotypes than those in patients with GSTM1, T1 and M1/T1 present genotypes (P <0.001).

Conclusions

Our results suggest that oxidative damage may be play a important role in patients with N-SCLC, and that GSTM1 and GSTT1 null genotypes may predispose the cells of patients with N-SCLC to increased oxidative damage.     

Inferior mesenteric vein serves as an alternative guide for transection of the pancreatic body during pancreaticoduodenectomy with concomitant vascular resection: a comparative study evaluating perioperative outcomes

Background

Tumors of the pancreatic head often involve the superior mesenteric and portal veins. The purpose of this study was to assess perioperative outcomes after pancreaticoduodenectomy (PD) with concomitant vascular resection using the inferior mesenteric vein (IMV) as a guide for transection of the pancreatic body (Whipple at IMV, WATIMV).

Methods

One hundred thirty-seven patients had segmental vein resection during PD between January 2006 and June 2013. Depending on whether the standard approach of creating a tunnel anterior to the mesenterico-portal vein (MPV) axis was achieved for pancreatic transection, patients were subjected to a standard PD with vein resection procedure (s-PD + VR, n = 75) or a modified procedure (m-PD + VR, n = 62). Within the m-PD + VR group, 28 patients underwent the WATIMV procedure, while 34 patients underwent the usual procedure of transection, or ‘central pancreatectomy’ (c-PD + VR).

Results

The volume of intraoperative blood loss and the blood transfusion requirements were significantly greater, and the venous wall invasion and neural invasion frequency were significantly higher in the m-PD + VR group compared with the s-PD + VR group. There were no significant differences in the length of hospitalization, postoperative morbidity, and grades of complications between the two groups. Multivariate logistic regression identified intraoperative blood transfusion (P = 0.004) and vascular invasion (P = 0.008) as the predictors of postoperative morbidity. Further stratification of the entire cohort of 62 (45%) patients who underwent m-PD + VR showed a higher rate of negative resection margins (96.4%) in the WATIMV group compared with the c-PD + VR group (76.5%) (P = 0.06). The volume of intraoperative blood loss (P = 0.013), and intraoperative blood transfusion requirements (P = 0.07) were significantly greater in the c-PD + VR group compared with the WATIMV group. Furthermore, high intraoperative blood loss and tumor stage were predictive of a positive resection margin.

Conclusions

‘Whipple at the IMV (WATIMV)’ has comparable postoperative morbidity with standard PD + VR. If IMV runs into the splenic vein, it could serve as an alternative guide for transection of the pancreatic body during PD + VR.     

Comparison of the safety and efficacy of biodegradable polymer drug-eluting stents versus durable polymer drug-eluting stents: a meta-analysis

Background

A meta-analysis was conducted to assess the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DESs).

Methods

PubMed, Science Direct, China National Knowledge Infrastructure, and Chongqing VIP databases were searched for randomized controlled trials comparing the safety and efficacy of BP-DESs versus durable polymer drug-eluting stents (DP-DESs). Efficacy included the prevalence of target lesion revascularization (TLR), target vessel revascularization (TVR), and late lumen loss (LLL), and safety of these stents at the end of follow-up for the selected research studies were compared.

Results

A total of 16 qualified original studies that addressed a total of 22,211 patients were included in this meta-analysis. In regard to efficacy, no statistically significant difference in TLR (odds ratio (OR) = 0.94, P = 0.30) or TVR (OR 1.01, P = 0.86) was observed between patients treated with BP-DESs and those with DP-DESs. However, there were significant differences in in-stent LLL (weighted mean difference [WMD] = −0.07, P = 0.005) and in-segment LLL (WMD = −0.03, P = 0.05) between patients treated with BP-DESs and with DP-DESs. In terms of safety, there was no significant difference in overall mortality (OR 0.97, P = 0.67), cardiac death (OR 0.99, P = 0.90), early stent thrombosis (ST) and late ST (OR 0.94, P = 0.76; OR 0.96, P = 0.73), or myocardial infarction (MI) (OR 0.99, P = 0.88) between patients treated with BP-DESs and with DP-DESs. However, there was a statistically significant difference in very late ST (OR 0.69, P = 0.007) between these two groups. In addition, the general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up.

Conclusion

BP-DESs are safe, efficient, and exhibit superior performance to DP-DESs with respect to reducing the occurrence of very late ST and LLL. The general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up.     

Medical students’ education on organ donation and its evaluation during six consecutive years: results of a voluntary,anonymous educational intervention study

Background

One of the main reasons for organ shortage is insufficient education on organ donation. Knowledgeable medical students could share the information with friends and families resulting in a positive attitude to organ donation of the general public.

Methods

During six consecutive years (2009 to 2014), we conducted a voluntary, anonymous educational intervention study on organ donation among fourth year medical students in the course of the main surgery lecture at the University of Essen, Germany.

Results

Questionnaires of 383 students were analyzed. Prior to the specific lecture on organ donation, 64% of the students carried a signed organ donor card with the intention to donate. Further information regarding organ donation was required by 37% of the students. The request for further information was statistically significantly higher among students without a donor card compared to organ donor card carriers (P < 0.0001). After the lecture, the number of students requiring further information decreased statistically significantly to 19% (P < 0.0001).

Conclusions

Already a 45-minute lecture for fourth year medical students significantly decreases their request for further information on organ donation and improves their attitude to organ donation. Continued training on organ donation will help medical students to become disseminators for this important topic in our society.     

Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C

Background

Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV.

Methods

One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and −675 T → A in CYBA.

Results

No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025).

Conclusions

The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.     

Establishing an osteosarcoma associated protein-protein interaction network to explore the pathogenesis of osteosarcoma

Background

The aim of this study was to establish an osteosarcoma (OS) associated protein-protein interaction network and explore the pathogenesis of osteosarcoma.

Methods

The gene expression profile {"type":"entrez-geo","attrs":{"text":"GSE9508","term_id":"9508"}}GSE9508 was downloaded from the Gene Expression Omnibus database, including five samples of non-malignant bone (the control), seven samples for non-metastatic patients (six of which were analyzed in duplicate), and 11 samples for metastatic patients (10 of which were analyzed in duplicate). Differentially expressed genes (DEGs) between osteosarcoma and control samples were identified by packages in R with the threshold of |logFC (fold change)| > 1 and false discovery rate < 0.05. Osprey software was used to construct the interaction network of DEGs, and genes at protein-protein interaction (PPI) nodes with high degrees were identified. The Database for Annotation, Visualization and Integrated Discovery and WebGestalt software were then used to perform functional annotation and pathway enrichment analyses for PPI networks, in which P < 0.05 was considered statistically significant.

Results

Compared to the control samples, the expressions of 42 and 341 genes were altered in non-metastatic OS and metastatic OS samples, respectively. A total of 15 significantly enriched functions were obtained with Gene Ontology analysis (P < 0.05). The DEGs were classified and significantly enriched in three pathways, including the tricarboxylic acid cycle, lysosome and axon guidance. Genes such as HRAS, IDH3A, ATP6ap1, ATP6V0D2, SEMA3F and SEMA3A were involved in the enriched pathways.

Conclusions

The hub genes from metastatic OS samples are not only bio-markers of OS, but also help to improve therapies for OS.     

Joint detection of ERCC1, TUBB3, and TYMS guidance selection of docetaxel, 5-fluorouracil and cisplatin (DDP) individual chemotherapy in advanced gastric cancer patients

Background

To investigate the guidance selection of docetaxel (D), cisplatin (DDP) (C), and 5-fluorouracil (5-FU) (F) as individual chemotherapy agents via joint detection of ERCC1, TUBB3, and TYMS genes in patients with advanced gastric cancer (AGC).

Method

Clinical data of 120 patients with AGC who enrolled in our hospital between May 2009 and May 2012 were analyzed. These patients were randomly assigned to experimental and control groups. The mRNA expression of ERCC1, TUBB3, and TYMS was measured by DNA chip technology in the experimental group. Different chemotherapies were administered according to the mRNA expression levels of the three genes, while DCF chemotherapy was directly applied to the control group. Correlation between the three genes’ mRNA levels, efficiency rate, the median time to progression (MTP), median survival time (MST) and adverse reactions was evaluated.

Results

As a result, there was a significant correlation between ERCC1 and TUBB3 mRNA expression (P = 0.005), but no obvious correlation between TUBB3 and TYMS or ERCC1 and TYMS. There was also no significant difference in the efficiency rate of chemotherapy (50% versus 55%; P = 0.357) and the MTP (10 months versus 7 months; P = 0.091) between the two groups. However, there was obvious significance in MST (13.7 months versus 11.6 months; P = 0.004). Additionally, the experimental group provided us with a more effective way for controlling adverse reactions to chemotherapy.

Conclusion

Combination regimen of D, C, and F in AGC patients according to their ERCC1, TUBB3, and TYMS mRNA expression level may reduce adverse reactions and improve MST.     

IGF2BP2 and obesity interaction analysis for type 2 diabetes mellitus in Chinese Han population

Background

The objective of this study was to systematically evaluate the contribution of the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to type 2 diabetes mellitus (T2DM) and its interaction with obesity to T2DM susceptibility.

Methods

To clarify whether IGF2BP2 is an independent risk factor for T2DM in Chinese population, we conducted a study with a total of 2,301 Chinese Han subjects, including 1,166 T2DM patients and 1,135 controls, for the genotype of a most common and widely studied polymorphism—rs4402960 of IGF2BP2. Genotyping was performed by iPLEX technology. Gene and environment interaction analysis was performed by using multiple logistic regression models.

Results

The repeatedly confirmed association between IGF2BP2 (rs4402960) and T2DM had not been replicated in this cohort (P = 0.182). Interestingly, we found that obese subjects (body mass index (BMI) ≥ 28.0 kg/m²) bearing the minor A allele had an increased risk to develop T2DM (P = 0.008 for allele analysis and P < 0.001 for genotype analysis).

Conclusions

The present study provided data suggesting that the wild C allele of IGF2BP2 (rs4402960) had a protective effect against T2DM in obese subjects of Chinese Han population.     

Plate osteosynthesis versus hemiarthroplasty in proximal humerus fractures – Does routine screening of systemic inflammatory biomarkers makes sense?

Background

Increases in C-reactive protein (CRP) and white blood cell (WBC) counts after orthopedic surgical procedures can give evidence of postoperative infection. However, there is a lack of knowledge about the kinetics of these biomarkers in cases with an uneventful clinical course after osteosynthesis of upper limb fractures. This study investigated CRP and WBC serum levels after osteosynthesis or hemiarthroplasty of humeral head fractures.

Methods

A retrospective study on patients with humeral head fractures who had open reduction and internal fixation via plate osteosynthesis (PO) (n = 64) or hemiarthroplasty (HA) (n = 28) without any complications in the postoperative clinical course. C-reactive protein serum levels (mg/l) and leukocyte counts (g/l) were assayed at several time points. Multiple regression analysis was performed to evaluate the influence of several confounding variables (the surgical procedure, duration of surgery, patient’s health status, and comorbidities) on the kinetics of CRP and WBC.

Results

Our data showed that CRP levels were statistically significantly higher in the HA cohort when compared to the PO cohort (p = 0.003). Moreover, daily measurement of CRP levels during the postoperative course showed that CRP peaked on the 2nd and 3rd days postoperatively in both cohorts and started to decrease afterward, reaching normal values on day 8 to 10. However, WBCs did not show any significant differences between the HA and PO cohorts. Finally, the choice of surgical procedure and the patient’s health status were associated with higher peak levels of CRP.

Conclusions

After osteosynthesis or hemiarthroplasty of humeral head fractures, CRP is a responsive serum parameter in the postoperative course of an uneventful inflammatory response. Abnormalities from these values should be interpreted carefully as they may give a hint as to postoperative complications such as infection.     

Clinical experience with modified Miccoli’s endoscopic thyroidectomy for treatment of thyroid carcinoma in 86 cases

Background

The main purpose of this study was to assess the feasibility and relevant applying techniques of total thyroidectomy for thyroid carcinoma with a modified Miccoli’s approach.

Methods

Eighty-six patients with thyroid carcinoma consecutively received radical operation from October 2007 to June 2012. A cavity above the gland was constructed by a modified suspension method using the suspension retractor with suction catheter after the pathway making. Eighty-six cases underwent the modified Miccoli’s endoscopic thyroidectomy using the ultrasonic scalpel and the space maintain-regulating device. Level VI lymph node dissection was performed using the method of inspection pit.

Results

All the procedures were completed successfully. The average detection rate of level VI lymph nodes, the average time of thyroidectomy and lymph nodes dissection were 7.27 ± 3.99 pieces per case, 51.32 ± 13.35 min, and 38.43 ± 15.24 min, respectively. With regard to postoperative complications, there were three cases of delayed transient hoarseness, two patients with transient numbness of hands and feet, one subject with chylous fistula, and no hemorrhage.

Conclusion

Total thyroidectomy for thyroid carcinoma can be safely performed with the modified Miccoli’s approach by using ultrasonic scalpel and the space maintain-regulating device. Application of these adaptive reforms can obviously reduce the difficulties in manipulation and have the advantages of minimal incisions, good cosmetic results, less bleeding, shorter hospital stay, and fewer complications.     

Calorie restriction inhibits ovarian follicle development and follicle loss through activating SIRT1 signaling in mice

Background

Silent information regulator 2 related enzyme 1 (SIRT1) is one of the key factors in the mechanism of calorie restriction (CR) extending lifespan of animals. The aim of the study is to investigate if CR prolongs ovarian lifespan in mice through activating SIRT1 signaling.

Methods

In the present study, 21 female C57BL/6 mice were divided into three groups: the control (n = 7), CR (n = 7), and SRT1720 (n = 7) groups. After the 26-week treatment, the number of ovarian follicles at each stage was counted, and Western blot was performed.

Results

The number of surviving follicles in ovaries of the SRT1720 group was less than that of the CR group but more than that of the normal control (NC) group. The number of atretic follicles in the ovaries of the SRT1720 group was similar to that of the CR group but less than that of the NC group. The number of primordial follicles in the ovaries of the SRT1720 group was less than that of the CR group but more than that of the NC group. The numbers of primary follicles, secondary follicles, antral follicles, and corpora lutea in the SRT1720 group were similar to those in the CR group. Western blot analysis showed that the expression of SIRT1, SIRT6, FOXO3a, and NRF1 proteins was upregulated, and p53 was downregulated in both the CR group and the SRT1720 group compared to the control group.

Conclusions

Our results indicate that CR inhibits the activation of primordial follicles and development of follicles at different stages, thus preserving the reserve of follicle pool (at least partly) through activating SIRT1 signaling.     

Diverse expression of selected cytokines and proteinases in synovial fluid obtained from osteoarthritic and healthy human knee joints

Background

Osteoarthritis (OA) is defined by signs and symptoms of inflammation within the affected joint. The aim of this study is to determine the mRNA expression levels of selected cytokines and matrix-metalloproteinases of cells found in synovial fluid (SF) obtained from osteoarthritic knee joints compared to healthy controls.

Methods

SF was obtained from 40 patients undergoing total knee arthroplasty due to evident OA and from 10 healthy controls. Expression of TNF-α, IL-1β, MMP-1 and MMP-3 was assayed among both groups by performing qPCR. Patients were configured concerning age, gender and BMI.

Results

IL-1β, MMP-1 and MMP-3 showed significantly higher expression among the OA group compared to control (P < 0.001). Strong correlation appeared between expression of MMP-1 and MMP-3 among OA patients (r = 0.856); no correlation was found between age, gender or BMI and cytokine/proteinase expression. Expression of IL-1β, MMP-1 and MMP-3 within SF was elevated in OA-patients.

Conclusion

Consequently, cells within SF expressing cytokines and proteinases may play a relevant role in the progression of joint destruction. Considering the fact that SF in an OA joint comprises abnormal amounts of detrimental bioactive proteins, temporary clearance, dilution or suppression/modulation by means of lavage or disease-modifying medication may be promising to constitute interim relief or even postpone disease progression due to decreased inflammatory and/or degrading activity within the articular environment.     

Influence of an acetate- and a lactate-based balanced infusion solution on acid base physiology and hemodynamics: an observational pilot study

Background

The current pilot study compares the impact of an intravenous infusion of Ringer’s lactate to an acetate-based solution with regard to acid–base balance. The study design included the variables of the Stewart approach and focused on the effective strong ion difference. Because adverse hemodynamic effects have been reported when using acetate buffered solutions in hemodialysis, hemodynamics were also evaluated.

Methods

Twenty-four women who had undergone abdominal gynecologic surgery and who had received either Ringer’s lactate (Strong Ion Difference 28 mmol/L; n = 12) or an acetate-based solution (Strong Ion Difference 36.8 mmol/L; n = 12) according to an established clinical protocol and its precursor were included in the investigation. After induction of general anesthesia, a set of acid–base variables, hemodynamic values and serum electrolytes was measured three times during the next 120 minutes.

Results

Patients received a mean dose of 4,054 ± 450 ml of either one or the other of the solutions. In terms of mean arterial blood pressure and norepinephrine requirements there were no differences to observe between the study groups. pH and serum HCO₃^- concentration decreased slightly but significantly only with Ringer’s lactate. In addition, the acetate-based solution kept the plasma effective strong ion difference more stable than Ringer’s lactate.

Conclusions

Both of the solutions provided hemodynamic stability. Concerning consistency of acid base parameters none of the solutions seemed to be inferior, either. Whether the slight advantages observed for the acetate-buffered solution in terms of stability of pH and plasma HCO₃^- are clinically relevant, needs to be investigated in a larger randomized controlled trial.     

Effect of surgical experience on imageless computer-assisted femoral component positioning in hip resurfacing – a preclinical study

Background

The clinical outcome of hip resurfacing (HR) as a demanding surgical technique associated with a substantial learning curve depends on the position of the femoral component. The aim of the study was to investigate the effects of the level of surgical experience on computer-assisted imageless navigation concerning precision of femoral component positioning, notching, and oversizing rate, as well as operative time.

Methods

Three surgeons with different levels of experience in both HR and computer-assisted surgery (CAS) prepared the femoral heads of 54 synthetic femurs using the Durom^TM Hip Resurfacing (Zimmer, Warsaw, IN, USA) system. Each surgeon prepared a total of 18 proximal femurs using the Navitrack® system (ORTHOsoft Inc., Montreal, Canada) or the conventional free-hand Durom^TM K-wire positioning jig. The differences between planned and postoperative stem shaft angle (SSA) and anteversion angle in standardized x-rays were measured and the operative time, not including the time for calibrating the CAS-system, was documented. Notching was evaluated by the three surgeons in a randomized manner. Oversizing was determined by the difference of the preoperative determined cap and the cap size advised by the CAS-system.

Results

CAS significantly reduced the overall mean deviation between planned and postoperative SSA in comparison with the conventional procedure (mean ± SD, 1 ± 1.7° vs. 7.4 ± 4.4°, P <0.01) regardless of the surgeon’s level of experience. The incidence of either varus or valgus SSA deviations exceeding 5° were 1/27 for CAS and 15/27 for the conventional method, respectively (P <0.001), corresponding to a reduction by 97%. Using CAS, the rate of notching was reduced by 100%.

Conclusions

The accuracy of femoral HR component orientation is significantly increased by use of CAS regardless of the surgeon’s level of experience in our preclinical study. Thus, imageless computer-assisted navigation can be a valuable tool to improve implant positioning in HR for surgeons at any stage of their learning curve.     

Is rs759853 polymorphism in promoter of aldose reductase gene a risk factor for diabetic nephropathy? A meta-analysis

Background

So far, a number of case-control or cohort studies have been carried out to investigate the relationship between rs759853 polymorphism in the promoter of aldose reductase (AR) gene and the risk of diabetic nephropathy (DN). However, the results have generated considerable controversy. We performed this study to clarify the linkage between this gene mutation and the risk of DN.

Methods

A comprehensive literature search of electronic databases and a well-organized meta-analysis were conducted.

Results

Twelve comparisons and 4,735 individuals from nine published case-control or cohort studies were included finally. From none to large heterogeneity was observed, therefore, both fixed and random models were used. Significant differences were found between AR rs759853 polymorphism and susceptibility of DN from both type 1 and type 2 diabetes in all genetic models (allele contrast, OR = 1.37, CI (1.18, 1.59), P < 0.0001; additive model, OR = 1.78, CI (1.25, 2.53), P = 0.01; recessive model OR = 1.33 CI (1.08, 1.63), P = 0.008; dominant model, OR = 1.52, CI (1.26, 1.84), P < 0.0001; codominance model OR = 1.30 (1.15, 1.47), P < 0.0001). In stratified meta-analyses for type 2 diabetes by ethnicity, the significant relationship was found in allele contrast and dominant model in Caucasians, and in allele contrast and codominance model in Asians. However, data do not support the linkage between this gene mutation and the progression of DN. There was no significant publication bias.

Conclusions

The evidence currently available shows that the AR rs759853 polymorphism may correlate with the susceptibility of DN. However, data do not support the association between this DNA variation and the progression of DN.     

Clinical implications of the quantitative detection of ID4 gene methylation in myelodysplastic syndrome

Background

Myelodysplastic syndrome (MDS) eventually transforms into acute leukemia (AL) in about 30% of patients. Hypermethylation of the inhibitor of DNA binding 4 (ID4) gene may play an important role in the initiation and development of MDS and AL. The aim of this study was to quantitatively assess ID4 gene methylation in MDS and to establish if it could be an effective method of evaluating MDS disease progression.

Methods

We examined 142 bone marrow samples from MDS patients, healthy donors and MDS-AL patients using bisulfite sequencing PCR and quantitative real-time methylation-specific PCR. The ID4 methylation rates and levels were assessed.

Results

ID4 methylation occurred in 27 patients (27/100). ID4 gene methylation was more frequent and at higher levels in patients with advanced disease stages and in high-risk subgroups according to WHO (P < 0.001, P < 0.001, respectively) and International Prognostic Scoring System (IPSS) (P = 0.002, P = 0.007, respectively) classifications. ID4 methylation levels changed during disease progression. Both methylation rates and methylation levels were significantly different between healthy donor, MDS patients and patients with MDS-AL (P < 0.001, P < 0.001, respectively). Multivariate analysis indicated that the level of ID4 methylation was an independent factor influencing overall survival. Patients with MDS showed decreased survival time with increased ID4 methylation levels (P = 0.011, hazard ratio (HR) = 2.371). Patients with ID4 methylation had shorter survival time than those without ID4 methylation (P = 0.008).

Conclusions

Our findings suggest that ID4 gene methylation might be a new biomarker for MDS monitoring and the detection of minimal residual disease.