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SHR0302, as a novel Janus kinase (JAK) inhibitor 1, is used for treatment of rheumatoid arthritis (RA) in humans. A novel and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for determining the concentration of SHR0302 in human plasma. A precipitation deproteinization method was used for plasma pretreatment with methanol. Detection was carried out on an Agilent 1,260 UPLC coupled with a Triple Quad 4000 mass spectrometer operated in positive multiple reaction monitoring mode, and the analytes were separated on a Synergi Polar-RP C 18 (50 × 2.0 mm, 4 μm, Phenomenex) analytical column with gradient elution of 0.1% formic acid, and 2 mmol/l ammonium acetate in water and 0.1% formic acid and 2 mmol/l ammonium acetate in methanol, The selected ion transitions were m/z 415.2 → 258.2 and m/z 398.2 → 258.2 for SHR0302 and SHR143181 (internal standard), respectively. A full validation, including selectivity, linearity, carryover, precision, accuracy, recovery, matrix effect, dilution integrity and stability, was carried out in human plasma. It was successfully applied to a pharmacokinetic study in Chinese healthy subjects after oral administration of SHR0302 tablet., (© 2022 John Wiley & Sons Ltd.)

Background: Estimating the growth of pulmonary sub-solid nodules (SSNs) is crucial to the successful management of them during follow-up periods. The purpose of this study is to (1) investigate the measurement sensitivity of diameter, volume, and mass of SSNs for identifying growth and (2) seek to establish a deep learning-based model to predict the growth of SSNs., Methods: A total of 2,523 patients underwent at least 2-year examination records retrospectively collected with sub-solid nodules. A total of 2,358 patients with 3,120 SSNs from the NLST dataset were randomly divided into training and validation sets. Patients from the Yibicom Health Management Center and Guangdong Provincial People's Hospital were collected as an external test set (165 patients with 213 SSN). Trained models based on LUNA16 and Lndb19 datasets were employed to automatically obtain the diameter, volume, and mass of SSNs. Then, the increase rate in measurements between cancer and non-cancer groups was studied to evaluate the most appropriate way to identify growth-associated lung cancer. Further, according to the selected measurement, all SSNs were classified into two groups: growth and non-growth. Based on the data, the deep learning-based model (SiamModel) and radiomics model were developed and verified., Results: The double time of diameter, volume, and mass were 711 vs. 963 days (P = 0.20), 552 vs. 621 days (P = 0.04) and 488 vs. 623 days (P< 0.001) in the cancer and non-cancer groups, respectively. Our proposed SiamModel performed better than the radiomics model in both the NLST validation set and external test set, with an AUC of 0.858 (95% CI 0.786-0.921) and 0.760 (95% CI 0.646-0.857) in the validation set and 0.862 (95% CI 0.789-0.927) and 0.681 (95% CI 0.506-0.841) in the external test set, respectively. Furthermore, our SiamModel could use the data from first-time CT to predict the growth of SSNs, with an AUC of 0.855 (95% CI 0.793-0.908) in the NLST validation set and 0.821 (95% CI 0.725-0.904) in the external test set., Conclusion: Mass increase rate can reflect more sensitively the growth of SSNs associated with lung cancer than diameter and volume increase rates. A deep learning-based model has a great potential to predict the growth of SSNs., Competing Interests: XY, YW, RL, HHY, JL, SL, BJ, SD, QN, WZ are employed by Guangdong Provincial People’s Hospital. BL is employed by South China University of Technology. Authors AL, JW, JF and HL are employed by Guangzhou Shiyuan Electronics Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Li, Yan, Lin, Liu, Wang, Fang, Liu, Hou, Song, Yang, Li, Jiang, Dong, Nie, Zhong, Wu and Yang.)

Niacin is indispensable for the growth and development of aquatic animals. However, the correlations between dietary niacin supplementations and the intermediary metabolism of crustaceans are still poorly elucidated. This study explored the effects of different dietary niacin levels on the growth, feed utilization, energy sensing, and glycolipid metabolism of oriental river prawn Macrobrachium nipponense . Prawns were fed with different experimental diets containing graded niacin levels (15.75, 37.62, 56.62, 97.78, 176.32, and 339.28 mg/kg, respectively) for 8 weeks. Weight gain, protein efficiency, feed intake, and hepatopancreas niacin contents all maximized in the 176.32 mg/kg group with significance noted with the control group ( P  <0.05), whereas the opposite was true for feed conversion ratio. Hepatopancreas niacin concentrations increased significantly ( P < 0.05) as dietary niacin levels increased, and peaked at the 339.28 mg/kg group. Hemolymph glucose, total cholesterol, and triglyceride concentrations all maximized in the 37.62 mg/kg group, while total protein concentration reached the highest value in the 176.32 mg/kg group. The hepatopancreas mRNA expression of AMP-activated protein kinase α and sirtuin 1 peaked at the 97.78 and 56.62 mg/kg group, respectively, and then both decreased as dietary niacin levels increased furtherly ( P < 0.05). Hepatopancreas transcriptions of the genes related to glucose transportation, glycolysis, glycogenesis, and lipogenesis all increased with increasing niacin levels up to 176.32 mg/kg, but decreased significantly ( P < 0.05) as dietary niacin levels increased furtherly. However, the transcriptions of the genes related to gluconeogenesis and fatty acid β -oxidation all decreased significantly ( P < 0.05) as dietary niacin levels increased. Collectively, the optimum dietary niacin demand of oriental river prawn is 168.01-169.08 mg/kg. In addition, appropriate doses of niacin promoted the energy-sensing capability and glycolipid metabolism of this species., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Jing-Wen Wang et al.)

Fragrances have many biological activities such as anti-anxiety, anti-depression, and improving cognitive memory. However, most fragrances are so volatile that the useful lifespan of the fragrances is very short and excessive fragrance concentration makes us uncomfortable. In this study, dual pH and temperature-sensitive nanogels named EG@CPMONGs were prepared to encapsulate eugenol. This nano-fragrance was then applied to silk. In the following, the effects of EG@CPMO-NGs on the regulation of central nervous systems were evaluated. Open-field tests showed that EG@CPMONGs had an obvious effect on stress relief. Elevated plus-maze tests proved the significant effect of EG@CPMO-NGs on anti-anxiety. Morris water maze tests demonstrated the positive impact of nano-fragrance on spatial learning and memory. Therefore, these dual pH and temperature-sensitive nanogels loaded with eugenol had significant and positive effects on the central nervous system.

Quercetin, a naturally occurring flavonoid, is mainly extracted from tea, onions, and apples. It has the underlying neuroprotective effect on experimental ischemic stroke. A systematic review and meta-analysis were used to assess quercetin's efficacy and possible mechanisms in treating focal cerebral ischemia. Compared with the control group, twelve studies reported a remarkable function of quercetin in improving the neurological function score (NFS) ( P < 0.05), and twelve studies reported a significant effect on reducing infarct volume ( P < 0.05). Moreover, two and three studies showed that quercetin could alleviate blood-brain barrier (BBB) permeability and brain water content, respectively. The mechanisms of quercetin against focal cerebral ischemia are diverse, involving antioxidation, antiapoptotic, anti-inflammation, and calcium overload reduction. On the whole, the present study suggested that quercetin can exert a protective effect on experimental ischemic stroke. Although the effect size may be overestimated because of the quality of studies and possible publication bias, these results indicated that quercetin might be a promising neuroprotective agent for human ischemic stroke. This study is registered with PROSPERO, number CRD 42021275656., Competing Interests: The authors claim that the present study was conducted without any business or financial relationships that could be interpreted as potential conflicts of interest., (Copyright © 2022 Chao Guo et al.)

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288., (© 2022 by The American Society of Hematology.)

Purpose: Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo., Methods: We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated., Results: The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models., Conclusion: ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Xu et al.)

Background: The drug therapy of venous thromboembolism (VTE) presents a significant economic burden to the health-care system in low- and middle-income countries. To understand which anticoagulation therapy is most cost-effective for clinical decision-making , the cost-effectiveness of apixaban (API) versus rivaroxaban (RIV), dabigatran (DAB), and low molecular weight heparin (LMWH), followed by vitamin K antagonist (VKA), in the treatment of VTE in China was assessed. Methods: To access the quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs), a long-term cost-effectiveness analysis was constructed using a Markov model with 5 health states. The Markov model was developed using patient data collected from the Xijing Hospital from January 1, 2016 to January 1, 2021. The time horizon was set at 30 years, and a 6-month cycle length was used in the model. Costs and ICERs were reported in 2020 U.S. dollars. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were used to test the uncertainties. A Chinese health-care system perspective was used. Results: In the base case, the data of 231 VTE patients were calculated in the base case analysis retrospectively. The RIV group resulted in a mean VTE attributable to 95% effective treatment. API, DAB, and VKA have a negative ICER (-187017.543, -284,674.922, and -9,283.339, respectively) and were absolutely dominated. The Markov model results confirmed this observation. The ICER of the API and RIV was negative (-216176.977), which belongs to the absolute inferiority scheme, and the ICER value of the DAB and VKA versus RIV was positive (110,577.872 and 836,846.343). Since the ICER of DAB and VKA exceeds the threshold, RIV therapy was likely to be the best choice for the treatment of VTE within the acceptable threshold range. The results of the sensitivity analysis revealed that the model output varied mostly with the cost in the DAB on-treatment therapy. In a probabilistic sensitivity analysis of 1,000 patients for 30 years, RIV has 100% probability of being cost-effective compared with other regimens when the WTP is $10973 per QALY. When WTP exceeded $148,000, DAB was more cost-effective than RIV. Conclusions: Compared with LMWH + VKA and API, the results proved that RIV may be the most cost-effective treatment for VTE patients in China. Our findings could be helpful for physicians in clinical decision-making to select the appropriate treatment option for VTE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sun, Cui, Cao, Huang, Xia, Wang, Wang, Yu and Ding.)

Background: High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia., Methods: This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 10 9 platelets per L or a platelet count of less than 50 × 10 9 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 10 9 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed., Findings: Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths., Interpretation: The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety., Funding: The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P&lt;0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P&lt;0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P&lt;0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P&lt;0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P&lt;0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P&lt;0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P&lt;0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P&lt;0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.

The hypomethylation of the Cyclin D1 (CCND1) promoter induced by excess oxidative stress likely promotes the development of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). We aimed to evaluate methylation status of the CCND1 promoter as a new plasma marker for the detection of HBV-HCC.We consecutively recruited 191 participants, including 105 patients with HBV-HCC, 54 patients with chronic hepatitis B (CHB), and 32 healthy controls (HCs). Using methylation-specific polymerase chain reaction, we identified the methylation status of the CCND1 promoter in plasma samples. We analyzed the expression levels of the CCND1 mRNA in peripheral blood mononuclear cells by using quantitative real-time PCR. We assessed the plasma levels of superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde by using enzyme-linked immunosorbent assays.Patients with HBV-HCC (23.81%) presented a reduced methylation frequency compared with patients with CHB (64.81%) or HCs (78.13%) (P < .001). When receiver operating characteristic curves were plotted for patients with HBV-HCC versus CHB, the methylation status of the CCND1 promoter yielded diagnostic parameter values for the area under the curve of 0.705, sensitivity of 76.19%, and specificity of 64.81%, thus outperforming serum alpha-fetoprotein (AFP), which had an area under the curve of 0.531, sensitivity of 36.19%, and specificity of 90.74%. Methylation of the CCND1 promoter represents a prospective diagnostic marker for patients with AFP-negative HBV-HCC and AFP-positive CHB. The expression levels of CCND1 mRNA was increased in patients with HBV-HCC compared with patients with CHB (Z = -4.946, P < .001) and HCs (Z = -6.819, P < .001). Both the extent of oxidative injury and antioxidant capacity indicated by the superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde levels were increased in patients with HBV-HCC. Clinical follow up of patients with HBV-HCC revealed a worse overall survival (P = .012, log-rank test) and a decreased progression-free survival (HR = 0.109, 95%CI: 0.031-0.384) for the unmethylated CCND1 group than methylated CCND1 group.Our study confirms that oxidative stress appears to correlate with plasma levels of CCND1 promoter methylation, and the methylation status of the CCND1 promoter represents a prospective biomarker with better diagnostic performance than serum AFP levels.

Metasequoia glyptostroboides is a living fossil and an endangered species listed in the International Union for Conservation of Nature (IUCN). Distinguishing the genotypes of all wild individuals of M. glyptostroboides is important to delimit management units and key germplasm resources. We characterized 28 novel polymorphic microsatellite loci using a streptavidin-biotin microsatellite-enriched library and Illumina high-throughput sequencing. Characteristics of each locus were tested using 140 individuals collected from five natural populations of M. glyptostroboides. The number of alleles per locus ranged from 3 to 20, with a mean number of about 8 alleles. The observed and expected heterozygosities in each population ranged from 0.0000 to 1.0000 and from 0.0000 to 0.8958, respectively. Four to nine loci were cross-amplified successfully in seven species of Cupressaceae. The novel SSR markers will provide a toolkit for DNA identification of all of the extant wild individuals guiding further conservation efforts of M. glyptostroboides.

To evaluate the clinical efficacy and safety of tripterygium glycosides (TG) in the treatment of henoch-schonlein purpura nephritis(HSPN). Seven English and Chinese databases (up to Nov. 9, 2017), were searched to collect the RCTs on TG for HSPN. Two researchers independently screened the literature according to inclusion criteria and exclusion criteria, extracted data, and evaluated the quality of the literature. After completion, cross-checking was performed and Meta-analysis was performed using RevMan 5.3 software. At the same time, different outcomes of the interventions were analyzed subgroupically. A total of 46 RCTs were included, with 1 659 in the experimental group and 1 596 in the control group. All the clinical studies showed a low quality. In terms of complete remission rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.82，95%CI[1.39，2.39];RR=2.03，95%CI[1.37，2.99]），the group with TG+GC performed better than the group with GC（RR=1.46，95%CI[1.32，1.60]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.35，95%CI[0.16，0.75]）. In terms of total effective rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.44，95%CI[1.19,1.74];RR=1.30，95%CI[1.16，1.46]），the group with TG+GC performed better than the group with GC（RR=1.27，95%CI[1.21，1.34]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.60，95%CI[0.43，0.85]）. No significant difference was found between the group with TG+GC and LEF+GC（RR=0.68，95%CI[0.30，1.53]）. In terms of urinary protein, urine occult blood negative time，the group with TG performed better than the group with conventional therapy（MD=-9.00，95% CI[-11.99，-6.01];MD=-12.00，95%CI[-16.13，-7.87]），the group with TG+GC performed better than the group with GC（MD=-8.86，95%CI[-10.08，-7.64];MD=-16.24，95%CI[-23.80，-8.67]）. In terms of recurrence rate, the group with TG+GC was lower than the group with GC（RR=0.13，95%CI[0.06，0.25]）, but there were no significant difference between the group with TG and conventional therapy（RR=0.43，95%CI[0.15，1.19]）. In adverse reactions, the common adverse effects of TG were gastrointestinal discomfort, liver damage and leucopenia. TG for the treatment of HSPN can improve clinical efficacy, reduce recurrence, and the adverse reactions are relatively safe. Due to the generally low methodological quality of the included studies, which affected the accuracy and reliability of the result. Therefore, more high-quality, large samples and multi-center randomized controlled trials are necessary for further evidence., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The organometallic cation 1 (Fe(bipy-NH 2 ) 3 2+ , bipy-NH 2 = 4,4'-diamino-2,2'-bipyridine), which was constructed in situ in solution, can bind CO 2 from air effectively with a stoichiometric ratio of 1:4 (1/CO 2 ), through the formation of "H-bonded CO 2 " species: [CO 2 -OH-CO 2 ] - and [CO 2 -CO 2 -OH] - . These two species, along with the captured individual CO 2 molecules, connected 1 into a novel 3D (three-dimensional) architecture, that was crystal 1·2(OH - )·4(CO 2 ). The adsorption isotherms, recycling investigations, and the heat capacity of 1 have been investigated; the results revealed that the organometallic cation 1 can be recycled at least 10 times for the real-world CO 2 capture applications. The strategies presented here may provide new hints for the development of new alkanolamine-related absorbents or technologies for CO 2 capture and sequestration.

Objective: To summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China., Methods: The factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression., Results: The immune type of t(8;21) AML patients was mainly with HLA-DR + , CD117 + , CD34 + , MPO + , CD38 + , CD13 + and CD33 + (>95%), part of them with CD19 + and CD56 + ; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×10 9 /L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×10 9 /L(P<0.05)., Conclusion: The clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×10 9 /L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.

Objective: To investigate the changes of hepcidin and ferropotin 1 expression in murine model of iron overload., Methods: The murine model of iron overload was established, C57BL/6 mice were injected with iron dextran intraperitoneally (10 mg) every 3 days for 4 weeks. Blood routine, serum ferritin and pathological sections were tested at the appointed time-point respectively (before iron injection, 2 weeks and 4 weeks after treatment of iron injection). The serum hepcidin was assayed by enzyme-linked immunosorbent method. The expression of ferroportin 1 in bone marrow cells was detected by RT-PCR and Western blot, respectively. The labile iron pool of bone marrow cells was measured by flow cytometry., Results: The absolute number and percentage of reticulocytes in the iron-overloaded mice were significantly decreased along with the increase of iron injection times (r=-0.938, r=-0.947), while no significant change was found in the number of white blood cells, hemoglobin level and platelet count. The level of serum ferritin was increased along with increase of iron injection time (r=0.894). Iron overload was found in pathological sections of different organs. Furthermore, serum hepcidin was increased along with increase of iron injection time (r=0.957). RT-PCR and Western blot analyses showed that the expressions of ferroportin 1 at mRNA and protein level were increased in the murine model of iron overload (P<0.05). Labile iron pool in bone marrow cells was also found to be increased in the murine model of iron overload(P<0.05)., Conclusion: The expressions of hepcidin and ferroportin 1 are increase in a murine model of iron overload, which may be contributed to the suppression effect on erythropoiesis in bone marrow.

ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) is the α-secretase that is involved in APP (β-amyloid precursor protein) processing. Enhancement of the nonamyloidogenic APP pathway by ADAM10 provides therapeutic potential for Alzheimer's disease (AD). By using high-throughput screening that targeted ADAM10, we determined that apicidin-an inhibitor of HDACs (histone deacetylases)-significantly increased mRNA and protein levels of ADAM10 in SH-SY5Y cells. A luciferase assay revealed that the nucleotides -444 to -300 in the ADAM10 promoter were sufficient to mediate this effect. In addition, knockdown of USF1 (upstream transcription factor 1) and HDAC2/3 prevented apicidin regulation of ADAM10. Moreover, USF1 acetylation was increased by apicidin, which enhanced the association of USF1 with HDAC2/3 and with the ADAM10 promoter. We further found that apicidin did not affect the phosphorylation of ERK or USF1; however, ERK inhibitor U0126 blocked the effect of apicidin on ADAM10. Finally, apicidin increased the level of α-site C-terminal fragment from APP and reduced the production of β-amyloid peptide 1-42. Collectively, our study provides evidence that ADAM10 expression can be regulated by HDAC2/3 inhibitor apicidin via USF1-dependent mechanisms in which ERK signaling plays an important role. Thus, HDAC regulation of ADAM10 might shed new light on the understanding of AD pathology.-Hu, X.-T., Zhu, B.-L., Zhao, L.-G., Wang, J.-W., Liu, L., Lai, Y.-J., He, L., Deng, X.-J., Chen, G.-J. Histone deacetylase inhibitor apicidin increases expression of the α-secretase ADAM10 through transcription factor USF1-mediated mechanisms., (© FASEB.)

Objective: To investigate the ability of Anopheles stephensi at different ages to transmit Plasmodium berghei and elucidate the possible mechanisms., Methods: To study and compare the susceptability of A. stephensi of different ages to P. berghei, 4-day and 25-day female A. stephensi were fed with P. berghei infected BALB/c mouse blood with parasitaemia 4%-8%. At 8 days after infection, the mosquitoes were dissected and the number of intestinal Plasmodium oocysts was counted under microscope. Difference in the susceptability to Plasmodium infection was analyzed between the two age groups. To study the intestinal bacteria load in A. stephensi, LB plate culture was used to detect the intestinal bacteria in the mosquitoes of the two groups before infection, and real-time quantitative PCR (qPCR) was performed to check the culturable bacteria and the total bacteria load. The expression levels of major immune response effectors cecropin（CEC1, CEC3）, defensin (DEF), gambicin (GAM), attacin (ATT), nitric oxide synthase (NOS), dual oxidase (DUOX), and thioester protein 1（TEP1） in 4-day and 25-day mosquitoes were determined by qPCR., Results: At 8 days after infection, the median of oocyst number in 4-day mosquitoes was 139, which was nearly 46 times of that in 25-day mosquitoes (median, 3)（P<0.01）. There was a significant difference in the intestinal bacteria load between 4-day and 25-day mosquitoes. The results of qPCR showed that the total bacteria load in 25-day mosquitoes was 1.5 times of that in 4-day mosquitoes (P<0.05). By LB plate culture, proliferation of 28 889 colony forming units (cfu) bacteria was found for 25-day mosquitoes, which was 9 times of that for 4-day mosquitoes（3 200 cfu）（P<0.05）. In addition, the NOS expression level in 25-day mosquitoes was 2.4 times of that in 4-day mosquitoes (P<0.01）, while the expression levels of antimicrobiota peptides ATT, DEF, CEC3, and CEC1 in 25-day mosquitoes were only 27%, 48%, 14%, and 61% of those in 4-day mosquitoes, respectively (P<0.05). The expression levels of GAM, DUOX, TEP1 showed no difference between the two groups., Conclusion: The antimicrobiota peptides in A. stephensi are significantly downregulated with age increase, together with increased intestinal bacteria load and NOS expression, resulting in enhanced resistance to Plasmodium.

Aim: To investigate the correlation between the Helicobacter pylori (H. pylori) infection and host genetic background of healthy populations in Indonesia., Methods: In March 2007, epidemiological studies were undertaken on the general population of a city in Indonesia (Mataram, Lombok). The participants included 107 men and 187 women, whose ages ranged from 6 to 74 years old, with an average age of 34.0 (± 14.4) (± SD). The H. pylori of subject by UBT method determination, and through the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method parsing the single nucleotide polymorphism of interleukin (IL)-8, IL-4, IL-1β, CD14, tumor necrosis factor (TNF-α) and tyrosine-protein phosphates non-receptor type 11 (PTPN11) genotypes. The experimental data were analyzed by the statistical software SAS., Results: The H. pylori infection rates in the healthy Indonesian population studied were 8.4% for men and 12.8% for women; no obvious differences were noted for H. pylori infection rates by sex or age. TC genotypes of IL-4, TC and CC genotypes of TNF-α, and GA genotypes of PTPN11, were higher in frequency. Both CC and TC genotype of TNF-α T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of (OR = 1.99; 95%CI: 0.67-5.89) and (OR = 1.66; 95%CI: 0.73-3.76), respectively. C allele of IL-1β T-31C gene locus was at a higher risk (OR = 1.11; 95%CI: 0.70-1.73) of H. pylori infection, but no statistical significance was found in our study., Conclusion: We reveal that the association between the TNF-α and IL-1β genotypes may be the susceptibility of H. pylori in the studied population.

Objective: To evaluate the clinical features, therapies and prognosis in patients with mucosa-associated lymphoid tissue (MALT) lymphoma in ocular adnexal marginal zone (OAML)., Methods: A retrospective analysis was made upon clinical data from 21 patients with OAML admitted into Beijing Tongren Hospital from June, 2008 to December, 2011., Results: There were 12 (57.1%) men and 9 (42.9%) women, with a median age of 57 (23 - 79) years old. Majority of patients had localized pathological changes. Among them, 16 patients (76.2%) were in stage IE, and 5 (23.8%) in stage IVE. Surgical resection as the sole treatment was performed in 13 patients (61.9%), and positron emission tomography CT(PET-CT) imaging demonstrated normal fluorine 18-fluorodeoxyglucose (FDG) uptake after surgical resection, who were managed with no further therapy. All the 13 patients were followed up for median 14 (5 - 38) months, and all in complete remission. Combination chemotherapy was given to 8 (38.1%) patients. Three patients in stage IE treated with COP (cyclophosphamide, vincristine and prednisone) or CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) were all in partial remission. Five patients in stage IVE were treated with COP/CHOP in combination with rituximab, and all in complete remission. The 3-year overall survival rate and disease-free survival rate in the total patients were 100.0% and 74.9% respectively., Conclusions: The patients with OAML generally have localized disease, show indolent clinical course, and present low lymphoma-related mortality. Surgical resection is a very important treatment in the patients with local disease. Systemic chemotherapy should be considered in patients at advanced stages. Rituximab in combination with chemotherapy can improve the remission rate.

The aim of this study was to analyze the efficacy of first-line chemotherapy in treating patients with ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Eight consecutive newly diagnosed ocular adnexal MALT lymphoma patients were treated with chemotherapy, in which 3 patients in stage IE were treated with a combination of cyclophosphamide, vincristine and prednisolone (COP) or cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP), 5 patients in stage IV were treated with COP/CHOP in combination with rituximab. The results showed that chemotherapy resulted in an overall response rate of 100%, 3 patients in stage IE were in partial remission (PR), 5 patients in stage IV were in complete remission (CR). After a median follow-up of 21 months, 3 patients in stage IE were still in PR status, 5 patients in stage IV were still in CR status, and no relapses or disease progression were observed. It is concluded that the first-line chemotherapy has been confirmed to be effective and well tolerated in patients with localized ocular adnexal MALT lymphoma. Rituximab combined with chemotherapy can increase remission rate, it is feasible option as first-line treatment for ocular adnexal MALT lymphoma.

Objective: This study aimed to investigate Chinese medical interns' cancer knowledge and associated factors, focusing on cancer screening., Methods: A questionnaire survey was conducted in ten leading Chinese medical schools from June to July in 2011. Medical interns were invited to fill the questionnaire., Results: Out of the 1350 copies sent, 1135 eligible responses were returned. Around 50% of interns had positive attitude toward oncology, but the knowledge score was low, particularly in screening. The percentages of scores were 44.8% (8.95/20) for overall and only 29.6% (2.07/7) for screening. The majority of internship length in oncology department was eight to fourteen days. Screening and prevention was ranked as third most taught, following diagnosis and treatment. Multivariate analysis showed that positive attitude to oncology correlated with positive self-evaluated overall (OR = 1.76, 95% CI (1.45, 2.12)) and screening (OR = 1.62, 95% CI (1.35, 1.95)) competence, but unexpectedly predicted lower screening score (OR = 0.77, 95% CI (0.61, 0.97)). Interns with positive self-evaluated screening competence were not found to possess higher cancer screening knowledge., Conclusion: Current medical education in Chinese medical schools fails to equip interns with optimal cancer knowledge, particularly in screening, even in interns who hold positive view to oncology. Interns' self-evaluated competence is not proportional to their knowledge scores.

In order to investigate the effect of anti-TGF-beta1 monoclonal antibody on the expansion of cord blood CD34(+) cells, the purified cord blood CD34(+) cells were divided into three groups: blank control group: purified cord blood CD34(+) cells cultured on day 0; control group: cells cultured for 3 days in the culture system, containing SCF, IL-3, IL-6 and FLT3-L; test group: cells cultured for 3 days in the same culture system as control group, but with anti-TGF-beta1 monoclonal antibody. The mononuclear cell counting (MNC), the expression of CD34 and c-kit, and CFU-GEMM, BFU-E and CFU-GM counting were detected in all three groups. The result showed that the expansion of MNCs, CD34(+) cells and CD34(+)c-kit(+) cells in test group [(2.35 +/- 0.25) x 10(5), (1.16 +/- 0.29) x 10(5), (1.09 +/- 0.26) x 10(5)] was significantly higher than that in control group [(1.25 +/- 0.13) x 10(5), (0.55 +/- 0.19) x 10(5), (0.51 +/- 0.2) x 10(5)](p < 0.01). The expansion of more primitive CD34(+)c-kit(-) subpopulation in test group [(12.95 +/- 3.17) x 10(3)] was even significantly higher than in control group (1.71 +/- 0.83) x 10(3) (p < 0.01). Colony forming assay showed that the number of earlier progenitor colony CFU-GEMM, BFU-E in test group [(16.3 +/- 4.72) x 10(3), (60.5 +/- 20.96) x 10(3)] was higher than that in control group [(5.0 +/- 2.58) x 10(3), (16.25 +/- 7.93) x 10(3)] (p < 0.01). The number of relatively mature CFU-GM between test group and control group was not statistical significance [(6.33 +/- 2.85) x 10(3) vs (4.0 +/- 2.28) x 10(3)](p > 0.05), but both were higher than that in blank group (0.75 +/- 0.29) x 10(3). These results demonstrated that anti-TGF-beta1 monoclonal antibody promoted the expansion of MNC and CD34(+) cells, and even more marked expansion of the more primitive progenitor cells-CD34(+)c-kit(-) cells. Meanwhile, it enhanced the output of more immature colony CFU-GEMM and BFU-E, but had no evident influence on the mature myeloid colony CFU-GM. It is concluded that the anti-TGF-beta1 monoclonal antibody can synergize other cytokines to enhance the proliferation of cord blood CD34(+) progenitor cells effectively, and it is more important that can reserve more primitive progenitor cells.

Understanding the physiopathology of affective disorders and their treatment relies on the availability of experimental models that accurately mimic aspects of the disease. Here we describe a mouse model of an anxiety/depressive-like state induced by chronic corticosterone treatment. Furthermore, chronic antidepressant treatment reversed the behavioral dysfunctions and the inhibition of hippocampal neurogenesis induced by corticosterone treatment. In corticosterone-treated mice where hippocampal neurogenesis is abolished by X-irradiation, the efficacy of fluoxetine is blocked in some, but not all, behavioral paradigms, suggesting both neurogenesis-dependent and -independent mechanisms of antidepressant action. Finally, we identified a number of candidate genes, the expression of which is decreased by chronic corticosterone and normalized by chronic fluoxetine treatment selectively in the hypothalamus. Importantly, mice deficient in one of these genes, beta-arrestin 2, displayed a reduced response to fluoxetine in multiple tasks, suggesting that beta-arrestin signaling is necessary for the antidepressant effects of fluoxetine.

Aim: To explore the effects of different concentrations of lactate on neuronal injury during hypoxia/reoxygenation (H/R) and its mechanism., Methods: Different concentrations of lactate (0, 0.5, 1.0, 2.0, 5.0 mmol/L) were added into medium after different duration of hypoxia, then reoxygenation for 24 h, cell survival rate and LDH release were assayed to determine neuronal damage, moreover, equal concentration of hydrochloric acid were used to mimic the changes of pH brought by lactate for investigating the mechanism of the effects of lactate on neuronal H/R injury., Results: Under normoxia and H/R 5.0 mmol/L lactate and hydrochloric acid induced or exacerbated neuronal injury. After 12 h and 24 h hypoxia exposure 1.0 mmol/L lactate was shown to be protective, 1.0 mmol/L hydrochloric acid had no effect on neuronal H/R damage., Conclusion: Lactate of lower concentration was demonstrated to be neuroprotective during H/R, this protective effect was shown to be due to lactate anions. In contrast, higher concentration of lactate could induce or aggravate neuronal damage under normoxia and H/R, perhaps via the mechanism which involved the changes of pH.

The study was purposed to explore the quantity, morphology and immunophenotype of dendritic cells (DC) acquired by co-cultivated system with 3 types of cytokines and sodium selenite (Se) from peripheral blood mononuclear cells (PBMNCs), and to investigate the effects of Se on inducing the cytotoxic T lymphocyte (CTL) to get specific anti-leukemic activity in vitro by DC pulsed with K562 cell frozen-thawed antigen (antigen cell loading). PBMNCs isolated from healthy donors were cultured in RPMI 1640 medium contained 10% FBS supplied with 3 cytokines (rhGM-CSF, rhIL-4, TNF-alpha) for 4 days, DCs harvested were divided into 4 groups, DCI: DC alone; DCII: DC + Se (adding 0.5 micromol/L of Se); DCIII: DC + K562 (pulsed with lysed K562 cells); DCIV: DC + Se + K562. Morphology of DCs was observed under microscope at day 7. The CD1a, CD40, CD83, and CD86 were detected by FCM. Cytotoxicity of T cells induced by DC were measured with LDH release test at day 12. The level of IL-12 in supernatant of cultured DCs were determined with ELISA. The results indicated that at 7th day DC in 4 groups showed characteristic morphology, the colony numbers of 4 groups were all higher than those before cultivation. There were no obvious differences of morphology and colony counts between DCI group and DCII group. The colony numbers of DCIII group and DCIV group increased, as well as the ratio of suspended cells enhanced. The expressions of CD1a, CD40, CD83 and CD86 in 4 groups of DC were significantly higher than those in PBMNC group (p < 0.01), the expressions of CD1a and CD40 in 4 groups of DC did not display significant difference (p > 0.05), the expressions of CD83 and CD86 in both DCIII group and DCIV group were all higher than those in DCI group and DCII group (p < 0.01), but their expressions of CD83 and CD86 in DCI and DCII were not significantly different (p > 0.05), as well as those in DCIII group and DCIV group. With the ratio of 25:1 between E:T, killing rate of CTL on K562 cells in 4 DC groups were 15.3 +/- 2.3%, 26.3 +/- 3.7%, 28.2 +/- 4.5% and 36.2 +/- 3.7% respectively, all obviously higher than those of T cell group without being sensitized by DCs (5.9 +/- 2.4%) (p < 0.01), The CTL effect in DCIV group was the highest, which was higher than those in other 3 DC groups (p < 0.01); the effects in both DCII and DCIII group were also higher than that in DCI group (p < 0.01), but their difference between DCII and DCIII groups did not show significance (p > 0.05). The levels of IL-12 in supernatant of DCI, DCII, DCIII and DCIV groups were 257.0 +/- 64.2, 328.1 +/- 43.9, 323.0 +/- 53.5 and 353.9 +/- 46.2 pg/ml respectively, all significantly higher than that in supernatant of T cell alone group without being sensitized by DCs (35.27 +/- 27.1 pg/ml) (p < 0.01), The levels in DCII, DCIII and DCIV groups were all higher than that in DCI group (p < 0.01), but their levels between DCII, DCIII and DCIV groups were not of significant difference (p > 0.05). It is concluded that matured DCs can be successfully obtained from PBMNCs by a culture system contained rhGM-CSF, rhIL-4 and TNF-alpha with or without low-dose of Se (0.5 micromol/L) in vitro. Using K562 cell frozen-thawed antigen, DC express more adhesive molecules and co-stimulating molecules (CD83, CD86), and increase the secretion of IL-12, as well as the killing effects of CTL on special target cells. Low dose of Se did not showed effects on quantity and morphology of matured DC harvested, as well as their expression of mature phenotypes, it raised levels of IL-12 secreted by DCs, reaching the same level as using K562 cell frozen-thawed antigen, and it showed synergistic effect on induction of CTL with K562 cell frozen-thawed antigen.

The search for an effective vaccine against toxoplasmosis remains a challenging and elusive goal. Combination of epitopes from different stages of Toxoplasma gondii life cycle is an optimal strategy to overcome the antigen complexity of the parasite. Based on published epitope derived from several promising candidate vaccine antigens, we construct a DNA vaccine encoding multi-epitope of T. gondii and CpG motif, with or without the A2/B subunit of cholera toxin as a genetic adjuvant. The immunity induced by this vaccine in BALB/c mice and the protection afforded against challenge with the highly virulent RH strain of T. gondii is assessed. This vaccine was able to elicit a significant humoral and cellular immune response in vaccinated mice. Furthermore, CTXA2/B as a genetic adjuvant could enhance the magnitude of immune responses as well as increased survival rate in mice infected with the lethal RH tachyzoites. This study is the first report of a multi-epitope DNA construct strategy as a potential DNA vaccine against toxoplasmosis.

Chronic treatments with selective serotonin reuptake inhibitors (SSRIs) have been shown to increase hippocampal neurogenesis. However, it is not known whether SSRIs impact the maturation and functional integration of newborn neurons. Here we examined the effects of subchronic and chronic fluoxetine on the structural and physiological properties of young granule cells. Our results show that doublecortin-positive immature neurons displayed increased dendritic arborization after chronic fluoxetine treatment. In addition, chronic but not subchronic fluoxetine elicited a decrease in the number of newborn neurons expressing immature markers and a corresponding increase in those expressing mature markers. These results suggest that chronic fluoxetine accelerates the maturation of immature neurons. We also investigated the effects of fluoxetine on a form of neurogenesis-dependent long-term potentiation (LTP) in the dentate gyrus. This form of LTP was enhanced by chronic fluoxetine, and ablation of neurogenesis with x-irradiation completely blocked the effects of chronic fluoxetine on LTP. Finally, we demonstrated that the behavioral effect of fluoxetine in the novelty-suppressed feeding test requires chronic administration and is blocked by x-irradiation. These results show that the effects of fluoxetine on LTP and behavior both require neurogenesis and follow a similar delayed time course. The effects of chronic fluoxetine on the maturation and functional properties of young neurons may therefore be necessary for its anxiolytic/antidepressant activity and contribute to its delayed onset of therapeutic efficacy.

Objective: To investigate the incidence of myopic retinopathy and its risk factors., Methods: The fundus of 1449 patients (2879 eyes) with myopia were retrospectively examined. The clinical relationship between myopic retinopathy and diopter, age, and sex was analyzed., Results: Myopic retinopathy was detected in 413 eyes (14.35%). Posterior pole retinal lesions were detected in 22 eyes (0.76%). Peripheral retinal lesions were found in 396 eyes (13.75%). According to their diopters, the myopic patients were divided into four groups: low, medium, high and super high myopia The incidence of peripheral retinal lesions was 4.18%, 8.72%, 19.18%, and 37.44% in these four groups, which significantly different (chi2 = 178.594, P<0.001). By age these patients were divided into three groups: I group, age <25; II group, age 25-34; III group, age >34. The incidences of peripheral retinal lesions in these three groups were 8.11%, 15.34%, and 24.59%, which were significantly different (chi2 = 76.090, P<0.001). The incidence of retinal lesion in male and female was 9.32% and 16.07%, respectively, which was significantly different (chi2 = 24.886, P<0.001). Posteriorpole retinal lesions were only detected in the highly or super highly myopic patients, all of them were more than 25 years. The incidence of posteriorpole retinal lesions in the highly and super highly myopia group was 0.86% and 6.67% respectively, which was significantly different (chi2 = 31.898, P<0.001). The incidence of posteriorpole retinal lesions in group II and group III was 0.55% and 3.55% respectively, which was significantly different (chi2 = 22.523, P<0.001)., Conclusions: The prevalence of retinal lesions in myopic patients is higher than that of emmetropia. The incidence of peripheral retinal lesions increases in patients with deeper diopters. Posterior pole retinal lesions usually occur in the myopic patients whose age are more than 25 years and diopter more than - 6.00 D. Careful examination of fundus is essential for early detection and timely treatment.

Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. In the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning. Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected. These findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions. In a parallel set of experiments, we show that long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures. These data show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.

Plant genomes appear to exploit the process of gene duplication as a primary means of acquiring biochemical and developmental flexibility. The best example is the gene encoding chalcone synthase (CHS, EC2.3.1.74), the first committed step in flavonoid biosynthesis. In this study, we examined the molecular evolution of three CHS family members of Phalaenopsis including a novel chs gene (phchs5), which is slowly evolved. The inferred phylogeny of the chs genes of Phalaenopsis with other two orchid plants, Bromoheadia finlaysoniana and Dendrobium hybrid, suggested that gene duplication and divergence have occurred before divergence of these three genera. Relatively quantitative RT-PCR analysis identified expression patterns of these three chs genes in different floral tissues at different developmental stages. Phchs5 was the most abundantly expressed chs gene in floral organs and it was specifically transcribed in petal and lip at the stages when anthocyanin accumulated (stage1-4). Phchs3 and phchs4 were expressed at much lower levels than phchs5. Phchs3 was expressed in pigmented tissue (including lip, petal and sepal) at middle stages (stages 2-4) and in colorless reproductive tissue at late stage (stage 5). Phchs4 was only expressed in petal at earlier stages (stage 1-3) and in lip at middle stage (stage 4). These results present new data on differentiation of gene expression among duplicate copies of chs genes in Phalaenopsis.

Objective: To compare the therapeutic effects of low-dose and high-dose interferon alpha-2b (IFN) treatment on chronic myelocytic leukemia (CML)., Methods: A real-time quantitative reverse transcriptase PCR (RQ-PCR) method was established to detect the fusion gene bcr-abl expression, thereby studying the reduction of leukemic cells. Thirty newly diagnosed CML patients, 21 males and 9 females, aged 14 - 69, were treated with hydroxyurea to keep the white blood cell count less than 20 x 10(9)/L, and then randomized into 2 groups: high-dose IFN group receiving IFN alpha-2b 5MIU 6 times per week for 3 - 6 months and low-dose IFN group receiving IFN alpha-2b 3MIU every other day for 3 - 6 months. Bone marrow was collected every month to Real-time PCR was used to detect the expression of bcr-abl mRNA. Mononuclear cells were isolated and RNA was extracted to detect the expression of fusion gene bcr-abl and a control gene GAPDH. The results were reported as the number of bcr-abl copies/GAPDH copy., Results: The established real-time quantitative PCR method could detect the bcr-abl molecules as low as 50 copies. The intra-assay coefficient of variation (CV) was less than 5% and the inter-assay CV was 5.13%. The median bcr-abl fusion gene expression level of 30 CML patients before IFN therapy was 0.098 (range: 0.010 - 5.799). The bcr-abl expression level decreased by 19.37% and 24.86% in the low-dose and high-dose IFN groups respectively after 3 months' therapy. No significant difference was observed between the two groups (P = 0.398). Relatively more side effects were observed in the high-dose IFN group than in low-dose group., Conclusion: RQ-PCR is a reliable method to monitor CML therapy by analyzing fusion gene bcr-abl expression. There is a difference in bcr-abl fusion gene expression levels among the newly diagnosed patients, and low-dose IFN is as effective as high-dose IFN in reducing bcr-abl expression but with less side effects.

The study was aimed to explore clinical result of cyclosporin A (CsA) and androgens for treatment of myelodysplastic syndrome (MDS) with refractory anemia. Four cases of MDS-RA were treated with CsA and androgens, while the changes of blood counts, bone marrow and chromosome were observed. The results showed that substantial hematological response was observed in all four patients, that their anemia improved and all transfusion-dependent patients achieved transfusion independence. In conclusion, CsA and Adr therapy was well tolerated. CsA and Adr therapy offer an alternative treatment of MDS with RA. The mechanisms of the benifical effect from this therapy remain the subject of an ongoing study.

Pseudorabies virus glycoprotein E (PRV gE) has been recognized as a suitable diagnostic antigen for pseudorabies. In order to produce gE antigen in large quantities and at low cost, a gene fragment encoding PRV gE epitopes was expressed in Pichia pastoris expression system. SDS-PAGE and Western blotting revealed that the expression product was two recombinant proteins, approximately 38 and 32 kDa, in the culture supernatant of P. pastoris integrant 72 h after induction. Protein concentration assay showed the expression product amounted to 106.7 mg/l, accounting for 66.67% of total culture supernatant proteins. An indirect PRV gE-ELISA was then established by using the recombinant expression product as a coating antigen. Cross-reactivity assay showed that this antigen was PRV specific. Reproducibility experiment displayed good consistency. Comparison of detection results of 348 field serum samples between PRV gE-ELISA and a commercially available PRV diagnostic kit showed there was no significant difference between these two methods (P > 0.05).

Recent studies showed that oxytocin plays an important role in nociceptive modulation in the central nervous system. The present study was undertaken to investigate the role of oxytocin in antinociception in the nucleus raphe magnus (NRM) of rats and the possible interaction between oxytocin and the opioid systems. Intra-NRM injection of oxytocin induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulation in rats. The antinociceptive effect of oxytocin was significantly attenuated by subsequent intra-NRM injection of the oxytocin antagonist 1-deamino-2-D-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. Intra-NRM injection of naloxone dose-dependently antagonized the increased HWLs induced by preceding intra-NRM injection of oxytocin, indicating an involvement of opioid receptors in oxytocin-induced antinociception in the NRM of rats. Furthermore, the antinociceptive effect of oxytocin was dose-dependently attenuated by subsequent intra-NRM injection of the mu-opioid antagonist beta-funaltrexamine (beta-FNA), but not by the kappa-opioid antagonist nor-binaltorphimine (nor-BNI) or the delta-opioid antagonist naltrindole. The results demonstrated that oxytocin plays an antinociceptive role in the NRM of rats through activating the oxytocin receptor. Moreover, mu-opioid receptors, not kappa and delta receptors, are involved in the oxytocin-induced antinociception in the NRM of rats.

The present study investigated the role of calcitonin gene-related peptide (CGRP) in the modulation of nociception in periaqueductal grey (PAG) of rats. Hindpaw withdrawal latencies (HWLs) were tested by hot-plate and Randall Selitto tests. The HWLs to thermal and mechanical stimulation increased significantly after intra-PAG administration of 0.26 or 0.13 nmol of CGRP, but not 0.026 nmol of CGRP. The anti-nociceptive effects induced by CGRP were significantly blocked by intra-PAG administration of 0.026 or 0.26 nmol of the CGRP1 receptor antagonist CGRP8-37. Furthermore, administration of CGRP into the decussation of superior cerebellar peduncle, out of PAG, did not elicit anti-nociceptive effects during 60 min after the injection. The results demonstrated that CGRP plays an important role in anti-nociception in PAG of rats, and CGRP1 receptor is involved in the CGRP-induced anti-nociception.

The p74 gene of Autographa californica multicasid nucleopolyhedrovirus (AcMNPV) bacmid was knockouted and substituted by the p74 gene of Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV), using RecA-mediated homologous recombination in the E. coli. No selection marker, which might influence the expression and function of p74 gene, was left in the modified p74 locus. The promoter of AcMNPV p74 gene directly controlled the expression of SpltMNPV p74 gene in the recombinant AcMNPV bacmid-polhSL74. RT-PCR showed that the substituted p74 gene was transcribed. Bioassay showed that the recombinant virus AcMNPV bacmid-polhSL74 could not infect the Argyrogramma agnata larvae per os, and thus showing the p74 gene is species-specific.

Objective: To analyze the relationship between Helicobacter pylori (Hp) in oral cavity and the Hp infection in stomach., Methods: 102 patients with gastric Hp infection and periodontitis were enrolled in this study. DNA was extracted from subgingival plaques, mouthwashes and stomach mucosa samples by using the glass-milk (SiO2) purification method. To identify the presence of Hp in these samples, PCR (polymerase chain reaction) was carried out, and two pairs of oligonucleotide primer were used to amplify a portion of gene urease C and gene cag A of Hp., Results: The rate of Hp detected in oral cavity was significantly higher in patients with positive Hp in stomach (43.1%, n=58) than in those with negative Hp in stomach (22.7%, n=44, P<0.05). After the treatment for gastric Hp infection for 4 weeks, the eradication rate of Hp in stomach was lower, but only slightly in patients with positive oral Hp (16/25, 64%) than in those with negative oral Hp (24/33, 72.7%). However, this difference became apparent (36.0% vs 63.6%, P<0.05) after one year of the treatment., Conclusions: The effectiveness of the eradication therapy for gastric Hp infection is affected by the presence of Hp in oral cavity. Oral colonization of Hp may imply that there is a risk of the relapses of gastric and duodenal Hp infection and ulcer after the antibiotics treatment for the eradication of Hp.