Chemical Constituents of Ajuga Lupulina and their Anti-Ferroptosis Activity.

Five new compounds (1, 2, 7, 12, and 16), along with fifteen known ones, were isolated from Ajuga lupulina Maxim. Their structures were revealed by analysing spectroscopic data (MS, NMR), and experimental and calculated ECD spectra was used to deduce the absolute configuration. Compound 16, with eight carbon atoms, was firstly isolated from the nature. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis in HT22 mouse hippocampal neuronal cells. Among them, the abietane-type diterpenoids (7-11) significantly inhibited ferroptosis with EC50 values of 0.83 µM, 2.05 µM, 0.96 µM, 1.47 µM, and 1.19 µM, respectively.

Identification of a novel lymphangiogenesis signature associated with immune cell infiltration in colorectal cancer based on bioinformatics analysis.

BACKGROUND: Lymphangiogenesis plays an important role in tumor progression and is significantly associated with tumor immune infiltration. However, the role and mechanisms of lymphangiogenesis in colorectal cancer (CRC) are still unknown. Thus, the objective is to identify the lymphangiogenesis-related genes associated with immune infiltration and investigation of their prognosis value. METHODS: mRNA expression profiles and corresponding clinical information of CRC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The lymphangiogenesis-related genes (LymRGs) were collected from the Molecular Signatures database (MSigDB). Lymphangiogenesis score (LymScore) and immune cell infiltrating levels were quantified using ssGSEA. LymScore) and immune cell infiltrating levels-related hub genes were identified using weighted gene co-expression network analysis (WGCNA). Univariate Cox and LASSO regression analyses were performed to identify the prognostic gene signature and construct a risk model. Furthermore, a predictive nomogram was constructed based on the independent risk factor generated from a multivariate Cox model. RESULTS: A total of 1076 LymScore and immune cell infiltrating levels-related hub genes from three key modules were identified by WGCNA. Lymscore is positively associated with natural killer cells as well as regulator T cells infiltrating. These modular genes were enriched in extracellular matrix and structure, collagen fibril organization, cell-substrate adhesion, etc. NUMBL, TSPAN11, PHF21A, PDGFRA, ZNF385A, and RIMKLB were eventually identified as the prognostic gene signature in CRC. And patients were divided into high-risk and low-risk groups based on the median risk score, the patients in the high-risk group indicated poor survival and were predisposed to metastasis and advanced stages. NUMBL and PHF21A were upregulated but PDGFRA was downregulated in tumor samples compared with normal samples in the Human Protein Atlas (HPA) database. CONCLUSION: Our finding highlights the critical role of lymphangiogenesis in CRC progression and metastasis and provides a novel gene signature for CRC and novel therapeutic strategies for anti-lymphangiogenic therapies in CRC.

Identification of Key Prognostic Alternative Splicing Events of Costimulatory Molecule-Related Genes in Colon Cancer.

OBJECTIVE: This study aimed to explore the key alternative splicing events in costimulatory molecule-related genes in colon cancer and to determine their correlation with prognosis. METHODS: Gene expression RNA-sequencing data, clinical data, and SpliceSeq data of colon cancer were obtained from The Cancer Genome Atlas. Differentially expressed alternative splicing events in genes were identified, Followed by correlation analysis of genes corresponding to differentially expressed alternative splicing events with costimulatory molecule-related genes. Survival analysis was conducted using differentially expressed alternative splicing events in these genes and a prognostic model was constructed. Functional enrichment, proteinprotein interaction network, and splicing factor analyses were performed. RESULTS: In total, 6504 differentially expressed alternative splicing events in 3949 genes were identified between tumor and normal tissues. Correlation analysis revealed 3499 differentially expressed alternative splicing events in 2168 costimulatory molecule-related genes. Moreover, 328 differentially expressed alternative splicing events in 288 costimulatory molecule-related genes were associated with overall survival. The prognostic models constructed using these showed considerable power in predicting survival. The ubiquitin A-52 residue ribosomal protein fusion product 1 and ribosomal protein S9 were the hub nodes in the protein-protein interaction network. Furthermore, one splicing factor, splicing factor proline and glutamine-rich, was significantly associated with patient prognosis. Four splicing factor-alternative splicing pairs were obtained from four alternative splicing events in three genes: TBC1 domain family member 8 B, complement factor H, and mitochondrial fission 1. CONCLUSION: The identified differentially expressed alternative splicing events of costimulatory molecule-related genes may be used to predict patient prognosis and immunotherapy responses in colon cancer.

Discovery and optimization of olanzapine derivatives as new ferroptosis inhibitors.

Ferroptosis is a new type of cell death associated with many human diseases. It is a new strategy to discover ferroptosis inhibitors for the treatment of ferroptosis-related diseases. Here the FDA-approved drug library containing 1160 molecules was screened for ferroptosis inhibitors in RSL3-induced HT22 mouse hippocampal neuronal cells. As a result, olanzapine showed potent ferroptosis inhibitory activity (EC50 = 1.18 µM). Structural optimization and the structure-activity relationships (SARs) analysis led to the synthesis of 41 new derivatives (4-44) and one known compound 45. Comparing with olanzapine, its derivative 36 showed nearly sixteen-folds improved ferroptosis inhibition and low cytotoxicity (EC50 = 0.074 µM, CC50 = 18.8 µM). Further mechanistic studies revealed that compound 36 specifically inhibited ferroptosis by its antioxidative ability. This work demonstrates that olanzapine protected RSL3-induced ferroptosis in HT22 cell, and its derivative 36 having nanomolar ferroptosis inhibitory activity merit to be developed for drugs against ferroptosis-related neurological diseases.

Chemical constituents of Ajuga forrestii and their anti-ferroptosis activity.

Six new neoclerodane diterpenoids (1-6), along with ten known compounds (7-16), were isolated from Ajuga forrestii. Their structures were elucidated by HRESIMS, 1D and 2D NMR, ECD calculation, and single-crystal X-ray diffraction analysis. The structure of a known neoclerodane diterpene ajudecunoid C (6) was revised based on the reported NMR empirical rules. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis in HT22 mouse hippocampal neuronal cells. Among them, compounds 8, 9, and 12 significantly inhibited RSL3-induced ferroptosis with EC50 values of 0.45 µM, 0.076 µM, and 0.14 µM.

Multipattern Mining Using Pattern-Level Contrastive Learning and Multipattern Activation Map.

Visual patterns are basic elements in images and represent the discernible regularity in the visual world. Thus, mining visual patterns is a fundamental task in computer vision. Most previous studies consider that only one visual pattern exists in a category, and then builds up a one-to-one mapping using category label. In reality, however, many categories include multiple patterns, which are many-to-one mappings. Without knowing the information of patterns, few existing pattern mining methods can discover and distinguish varied patterns in a category. To tackle this problem, we propose a novel framework, PaclMap, which learns medium-grained features to represent patterns. It includes an unsupervised pattern-level contrastive learning and a multipattern activation map. Their joint optimization encourages the network to mine both discriminative and frequent patterns in a category. Extensive experiments conducted on four benchmark datasets (Place-20, imagenet large scale visual recognition challenge (ILSVRC)-20, visual object classes (VOC), and Travel) demonstrate that PaclMap outperforms six state-of-the-art methods with average improvements of 2.9% on accuracy and 12.3% on frequency, respectively.

Carbon Nanotube Based Radio Frequency Transistors for K-Band Amplifiers.

Owing to the combination of high carrier mobility and saturation velocity, low intrinsic capacitance, and excellent stability, the carbon nanotube (CNT) has been considered as a perfect semiconductor to construct radio frequency (RF) field-effect transistors (FETs) and circuits with an ultrahigh frequency band. However, the reported CNT RF FETs usually exhibited poor real performance indicated by the as-measured maximum oscillation frequency (fmax), and then the amplifiers, which are the most important and fundamental RF circuits, suffered from a low power gain and a low frequency band. In this work, we build RF transistors on solution-derived randomly orientated CNT films with improved quality and uniformity. The randomly orientated CNT film FETs exhibit the record as-measured maximum fmax of 90 GHz, demonstrating the potential for over 28 GHz (at least one-third of 90 GHz) 5G mmWave (frequency range 2) applications. Benefiting from the large-scale uniformity of CNT films, FETs are designed and fabricated with a large channel width to present low internal resistance for the standard 50 Ω impedance matching guide line, which is critical to construct an RF amplifier. Furthermore, we first demonstrate amplifiers with a maximum power gain up to 11 dB and output third-order intercept point (OIP3) of 15 dBm, both at the K-band, which represents the record of a CNT amplifier and is even comparable with a commercial amplifier based on III-V RF transistors.

Strengthened Complementary Metal-Oxide-Semiconductor Logic for Small-Band-Gap Semiconductor-Based High-Performance and Low-Power Application.

Silicon-based complementary metal-oxide-semiconductor (CMOS) has been the mainstream logic style for modern digital integrated circuits (ICs) for decades but will meet its performance limits soon. Extensive investigations have thus been carried out using other semiconductors, especially those with extremely high carrier mobility. However, these materials usually have small or even zero band gap, which leads inevitably to large leakage current or voltage loss in ICs based on these semiconductors. In this work, we propose and demonstrate a strengthened CMOS (SCMOS) logic style using modified field-effect transistors (FETs) to solve this problem, that is, to achieve high performance, utilizing the high carrier mobility in these materials, and to reduce the current leakage resulting from their small band gap. Conventional CMOS FETs are modified to have an asymmetric structure where an additional assistant gate is introduced near the drain to further lower the potential barrier in on-state and to increase the barrier in off-state. SCMOS ICs are constructed using these modified asymmetric CMOS FETs, which demonstrate perfect rail-to-rail output with negligible voltage loss and 3 orders of magnitude suppression of the static power consumption and an operating speed similar to or even higher than that of CMOS ICs. Here, SCMOS is demonstrated using carbon nanotubes, but, in principle, this logic style can be used in ICs based on any small-band-gap semiconductors to provide simultaneously high performance and low power consumption.

Aligned, high-density semiconducting carbon nanotube arrays for high-performance electronics.

Single-walled carbon nanotubes (CNTs) may enable the fabrication of integrated circuits smaller than 10 nanometers, but this would require scalable production of dense and electronically pure semiconducting nanotube arrays on wafers. We developed a multiple dispersion and sorting process that resulted in extremely high semiconducting purity and a dimension-limited self-alignment (DLSA) procedure for preparing well-aligned CNT arrays (within alignment of 9 degrees) with a tunable density of 100 to 200 CNTs per micrometer on a 10-centimeter silicon wafer. Top-gate field-effect transistors (FETs) fabricated on the CNT array show better performance than that of commercial silicon metal oxide-semiconductor FETs with similar gate length, in particular an on-state current of 1.3 milliamperes per micrometer and a recorded transconductance of 0.9 millisiemens per micrometer for a power supply of 1 volt, while maintaining a low room-temperature subthreshold swing of <90 millivolts per decade using an ionic-liquid gate. Batch-fabricated top-gate five-stage ring oscillators exhibited a highest maximum oscillating frequency of >8 gigahertz.

Probiotics maintain the intestinal microbiome homeostasis of the sailors during a long sea voyage.

The challenging conditions encountered during long sea voyages increase the risk of health-threatening physiological and psychological stress for sailors compared with land-based workers. However, how the intestinal microbiota responds to a long sea voyage and whether there is a feasible approach for protecting gut health during sea voyage are still unexplored. Here, we designed a 30-d longitudinal study including a placebo group (n = 42) and a probiotic group (n = 40) and used shotgun metagenomic sequencing to explore the impacts of sea voyage on the intestinal microbiome of sailors. By comparing the intestinal microbiome of subjects in the placebo group at baseline (d 0) and at the end of the sea voyage (d 30), we observed an alteration in the intestinal microbiome during the long sea voyage based on the microbial structure; the results revealed an increase in the species Streptococcus gordonii and Klebsiella pneumoniae as well as a decrease in some functional features. However, the change in the microbial structure of sailors in the probiotic group between d 0 and d 30 was limited, which indicated a maintenance effect of probiotics on intestinal microbiome homeostasis. At the metagenomic strain level, a generally positive correlation was observed between probiotics and the strains belonging to Bifidobacterium longum and Bifidobacterium animalis, whereas a common negative correlation was observed between probiotics and Clostridium leptum; this result revealed the potential mechanism of maintaining intestinal microbiome homeostasis by probiotics. The present study provided a feasible approach for protecting gut health during a long sea voyage.

Carbon Nanotube Film-Based Radio Frequency Transistors with Maximum Oscillation Frequency above 100 GHz.

Carbon nanotubes (CNTs) have been considered a preferred channel material for constructing high-performance radio frequency (RF) transistors with outstanding current gain cutoff frequency (fT) and power gain cutoff frequency (fmax) but the highest reported fmax is only 70 GHz. Here, we explore how good RF transistors based on solution-derived randomly oriented semiconducting CNT films, which are the most mature CNT materials for scalable fabrication of transistors and integrated circuits, can be achieved. Owing to the significantly reduced number of CNT/CNT junctions obtained by scaling the channel length down to below 100 nm, we realized RF field-effect transistors (FETs) with maximum transconductance Gm up to 0.38 mS/µm, which is the record among CNT-based RF FETs. After de-embedding the pad-induced capacitances and resistances, the CNT FETs with different gate lengths (Lg) exhibit fT as high as 103 GHz (intrinsically 281 GHz) or fmax up to 107 GHz (intrinsically 190 GHz), which are the records among CNT-based RF FETs. In particular, the CNT FETs with an Lg of 50 nm present pad de-embedding fT of 86 GHz and fmax of 85 GHz, and represent the best CNT RF transistor in terms of comprehensive performance to date. To demonstrate the actual high-speed and scalable fabrication of our CNT RF FETs, we fabricated CNT FET-based five-stage ring oscillators with oscillation frequencies above 5 GHz.

Long-term follow-up of children with acute promyelocytic leukemia treated with Beijing Children's Hospital APL 2005 protocol (BCH-APL 2005).

We studied the outcomes of children with APL treated by the Beijing Children's Hospital's (BCH) acute promyelocytic leukemia (APL) 2005 protocol (BCH-APL2005). The clinical data of 77 patients enrolled from January 2005 to June 2015 were analyzed retrospectively. The hematologic complete remission (CR) rate and overall survival (OS) rate were evaluated between standard-risk (SR) and high-risk (HR) groups. Prognostic factors and complications were investigated in these two groups. CR in the SR and HR groups was 96.4% (54/56) and 85.7% (18/21), respectively, while the 10-year OS was 94.6% (53/56) and 76.2% (16/21), respectively. The cumulative incidence of early death was 6.5% (5/77), and the SR and HR groups were 1.8% (1/56) and 19.0% (4/21), respectively. Only two patients relapsed, and the relapse rate was 2.6% (2/77). According to Kaplan-Meier analysis, the SR group had a significantly better long-term survival than HR counterparts (p= .016). Initial leukocyte count was the only prognostic factor (p= .016) by univariate analysis, while other factors, such as FLT3-ITD and platelet count, had no correlation with prognosis. In addition, early deaths were mainly due to intracranial hemorrhage. Although the combination of all-trans retinoic acid (ATRA) and chemotherapy can improve the outcome of APL patients, the early deaths and anthracycline-related cardiac toxicity were relatively higher in our study. Current efforts focus on reducing or even avoiding chemotherapy in APL children and rest on the frontline regimen of intravenous arsenic trioxide or oral realgar-indigo naturalis formula plus ATRA, which is the direction for APL treatment.

Coupling Between Interleukin-1R1 and Necrosome Complex Involves in Hemin-Induced Neuronal Necroptosis After Intracranial Hemorrhage.

Background and Purpose- Accumulated evidence suggests that hemin-a breakdown product of hemoglobin-plays a pivotal role in the inflammatory injuries that result after hemorrhagic stroke through the Toll Like Receptor 2-Toll Like Receptor 4 signal pathway. However, the mechanism of how hemin triggers neuronal necroptosis directly after intracranial hemorrhage (ICH) is still an area of active research. As animal model and preclinical studies have shown, the recombinant interleukin-1 receptor antagonist (IL-1RA) improves clinical outcomes after stroke. As such, we have chosen to investigate the mechanism of how IL-1RA exerts protective effect in hemin-induced neuronal necroptosis after ICH. Methods- Our ICH model was induced by hemin injection in C57BL/6 mice and IL-1R1-/- mice. In addition, we used primary cultured neurons to assess hemin-induced cell death. Co-immunoprecipitation, immunoblot, immunofluorescent staining, neurological deficit scores, and brain water content were used to study the mechanisms of IL-1R1 modulation in neuronal necroptosis both in vitro and in vivo. Results- Free hemin could mediate neuronal necroptosis directly by assembling necrosome complex and then to trigger cell death. This phenomenon was driven by IL-1R1 as IL-1R1 can form a complex with necrosome. After treatment with IL-1RA, both the expression and translocation of the necrosome decreased while disruption of the interaction between IL-1R1 and RIP1/RIP3 (receptor interacting protein 1/3) increased neuron survival. In addition, the IL-1R1-deficient mice demonstrated lower levels of necrosome components, including RIP1, RIP3, and MLKL (mixed lineage kinase domain-like protein), compared with control groups after hemin treatment. In addition, the neurological deficit scores, brain water content, and inflammatory response were all also reduced in the IL-1R1-deficient mice. Conclusions- Functional inhibition of the interaction between IL-1R1 and the necrosome complex improves neuron survival and promotes the recovery of neurological function in experimental ICH. Targeting IL-1R1/RIP1/RIP3 assembly could be a promising therapeutic strategy for patients with ICH.

Characterizing pollutant emissions from mosquito repellents incenses and implications in risk assessment of human health.

Mosquito-repellent incense is one of the most popular products used for dispelling mosquitos during summer in China. It releases large amounts of particulate and gaseous pollutants which constitute a potential hazard to human health. We conducted chamber experiment to characterize major pollutants from three types of mosquito-repellent incenses, further assessed the size-fractionated deposition in human respiratory system, and evaluated the indoor removing efficiency by fresh air. Results showed that the released pollutant concentrations were greater than permissible levels in regulations in GB3095-2012, as well as suggested by the World Health Organization (WHO). Formaldehyde accounted for 10-20% of the total amount of pollutants. Fine particles dominated in the total particulate concentrations. Geometric standard deviation (GSD) of particle number size distributions was in the range of 1.45-1.93. Count median diameter (CMD) ranged from 100 to 500 nm. Emission rates, burning rates and emission factors of both particulate and gaseous pollutants were compared and discussed. The deposition fractions in pulmonary airway from the disc solid types reached up to 52.7% of the total deposition, and the largest deposition appeared on juvenile group. Computational Fluid Dynamics (CFD) modellings indicated air-conditioner on and windows closed was the worst case. The highest concentration was 180-200 times over the standard limit.

[Establishment of pelvic nerve denervation modal in mice].

OBJECTIVE: To establishment and verify pelvic nerve denervation (PND) model in mice. METHODS: (1) Establishment of models. Seventy-two healthy male SPE class C57 mice with age of 7 weeks and body weight of (25±1) g were chosen. These 72 mice were randomly divided into PND group containing 36 mice and sham operation group containing 36 mice. Referring to the establishment method of PND rats, after anesthesia, a laparotomy was performed on the mouse with an abdominal median incision. Under the dissection microscope, the pelvic nerves behind and after each sides of the prostate gland were bluntly separated with cotton swabs and cut with a dissecting scissor. After the operation, the urination of mice was assisted twice every day. For the mice of sham operation group, the pelvic nerves were only exposed without cutting. (2) Detection of models. Colonic transit test was performed in 18 mice chosen randomly from each group to detect the colonic transit ratio (colored colon by methylene blue/ whole colon) and visceral sensitivity tests was performed in the rest mice to observe and record the changes of electromyogram. RESULTS: Three mice died of colonic transit test in each group. Uroschesis occurred in all the mice of PND group and needed bladder massage to assist the urination. Colonic transit test showed that the colonic transit ratios of sham operation group at postoperative day (POD) 1, 3 and 7 were (0.4950±0.3858)%, (0.6386±0.1293)% and (0.6470±0.1088)% without significant difference (F=0.3647, P=0.058), while in PND group, the colonic transit ratio at POD 7 [(0.6044±0.1768) %] was obviously higher than that both at POD 3[(0.3876±0.1364)%, P=0.022] and POD 1[(0.2542±0.0371)%, P=0.001], indicating a recovery trend of colonic transit function (F=9.143, P=0.004). Compared with the sham operation group, the colonic transit function in PND group decreased significantly at POD 1 and POD 3(both P<0.05), and at POD 7, there was no significant difference between two groups. Visceral sensitivity test showed that the visceral sensitivity of sham operation group at POD 1, 3 and 7 was 24.2808±9.5566, 33.6725±7.9548 and 43.9086±12.1875 with significant difference (F=5.722, P=0.014). The visceral sensitivity of PND group at POD 1, 3 and 7 was 11.7609±2.1049, 21.8415±8.1527 and 26.2310±4.2235 with significant difference as well (F=11.154, P=0.001). The visceral sensitivity at POD 3 and POD 7 was obviously higher than that at POD 1 (P=0.006, P<0.001), and there was no significant difference between POD 3 and POD 7 (P=0.183). Compared with sham operation group, the visceral sensitivity of PND group decreased significantly at POD 1, 3 and 7(all P<0.05). CONCLUSIONS: Denervation of pelvic nerves can obviously decrease the colonic transit function and the visceral sensitivity of mice, but these changes can recover over time, which suggests that the establishment of PND model in mice is successful.

Expression of transient receptor potential ankyrin 1 correlating to the recovery of colonic transit after pelvic nerve denervation in rats.

BACKGROUND: It has been reported that colorectal motility dysfunction due to pelvic nerve (PN) damage is restored overtime. However, the adaptive mechanism is unknown. Previous studies implied that transient receptor potential ankyrin 1 (TRPA1) mediated sensory nerve signal input plays a crucial role in gut motility regulation. The present study aimed to observe the colorectal motility restoration in rats after PN transection and to explore the change of TRPA1 protein expression in this adaptive process. METHODS: Seventy-eight adult rats were divided into two groups randomly: sham and PN cut. Colonic transit function was determined with radioisotope method by calculating the geometric center (GC) of the distribution of 51Cr at postoperative days (POD) 1, 3, and 7. Expression of TRPA1 in the proximal and distal colon mucosa was detected with Western blotting at POD 1, 3, and 7. RESULTS: At POD 1, the colonic transit in PN cut group was significantly delayed (GC = 4.91 ± 0.41, P < 0.05), when compared with the sham group (GC = 5.76 ± 0.85). A significant trend toward recovery was noted in the PN cut group at POD 3 (GC = 5.58 ± 0.36) and POD 7 (GC = 6.44 ± 0.78). Western blot demonstrated attenuated expression of TRPA1 in the distal colon mucosa after PN denervation at POD 1 (0.39 ± 0.12) compared with that of the shams. A significant trend of increasing expression of TRPA1 was demonstrated in the PN cut group at POD 3 (0.78 ± 0.10) and at POD 7 (1.06 ± 0.13). CONCLUSIONS: Delayed colonic motility due to PN denervation gradually restored overtime, which may relate to the corresponding expression of TRPA1 in the distal colonic mucosa of rats.

[Clinical Characteristics and Treatment Efficacy of Children with SIL/TAL1 Positive T-Cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the clinical features, treatment and prognosis of children with SIL-TAL1 fusion gene positive T-cell acute lymphoblastic leukemia (T-ALL). METHODS: The data of 101 children with T-ALL were collected from April 2005 to November 2012 in Beijing Children's Hospital. The common clinical features, early treatment response, minimal residual disease (MRD), event-free survival (EFS) and relapse-free survival (RFS) were compared between children with SIL-TAL1 positive and negative T-ALL. The treatment efficacy in children with SIL-TAL1 positive T-ALL was compared between BCH-2003 and CCLG-2008 protocol. RESULTS: Out of 101 cases, 22 cases (21.9%) of T-ALL carried SIL-TAL1 fusion gene. The distribution of sex, age, response to prednisone and central nervous system (CNS) involvement were no significant different at diagnosis between SIL-TAL1 positive and negetive patients. However, the WBC count in SIL-TAL1 positive cases were significantly higher than that of SIL-TAL1 negative cases at diagnosis (P<0.05). Additionally, MRD levels were not significantly different between children with SIL-TAL1 positive or negative T-ALL at 3 time points including: after the remission induction therapy, before delayed intensive therapy II and before maintenance therapy. However, the number of cases with high MRD levels before consolidation therapy were more in SIL-TAL1 positive group than that in SIL-TAL1 negative group (P<0.05). The cases with high MRD levels before delayed intensive therapy I was more in SIL-TAL1 negative group than that in the SIL-TAL1 positive group (P>0.05). Besides, there were no significant differences in 5-year EFS and RFS between the two groups. The risk of 22 children with SIL-TAL1 positive acute T-ALL was again stratified according to the typing stemdard in CCLG-2008 protocol, as a result, the risk in BCH-2003 group (10 cases) was significantly higher than that in BCH-2008 group (12 cases) (P<0.05), but no significant difference was found in common clinical features, early treatment response, MRD levels and treatment efficacy. CONCLUSIONS: Although WBC level was significantly higher in SIL-TAL1 positive group than that in SIL-TAL1 negative group, the treatment efficacy in SIL-TAL1 positive group was similar to SIL-TAL1 negative group. Meanwhile, the children with SIL-TAL1+ T-ALL may respond poorly to early intensive therapy, the BCH-2003 protocol may be more suitable for the patients with this subtype of leukemia.

[Predictive value of CA125 in peritoneal metastasis and prognosis of patients with gastric carcinoma].

OBJECTIVE: To investigate the predictive value of serum CA125 in peritoneal metastasis, and to examine the association of CA125 with the prognosis. METHODS: Clinical data of 1285 gastric cancer patients admitted to the Qilu Hospital from March 2003 to September 2008 were retrospectively reviewed. The sensitivity, specificity and accuracy of serum CA125 for peritoneal metastasis were analyzed. Clinicopathological characteristics and survival were compared between patients with normal serum CA125 level(≤35 µg/L) and patients with elevated serum CA125 level(>35 µg/L). RESULTS: The specificity, sensitivity and accuracy of serum CA125 for peritoneal metastasis were 96.0%, 13.8% and 81.2%, respectively. A significantly higher incidence of peritoneal metastasis was observed in the patients with elevated serum CA125 level as compared to those with normal serum CA125 level(43.2% vs. 16.5%). CA125 was an independent predictor of peritoneal metastasis(RR=3.475, 95% CI:2.124-5.685). The 5-year overall survival rate in patients with elevated serum CA125 level was 13.5%, which was significantly lower than that of patients with normal serum CA125 level (49.8%, P<0.01). CA125 was an independent prognostic factor of gastric cancers(HR=2.049, 95%CI:1.355-2.873). CONCLUSION: Serum CA125 is useful in predicting peritoneal metastasis and prognosis of gastric cancer, which should be used as a routine examination of gastric cancer patients.

[Comparison of the efficacy of two chemotherapy protocols for children with TEL-AML1[STBZ] fusion gene positive acute lymphoblastic leukemia].

This study was aimed to compare the curative effect of BCH - 2003 protocol and CCLG - 2008 protocol for children with TEL-AML1 fusion gene positive childhood acute lymphoblastic leukemia (ALL) and to investigate the more suitable protocol for this subtype of childhood leukemia. The clinical data for children with TEL-AML1 fusion gene positive ALL admitted from January 2003 to October 2010 in Hematology Center of Beijing Children's Hospital were collected. The common clinical characteristics including prednisone response at day 8, minimal residual disease (MRD) at the end of induction of remission (day 33), event free survival (EFS), relapse free survival (RFS) were compared. The results showed that out of 204 children with TEL-AML1 fusion gene positive ALL, 134 and 70 patients were treated by BCH-2003 protocol and CCLG-2008 protocol respectively. There were no statistical difference in age, white blood cell count in peripheral blood at presentation, prednisone response and CNS involvement. However, there were more boys in CCLG-2008 group (P = 0.025). The negative rate of MRD at day 33 in BCH-2003 group was lower than that in CCLG-2008 group (P = 0.013). After re-stratifying the patients in CCLG-2008 group according to the stratification criteria of BCH-2003 protocol, the negative rate of MRD at day 33 of patients with intermediate risk remained higher in BCH-2003 group than that in CCLG-2008 group (P = 0.014) . However, no significant difference in the patients with standard risk was found. There were also no significant statistical differences in the incidence of severe infection, EFS and RFS, (P = 1.000, P = 0.327,P = 0.251 respectively) during chemotherapy. It is concluded that for children with TEL-AML1 fusion gene positive ALL, the induction of remission of BCH - 2003 protocol can decrease leukemic load more quickly than that of CCLG - 2008 protocol. However, the outcome of the patients treated by the two protocols is similar.

[Evaluation of the efficacy of two successive protocols on pediatric acute lymphoblastic leukemia with E2A-PBX1 fusion gene].

OBJECTIVE: To evaluate the efficacy of BCH-03 and CCLG-08 protocols in treating E2A-PBX1 pediatric acute lymphoblastic leukemia (ALL). METHOD: From January 2003 to January 2011, 59 ALL patients identified as E2A-PBX1 were analyzed in a retrospective study. There were 37 and 22 patients treated with Protocol BCH-03 and CCLG-08, respectively. The clinical characteristics at diagnosis, response to early treatment, the time of relapse, relapse-free survival (RFS) and event-free survival (EFS) in the two groups were analyzed. RESULT: There were no significant differences in gender, age, initial white blood cell count, the central nervous system involvement, immunophenotype, prednisone response, the rate of complete remission, and the time of relapse between the two groups (P > 0.05). The only difference in induction therapy of the two protocols existed in the glucocorticoids used, that is, BCH-03 used 60 mg/m(2) prednisolone and CCLG-08 used 6 mg/m(2) dexamethasone. The doses of vincristine, daunorubicin and L-asparaginase were the same in the two groups. At the end of induction therapy, the MRD negativity rate in BCH-03 group was significantly higher than that in CCLG-08 group (84.2% vs. 47.1%, P = 0.018). The incidences of severe infection of the two groups during induction of remission were similar (P = 0.135). The EFS of BCH-03 group was significantly superior to that of CCLG-08 group (94.5% vs. 71.5%, P = 0.010), and the RFS of BCH-03 group tended to be better than that of CCLG-08 group (94.5% vs. 78.6%, P = 0.059). CONCLUSION: Compared to Protocol CCLG-08, Protocol BCH-03 was more effective for pediatric E2A-PBX1 ALL, and 60 mg/m(2) prednisolone was more suitable for the induction therapy of this subtype of pediatric ALL.