[Establishment of a patient-derived xenograft humanized mouse model for hepatoblastoma in children].

Objective: To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor. Methods: A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children's data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by χ (2) test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. Results: After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, P = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma's PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, ß-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. Conclusion: A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.

[Clinical features and prognostic analysis of hepatoblastoma in children under six years old].

Objective: To summarize and analyze the clinical features, treatment effects and related factors affecting the prognosis of hepatoblastoma (HB) in children under six years old. Methods: Clinical data of 382 children with HB under six years old who were pathologically diagnosed at the Pediatric Single Center of Beijing Tongren Hospital from May 2005 to May 2019 were analyzed retrospectively. The factors affecting the treatment effect and survival rate of HB were analyzed. The independent risk factors affecting the prognosis of HB were studied by Cox regression model. The χ(2) test was used to compare the enumeration data between groups. Kaplan-Meier method was used for survival analysis. Log-rank test was used to compare the survival rates among subgroups. Results: Children enrolled were with median age of 1.75 (0.08 ~ 5.92) years old and a male to female ratio of 1.5. Alpha-fetoprotein (AFP) median level was 197 406.5 µg/L at initial diagnosis, and the pathological tissue type was mainly epithelial (55.8%). Preoperative PRETEXT stage was mostly stage III (58.6%). 86 cases (22.5%) had portal vein or hepatic vein, and vena cava invasion. 73 cases (19.1%) had extrahepatic adjacent tissues and organs invasion. Twenty-four cases (6.3%) had tumor rupture and bleeding. 171 cases (44.8%) had distant metastases, and 96 cases (25.1%) had multiple intrahepatic lesions. Patients were followed-up to May 2020 (median follow-up time was 56 months). After comprehensive treatment, 218 cases were completely relieved, and 69 cases were partially relieved, and the treatment efficiency was 75.1%. Kaplan-Meier survival analysis showed that the 1, 3, and 5-years overall survival rates (OS) were 93.7%, 84.0%, and 73.9%, respectively, and the event-free survival rates were 90.5%, 79.2%, and 67.5%, respectively. Comparison of the clinical factors of 5-year OS showed that AFP < 100 µg/L (HR = 3.341, P = 0.005), PRETEXT stage IV (HR = 4.026, P = 0.001), vascular invasion (HR = 2.178, P = 0.019) and distant metastasis (HR = 2.634, P = 0.010) were independent risk factors in each subgroup affecting the prognosis of children with HB, and the difference was statistically significant. Conclusion: HB prognosis is related to AFP level, PRETEXT stage, presence or absence of vascular invasion and distant metastasis. Therefore, its survival and prognosis will be different in the presence of different risk factors.

Identification and characterization of circRNAs in maize seedlings under deficient nitrogen.

Here, deep sequencing results of the maize transcriptome in leaves and roots were compared under high-nitrogen (HN) and low-nitrogen (LN) conditions to identify differentially expressed circRNAs (DECs). Circular RNAs (circRNAs) are covalently closed non-coding RNA with widely regulatory potency that has been identified in animals and plants. However, the understanding of circRNAs involved in responsive nitrogen deficiency remains to be elucidated. A total of 24 and 22 DECs were obtained from the leaves and roots, respectively. Ten circRNAs were validated by divergent and convergent primers, and 6 DECs showed the same expression tendency validated by reverse transcriptase-quantitative PCR. Integrating the identified differentially expressed miRNAs, 34 circRNAs could act as miRNA decoys, which might play important roles in multiple biological processes, including organonitrogen compound biosynthesis and regulation of the metabolic process. A total of 51 circRNA-parent genes located in the genome-wide association study identified loci were assessed between HN and LN conditions and were associated with root growth and development. In summary, our results provide valuable information regarding further study of maize circRNAs under nitrogen deficiency and provide new insights into screening of candidate genes as well as the improvement of maize regarding nitrogen deficiency resistance. CircRNA-miRNA-mRNA co-expression networks were constructed to explore the circRNAs that participated in biological development and nitrogen metabolism.

Wharton's Jelly-derived mesenchymal stem cells suppress apoptosis of nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway.

OBJECTIVE: Aberrant apoptosis of nucleus pulposus cells (NPCs) is one of the most remarkable pathological changes in intervertebral disc degeneration (IDD) development. Albeit the advances in the application of stem cell-based therapy in IDD treatment, the molecular mechanisms underlying the anti-apoptotic actions of mesenchymal stem cell (MSC) remain poorly elucidated. PATIENTS AND METHODS: The expression patterns of apoptosis-related proteins and Wnt/ß-catenin-related genes in NP samples isolated from patients with mild or severe IDD were compared by performing immunoblot assay and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. NPCs were in vitro treated with compression to induce apoptosis and then co-cultured with Wharton's Jelly-derived MSCs without direct interaction. After that, flow cytometry was carried out to detect the apoptosis rate of NPCs and the activity of Wnt/ß-catenin pathway was determined. DKK-1 was used to inhibit Wnt signaling, in prior to evaluation of the effects of WJ-MSCs on apoptosis within the co-cultured NPCs. RESULTS: Compared to the mild IDD group, there was a significant increase in the expression of Caspase-3 and Bax in the NP tissues from severe IDD patients, whereas Bcl-2 displayed an opposite result. In addition, the expression of Wnt 3a, Wnt 5a, Wnt 10a, GSK-3ß, cyclinD1 and ß-catenin was notably augmented in parallel with IDD progression. After compression treatment, the proportion of apoptotic NPCs was increased, which was then dramatically reversed by WJ-MSCs co-culture. Likewise, WJ-MSCs suppressed compression-induced Wnt-related gene expression and blocking Wnt/ß-catenin pathway using DKK-1 enhanced the anti-apoptotic impacts of WJ-MSCs. In the presence of DKK-1, there was no significant difference between NPCs co-cultured with WJ-MSCs and those cells cultured alone. CONCLUSIONS: WJ-MSCs attenuate the compression-induced apoptosis in NPCs and inhibit the activation of Wnt/ß-catenin signaling. Blocking Wnt/ß-catenin pathway further facilitates the actions of WJ-MSCs in anti-apoptosis, indicating that Wnt/ß-catenin signaling plays a crucial role in this process and may function as a potential therapeutic target for IDD treatment.

LncRNA FGD5-AS1/miR-5590-3p axis facilitates the proliferation and metastasis of renal cell carcinoma through ERK/AKT signalling.

OBJECTIVE: Amongst noncoding RNAs, competing endogenous RNAs (ceRNAs) are popular and interesting regulatory mechanisms involved in oncogenesis and tumour progression. LncRNA FGD5-AS1, also known as miR-5590-3p, is involved in the regulatory role of ceRNA in many cancers. However, the roles of lncRNA FGD5-AS1 or miR-5590-3p in renal cell carcinoma (RCC) remain unclear. We investigated how FGD5-AS1 and miR-5590-3p regulated clear cell proliferation and metastasis in RCC. PATIENTS AND METHODS: Real Time-quantitative PCR (RT-qPCR) was used to detect the expression of FGD5-AS1 in tumour issues and renal cancer cell lines. MTT, scratch test and transwell assay were performed to confirm the effect of FGD5-AS1 on the proliferation, migration or invasion of the above cell lines. RNA pull-down and Luciferase assays were used to detect the target site between FGD5-AS1 and miR-5590-3p. In addition, we examined the proteins related to ERK/AKT signalling related via Western blot analysis. Finally, we used the RT-qPCR method to detect the mRNA levels of E-cadherin and vimentin. RESULTS: LncRNA FGD5-AS1 was highly expressed in renal cancer tissues, especially in patients with metastasis. This effect facilitated the proliferation, migration, epithelial-mesenchymal transition and invasion of renal cancer cells. Silencing the expression of FGD5-AS1 with FGD5-AS1 siRNA significantly inhibited the malignancy of tumour cells. RNA pull-down and Luciferase assays demonstrated that FGD5-AS1 targeted miR-5590-3p to interact with miR-5590-3p negatively. Furthermore, miR-5590-3p inhibitors could eliminate the FGD5-AS1 siRNA-induced upregulation of E-cadherin and downregulation of vimentin. CONCLUSIONS: Mechanistically, lncRNA FGD5-AS1 can competitively interact with miR-5590-3p and regulate the downstream signalling of ErkAKT to enhance the malignancy of tumours. This lncRNA could become a potential target molecule for treating and diagnosing RCC.

[Case-control survey on relationship between laryngopharyngeal reflux and vocal fold polyps].

Objective: To investigate whether laryngopharyngeal reflux(LPR) is an independent risk factor for vocal fold polyps and to analyze the potential mechanism. Methods: Case control survey was designed. Subjects who came to the Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Chongqing Medical University from September 2018 to December 2019, including 152 cases with vocal fold polyps and 176 cases with normal vocal folds, were selected. All the subjects filled in a questionnaire and were assessed by the reflux symptom index (RSI) and the reflux finding score (RFS) scale. RSI>13 and(or) RFS>7 were classified as LPR. Chi-square test, univariate and multivariate unconditional logistic regression models were used for statistical analysis. Results: The incidence of LPR and throat clearing in vocal fold polyps group (47.37%, 73.68%) was significantly higher than that in control group (27.27%, 59.09%), with statistically significant difference (P<0.001, P=0.005, respectively). The incidence of troublesome cough, indigestion or stomach acid coming up was no difference between the two groups(P=0.672, P=0.099). Multivariate unconditional logistic regression analysis showed that LPR (OR=1.815, 95%CI:1.061-3.103), occupational exposure(OR=2.655, 95%CI:1.397-5.042), spicy food(OR=1.958, 95%CI:1.142-3.355) were risk factors for vocal fold polyps. Conclusion: LPR, occupational exposure, spicy food are independent risk factors for vocal fold polyps. Frequent throat clearing caused by LPR may be the main cause of vocal ford polyps. In order to prevent vocal fold polyps, we need to take action to treat laryngopharyngeal reflux disease actively.

MiR-30a-3p promotes ovariectomy-induced osteoporosis in rats via targeting SFRP1.

OBJECTIVE: To explore the effect of miR-30a-3p on osteoporosis in rats after ovariectomy. MATERIALS AND METHODS: The ovariectomized (OVX) rat model was established to mimic postmenopausal osteoporosis. The primary bone marrow mesenchymal stem cells (BMMSCs) isolated from female rats were transfected with mimic or inhibitor. Real Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were used to examine the expressions of miR-30a-3p and osteoporosis-related proteins. The bone mineral density (BMD) was detected via micro-Computed Tomography (CT) and the bone histomorphometry was performed. Luciferase assay was also performed to confirm whether SFRP1 is a target of miR-30a-3p. RESULTS: According to micro CT, BMD significantly declined in OVX group. MiR-30a-3p and SFRP1 were negatively correlated after ovariectomy. SFRP1 was acknowledged as a target of miR-30a-3p. Besides, the miR-30a-3p inhibitor promoted osteogenic differentiation in vitro and bone formation in vivo. CONCLUSIONS: MiR-30a-3p inhibitor promotes bone formation through decreasing SFRP1 expression and miR-30a-3p may be a potential novel molecular target in the treatment of osteoporosis.

[Clinical features, treatment and prognosis of retinoblastoma in distant metastasis stage].

Objective: To summarize the clinical features, treatment and prognosis of retinoblastoma (RB) patients in distant metastasis stage. Methods: Retrospective case series study. Clinical data of 24 cases (30 eyes) with diagnosis of distant metastasis stage RB were collected in pediatrics department of Beijing Tongren Hospital affiliated with Capital Medical University, from September 2005 to December 2013. In these cases, including 11 male cases and 13 female cases, the treatment age ranged from 7 months to 9 years with the median of 26 months. There were 18 unilateral cases (12 cases of right eye and 6 cases of left eye) and 6 bilateral cases. All cases were treated with surgery, chemotherapy and radiotherapy. The adverse reaction, blood routine and biochemical routine were monitored dynamically and regularly during treatment. The clinical manifestations and auxiliary examination were combined to evaluate the therapeutic effect. Determining the prognosis with death and survival, the survival curve and the median survival time were calculated by the product limit method. Results: The results of pathologic examination of 13 cases showed 11 cases of optic nerve involvement, 6 cases of optic nerve and choroid involvement, 1 case of post laminar involvement, 1 case of cornea and conjunctiva involvement. The most common metastatic site was central nerve system (CNS) (23 cases), followed by orbital involvement (10 cases). Other metastatic sites included bone (9 cases), bone marrow (1 case), pleura (1 case) and lymph node (1 case). 23 patients with CNS metastasis underwent systemic chemotherapy and intrathecal injection. The toxicity and side effects of radiotherapy and chemotherapy were evaluated and classified as grade I-II. Those adverse effects were tolerated by all cases. Followed up to December 31, 2015, all patients with CNS metastasis died and the median survival time was 6 months. Only 1 patient without CNS metastasis disease-free survived for 64 months. Conclusions: The most common metastasis site of RB was CNS. The overall prognosis of RB with distant metastasis was poor, in spite of given combined treatment mainly including surgery, chemotherapy and radiotherapy. But the prognosis of RB patients without CNS metastasis in distant metastasis stage was better than with CNS metastasis. (Chin J Ophthalmol, 2017, 53: 121-126).

[Treatment and prognostic analysis of retinoblastoma patients with choroid invasion].

Objective: To observe the treatment and prognosis of choroid invasion of retinoblastoma (RB) in children. Method: A total of 149 children who had been diagnosed with unilateral RB and received enucleation disclosing tumor invasion to choroid from January 2006 to December 2013 in Beijing Tongren Hospital were recruited in this study. Choroid involvement was classified as massive choroid invasion and focal choroid invasion. Massive choroid invasion was defined as a maximum diameter of invasive tumor focus of 3 mm or more in diameter that might reach the scleral tissue. Focal choroid invasion was defined as a tumor focus of less than 3 mm in diameter without involvement of sclera. The treatment was delivered according to the invasive status of tumor with combination of histopathological high risk factors. The prognosis of different degrees of choroid invasion was observed. They were divided into two groups according to whether the merger of other high histopathologic risk factors, the survival situation was compared. The subjects were followed up for 1 to 9 years (the median follow-up time: 4 years and 1 month). Result: Among the 149 subjects, 90 were boys and 59 were girls. The right eye was affected in 81 patients and the left eye in 68 patients. Sixteen patients died, resulting in an overall survival rate of 89.3%. Among massive choroid invasion in 47 cases, 9 patients experienced disease recurrence and death resulting in a survival rate of 80.9%. While the focal choroid invasion was found in 102 cases, only 7 children had disease relapsed and died resulting in a survival rate of 93.1% which was statistically significant (χ2=5.067, P=0.024). Among 8 patients with massive choroid invasion without pathological high-risk factors, no death occurred, while in other 39 patients with high-risk factors, 9 died with a mortality rate of 23.1%, however, the difference was not statistically significant (Fisher's exact probability method, P=0.323). Among 60 patients with focal choroid invasion without pathological high-risk factors, no death was observed, while among the other 42 patients presenting high-risk factors, 7 of them died with a mortality rate of 16.7% (Fisher's exact probability method, P=0.003). Cox multivariate analysis showed that massive choroid invasion and surgical margin of the optic nerve were influential factors of prognosis. Conclusion: Patients with focal choroid invasion have a low disease recurrence and may not receive adjuvant chemotherapy. Patients with massive choroid invasion without presenting pathological high-risk factors warrant further prospective study to assess whether adjuvant chemotherapy is needed. However chemotherapy is recommended for those with massive choroid invasion presenting with risk factors to avoid the high disease recurrence in such patients.

TLR and NLRP3 inflammasome-dependent innate immune responses to tumor-derived autophagosomes (DRibbles).

Autophagosomes derived from tumor cells, also referred to as defective ribosomal products in blebs (DRibbles), have been previously shown to stimulate potent T-cell responses and mediate tumor regression when used as therapeutic cancer vaccines in multiple preclinical cancer models. In this report, we investigated the underlining mechanisms by which DRibbles induced T-cell activation, particularly how DRibbles activated antigen-presenting cells (APCs). We found that DRibbles could induce a rapid differentiation of monocytes and DC precursor (pre-DC) cells into functional APCs. DRibbles triggered innate receptor signaling via Toll-like Receptors (TLR)-2, TLR4, TLR7, TLR8, and nucleotide-binding oligomerization domain-containing protein 2 (NOD2), but not TLR3, TLR5, or TLR9. DRibbles induced PBMCs to produce pro-inflammatory cytokines, such as IL-6, IL-10, TNF-α, and IL-1ß. DRibbles induced IL-1ß release from PBMC or THP-1 cells without LPS priming, but required the core machinery of NLRP3 inflammasomes. Active endocytosis was required for inflammasome activation and cross presentation, and blocking endosome acidification or the ER-associated degradation (ERAD) pathway resulted in opposite effects on these two processes. Our data show that DRibbles could induce strong innate immune responses via multiple pattern recognition receptors, and explain why DRibbles could function as excellent antigen carriers to induce adaptive immune responses to both tumor cells and viruses. In contrast to the well-established inhibitory effect of autophagy on the inflammasome activation of APCs, our study demonstrates that isolated autophagosomes (DRibbles) from antigen donor cells activate inflammasomes by providing first and second signals required for IL-1ß production by PMBC.

Effect of Bacillus subtilis Natto on Meat Quality and Skatole Content in TOPIGS Pigs.

This study investigated the effect of Bacillus subtilis (B. subtilis) natto on meat quality and skatole in TOPIGS pigs. Sixty TOPIGS pigs were randomly assigned to 3 groups (including 5 pens per group, with 4 pigs in each pen) and fed with basic diet (control group), basic diet plus 0.1% B. subtilis natto (B group), and basic diet plus 0.1% B. subtilis natto plus 0.1% B. coagulans (BB group), respectively. All pigs were sacrificed at 100 kg. Growth performance, meat quality, serum parameters and oxidation status in the three groups were assessed and compared. Most parameters regarding growth performance and meat quality were not significantly different among the three groups. However, compared with the control group, meat pH24, fat and feces skatole and the content of Escherichia coli (E. Coli), Clostridium, NH3-N were significantly reduced in the B and BB groups, while serum total cholesterol, high density lipoprotein, the levels of liver P450, CYP2A6, and CYP2E1, total antioxidant capability (T-AOC) and glutathione peroxidase and Lactobacilli in feces were significantly increased in the B and BB groups. Further, the combined supplementation of B. subtilis natto and B. coagulans showed more significant effects on the parameters above compared with B. subtilis, and Clostridium, and NH3-N. Our results indicate that the supplementation of pig feed with B. subtilis natto significantly improves meat quality and flavor, while its combination with B. coagulans enhanced these effects.

Gradual onset and recovery of the Younger Dryas abrupt climate event in the tropics.

Proxy records of temperature from the Atlantic clearly show that the Younger Dryas was an abrupt climate change event during the last deglaciation, but records of hydroclimate are underutilized in defining the event. Here we combine a new hydroclimate record from Palawan, Philippines, in the tropical Pacific, with previously published records to highlight a difference between hydroclimate and temperature responses to the Younger Dryas. Although the onset and termination are synchronous across the records, tropical hydroclimate changes are more gradual (>100 years) than the abrupt (10-100 years) temperature changes in the northern Atlantic Ocean. The abrupt recovery of Greenland temperatures likely reflects changes in regional sea ice extent. Proxy data and transient climate model simulations support the hypothesis that freshwater forced a reduction in the Atlantic meridional overturning circulation, thereby causing the Younger Dryas. However, changes in ocean overturning may not produce the same effects globally as in Greenland.

Clinical effectiveness of multimodality treatment on advanced pediatric hepatoblastoma.

OBJECTIVES: To investigate the effect of multimodality treatment of advanced paediatric hepatoblastoma and the factors affecting the prognosis. PATIENTS AND METHODS: 35 childhood patients were treated with multimodality treatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stem cell transplantation. Patients were followed up every month. RESULTS: 33 patients completed the follow-up, of which 17 were in complete remission, 5 were in partial remission, 1 case got worse, and 10 died. The remission rate was 66.7% (22/33), and the overall survival rate was 69.7% (23/33). 1 patient with advanced hepatoblastoma got high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (APBSCT) treatment, and a primary lesion by 18 x 15 x 9 cm reduced to 10 x 8 x 4 cm. Remote metastases significantly alleviated, and partial remission reached six months. The overall survival was 9 months after transplantation. Patients with the mixed phenotype of hepatoblastoma had a worse prognosis than with the epithelial phenotype (p < 0.001), and patients in stage IV had a lower survival rate than in stage III (p < 0.001). CONCLUSIONS: Multimodality treatment can effectively improve remission rate and prolong the survival of children with the advanced hepatoblastoma. In addition, alpha-fetoprotein (AFP), hepatoblastoma pathological classification and staging are of great use in prediction of prognosis.

Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer.

BACKGROUND: This study was aimed to detect post-chemotherapeutic circulating tumour cells (CTCs) in stage III colon cancer patients and identify those who were at high risk of relapse. METHODS: We used human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) as the biomarkers to detect CTCs in 90 stage III colon cancer patients undergoing curative resection followed by mFOLFOX chemotherapy. RESULTS: Post-chemotherapeutic relapse occurred in 30 (33.3%) patients. By univariate analysis and multivariate proportional hazards regression analysis, perineural invasion (hazard ratio (HR): 2.752; 95% confidence interval (CI): 1.026-7.381), high post-chemotherapeutic serum CEA levels (HR: 2.895; 95% CI: 1.143-7.333) and persistent presence of post-chemotherapeutic CTCs (HR: 6.273; 95% CI: 2.442-16.117) were independent predictors of post-chemotherapeutic relapse. In addition, the persistent presence of post-chemotherapeutic CTCs strongly correlated with reduced disease-free survival and overall survival. Accuracy of detecting relapse in post-chemotherapeutic stage III colon cancer patients by analysing the persistent presence of post-chemotherapeutic CTCs was higher than that by post-chemotherapeutic CEA levels (odds ratio: 50.091 vs 5.211). CONCLUSION: The persistent presence of post-chemotherapeutic CTCs is a potential powerful surrogate marker for determining clinical outcome in stage III colon cancer patients receiving adjuvant mFOLFOX chemotherapy.

Anomalous line shape of the cross section for e{+}e{-}--> hadrons in the center-of-mass energy region between 3.650 and 3.872 GeV.

We observe an obvious anomalous line shape of the e;{+}e;{-}--> hadrons total cross sections in the energy region between 3.700 and 3.872 GeV. It is inconsistent with the explanation for only one simple psi(3770) resonance with a statistical significance of 7sigma. The anomalous line shape may be explained by two possible enhancements of the inclusive hadron production near the center-of-mass energies of 3.764 and 3.779 GeV, indicating that either there is likely a new structure in addition to the psi(3770) resonance around 3.773 GeV, or there are some physics effects reflecting the DD[over ] production dynamics.

Search for the invisible decay of J/psi in psi(2S) --> pi(+)pi(-) J/psi.

Using psi(2S) --> pi(+)pi(-) J/psi events in a sample of 14.0 x 10(6) psi(2S) decays collected with the BES-II detector, a search for the decay of the J/psi to invisible final states is performed. No signal is found, and an upper limit at the 90% confidence level is determined to be 1.2 x 10(-2) for the ratio B(J/psi --> invisible)/B(J/psi-->mu(+)mu(-)). This is the first search for J/psi decays to invisible final states.

Observation of Y(2175) in J/psi --> etaphif0 (980).

The decays of J/psi --> etaphif(0)(980)[eta --> gammagamma, phi --> K(+) K(-), f(0)(980) --> pi(+)pi(-)] are analyzed using a sample of 5.8 x 10(7) J/psi events collected with the BESII detector at the Beijing Electron-Positron Collider. A structure at around 2.18 GeV/c(2) with about 5 sigma significance is observed in the phif(0)(980) invariant mass spectrum. A fit with a Breit-Wigner function gives the peak mass and width of m = 2.186+/-0.010(stat)+/-0.006(syst) GeV/c(2) and Gamma = 0.065+/-0.023(stat)+/-0.017(syst) GeV/c(2), respectively, which are consistent with those of Y(2175), observed by the BABAR Collaboration in the initial-state radiation process e(+)e(-) --> gamma(ISR) phif(0)(980). The production branching ratio is determined to be Br(J/psi --> etaY(2175))Br(Y(2175)- -> phif(0)(980))Br(f(0)(980) --> pi(+)pi(-)) = [3.23+/-0.75(stat)+/-0.73(syst)] x 10(-4), assuming that the Y(2175) is a 1(--) state.

Measurement of psi2S radiative decays.

Using 14 x 10(6) psi(2S) events accumulated at the BESII detector, we report first measurements of branching fractions or upper limits for psi(2S) decays into gammapp, gamma2(pi+pi-), gammaKS0K+pi-+c.c., gammaK+K-pi+pi-, gammaK*0K-pi++c.c., gammaK*0K*0, gammapi+pi-pp, gamma2(K+K-), gamma3(pi+pi-), and gamma2(pi+pi-)K+K- with the invariant mass of hadrons below 2.9 GeV/c2. We also report branching fractions of psi(2S) decays into 2(pi+pi-)pi0, omegapi+pi-, omegaf2(1270), b1+/-pi-/+, and pi02(pi+pi-)K+K-.

Activation of the c-myc p1 promoter in Burkitt's lymphoma by the hs3 immunoglobulin heavy-chain gene enhancer.

The expression of c-myc is deregulated in Burkitt's lymphoma by the translocation t(8;14). Most of the increased c-myc expression is from the P1 promoter, which is normally a minor promoter. How the P1 promoter is activated by the immunoglobulin heavy chain gene enhancers is not understood. We identified a YY1 site in the immunoglobulin heavy-chain gene HS3 enhancer, which increased c-myc P1 promoter activity, and a MARE site, which decreased c-myc P1 activity. Small Maf proteins bound to the MARE site both in vitro and in vivo, recruited histone deacetylase 2, and resulted in deacetylation of histones H3 and H4 at the c-myc promoter region. In contrast, YY1 recruited CBP and increased histone acetylation at the c-myc promoter. Rb interacts with YY1 to prevent DNA binding in normal B cells, but no significant interaction with YY1 was detected in Burkitt's cells, and binding of YY1 to the HS3 enhancer was observed by chromatin immunoprecipitaton. Increased expression of MafK and/or decreased expression of YY1 by silencing RNA downregulated endogenous c-myc mRNA levels and increased the sensitivity of the cells to doxorubicin. Mutation of the major active sites (nuclear factor-kappa B and YY1) in the enhancers prevented c-myc activation.