Cone Beam Computed Tomography in observing the presence and location of canalis sinuosus.

OBJECTIVE: Cone Beam Computed Tomography (CBCT) was used to observe and describe the distribution of canalis sinuosus (CS) in the Chinese population and the location of CS in the maxillary alveolar bone, so as to help oral surgeons evaluate the intraoperative risk and prognosis before maxillary surgery and reduce the complications caused by the injury of this structure in anterior surgery. PATIENTS AND METHODS: CBCT images of 600 patients admitted from 2021 to 2022 were collected to observe the anatomical structure of CS in the maxillary region. The following parameters were recorded: age, sex, number of CS, left and right distribution of CS, CS diameter, and location. Statistical analysis was performed on all of the collected data. RESULTS: The discovery rate of CS in this study was 59.75%, and it is commonly found in the lateral incisor area (64.82%). No significant difference can be found in the presence and number of CS in different gender and age groups (p>0.05). CONCLUSIONS: The use of high-resolution CBCT before implantation is of irreplaceable significance in the diagnosis and analysis of CS, which is conducive to reducing implantation complications and failure rate. The incidence of CS was independent of age or sex, while the location of CS was statistically significant.

Source apportionment and ozone formation mechanism of VOCs considering photochemical loss in Guangzhou, China.

Understanding the sources and impact of volatile organic compounds (VOCs) on ozone formation is challenging when the traditional method does not account for their photochemical loss. In this study, online monitoring of 56 VOCs was carried out in summer and autumn during high ozone pollution episodes. The photochemical age method was used to evaluate the atmospheric chemical loss of VOCs and to analyze the effects on characteristics, sources, and ozone formation of VOC components. The initial concentrations during daytime were 5.12 ppbv and 4.49 ppbv higher than the observed concentrations in the summer and autumn, respectively. The positive matrix factorization (PMF) model identified 5 major emission sources. However, the omission of the chemical loss of VOCs led to underestimating the contributions of sources associated with highly reactive VOC components, such as those produced by biogenic emissions and solvent usage. Conversely it resulted in overestimating the contributions from VOC components with lower chemical activity such as liquefied petroleum gas (LPG) usage, vehicle emissions, and gasoline evaporation. Furthermore, the estimation of ozone formation may be underestimated when the atmospheric photochemical loss is not taken into account. The ozone formation potential (OFP) method and propylene-equivalent concentration method both underestimated ozone formation by 53.24 ppbv and 47.25 ppbc, respectively, in the summer, and by 40.34 ppbv and 26.37 ppbc, respectively, in the autumn. The determination of the ozone formation regime based on VOC chemical loss was more acceptable. In the summer, the ozone formation regime changed from the VOC-limited regime to the VOC-NOx transition regime, while in the autumn, the ozone formation regime changed from the strong VOC-limited regime to the weak VOC-limited regime. To obtain more thorough and precise conclusions, further monitoring and analysis studies will be conducted in the near future on a wider variety of VOC species such as oxygenated VOCs (OVOCs).

[Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia].

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.

[Analysis of vaginal microecology in 23 181 cases of the gynecological female outpatients].

Objective: To analyze the vaginal microecological status of vaginitis population and non-vaginitis population of gynecological female outpatients. Methods: A total of 30 265 women who visited the gynecological outpatient clinic of Beijing Obstetrics and Gynecology Hospital from December 2018 to December 2020 completed vaginal microecological examination. After removing the follow-up patients, 23 181 women were divided into group with symptoms and signs of vaginitis (6 697 cases) and group without symptoms and signs of vaginitis (16 484 cases), according to whether the women with symptoms and signs of vaginitis or not. And the vaginal microecological status of the two groups was compared and analyzed. Results: (1) The total detection rate of vaginitis in the initial women was 34.87% (8 083/23 181), of which 46.10% (3 087/6 697) in group with symptoms and signs of vaginitis and 30.31% (4 996/16 484) in group without symptoms and signs of vaginitis, nearly 1/3 of the gynecological outpatients without signs and symptoms of vaginitis had vaginitis. (2) Among the types of simple vaginitis, vulvovaginal candidiasis (VVC) was the most frequent in group with symptoms and signs of vaginitis (16.01%, 1 072/6 697), followed by aerobic vaginitis (AV; 12.83%, 859/6 697), with significant differences compared with group without symptoms and signs of vaginitis (all P<0.001). There were no statistical differences between the two groups of bacterial vaginosis (BV) and trichomonal vaginitis (TV), indicating that BV and TV were more likely to be neglected (all P>0.05). (3) The proportion of various combinations of vaginitis among 2 632 cases of mixed vaginitis were, in descending order: BV+AV, VVC+AV, BV+AV+VVC, AV+TV, AV+TV+BV, BV+VVC. (4) Microecological analysis of 15 098 cases diagnosed with non-vaginitis had normal flora (including those with normal flora and those with normal flora but decreased function) in 14 013 cases (92.81%, 14 013/15 098), abnormal flora in 429 cases (2.84%, 429/15 098) and the BV intermediate in 656 cases (4.34%, 656/15 098); this indicated that the vast majority of the microecological tests were normal in the vaginal microbiota of those without vaginitis. Conclusions: Microecological examination could diagnose multiple pathogenic infections at once, and is especially important as a guide for the definitive diagnosis of mixed vaginitis and vaginitis with atypical clinical symptoms. Vaginal infections such as BV and TV that are easily overlooked should be concerned.

[GNB2L1 gene expression and clinical value in hepatocellular carcinoma based on bioinformatics].

Objective: To analyze guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1) expression based on bioinformatics, so as to evaluate its role and its relationship with survival rate during the occurrence and development of hepatocellular carcinoma. Methods: GEPIA, UALCAN and HPA databases were used to analyze the expression level of GNB2L1 and its relationship with HCC survival rate. Mutations in the GNB2L1 gene and their impact on survival were analyzed using the cBioPortal database. LinkedOmics database was used to analyze GNB2L1-related genes in HCC. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed simultaneously. STEING database was used to construct the GNB2L1 protein interaction network. TIMER database was used to analyze the relationship between GNB2L1 gene expression and immune infiltration in hepatocellular carcinoma. Differential expression of GNB2L1 in plasma platelets of HCC patients and healthy controls was analyzed using mRNA-based sequencing technology. Data between groups were compared using an independent-samples t-test. Results: GNB2L1 expression level was significantly increased in HCC tissues (P<0.05), and its expression was significantly correlated with body weight, classification and stage (P<0.05). The overall survival rate was higher in GNB2L1 low expression group (P<0.001). GNB2L1 and its related genes were related to biological process regulation, metabolic process, protein binding, oxidative phosphorylation, JAK-STAT signaling pathway, Ras signaling pathway and so on. GNB2L1 had interaction with RPS12, RPS11 and RPL19, and participated in multiple biological processes such as liver regeneration and positive regulation of endogenous apoptotic signaling pathway. GNB2L1 expression was significantly positively correlated with the infiltration degree of various immune cells in HCC (P<0.05). Cox regression analysis showed that GNB2L1 was an independent risk factor for lower survival rate in patients with HCC [Hazard ratio (95% confidence interval)=1.456 (1.034~2.051), P=0.031]. GNB2L1expression levels were significantly higher in platelets of HCC patients than that of healthy controls (10.40±1.36 vs. 9.58±0.51, t=2.194, P=0.037). Conclusion: GNB2L1 has high expression and close relationship to survival rate in HCC. Therefore, GNB2L1 may be a potential biomarker of HCC.

[Analysis of resistance and sensitivity of 1 200 strains of vulvovaginal candidiasis in China to five common antifungal drugs].

Objective: To test the antibiotic susceptibility of vulvovaginal candidiasis pathogenic strains to 5 antifungal drugs commonly used in clinic. Methods: A total of 1 200 vulvovaginal candida patients from 23 gynecological and family planning outpatient departments in China were enrolled. Their vaginal secretions were collected for candida strain isolation and species identification. According to Clinical and Laboratory Standards Institute (CLSI) M27-S3, the sensitivity of 1 200 strains to clotrimazole, fluconazole, miconazole, itraconazole and nystatin was tested. Results: (1) The sensitivity and resistance of 1 200 vulvovaginal candidiasis pathogens to 5 antifungal drugs were statistically different (χ2=3 513.201, P<0.01). (2) All strains had higher sensitivity to nystatin [99.92% (1 199/1 200)], followed by miconazole [92.25% (1 107/1 200)] and clotrimazole [87.17% (1 046/1 200)]. All strains had higher resistance to fluconazole [69.17% (830/1 200)], while itraconazole was 50.83% (610/1 200). (3) There was no significant difference between candida albicans and non-candida albicans in drug sensitivity to nystatin (P=0.315) and miconazole (P=0.425). (4) Candida albicans and non-candida albicans showed different sensitivity to clotrimazole, fluconazole and itraconazole, respectively. Compared with non-candida albicans, candida albicans showed higher sensitivity to clotrimazole [susceptibility rate: 73.01% (165/226) vs 90.45% (881/974); P<0.001] and higher resistance to fluconazole [resistance rate: 50.88% (115/226) vs 73.41% (715/974); P<0.001]. Although the drug sensitivity of itraconazole was not high, the susceptibility rate of candida albicans to itraconazole was slightly higher than that of non-candida albicans [37.68% (367/974) vs 23.89% (54/226)], and the drug resistance rate was lower [49.28% (480/974) vs 57.52% (130/226)]. Conclusions: The sensitivity of 1 200 strains of candida to 5 antifungal drugs is significantly different, the sensitivity rate of nystatin, miconazole and clotrimazole are higher, but the resistance rate of fluconazole and itraconazole are higher. The sensitivity of candida albicans and non-candida albicans to the same drug is also significantly different. It is suggested that in clinical diagnosis and treatment, we should pay attention to the identification of candida and drug sensitivity test, so as to select antifungal drugs rationally.

MiR-20a suppresses proliferation and facilitates apoptosis of breast cancer cells via the MTOR signaling pathway.

OBJECTIVE: The paper aimed to explore the role of micro ribonucleic acid (miR)-20a in regulating the proliferation and apoptosis of breast cancer cells. MATERIALS AND METHODS: The expression of miR-20a in breast cancer cells was analyzed via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry were employed to analyze the proliferation and apoptosis of cells. Thereafter, the target proteins of miR-20a were predicted using TargetScan, a website for miRNA target gene prediction, and the interaction between miR-20a and the target genes was detected through the Luciferase reporter gene assay, qRT-PCR assay, and Western blotting. Finally, the miR-20a inhibitor and target gene expression plasmids were co-transfected for rescue experiment to study whether the target genes participate in the inhibitory effect of miR-20a on the proliferation of breast cancer cells. RESULTS: It was found that the expression of miR-20a was upregulated in breast cancer cell lines. Silencing miR-20a expression inhibited the proliferation and promoted the apoptosis of breast cancer cell. Besides, it was demonstrated that late endosomal/lysosomal adaptor, mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) activator 3 (LAMTOR3) were a direct target of miR-20a. The knockdown of LAMTOR3 expression repressed the influence of miR-20a on the proliferation of breast cancer cells. CONCLUSIONS: MiR-20a targets LAMTOR3 gene to regulate the mTOR signaling pathway, thereby suppressing the proliferation and facilitating the apoptosis of breast cancer cells. It suggests that miR-20a exerts a carcinogenic effect in breast cancer, which may be a potential target for the treatment of breast cancer.

[Impact of achievement of "90-90-90" goals on reduction in new HIV infections in Shandong province based on risk estimation equation].

Objective: To explore the impact of achievement of the "90-90-90" goals on reductions in HIV incidence in Shandong province. Methods: An algebraic method was developed to link new HIV infections and the "90-90-90" goals in Shandong province. The risk estimation equation was used to analyze the effect of achievement of the "90-90-90" goals on reductions of HIV incidence, and explore the impact of application of antiviral therapy based prevention and control strategy on reduction of new HIV infections. Results: If "90-90-90" goals were achieved in 2020 in Shandong compared with annual new HIV infections in 2010, the percentage of reduction would be 17.27%, 35.99% and 67.55% respectively when transmission rate decreased by 26.00%, 53.00% and 96.00% respectively. Compared with 2017, when the transmission rate decreased by 53.00%, the annual new HIV infections would has a decrease of 10.10% if the rates of diagnosis and ART reached 90.00%; the annual new HIV infections would has a decrease of 20.80% if the rates of diagnosis and viral suppression reached 90.00%; the annual new HIV infections would has a decrease of 12.29% if the rates of ART and viral suppression reached 90.00%. Conclusions: HIV incidence would decrease with the achievement of "90-90-90" goals in Shandong. Compared with the improvement of ART, the improvement in diagnosis of HIV infection and viral suppression would result in more rapid decrease of new HIV infections. Besides expanding ART coverage, more attention should be paid to the strengthening of the diagnosis of HIV infection and viral suppression in Shandong.

[Preliminary study of a mask filtration test device with respiratory simulation].

Objective: To develop an air particulate protective mask filter test device that can simulate the dynamics process of human breathing. Methods: The new device used two air pumps working alternately to simulate the dynamics process of human breathing. On March 4th to 17th, 2017, the new device and the traditional one-way airflow mask filtration test device were used to measure the internal and external particle levels of 39 masks of 13 models of 6 brands, and then the filtration efficiency of the mask was calculated and the test results were compared. Results: For the mask without breathing valve, there was no statistically significant difference between the filter efficiency test results of the new device and the traditional unidirectional airflow filter performance test device (P>0.05) . For masks with breathing valves, the new device detected that three of them had lower filtration efficiency (99.50% vs 98.63%, P<0.01) . After sealing the mask breathing valve with glue, the filtering efficiency of the mask with a breathing valve detected by the new device significantly improved (98.63% vs 99.50%, P<0.01) . Conclusion: This new device can simulate the dynamic process of human exhalation and inhalation, and measure the filtration efficiency of the mask. For masks with breathing valves, the new device makes it easier to detect the decrease in the filtering efficiency of the mask caused by the breathing valve.

LncRNA GIHCG regulates microRNA-1281 and promotes malignant progression of breast cancer.

OBJECTIVE: This study aimed to investigate the expression characteristics of long non-coding RNA (lncRNA) GIHCG in breast cancer (BCa), and further investigate its role in BCa and its relationship with clinical characteristics and prognosis. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine GIHCG expression in 53 pairs of BCa tumor tissues and adjacent tissues. The interaction between the level of GIHCG and the clinical indicators of BCa and the prognosis of patients was then analyzed. Lentivirus was transfected into BCa cell lines to construct the GIHCG knockdown model. The cell counting kit-8 (CCK-8), cell cloning, and 5-Ethynyl-2'-deoxyuridine (EdU) assays were performed to analyze the influence of GIHCG on the biological function of BCa cells, as well as to explore whether it could play a role via modulating microRNA-1281. RESULTS: QRT-PCR results showed that the GIHCG level was remarkably higher in the BCa tumor tissue than in adjacent ones. Compared with patients with low expression of GIHCG, patients with high expression of GIHCG had higher pathological grades and a lower overall survival. Besides, the proliferation ability of BCa cells in GIHCG knockdown group was significantly decreased compared with NC group. QRT-PCR results indicated that silencing GIHCG increased the expression of miR-1281, thereby promoting the malignant progression of BCa. Also, the silence of miR-1281 reversed the effect of GIHCG on the proliferative capacity of BCa, thus increasing the cell anti-apoptotic ability. CONCLUSIONS: GIHCG levels were remarkably increased in both BCa tissues and cells, which was related to the pathological stage and poor prognosis of BCa patients. Besides, GIHCG might promote the malignant progression of BCa by inhibiting microRNA-1281.

[The safety of decitabine as bridging pretreatment regimen before hematopoietic stem cell transplantation in pediatric hematological malignancies].

The safety of decitabine as bridging treatment before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with refractory hematological malignancies was evaluated. All 11 cases succeeded in hematopoietic reconstitution. The main adverse reaction was hematological toxicity. Neither did infections occur, nor drug-induced liver damage and renal impairment during decitabine administration. Most cases showed grade Ⅰ-Ⅱgastrointestinal adverse events. One case was diagnosed as severe acute graft versus host disease and died of intracranial hemorrhage on day 61 after allo-HSCT. The other 10 patients survived. Decitabine bridge is a safe regimen before allo-HSCT in children with refractory hematological malignancies.

Identification of lipopeptides produced by Bacillus subtilis Czk1 isolated from the aerial roots of rubber trees.

We obtained a strain of Bacillus subtilis, which we named Czk1, from the aerial roots of rubber trees. This bacterial isolate exhibits strong antagonistic activity against Ganoderma pseudoferreum, Phellinus noxius, Helicobasidium compactum, Rigidoporus lignosus, Sphaerostilbe repens, and Colletotrichum gloeosporioides. Our earlier research has shown that the antagonistic activity of a fermentation supernatant Czk1 isolate produces a complex mixture of lipopeptides. In this study, we used methanol to extract crude lipopeptides, purified them using a Sephadex G-25 column, cloned the lipopeptide genes, and analyzed purified fractions by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) to identify the lipopeptides from B. subtilis strain Czk1. The cloned lipopeptide genes included those that encode the enzymes lpa, ituD, sfp, and fenB. The crude lipopeptides were purified and found in five fractions. Further analysis revealed that five fractions of the purified composition contained members of the surfactin, iturin, fengycin, and bacillomycin families of antibiotics. This suggests that these lipopeptides from strain Czk1 have potential as plant disease biocontrol agents.

miR-302 regulates pluripotency, teratoma formation and differentiation in stem cells via an AKT1/OCT4-dependent manner.

Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self-renewal and pluripotency, and promotes hPSC differentiation. The underlying mechanism is that the high endogenous expression of miR-302 suppresses the AKT1 expression by directly targeting its 3'UTR and subsequently maintains the pluripotent factor OCT4 at high level. Our findings reveal that miR-302 regulates OCT4 by suppressing AKT1, which provides hPSCs two characteristics related to their potential for clinical applications: the benefit of pluripotency and the hindrance of teratoma formation. More importantly, we demonstrate that miR-302 upregulation cannot lead OCT4 negative human adult mesenchymal stem cells (hMSCs) to acquire the teratoma formation in vivo. Whether miR-302 upregulation can drive hMSCs to acquire a higher differentiation potential is worthy of deep investigation.

Neural correlates of inhibitory control and visual processing in youths with attention deficit hyperactivity disorder: a counting Stroop functional MRI study.

BACKGROUND: Despite evidence of inhibitory control and visual processing impairment in attention deficit hyperactivity disorder (ADHD), knowledge about its corresponding alterations in the brain is still evolving. The current study used counting Stroop functional MRI and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate if brain activation of inhibitory control and visual processing would differ in youths with ADHD relative to neurotypical youths. METHOD: We assessed 25 youths with ADHD [mean age 10.9 (s.d.=2.2) years] and 23 age-, gender- and IQ-matched neurotypical youths [mean age 11.2 (s.d.=2.9) years]. The participants were assessed by using the Wechsler Intelligence Scale for Children, third edition, and two tests from the CANTAB: rapid visual information processing (RVP) and pattern recognition memory (PRM) outside the scanner. RESULTS: Youths with ADHD showed more activation than neurotypical youths in the right inferior frontal gyrus [Brodmann area (BA) 45] and anterior cingulate cortex, which were correlated with poorer performance on the RVP test in the CANTAB. In contrast, youths with ADHD showed less activation than neurotypical youths in the left superior parietal lobule (BA 5/7), which was correlated with the percentage of correct responses on the PRM test in the CANTAB. CONCLUSIONS: Our findings suggest that youths with ADHD might need more inhibitory control to suppress interference between number and meaning and may involve less visual processing to process the numbers in the counting Stroop task than neurotypical youths.

Citrullinated vimentin stimulates proliferation, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression of fibroblast-like synoviocytes in rheumatoid arthritis.

OBJECTIVES: We aimed to investigate the possible effects of vimentin (Vim) and citrullinated Vim (cVim) on proliferation capacity, pro-inflammatory cytokine secretion, and the expression of peptidylarginine deiminase type 4 (PADI4) and receptor activator of nuclear factor kappa B ligand (RANKL) in cultured fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. METHOD: Human native Vim was citrullinated with rabbit PAD in vitro and detected using a Western blot assay with anti-modified citrulline antibody (anti-MC Ab). FLSs from RA or OA synovial samples were stimulated with Vim or cVim. Cell proliferation capacity was determined using the Celltiter 96 AQueous cell proliferation assay. The concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The expression of PADI4 and RANKL was measured by real-time polymerase chain reaction (RT-PCR) and a Western blot assay. RESULTS: Our Western blot assay with anti-MC Ab indicated that the amount of cVim increased significantly after Vim had been incubated with rabbit PAD in vitro. The proliferation capacity and secretion of TNF-α and IL-1 were significantly enhanced in the FLSs of RA patients when treated with cVim. However, when treated with Vim, an inhibitory effect on the proliferation capacity was noted in the FLSs from RA and also from OA patients. cVim significantly increased the expression of PADI4 and RANKL in the FLSs from RA patients. CONCLUSION: cVim seems to have remarkable biological effects on RA as confirmed by the stimulation of proliferation capacity, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression in the FLSs of RA patients.

(4aR*,8aS*)-2,3-Diphenyl-4a,5,6,7,8,8a-hexa-hydro-quinoxaline.

In the title compound, C(20)H(20)N(2), the quinoxaline ring adopts a very distorted half-chair conformation [N=C-C=N = 22.7 (2)° for the nominally coplanar atoms] and the cyclo-hexane ring adopts a chair conformation. The quinoxaline and cyclo-hexane rings are cis-fused. The two phenyl rings form a dihedral angle of 63.88 (7)°.

Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin.

The flavonol aglycone isorhamnetin shows anti-proliferative activity in a variety of cancer cells. Previous work, from our laboratory showed that isorhamnetin inhibits the proliferation of human esophageal squamous carcinoma Eca-109 cells in vitro, but only after 72 h of exposure. This led us to propose that isorhamnetin exposure induces a cellular stress response that inhibits the antiproliferative and apoptotic effects of the compound during early exposure. To test this hypothesis, the present study examined the effects of isorhamnetin on Eca-109 cells during the first 72 h of exposure. Cell growth was assessed using the trypan blue exclusion assay, and expression of IκBα, NF-κB/p65, NF-κB/p50, phospho-Akt, Bcl-2, COX-2, Mcl-1, Bax, p53 and Id-1 were analyzed by Western blot. During the first 72 h of exposure, NF-κB/p65 and NF-κB/p50 accumulated in nuclei and expression of COX-2, Bcl-2 and Mcl-1 increased. In contrast, expression of IκBα and Bax fell initially but later increased. Expression of phospho-Akt and p53 showed no detectable change during the first 48 h. Pretreatment with the NF-κB inhibitor MG132 before exposure to isorhamnetin blocked the nuclear accumulation of p50 and p65, thereby inhibiting cell proliferation. These results show that during early exposure of Eca-109 cells to isorhamnetin, the NF-κB signaling pathway is activated and COX-2 expression increases, and this increase in expression partially inhibits isorhamnetin-induced apoptosis. Beyond 72 h of exposure, however, the apoptotic effect of isorhamnetin dominates, leading to inhibition of the NF-κB pathway and of cellular proliferation. These results will need to be taken into account when exploring the use of isorhamnetin against cancer in vivo.

Simultaneous blockade of costimulatory signals CD28-CD80 and CD40-CD154 combined with monoclonal antibody against CD25 induced a stable chimerism and tolerance without graft-versus-host disease in rat.

BACKGROUND: The conditioning regimen to induce chimerism for immune tolerance is usually accompanied by high toxicity and graft-versus-host disease (GVHD). Our aim was to explore a nontoxic strategy for the induction of mixed chimerism by pretreatment with anti-CD25 monoclonal antibody (mAb), cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4Ig) and anti-CD154 mAb. METHODS: A total of 30 Lewis recipient rats (RT1l) were randomly divided into control (A and B) and treated (C, D and E) groups. Recipients serving as controls were without any pretreatment (group A) or pretreated with anti-CD25 mAb, CTLA4Ig and anti-CD154 mAb on days 0, 2, 4, 6 and 8 without bone marrow transplantation (BMT; group B). In the treated groups, the recipients were pretreated with anti-CD25 mAb and CTLA4Ig (group C), with anti-CD25 mAb and anti-CD154 mAb (group D) or with anti-CD25 mAb, CTLA4Ig and anti-CD154 mAb (group E) on days 0, 2, 4, 6 and 8 plus BMT [2 × 10(8) unmodified whole bone marrow cells from Brown Norway donor rats (RT1n)] on day 0. Full-thickness skin grafts from donor-specific Brown Norway rats were grafted to the dorsal thoracic wall of Lewis recipients on day 8. GVHD was assessed after BMT, and chimerism and T cell apoptosis on days 7, 21, 35 and 49 were detected by flow cytometry. RESULTS: GVHD was not observed in any groups. On days 7, 21 and 35, hematopoietic chimerism was present and maintained in the recipients of the 3 treated groups (groups C, D and E), and thereafter disappeared on day 49. The rate of chimerism in group E was significantly higher compared to that in group C on day 7 and that in group C or D on day 21, but there was no significant difference on day 35 among the 3 groups. The rate of T cell apoptosis in group C, D or E was significantly higher than in group A or B on days 14, 21 and 35. The grafted skin survival in group C, D or E was longer than in group A or B, and survival was significantly longer in group E than in group C or D. CONCLUSION: Preconditioning with anti-CD25 mAb, CTLA4Ig and anti-CD154 mAb could effectively induce chimerism and immune tolerance without GVHD in a major histocompatibility complex-disparate rat model. This strategy may be attractive for induction of transplantation tolerance. T cell apoptosis is one of the important considerations in tolerance induction.

Saikosaponins: a potential treatment option for systemic lupus erythematosus.

While the exact cause of systemic lupus erythematosus (SLE) is still unknown, modern medicine has a number of effective treatments for this complex disorder. Corticosteroid hormones help reduce inflammation, antimalarial treatments address flare-ups and immunosuppressive medications work to keep the immune system in check. All these therapies are well tolerated, but accompany an increased risk of infection and nephrotoxicity. Recently, several studies showed that a number of natural and herbal products may also help some SLE patients deal with the debilitating symptoms. In this brief report, we proposed a traditional Chinese medicinal herb--Saikosaponins, and discussed its potential as a treatment option for SLE.

A functional haplotype and expression of the PADI4 gene associated with increased rheumatoid arthritis susceptibility in Chinese.

To evaluate the association of single-nucleotide polymorphisms (SNPs) in PADI4 mRNA with rheumatoid arthritis (RA) in a Chinese population, we examined the distribution of four exonic SNPs of the PADI4 gene (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C and padi4_104*T/C) and PADI4 gene expression in 70 RA patients and 81 controls. Increased RA susceptibility was associated with the minor alleles of padi4_89 (P = 0.012), padi4_90 (P = 0.002), padi4_104 (P = 0.001) and the functional haplotype carrying the four minor alleles (P = 0.008). Human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles were also associated with increased RA susceptibility, and the individuals with minor alleles of four exonic SNPs and SE alleles showed more increased RA susceptibility. The PADI4 expression was significantly higher in RA patients than in controls (P < 0.001). HLA-DRB1 SE alleles and the genotypes carrying the minor alleles of four SNPs were associated with increased PADI4 expression. It is concluded that PADI4 SNPs, functional haplotype and PADI4 expression may contribute to an inherited predisposition to RA in a Chinese population.