[A comparative study of rigid gas permeable corneal contact lenses versus frame glasses for refractive correction of postoperative aphakic eyes after congenital cataract surgery in infants and children].

Objective: The aim of this paper is to compare the refractive correction effects of rigid gas permeable contact lenses (RGPCL) and spectacle correction in children with aphakia after congenital cataract surgery. Methods: This was a prospective non-randomized controlled trial. Children with aphakic eyes after congenital cataract surgery, who underwent vision correction in the Strabismus and Pediatric Ophthalmology Clinic of Beijing Tongren Hospital affiliated with Capital Medical University from April 2012 to November 2019, were continuously collected. Those who voluntarily chose to wear RGPCL for refractive correction were included in the experimental group. Patients with monocular disease were in trial group 1, and patients with binocular disease were in trial group 2. Patients who chose to wear frame glasses for refractive correction were included in the control group. Patients with monocular disease were in control group 1, and patients with binocular disease were in control group 2. Regional origin, medical history, and family information were collected at the first diagnosis. During the follow-up, adverse reactions occurring during the process of wearing glasses were recorded. The Teller acuity card was used for visual examination to obtain the best-corrected visual acuity and convert it into the logarithm of the minimum resolution angle. The degree of nystagmus was determined according to the amplitude and frequency of nystagmus. Treatment cost, treatment compliance, and the reasons for adopting or not adopting RGPCL were analyzed through a questionnaire completed by the parents of children with RGPCL. Results: A total of 203 children (344 eyes) who underwent congenital cataract surgery were included, including 124 males (210 eyes) and 79 females (134 eyes). The age range was 3 to 36 months. There were 28 cases in the experimental group, including 19 cases in trial group 1 and 9 cases in trial group 2. There were 175 cases in the control group, including 43 cases in control group 1 and 132 cases in control group 2. Except for 6 months of age, the visual acuity of the experimental group was better than that of the control group, and the differences were statistically significant (P<0.05). The visual acuity of children in trial group 1 was better than that of children in control group 1 at the same age. Among them, at 12 months of age [1.54 (1.27, 1.97), 1.84 (0.97, 2.12)], 18 months of age [1.27 (0.97, 1.84), 1.84 (0.97, 2.12)], 24 months of age [1.54 (1.27, 1.84), 1.84 (0.97, 2.12)], and 30 months old [0.97 (0.66, 1.27), 1.54 (0.66, 2.12)], the difference was statistically significant (P<0.001). The visual acuity of children in trial group 2 was better than that in control group 2 at the same age. Among them, at 18 months old [1.27 (0.97, 1.54), 1.27 (0.66, 2.12)], 24 months old [0.97 (0.66, 1.27), 1.27 (0.66, 2.12)], and 30 months old [1.27 (0.66, 2.12)], the difference was statistically significant (P<0.05). The remission rate of nystagmus in the experimental group was 8/9 (8 cases), the remission rate of nystagmus in the control group was 34.40% (32 cases), and the exacerbation rate was 29.03% (27 cases). The average annual cost of the experimental group was 25 125 yuan, and that of the control group was 2 511 yuan. Conclusions: RGPCL is a well-tolerated, safe, and effective treatment for infants and young children. The visual acuity and degree of nystagmus were significantly improved in children who wore RGPCL for aphakia refractive correction after congenital cataract surgery compared with spectacle correction.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

[Changes of brain network characteristics in patients with depression before and after precise repetitive transcranial magnetic stimulation].

Objective: To investigate the changes of brain network characteristics in patients with depression before and after precise repetitive transcranial magnetic stimulation (rTMS) treatment. Methods: Patients with depression in the Second Affiliated Hospital of Xinxiang Medical University and healthy volunteers in the community of Xinxiang city from February 2018 to March 2019 were simultaneously recruited. The left dorsolateral prefrontal cortex was precisely selected as the stimulation target through the latest Human Brainnetome Atlas, and the near infrared navigation was used to achieve accurate brain stimulation treatment in combination with the structural magnetic resonance data. Moreover, functional connectivity was analyzed before and after rTMS treatment in significantly altered brain areas of patients with depression. Results: Nineteen patients (11 males and 8 females) with depression were included, aged (34±11) years. Meanwhile, 22 healthy controls (9 males and 13 females), aged (30±9) years, were also enrolled. Functional connectivity of insular cortex was decreased in depression patients when the insula was analyzed as the target area (P<0.05). The functional connection from insula to middle frontal lobe and superior parietal lobe in patients with depression decreased before rTMS treatment (P<0.05), but increased after rTMS treatment (P<0.05). The functional connection between dIg_L of the insula and the right middle prefrontal lobe was correlated with Beck Anxiety Index (BAI) before rTMS treatment and Beck Depression Index (BDI) after rTMS treatment (r=0.737, P=0.003; r=0.696, P=0.005). Conclusions: Abnormal functional connectivity of insula may be the brain imaging mechanism of rTMS treatment. Precise brain region selection based on Human Brainnetome Atlas provides a new technical method for clinical rTMS precision treatment.

[The impact of donor-to-recipient gender compatibility on outcomes of haploid hematopoietic stem cell transplantation in patients with hematological malignancies].

Objective: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. Methods: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) . Results: ① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups (P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups (P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively (P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % (P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

Photoluminescence and magnetism integrated multifunctional black phosphorus probes through controllable PO bond orbital hybridization.

Biological probes with integrated photoluminescence and magnetism characteristics play a critical role in modern clinical diagnosis and surgical protocols combining fluorescence optical imaging (FOI) with magnetic resonance imaging (MRI) technology. However, traditional magnetic semiconductors can easily generate a spin splitting at the Fermi level and half-metallic electronic occupation, which will sharply reduce the radiation recombination efficiency of photogenerated carriers. To overcome this intrinsic contradiction, we propose a controllable oxidation strategy to introduce some particular PO bonds into black phosphorus nanosheets, in which the p orbital hybridization between P and O atoms not only provides some carrier recombination centers but also leads to a room-temperature spin polarization. As a result, the coexistence of photoluminescence and magnetism is realized in multifunctional black phosphorus probes with excellent biocompatibility. This work provides a new insight into integrating photoluminescence and magnetism together by intriguing atomic orbital hybridization.

Measurement of the toroidal radiation asymmetry during massive gas injection triggered disruptions on J-TEXT.

Disruptions have the potential to cause severe damage to large tokamaks like ITER. The mitigation of disruption damage is one of the essential issues for the tokamak. Massive gas injection (MGI) is a technique in which large amounts of a noble gas are injected into the plasma in order to safely radiate the plasma energy evenly over the entire plasma-facing wall. However, the radiated energy during the disruption triggered by massive gas injection is found to be toroidally asymmetric. In order to investigate the spatial and temporal structures of the radiation asymmetry, the radiated power diagnostics for the J-TEXT tokamak have been upgraded. The multi-channel arrays of absolute extreme ultraviolet photodiodes have been upgraded at four different toroidal positions to investigate the radiation asymmetries during massive gas injection. It is found that the toroidal asymmetry is associated with plasma properties and MGI induced MHD activities.

[Effects of metformin and adiponectin on endometrial cancer cells growth].

OBJECTIVE: To determine the effect of metformin and adiponectin on the proliferation of EC cells and the relationship between metformin and adiponectin. METHODS: The proliferation impact of different concentrations of metformin and adiponectin on two types of EC cells ishikawa (IK) and HEC-1B was confirmed by CCK-8 method. qRT-PCR and Western blot were used to detect the effect of different concentrations of metformin on the changes of adiponectin receptors (AdipoR1 and AdipoR2) of the EC cells both in mRNA and protein level and the role of compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, on the above effects. RESULTS: (1) Both metformin and adiponectin could significantly promote the proliferation of endometrial cancer (EC) cells in a time and concentration dependent manner (P<0.05).(2)Metformin and adiponectin had synergy anti-proliferative effect on EC cells and the combination index (CI) value of IK cells was 0.906 34 and of HEC-1B cells was 0.827 65. (3)qRT-PCR was used to detect the mRNA levels of AdipoR1 and AdipoR2 after 5 mmol/L and 10 mmol/L metformin, respectively, stimulating IK and HEC-1B cells for 48 hours and the mRNA expressions of AdipoR1 and AdipoR2 were significantly increased when compared with the control group (0 mmol/L)(IK: AdipoR1 of 5 mmol/L and 10 mmol/L group: P<0.001,AdipoR2 of 5 mmol/L group: P<0.001; HEC-1B: AdipoR1 of 5 mmol/L group: P<0.001, 10 mmol/L group: P=0.023, AdipoR2 of 5 mmol/L group: P<0.001, 10 mmol/L group: P=0.024). When combined with compound C, the RNA levels of AdipoR1 and AdipoR2 were not different compared with the control group (0 mmol/L, P>0.05). (4) Western blot was used to detect the protein levels of AdipoR1 and AdipoR2 after 5 mmol/L and 10 mmol/L metformin, stimulating IK and HEC-1B cells for 48 hours and the protein level was significantly increased when compared with the control group (0 mmol/L)(IK: AdipoR1 of 5 mmol/L group: P=0.04, 10 mmol/L group: P=0.033, AdipoR2 of 5 mmol/L group: P=0.044, 10 mmol/L group: P=0.046; HEC-1B: AdipoR1 of 5 mmol/L group: P=0.04, 10 mmol/L group: P=0.049, AdipoR2 of 5 mmol/L group: P=0.043, 10 mmol/L group: P=0.035). When combined with compound C,the protein levels of AdipoR1 and AdipoR2 were not different compared with the control group (0 mmol/L, P>0.05). CONCLUSION: We find that metformin and adiponectin have synergy anti-proliferative effect on EC cells. Besides, metformin can increase adiponectin receptors expressions of EC cells both in mRNA and protein levels and this effect is accomplished by the activation of AMPK signaling pathway.

Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-ß downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-ß. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.

Downregulation of miR-218 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling.

Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis. Overexpression of miR-218 inhibited cell migration and invasion as well as the EMT process. Of particular importance, miR-218 was involved in the metastatic process of lung cancer cells in vivo by suppressing local invasion and distant colonization. We identified Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells to cisplatin treatment through suppression of Slug and ZEB2. These findings highlight an important role of miR-218 in the regulation of EMT-related traits and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic strategy by targeting miR-218 in NSCLC.

Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD).

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

[Clinical and electrophysiological studies of oxaliplatin-induced peripheral neuropathy].

OBJECTIVE: To identify the sensitive scales and the early change of nerve conduction for chronic oxaliplatin-induced peripheral neuropathy (OXLIPN), and to investigate correlation between the symptoms of acute OXLIPN and chronic OXLIPN. METHODS: Between December 2014 and August 2015, 16 colorectal cancer patients confirmed by pathology, from department of Oncology, Chinese PLA General Hospital, scheduled to receive XELOX, completed the acute neurotoxic symptoms questionnaire at the end of 1 cycles and the scales of TNSc and NCI-CTC at the baseline and the end of 4 cycles. Nerve conduction studies (bilateral peroneal nerves and sural nerves) were performed in 11 patients at the baseline and the end of 4 cycles. RESULTS: After chemotherapy, TNSc increased 1-9 points for all cases, while NCI-CTC increased 1 point for only 9 cases, the remaining 7 cases had the same NCI-CTC score before and after chemotherapy, where TNSc increased 1-6 points. Left sural nerve a-SNAP (amplitude of sensory nerve action potential) was (15.3±5.8)µV before chemotherapy and(12.3±5.0)µV after chemotherapy. Right sural nerve a-SNAP was (17.4±8.6)µV before chemotherapy and (13.3±6.7)µV after chemotherapy. After chemotherapy, these datum were significantly reduced for left peroneal nerve distal and proximal a-CMAP (amplitude of compound muscle action potential), bilateral sural nerve a-SNAP and left sural nerve SCV (sensory conduction velocity) (P<0.05). After chemotherapy, TNSc was correlated significantly with the acute neurotoxic symptoms questionnaire (Spearman r=0.698, P=0.003). CONCLUSIONS: TNSc is more sensitive to the severity and changes in chronic OXLIPN than NCI-CTC. Sural nerve a-SNAP has a higher sensitivity for the early changes of nerve conduction studies in chronic OXLIPN. Patients who have more symptoms of acute OXLIPN are those who eventually develop more severe chronic OXLIPN.

Susceptibility to oral squamous cell carcinoma: correlation with variants of CYP1A1-MspI, GSTT1, GSTM1, ALDH2, EC-SOD and Lifestyle factors.

In order to investigate the association between polymorphisms in genes encoding metabolizing enzymes (CYP1A1-MspI, EC-SOD (extracellular superoxide dismutase), GSTT1, GSTM1, ALDH2), cigarette and alcohol consumption, and the risk of oral squamous cell carcinoma, we conducted a prospective case-control study comprised of 750 individuals with oral squamous cell carcinoma (OSCC) and 750 healthy individuals. Data about smoking and drinking habits were collected along with other demographic and clinical information. Peripheral blood samples were collected for DNA extraction, and polymerase chain reaction (PCR) and PCR-RFLP (restriction fragment length polymorphism) were used to determine genotypes of CYP1A1, EC-SOD, GSTT1, GSTM1, ALDH2. The results showed that smoking and alcohol consumption were significantly more common among patients than controls (p <0.05). There were significant differences in the genotype distribution for each locus between groups, with the CYP1A1 (m2/ m2), EC-SOD (C/G), GSTT1 [-], GSTM1 [-] and ALDH2 (non G/G) genotypes being more common among patients (p <0.05). Furthermore, the majority of patients had at least two or more variant genotypes, while controls had one or no variant genotype (p <0.05). Finally, multiple variant genotypes combined with smoking, drinking, or both smoking and drinking significantly increased the risk of OSCC, with greater increase for heavier smoking/drinking. In brief, genetic polymorphism of CYP1A1, EC-SOD, GSTT1, GSTM1, and ALDH2 and smoking and drinking history are closely associated with susceptibility to OSCC.

Spreading patterns, prognostic factors and treatment outcomes of nasopharyngeal papillary adenocarcinoma and salivary gland-type carcinomas.

OBJECTIVES: In this study, we aim to analyse the different spreading patterns, prognostic factors and treatment outcomes of nasopharyngeal papillary adenocarcinoma (NPAC) and salivary gland-type carcinomas (NPCs). DESIGN, SETTING AND PARTICIPANT: The current study report on a retrospective analysis of oncologic outcome of 76 pathologically confirmed consecutive cases of nasopharyngeal adenocarcinomas (NAC), including 31 NPAC, 33 adenoid cystic carcinomas (ACC) and 12 mucoepidermoid carcinomas (MEC). MAIN OUTCOME MEASURE: Overall survival rates (OS) and disease-free survival rates (DFS). RESULTS: In 12 patients with cranial nerve (CN) palsy, there were ACC (n = 9), NPAC (n = 2) and MEC (n = 1) (P = 0.016). CT-/MRI-detected CN involvements were found in 22 patients. Lymph node metastasis was observed in 25.8% of NPAC (n = 8), 12.1% of ACC (n = 4) and 8.3% of MEC (n = 1). Significant differences were observed in 5-year overall survival (OS) and disease-free survival (DFS) rates between patients with and without CT-/MRI-detected CN involvement (P = 0.002 and P = 0.002, respectively), and similar results were found between patients with and without lymph node metastasis (P = 0.002 and P = 0.018, respectively). In 37 patients with early-stage disease (stages I-II), significant differences were observed in 5-year OS and DFS rates between the surgical and non-surgical treated groups (P = 0.031 and P = 0.012, respectively). In 39 patients with advanced-stage disease (stages III-IV), significant or marginally differences were observed in DFS and OS between the chemoradiotherapy and non-chemoradiotherapy groups (P = 0.007 and P = 0.062, respectively). CONCLUSIONS: ACC has a higher CN invasion than NPAC and MEC, and NPAC has the highest rate of lymphatic metastases. CT-/MRI-detected CN involvements and lymph node metastasis indicate a negative impact on the prognosis. The outcome of surgical patients in our series is encouraging in early-stage NPAC and NPCs, and chemoradiotherapy may be the optimal treatment for the advanced-stage patients.

Comparative analysis of phylogenetic relationships, morphologies, and pathogenicities among Curvularia lunata isolates from maize in China.

To understand the effects of disease-resistant maize varieties and new cropping systems on the population of Curvularia lunata, 52 isolates of C. lunata were collected in China from 2011 to 2013. The isolates were analyzed in terms of phylogenetic relationships, morphology, and pathogenicity. Phylogenetic analysis showed that the 52 isolates clustered into 2 distinct clusters with further subdivisions, suggesting the emergence of new genetic divergence within C. lunata. Results of morphology and pathogenicity analyses demonstrated that there were significant differences among these isolates: 27 isolates were classified as fast growing, 5 as slow growing, and 20 as moderate growing. Three isolates had white-colored colonies, 13 had yellowish green-colored colonies, and the remaining isolates had dark green-colored colonies. Furthermore, conidiation rates were assessed: 30 isolates were characterized as having low conidiation rates, 15 as having medium conidiation rates, and the remaining 7 isolates as having high conidiation rates. Eleven of the isolates appeared to be strongly pathogenic against maize, 15 isolates proved to be weakly pathogenic against maize, and the remaining isolates were regarded to be moderately pathogenic. Interestingly, correlation analysis demonstrated a negative correlation between the growth rate and the pathogenicity of the isolates, while a positive correlation was observed between the conidiation rate and the pathogenicity. No correlation was observed between the colony color and the pathogenicity of the isolates.

Regulatory circuit of PKM2/NF-κB/miR-148a/152-modulated tumor angiogenesis and cancer progression.

Upregulation of the embryonic M2 isoform of pyruvate kinase (PKM2) emerges as a critical player in the cancer development and metabolism, yet the underlying mechanism of PKM2 overexpression remains to be elucidated. Here we demonstrate that IGF-1/IGF-IR regulates PKM2 expression by enhancing HIF-1α-p65 complex binding to PKM2 promoter. PKM2 expression is regulated by miR-148a/152 suppression. PKM2 directly interacts with NF-κB p65 subunit to promote EGR1 expression for regulating miR-148a/152 feedback circuit in normal cells, but not in cancer cells because of the DNA hypermethylation of miR-148a and miR-152 gene promoters. The silencing of miR-148a/152 contributes to the overexpression of PKM2, NF-κB or/and IGF-IR in some cancer cells. We show that disruption of PKM2/NF-κB/miR-148a/152 feedback loop can regulate cancer cell growth and angiogenesis, and is also associated with triple-negative breast cancer (TNBC) phenotype, which may have clinical implication for providing novel biomarker(s) of TNBC and potential therapeutic target(s) in the future.

LNK (SH2B3): paradoxical effects in ovarian cancer.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers.

First survey of helminths in adult goats in Hunan Province, China.

The objective of the present survey was to reveal the prevalence of helminths in adult goats in Hunan Province, the People's Republic of China. From July 2010 through February 2013, a total of 479 goats slaughtered in local abattoirs and markets were examined for the presence of helminths using a helminthological approach. Eighty-six percent of the examined goats were infected with at least one species of helminths. In total, 15 genera of helminths were found representing 2 phyla, 3 classes, 5 orders, and 11 families. Oesophago-stomum, Ostertagia and Haemonchus were the most prevailing nematode genera, Eurytrema was the predominant trematode genus detected, whereas the infection of adult goats with cestodes was not common, with Cysticercus tenuicollis being the most common genus. The worm burdens showed obvious seasonal variation in that nematodes and cestodes were abundant in summer and winter, and the trematodes peaked in winter, which was consistent with the seasonal precipitation of Hunan Province. The geographical distribution of helminths in goats ascended with altitude. Goats in the mountainous areas were more severely infected with helminths than goats in the hilly areas, whereas infection of goats with helminths was much less in the lake areas. The present investigation highlights the high prevalence of helminths in adult goats in Hunan Province, China, which provides baseline data for assessing the effectiveness of future prevention and controlling measures against helminth infection in adult goats in this province and elsewhere.