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Background: Complement component(C7) gene has been shown to influence the prognosis in Hepatocellular carcinoma (HCC) patients. The association between C7 and HCC recurrence after orthotopic liver transplantation (OLT), however, is still unknown. The purpose of this study was to evaluate whether the donor and recipient C7 gene polymorphisms are related to HCC recurrence after OLT in the Han Chinese population.Methods: A total of 73 consecutive patients with HCC who had undergone OLT, both donors and recipients, were involved in this research. A single nucleotide polymorphism of C7, rs9292795, was genotyped using Sequenom MassARRAY in the cohort. The expression of C7 and the association between C7 gene polymorphisms and HCC recurrence following OLT were analyzed by bioinformatics and statistical analysis, respectively.Results: As shown in database, the expression of C7 was higher in HCC tissues than that in normal tissues, and represented a worse prognosis. We also found that recipient C7 rs9292795 polymorphism, rather than the donor, was significantly associated with HCC recurrence after OLT. Multivariate logistic regression analysis confirmed that TNM stage (P = 0.001), Milan criteria (P = 0.000) and recipient rs9292795 genotype (TT vs AA/AT, P = 0.008) were independent risk factors for HCC recurrence. Furthermore, the recipient carrying AA/AT showed higher recurrence-free survival (RFS) and overall survival (OS) than that carrying TT (P < 0.05). In Cox proportional hazards model, TNM stage, recipient rs9292795 genotype, and Milan criteria were identified as independent factors for RFS and OS (P < 0.05) as well as pre-OLT serum alpha fetoprotein (AFP) level was associated with OS (P < 0.05).Conclusions: Recipient C7 rs9292795 gene polymorphism is related to the recurrence of HCC after OLT, which may be a helpful prognostic marker for HCC patients who receive OLT. [ABSTRACT FROM AUTHOR]

Background: Endophthalmitis is a rare but severe complication following PPV. The incidence of endophthalmitis varies between 20-gauge, 23-gauge, and 25-gauge incisions. The incidence and clinical features of endophthalmitis after 23-gauge PPV in an eye hospital in China was reported in this study.Methods: Data of the eyes that underwent 23-gauge PPV from January 2011 to December 2014 at the Eye Hospital of Wenzhou Medical University was retrospectively collected. All the information was obtained from the electronic medical system. The exclusion criteria included: (1) preoperative diagnosis of endophthalmitis; (2) history of vitrectomy; (3) intraocular surgery within 6 months; (4) history of ocular penetrating trauma; (5) sutures for any of the 3 sclerotomy incisions; (6) patients with cancer, acquired immune deficiency syndrome, or taking drugs that may influence the immune system. The diagnosis of endophthalmitis was based on clinical characteristics and/or culture results from an operative sample.Results: Three thousand nine hundred seventy nine eyes that underwent 23-gauge PPV surgery were included in this study. Among these eyes, 3 eyes developed endophthalmitis after surgery, giving an incidence of 0.075% (3/3979). The period in which endophthalmitis developed ranged from 1 to 5 days post-operation. The visual acuity decreased to hand motions or light perception postoperatively. The culture of aqueous and vitreous of the 2 eyes revealed Staphylococcus epidermidis and enterococcus faecalis respectively, however was negative for the third eye. All 3 eyes had a favorable response to the treatment of vitreous tap and intravitreal antibiotics injection. Two eyes gained visual acuity of 0.05 and 0.5, respectively at the final visit.Conclusions: Endophthalmitis is a rare but sight-threatening complication after 23-gauge pars plana vitrectomy. The peak duration of onset was within 5 days post-operation, with gram positive cocci being the common pathogenic organism. [ABSTRACT FROM AUTHOR]

Background: The near work and outdoor activity are the most important environmental risk factors for myopia. However, data from Chinese rural children are relatively rare and remain controversial. Therefore, the purpose of this study was to evaluate the relationship of both near work and outdoor activities with refractive error in rural children in China.Methods: In this cross-sectional study, 572 (65.1%) of 878 children (6-18 years of age) were included from the Handan Offspring Myopia Study (HOMS). Information from the parents on these children, as well as the parent's non-cycloplegic refraction, were obtained from the database of the Handan Eye Study conducted in the years 2006-2007. A comprehensive vision examination, including cycloplegic refraction, and a related questionnaire, were assessed on all children.Results: The overall time spent on near work and outdoor activity in the children was 4.8 ± 1.6 and 2.9 ± 1.4 h per day, respectively. Myopic children spent more time on near work (5.0 ± 1.7 h vs.4.7 ± 1.6 h, p = 0.049), while no significant difference was found in outdoor activity hours (2.8 ± 1.3 h vs. 3.0 ± 1.4 h, p = 0.38), as compared to non-myopic children. In the multiple logistic analysis, in general, no association between near work and myopia was found after adjusting for the children's age, gender, parental refractive error, parental educational level, and daily outdoor activity hours [odds ratio (OR), 95% confidence interval (CI): 1.10, 0.94-1.27]. However, a weak protective effect of the outdoor activity on myopia was found (OR, 95% CI: 0.82, 0.70-0.96), after adjusting for similar confounders.Conclusions: In general, no association between near work and myopia was found, except for the high near work subgroup with moderate outdoor activity levels. A weak protective effect of outdoor activity on myopia in Chinese rural children was observed. [ABSTRACT FROM AUTHOR]

Background: To investigate whether poor glycemic control status has a negative impact on survival outcomes and tumor response to chemotherapy in patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC).Methods: A retrospective cohort study was conducted to examine LACC patients undergoing NACT and radical hysterectomy between 2002 and 2011. Patients were divided into three groups: patients without diabetes mellitus (DM), diabetic patients with good glycemic control, and diabetic patients with poor glycemic control. Hemoglobin A1c (HbA1c) levels were used to indicate glycemic control status. Recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed using log-rank tests and Cox proportional hazards models.Results: In total, 388 patients were included and had a median follow-up time of 39 months (range: 4-67 months). Diabetes mellitus (DM) was diagnosed in 89 (22.9%) patients, only 35 (39.3%) of whom had good glycemic control prior to NACT (HbA1c < 7.0%). In survival analysis, compared with patients with good glycemic control and patients without DM, patients with poor glycemic control (HbA1c ≥ 7.0%) exhibited decreased recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). In multivariate analysis, HbA1c ≥ 7.0% was identified as an independent predictor for decreased RFS (hazard ratio [HR] = 3.33, P < 0.0001), CSS (HR = 3.60, P < 0.0001) and OS (HR = 4.35, P < 0.0001). In the subgroup of diabetic patients, HbA1c ≥ 7.0% prior to NACT had an independent negative effect on RFS (HR = 2.18, P = 0.044) and OS (HR = 2.29, P = 0.012). When examined as a continuous variable, the HbA1c level was independently associated with decreased RFS (HR = 1.39, P = 0.002), CSS (HR = 1.28, P = 0.021) and OS (HR = 1.27, P = 0.004). Both good (odds ratio [OR] = 0.06, P < 0.0001) and poor glycemic control (OR = 0.04, P < 0.0001) were independently associated with a decreased likelihood of complete response following NACT.Conclusions: Poor glycemic control is an independent predictor of survival and tumor response to chemotherapy for patients receiving NACT for LACC. [ABSTRACT FROM AUTHOR]

Background: Tissue inhibitor matrix metalloproteinase 1 (TIMP1) plays a vital role in carcinogenesis, yet its precise functional roles and regulation remain unclear. In this study, we aim to investigate its biological function and clinical significance in human colon cancer. Methods: We analyzed the expression of TIMP1 in both public database (Oncomine and TCGA) and 94 cases of primary colon cancer and matched normal colon tissue specimens. The underlying mechanisms of altered TIMP1 expression on cell tumorigenesis, proliferation, and metastasis were explored in vitro and in vivo. Results: TIMP1 was overexpressed in colon tumorous tissues and lymph node metastasis specimens than in normal tissues. The aberrant expression of TIMP1 was significantly associated with the regional lymph node metastasis (p = 0.033), distant metastasis (p = 0.039), vascular invasion (p = 0.024) and the American Joint Committee on Cancer (AJCC) stage (p = 0.026). Cox proportional hazards model showed that TIMP1 was an independent prognostic indicator of disease-free survival (HR = 2.603, 95 % CI: 1.115-6.077, p = 0.027) and overall survival (HR = 2.907, 95 % CI: 1.254-6.737, p = 0.013) for patients with colon cancer. Consistent with this, our findings highlight that suppression of TIMP1 expression decreased proliferation, and metastasis but increased apoptosis by inducing TIMP1 specific regulated FAK-PI3K/AKT and MAPK pathway. Conclusion: TIMP1 might play an important role in promoting tumorigenesis and metastasis of human colon cancer and function as a potential prognostic indicator for colon cancer. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC).Methods: This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004-2010) and National Health Insurance (2004-2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure).Results: A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08-1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18-1.78, P = .0003).Conclusion: Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC. [ABSTRACT FROM AUTHOR]

Background: In highly complex social settings, an animal's motivational drive to pursue an object depends not only on the intrinsic properties of the object, but also on whether the decision-making animal perceives an object as being the most desirable among others. Mimetic desire refers to a subject's preference for objects already possessed by another subject. To date, there are no appropriate animal models for studying whether mimetic desire is at play in guiding the decision-making process. Furthermore, the neuropharmacological bases of decision-making processes are not well understood. In this study, we used an animal model (rat) to investigate a novel food-foraging paradigm for decision-making, with or without a mimetic desire paradigm.Results: Faced with the choice of foraging in a competitive environment, rats preferred foraging for the desirable object, indicating the rats' ability for decision-making. Notably, treatment with the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, but not with the dopamine D1 or D2 receptor antagonists, SCH23390 and haloperidol, respectively, suppressed the food foraging preference when there was a competing resident rat in the cage. None of these three antagonists affected the food-foraging preference for palatable food. Moreover, MK-801 and SCH23390, but not haloperidol, were able to abolish the desirable environment effect on standard food-foraging activities in complex social settings.Conclusions: These results highlight the concept that mimetic desire exerts a powerful influence on food-foraging decision-making in rats and, further, illustrate the various roles of the glutamatergic and dopaminergic systems in mediating these processes. [ABSTRACT FROM AUTHOR]

Background: Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions. Results: We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL. Conclusions: PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury. [ABSTRACT FROM AUTHOR]

Hepatic hemangioma patients with Kasabach-Merritt syndrome have reportedly been cured by liver transplantation. However, liver transplantation as a potential cure for a stable patient without Kasabach-Merritt syndrome remains debatable. We report the case of a 27-year-old female patient with a giant hepatic hemangioma. The hemangioma measured 50 x 40 x 25 cm in size and weighed 15 kg, which is the largest and heaviest hemangioma reported in the literature. The patient showed jaundice, ascites, anemia, and appetite loss; but no disseminated intravascular coagulation was observed through laboratory findings. We successfully operated using a right lobe graft without the middle hepatic vein from a 55-yearold donor. At the long-term follow-up, the patient experienced two acute rejections, which were confirmed by biopsy. However, the patient still survives with good graft function after 50 months. [ABSTRACT FROM AUTHOR]

Background Feuts in fetu is a rare congenital anomaly and is defined as a monozygotic twin incorporated into the abdomen of its sibling during development. Feuts in fetu is often overlooked in the differential diagnosis of an abdominal mass. Unlike teratomas, fetus in fetu is a benign disorder. Case presentation We describe the clinical characteristics of two patients, a thirty-months old boy who was found to have abdominal distension and a neonate who was diagnosed antenatally with abdominal mass. Computed tomography scan revealed the mass in which the contents favor a fetus in fetu rather than a teratoma. Surgical removal revealed that the anencephalic fetus have limb buds situated relative to a palpable vertebral column, supporting the diagnosis of feuts in fetu. In the present report, presentation, diagnosis, pathology, management, and recent literature are also reviewed. Conclusion Fetus in fetu is a rare entity that typically presents in infancy and early childhood. It should be differentiated from a teratoma because of the teratoma's malignant potential. Preoperative diagnosis is based on radiologic findings. The treatment of fetus in fetu is operative to relieve obstruction, prevent further compression and possible complications. Complete excision allows confirmation of the diagnosis and lowers the risk of recurrence. [ABSTRACT FROM AUTHOR]

Background: Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research. Objectives: Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared. Methods: In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice. Results: All the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs. Conclusions: These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more scientific understandings on the nanotoxicity of amphiphilic polymeric micelles. [ABSTRACT FROM AUTHOR]

Background: Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC). Methods: MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays. Results: MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells. Conclusions: MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients. [ABSTRACT FROM AUTHOR]

Background: Severe acute pancreatitis (SAP) remains a potentially life-threatening disease. Gastrointestinal motility disturbance such as intestinal ileus is seen in every case. By now, the mechanisms of pancreatitis-induced ileus are largely unknown. The main purpose of the present study was to observe changes of nitric oxide synthase-immunoreactive (NOS-IR) neurons in ileal myenteric ganglia in SAP rats with gastrointestinal dysmotility, trying to explore underlying nervous mechanisms of pancreatitis-induced ileus.Methods: Twenty Sprague Dawley rats were randomly divided into sham operated group and SAP group. SAP was induced by retrograde cholangiopancreatic duct injection of 5% sodium taurocholate. Abdominal X-ray and intestinal transit were performed to detect the existence of paralytic ileus and intestinal dysmotility. Pathological damage of pancreas was evaluated. Double-immunolabeling was employed for the whole-mount preparations of ileal myenteric ganglia. The morphology of NOS-IR neurons were observed and the percentage of NOS-IR neurons was calculated based on the total Hu-immunoreactive neurons. Total RNA of ileum was extracted according to Trizol reagent protocol. Neuronal NOS (nNOS) mRNA expression was evaluated by RT-PCR.Results: The small intestinal transit index in the SAP group was significantly lower compared with the sham operated group (29.21±3.68% vs 52.48±6.76%, P<0.01). The percentage of NOS-IR neurons in ileal myenteric ganglia in the SAP group was significantly higher than that in the sham operated group (37.5±12.28% vs 26.32±16.15%, P<0.01). nNOS mRNA expression in ileum of SAP group was significantly higher than that in the sham operated group (1.02±0.10 vs 0.70±0.06, P<0.01).Conclusions: The increased quantity of NOS-IR neurons in ileal myenteric ganglia and increased nNOS mRNA expression may suggest nNOS over expression as one of the nervous mechanisms of gastrointestinal dysmotility in SAP rat. [ABSTRACT FROM AUTHOR]

Background: The near work and outdoor activity are the most important environmental risk factors for myopia. However, data from Chinese rural children are relatively rare and remain controversial. Therefore, the purpose of this study was to evaluate the relationship of both near work and outdoor activities with refractive error in rural children in China., Methods: In this cross-sectional study, 572 (65.1%) of 878 children (6-18 years of age) were included from the Handan Offspring Myopia Study (HOMS). Information from the parents on these children, as well as the parent's non-cycloplegic refraction, were obtained from the database of the Handan Eye Study conducted in the years 2006-2007. A comprehensive vision examination, including cycloplegic refraction, and a related questionnaire, were assessed on all children., Results: The overall time spent on near work and outdoor activity in the children was 4.8 ± 1.6 and 2.9 ± 1.4 h per day, respectively. Myopic children spent more time on near work (5.0 ± 1.7 h vs.4.7 ± 1.6 h, p = 0.049), while no significant difference was found in outdoor activity hours (2.8 ± 1.3 h vs. 3.0 ± 1.4 h, p = 0.38), as compared to non-myopic children. In the multiple logistic analysis, in general, no association between near work and myopia was found after adjusting for the children's age, gender, parental refractive error, parental educational level, and daily outdoor activity hours [odds ratio (OR), 95% confidence interval (CI): 1.10, 0.94-1.27]. However, a weak protective effect of the outdoor activity on myopia was found (OR, 95% CI: 0.82, 0.70-0.96), after adjusting for similar confounders., Conclusions: In general, no association between near work and myopia was found, except for the high near work subgroup with moderate outdoor activity levels. A weak protective effect of outdoor activity on myopia in Chinese rural children was observed.

Background: The objective of this study is to investigate the outcomes and safety of using percutaneous anterior C1/2 transarticular screw fixation as a salvage technique for odontoid fracture if percutaneous odontoid screw fixation fails., Methods: Fifteen in 108 odontoid fracture patients (planned to be treated by percutaneous anterior odontoid screw fixation) were failed to introduce satisfactory odontoid screw trajectory. To salvage this problem, we chose the percutaneous anterior C1/2 transarticular screw fixation technique in treatment of these patients. The visual analogue score (VAS) of neck pain and Neck Disability Index (NDI) of all patients were scored at pre-operation, 3 months after operation, and final follow-up. Additional, technique-related complications were recorded and collected., Results: Percutaneous C1/2 transarticular screw fixation was performed successfully in all 15 patients whose odontoid screw fixation failed. No technique-related complications (such as nerve injury, spinal cord injury, and esophageal injury) occurred. The VAS of neck pain and NDI score improved significantly (P = 0.000) after operation, and no significant differences were found when compared to 93 non-salvage patients who successfully performed the percutaneous anterior odontoid screw fixation. No screw loose or breakage occurred, all of the odontoid fractures achieve radiographic fusion, bony fusion bridge could be observed at the C1/2 lateral articular facet on 9/15 patients., Conclusions: We suggest that percutaneous anterior C1/2 transarticular screw fixation is a good alternative salvage technique if percutaneous odontoid screw fixation failed, and it is a minimally invasive, feasible, and safe technique.

Background: To investigate whether poor glycemic control status has a negative impact on survival outcomes and tumor response to chemotherapy in patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC)., Methods: A retrospective cohort study was conducted to examine LACC patients undergoing NACT and radical hysterectomy between 2002 and 2011. Patients were divided into three groups: patients without diabetes mellitus (DM), diabetic patients with good glycemic control, and diabetic patients with poor glycemic control. Hemoglobin A 1c (HbA 1c ) levels were used to indicate glycemic control status. Recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed using log-rank tests and Cox proportional hazards models., Results: In total, 388 patients were included and had a median follow-up time of 39 months (range: 4-67 months). Diabetes mellitus (DM) was diagnosed in 89 (22.9%) patients, only 35 (39.3%) of whom had good glycemic control prior to NACT (HbA 1c  < 7.0%). In survival analysis, compared with patients with good glycemic control and patients without DM, patients with poor glycemic control (HbA 1c  ≥ 7.0%) exhibited decreased recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). In multivariate analysis, HbA 1c  ≥ 7.0% was identified as an independent predictor for decreased RFS (hazard ratio [HR] = 3.33, P < 0.0001), CSS (HR = 3.60, P < 0.0001) and OS (HR = 4.35, P < 0.0001). In the subgroup of diabetic patients, HbA 1c  ≥ 7.0% prior to NACT had an independent negative effect on RFS (HR = 2.18, P = 0.044) and OS (HR = 2.29, P = 0.012). When examined as a continuous variable, the HbA 1c level was independently associated with decreased RFS (HR = 1.39, P = 0.002), CSS (HR = 1.28, P = 0.021) and OS (HR = 1.27, P = 0.004). Both good (odds ratio [OR] = 0.06, P < 0.0001) and poor glycemic control (OR = 0.04, P < 0.0001) were independently associated with a decreased likelihood of complete response following NACT., Conclusions: Poor glycemic control is an independent predictor of survival and tumor response to chemotherapy for patients receiving NACT for LACC.

Background: Previous studies have reported that eEF-2 kinase is associated with tumour cell sensitivity to certain therapies. In the present study, we investigated the relationship between eEF-2 kinase and lapatinib, a dual inhibitor of EGFR and HER-2, in nasopharyngeal carcinoma (NPC) cells., Methods: The effect of treatment on the growth and proliferation of NPC cells was measured by three methods: cell counting, crystal violet staining and colony counting. Apoptosis was evaluated by flow cytometry to determine Annexin V-APC/7-AAD and cleaved PARP levels, and the results were further confirmed by Western blot analysis. The expression of eEF-2 kinase and the impacts of different treatments on different signalling pathways were analysed by Western blot analysis., Results: The expression of eEF-2 kinase was significantly associated with NPC cell sensitivity to lapatinib. Therefore, suppression of this kinase could increase the cytocidal effect of lapatinib, as well as reduce cell viability and colony formation. Furthermore, inhibition of eEF-2 kinase, by either RNA interference (eEF-2 kinase siRNA or shRNA) or pharmacological inhibition (NH125), enhanced lapatinib-induced apoptosis of NPC cells. The results also showed that lapatinib combined with NH125 had a synergistic effect in NPC cells. In addition, mechanistic analyses revealed that downregulation of the ERK1/2 and Src pathways, but not the AKT pathway, was involved in this sensitizing effect., Conclusions: The results of this study suggest that targeting eEF-2 kinase may improve the efficacy of therapeutic interventions such as lapatinib in NPC cells.

Background: Chinese traditional "eye exercises of acupoints" have been advocated as a compulsory measure to reduce visual symptoms, as well as to retard the development of refractive error, among Chinese students for decades. The exercises are comprised of a 5-min, bilateral eye acupoint self-massage. This study evaluated the possible effect of these eye exercises among Chinese rural students., Methods: Eight hundred thirty-six students (437 males, 52.3 %), aged 10.6 ± 2.5 (range 6-17) years from the Handan Offspring Myopia Study (HOMS) who completed the eye exercises and vision questionnaire, the convergence insufficiency symptom survey (CISS) questionnaire, and had a cycloplegic refraction were included in this study., Results: 121 (14.5 %) students (64 males, 52.9 %) performed the eye exercises of acupoints in school. The multiple odds ratio (OR) and 95 % confidence interval (CI) for those having a "serious attitude" towards performing the eye exercises (0.12, 0.03-0.49) demonstrated a protective effect for myopia, after adjusting for the children's age, gender, average parental refractive error, and the time spent on near work and outdoor activity. The more frequently, and the more seriously, the students performed the eye exercises each week, the less likely was their chance of being myopic (OR, 95 % CI: 0.17, 0.03-0.99), after adjusting for the same confounders. However, neither the "seriousness of attitude" of performing the eye exercises (multiple β coefficients: -1.58, p = 0.23), nor other related aspects of these eye exercises, were found to be associated with the CISS score in this sample., Conclusions: The traditional eye exercises of acupoints appeared to have a modest protective effect on myopia among these Chinese rural students aged 6-17 years. However, no association between the eye exercises and near vision symptoms was found.

Background: Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC)., Methods: This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004-2010) and National Health Insurance (2004-2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure)., Results: A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08-1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18-1.78, P = .0003)., Conclusion: Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC.

Background: To study the differences in ophthalmology resident training between China and the Hong Kong Special Administrative Region (HKSAR)., Methods: Training programs were selected from among the largest and best-known teaching hospitals. Ophthalmology residents were sent an anonymous 48-item questionnaire by mail. Work satisfaction, time allocation between training activities and volume of surgery performed were determined., Results: 50/75 residents (66.7 %) from China and 20/26 (76.9 %) from HKSAR completed the survey. Age (28.9 ± 2.5 vs. 30.2 ± 2.9 years, p = 0.15) and number of years in training (3.4 ± 1.6 vs. 2.8 ± 1.5, p = 0.19) were comparable between groups. The number of cataract procedures performed by HKSAR trainees (extra-capsular, median 80.0, quartile range: 30.0, 100.0; phacoemulsification, median: 20.0, quartile range: 0.0, 100.0) exceeded that for Chinese residents (extra-capsular: median = 0, p < 0.0001; phacoemulsification: median = 0, p < 0.0001). Chinese trainees spent more time completing medical charts (>50 % of time on charts: 62.5 % versus 5.3 %, p < 0.0001) and received less supervision (≥90 % of training supervised: 4.4 % versus 65 %, p < 0.0001). Chinese residents were more likely to feel underpaid (96.0 % vs. 31.6 %, p < 0.0001) and hoped their children would not practice medicine (69.4 % vs. 5.0 %, p = 0.0001) compared HKSAR residents., Conclusions: In this study, ophthalmology residents in China report strikingly less surgical experience and supervision, and lower satisfaction than HKSAR residents. The HKSAR model of hands-on resident training might be useful in improving the low cataract surgical rate in China.

Background: Occult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP., Methods: A total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed., Results: Of the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence., Conclusions: Perioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.

Background: Traditional Chinese eye exercises of acupoints involve acupoint self-massage. These have been advocated as a compulsory measure to reduce ocular fatigue, as well as to retard the development of myopia, among Chinese school children. This study evaluated the impact of these eye exercises among Chinese urban children., Methods: 409 children (195 males, 47.7%), aged 11.1 ± 3.2 (range 6-17) years, from the Beijing Myopia Progression Study (BMPS) were recruited. All had completed the eye exercise questionnaire, the convergence insufficiency symptom survey (CISS), and a cycloplegic autorefraction. Among these, 395 (96.6%) performed the eye exercises of acupoints. Multiple logistic regressions for myopia and multiple linear regressions for the CISS score (after adjusting for age, gender, average parental refractive error, and time spent doing near work and outdoor activity) for the different items of the eye exercises questionnaire were performed., Results: Only the univariate odds ratio (95% confidence interval) for "seriousness of attitude" towards performing the eye exercises of acupoints (0.51, 0.33-0.78) showed a protective effect towards myopia. However, none of the odds ratios were significant after adjusting for the confounding factors. The univariate and multiple β coefficients for the CISS score were -2.47 (p = 0.002) and -1.65 (p = 0.039), -3.57 (p = 0.002) and -2.35 (p = 0.042), and -2.40 (p = 0.003) and -2.29 (p = 0.004), for attitude, speed of exercise, and acquaintance with acupoints, respectively, which were all significant., Conclusions: The traditional Chinese eye exercises of acupoints appeared to have a modest effect on relieving near vision symptoms among Chinese urban children aged 6 to 17 years. However, no remarkable effect on reducing myopia was observed.

Background: HLA-DRB1 allele polymorphisms have been reported to be associated with hepatocellular carcinoma susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to explore whether specific HLA-DRB1 alleles (DRB1*07, DRB1*12, DRB1*15) confer susceptibility to hepatocellular carcinoma., Methods: Case-control studies on HLA-DRB1 alleles association with HCC were searched up to January 2010 through a systematic review of the literature. The odds ratios (ORs) of HLA-DRB1 allele distributions in patients with hepatocellular carcinoma were analyzed against healthy controls. The meta-analysis software REVMAN 5.0 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity., Results: Eight case-control studies were included in the final analysis. Among the 3 HLA-DRB1 alleles studied, DRB1*07 and DRB1*12 were significantly associated with the risk of HCC in the whole populations (OR = 1.65, 95% CI: 1.08-2.51, P = 0.02 and OR = 1.59, 95% CI: 1.09-2.32, P = 0.02, respectively). No significant association was established for DRB1*15 allele with HCC in the whole populations. Subgroup analysis by ethnicity showed that DRB1*07, DRB1*12 and DRB1*15 alleles significantly increased the risk of hepatocellular carcinoma in Asians (OR = 2.10, 95% CI: 1.06-4.14, P = 0.03; OR = 1.73, 95% CI: 1.17-2.57, P = 0.006 and OR = 2.88, 95%CI: 1.77-4.69, P <0.001, respectively)., Conclusion: These results support the hypothesis that specific HLA-DRB1 alleles might influence the susceptibility of hepatocellular carcinoma. Large, multi-ethnic confirmatory and well designed studies are needed to determine the host genetic determinants of hepatocellular carcinoma.

Background: To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC)., Methods: The Aurora B and Aurora A mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the p53 and β-catenin genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of p53 and exon 3 of β-catenin. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines., Results: Aurora B was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of Aurora B was associated with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was inversely associated with β-catenin mutation (P = 0.002). Aurora B overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that Aurora B overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of p53 and β-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis., Conclusion: Aurora B overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.

Background: Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective., Methods: A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the "case group" and the "control group", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs., Results: After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases., Conclusion: Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.