The super-resolution reconstruction in diffusion-weighted imaging of preoperative rectal MR using generative adversarial network (GAN): Image quality and T-stage assessment.

AIMS: To assess the feasibility of using a generative adversarial network (GAN) to improve diffusion-weighted imaging (DWI) resolution in rectal MR scans for rectal carcinoma (RC), and to evaluate both the image quality and the diagnostic utility of super-resolution DWI (SR-DWI) in T stage assessment. MATERIALS AND METHODS: In this retrospective investigation, a total of 291 patients diagnosed with RC during the period spanning May 2018 to December 2021 were included. The generated SR-DWI was evaluated against the original DWI using multi-scale structural similarity and peak signal-to-noise ratio. Two radiologists scored the SR-DWI and original DWI using a 4-point Likert scale in image quality. Moreover, both radiologists independently evaluated the T category staging based on T2WI and SR-DWI. Interobserver agreement was assessed using Cohen's kappa. RESULTS: The PSRN and MS-SSIM values of SR-DWI (4 ×) were significantly higher compared to those of SR-DWI (16 ×). Regarding the details of anatomic structures and overall image quality parameters, both radiologists exhibited a preference for SR DWI with 16 × enlargement over SR DWI with 4 × enlargement, yielding significantly superior ratings (both p < 0.001). The T-staging accuracy rates of SR-DWI (16 ×) performed by radiologist 1 and radiologist 2 were significantly superior to those achieved with T2WI (0.621 vs. 0.768, p = 0.027; 0.653 vs 0.810, p = 0.014). CONCLUSIONS: Our study demonstrates that the adapted super-resolution approach can significantly improve the overall image quality and details of anatomic structure of DWI in rectal MR. And SR-DWI offer better diagnostic accuracy in RC T staging when compared with T2WI.

[Risk factors analysis and prediction model establishment of contralateral central lymph node metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma].

Objective: To explore the risk factors of contralateral central lymph nodes (Cont-CLNs) metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma and establish a prediction model. Methods: The clinical data of 206 patients receiving thyroid cancer surgery at Nantong University Affiliated Hospital between January 2021 and June 2023 were retrospectively analyzed, including 50 males and 156 females, with an age of [M(Q1, Q3)] 49.0(33.8, 57.0) years old. The risk factors of Cont-CLNs metastasis were screened by univariate analysis and multivariate logistic regression analysis. A nomogram was constructed for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC. The area under the receiver operating characteristic (ROC) curve(AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the model's predictive ability, accuracy, and clinical applicability, respectively. R language was used to randomly select 70% of the patients to establish a validation group for internal validation of the model. Results: Patients were divided into a metastasis group (n=56) and a non-metastasis group (n=150) based on the occurrence of Cont-CLNs metastasis. The ages of the two groups were 39.0 (28.0, 56.8) years and 51.0 (38.8, 57.0) years, respectively. There were statistically significant differences in gender, maximum tumor diameter (>1 cm), ipsilateral central lymph nodes (Ipsi-CLNs) metastasis, number of Ipsi-CLNs metastases (≥4), and lateral lymph node metastasis and Cont-CLNs metastasis between the two groups (all P<0.05). The results of multivariate logistic regression analyses showed that males(OR=2.926, 95%CI: 1.063-8.051), maximum tumor diameter>1 cm(OR=4.471, 95%CI: 1.344-14.877), and number of Ipsi-CLNs metastases≥4 (OR=5.011, 95%CI: 1.815-13.834) were risk factors for Cont-CLNs metastasis (all P<0.05). The AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model in the modeling group were 0.821 (95%CI: 0.744-0.898), 82.5%, and 63.4%, respectively. In the internal validation group, the AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model were 0.810 (95%CI: 0.717-0.902), 63.3%, and 83.7%, respectively. The calibration curves of the modeling group and the validation group showed that the model had good calibration ability. The DCA curves of the modeling group and the validation group indicated that the prediction model had good clinical adaptability. Conclusions: The prediction model constructed in this study has good predictive performance for Cont-CLNs metastasis in intermediate-to-high uPTC. When patient with intermediate-to-high risk uPTC is male, with maximum tumor diameter>1 cm, and the number of Ipsi-CLNs metastases≥4 should be alert to Cont-CLNs metastasis, and bilateral central lymph node dissection may be considered.

[Differential diagnosis model of benign and malignant breast BI-RADS category 4 nodules based on serum SP70 and conventional laboratory indicators].

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.

[Suppression of HMGB1 inhibits neuronal autophagy and apoptosis to improve neurological deficits in rats following intracerebral hemorrhage].

OBJECTIVE: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats. METHODS: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 µL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA. RESULTS: The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05). CONCLUSION: Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.

[Clinical analysis of penetrating keratoplasty for infants with congenital corneal opacity].

Objective: To investigate the corneal graft survival and related risk factors of primary penetrating keratoplasty in congenital corneal opacity infants. Methods: It was a retrospective cohort study. Data were collected from forty-two infants (51 eyes) who were aged ≤12 months and diagnosed with congenital corneal opacity in Beijing Tongren Hospital and Beijing Anzhen Hospital from January 1, 2017 to January 31, 2018. The mean age at surgery was (5.7±2.2) months (3-12 months). The mean follow-up duration was (28.6±2.6) months (24-33 months). All the patients underwent penetrating keratoplasty. The status of the corneal grafts and complications were observed and recorded during the regular follow-up. The survival probabilities were estimated by using the Kaplan-Meier and Log-rank test. The graft survival between different influence factors was analyzed by using the χ2 test. Results: The Kaplan-Meier survival rates for penetrating keratoplasty were 84.3% (43/51) at 6 months, 78.4% (40/51) at 12 months and 60.8% (31/51) at the last follow-up. The presence of corneal neovascularization was significantly correlated with graft failure (χ²=5.264, P=0.022). The graft survival differed between eyes receiving combined surgery and mere penetrating keratoplasty and in eyes with varied surgical indications (P=0.039, <0.01). Increased intraocular pressure (7 eyes, 13.7%) and persistent epithelial defects (7 eyes, 13.7%) were the most common postoperative complications, followed by complicated cataract (4 eyes, 7.8%) and posterior capsule opacification (2 eyes, 3.9%). Conclusions: The graft survival rate was satisfactory following pediatric keratoplasty although it had a tendency to decrease with the follow-up time. Corneal neovascularization was a major risk factor of graft failure. Surgical indications and procedures also had a certain effect on the graft survival.

[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

Hydrogel particles improve detection of SARS-CoV-2 RNA from multiple sample types.

Here we present a rapid and versatile method for capturing and concentrating SARS-CoV-2 from contrived transport medium and saliva samples using affinity-capture magnetic hydrogel particles. We demonstrate that the method concentrates virus from 1 mL samples prior to RNA extraction, substantially improving detection of virus using real-time RT-PCR across a range of viral titers (100-1,000,000 viral copies/mL) and enabling detection of virus using the 2019 nCoV CDC EUA Kit down to 100 viral copies/mL. This method is compatible with commercially available nucleic acid extraction kits (i.e., from Qiagen) and a simple heat and detergent method that extracts viral RNA directly off the particle, allowing a sample processing time of 10 min. We furthermore tested our method in transport medium diagnostic remnant samples that previously had been tested for SARS-CoV-2, showing that our method not only correctly identified all positive samples but also substantially improved detection of the virus in low viral load samples. The average improvement in cycle threshold value across all viral titers tested was 3.1. Finally, we illustrate that our method could potentially be used to enable pooled testing, as we observed considerable improvement in the detection of SARS-CoV-2 RNA from sample volumes of up to 10 mL.

[Diffusion tensor imaging and visual evoked potentials in pediatric patients with sellar region lesions].

Objiective: To evaluate the prognosis of visual function and the impact of surgery in pediatric patients with sellar mass lesions, as evidenced by diffusion tensor imaging (DTI) and visual evoked potentials. Methods: Twenty patients with sellar mass lesions were included in the study. DTI and visual evoked potentials were obtained before and after surgery. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for both optic nerves. DTI parameters and visual evoked potential amplitudes were compared for all patients to assess the correlation between DTI parameters and visual function. Results: The 20 patients were divided into two groups according the relationship between the lesions and the optic chiasm. The FA values increased significantly after operation, while the ADC values decreased (P<0.05). And the average amplitude of visual evoked potentials after operation was significantly higher than before operation (P<0.05). Conclusions: DTI assessments of the affected sides, with the resulting FA and ADC values, may help to estimate the visual improvement produced by surgical therapy in the early postoperative period. Surgical removal can improve visual function dramatically.

SETD5-AS1 stimulates neuron death in stroke via promoting PTEN expression.

OBJECTIVE: To investigate the specific role of long non-coding RNA (lncRNA) SETD5-AS1 in regulating stroke development, and its underlying mechanism. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) model and OGD/R (oxygen-glucose deprivation/reoxygenation) model were constructed for exploring the mechanism of ischemia-reperfusion injury induced by ischemic stroke. SETD5-AS1 expression in brain tissues of ischemic stroke mice and control mice was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of N2a cells were detected after transfection of overexpression plasmid or siRNA SETD5-AS1. The downstream gene of SETP5-AS1 was predicted by Starbase and PTEN was screened out. Both mRNA and protein expressions of PTEN in MCAO model and OGD/R model were detected. Furthermore, the binding condition of SETD5-AS1 and PTEN was verified by dual-luciferase reporter gene assay, RNA pull-down assay and RNA binding protein immunoprecipitation (RIP). The regulatory effect of SETD5-AS1 on PI3K/AKT pathway was detected by Western blot. RESULTS: SETD5-AS1 was highly expressed in the ischemia-reperfusion injury model. Overexpression of SETD5-AS1 in N2a cells resulted in increased apoptosis and decreased proliferation. PTEN expression was upregulated in MCAO model and OGD/R model. Dual-luciferase reporter gene assay indicated that SETD5-AS1 can promote PTEN transcription. The binding condition of SETD5-AS1 and PTEN was further verified by RNA pull-down assay and RIP. Overexpression of SETD5-AS1 in N2a cells inhibited PI3K/AKT pathway. CONCLUSIONS: SETD5-AS1 is highly expressed in the ischemia-reperfusion injury model. SETD5-AS1 participates in the development of ischemic stroke by activating PTEN and inhibiting PI3K/AKT pathway.

Real-time 6DoF pose recovery from X-ray images using library-based DRR and hybrid optimization.

PURPOSE: Real-time 6 degrees of freedom (6DoF) pose recovery and tracking from X-ray images is a key enabling technology for many interventional imaging applications. However, real-time 2D/3D registration is a very challenging problem because of the heavy computation in iterative digitally reconstructed radiograph (DRR) generation. In this paper, we propose a real-time 2D/3D registration framework using library-based DRRs to achieve high computational efficiency. METHOD: The proposed method pre-computes a library of canonical DRRs and reconstructs library-based DRRs (libDRRs) during registration without online rendering. The transformation parameters are decoupled to 2 geometry-relevant and 4 geometry-irrelevant ones so that canonical DRRs only need to cover the variation of 2 geometry-relevant parameters, making it practical to be pre-computed and stored. The 2D/3D registration using libDRRs is then solved as a hybrid optimization problem, i.e., continuous in geometry-irrelevant parameters while discrete in geometry-relevant parameters. RESULTS: On 5 fluoroscopic sequences with 246 frames acquired during animal studies with a transesophageal echocardiography (TEE) probe in the field of view, 6DoF tracking of the TEE probe using the proposed method achieved a mean target registration error in the projection direction (mTREproj) of 0.81 mm, a success rate of 100 % (defined as mTREproj [Formula: see text]2.5 mm), and a registration frame rate of 23.1 fps on a pure CPU-based implementation executed in a single thread. CONCLUSION: Using libDRRs with a hybrid optimization can significantly improve the computational efficiency (up to tenfold) for 6DoF pose recovery and tracking with little degradation in robustness and accuracy, compared to conventional intensity-based 2D/3D registration using ray casting DRRs with a continuous optimization.

Association between SNPs in vascular endothelial growth factor polymorphisms and risk of renal cell carcinoma: a case-control study.

We conducted this case-control study to assess the role of the VEGF -2578C/A, +1612G/A, +936C/T and -634G/C gene polymorphisms in the development of renal cell carcinoma (RCC). A hospital-based case-control study was conducted in a 360 consecutive primary RCC patients and 360 age and gender-matched controls during January 2010 and January 2014. The polymerase chain reaction-restriction fragment length polymorphism was used for VEGF -2578C/A, +1612G/A, +936C/T and -634G/C genotyping. Multivariate conditional logistic regression analyses showed that subjects carrying the AA and the CA+AA genotypes of VEGF -2578C/A had significant association with increased risk of RCC compared to those having the CC genotype, and the ORs (95%CI) were 1.77 (1.10-2.85) and 1.37 (1.01-1.86), respectively. Using the conditional logistic regression model, CA+AA genotype of VEGF -2578C/A had a significantly increased risk of RCC in ever cigarette smokers, and individuals with hypertension, and the ORs (95%CI) were 1.93 (1.08-3.45) and 2.57 (1.06-6.57), respectively. In conclusion, our results showed that AA genotype of VEGF -2578C/A genetic variants is associated with increased risk of RCC.

INHIBITORY EFFECT OF TETRAMETHYLPYRAZINE ON HEPATOCELLULAR CARCINOMA: POSSIBLE ROLE OF APOPTOSIS AND CELL CYCLE ARREST.

Hepatocellular carcinoma (HCC) is the fifth most common cancer. An important approach to control HCC is chemoprevention. This study aims at investigating the antitumor effect of Tetramethylpyrazine (TMP). Rats were injected with N-Nitrosodiethylamine (DEN) to establish HCC. Tumor development was observed. Liver function was evaluated. Apoptosis and cell cycle arrest-related makers and signaling cascades were determined by Western blot, RT-PCR and flow cytometric analysis. The administration of TMP could significantly inhibit tumor development in DEN-induced HCC rats, shown by reduced incidence of tumor, decreased number of tumor nodules and reduced maximal size of tumor. DEN-induced increase of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities were significantly inhibited by TMP. TMP exhibited inhibitory effect on HCC through induction of apoptosis and cell cycle arrest in rats. TMP induced apoptosis through increasing Bax, decreasing Bcl-2, increasing the release of cytochrome c, and activating caspase, which consisted of the mitochondrial apoptotic pathway. TMP induced G2/M cell cycle arrest through down-regulation of cyclin B1/cdc2. In addition, inhibition of Akt and ERK signaling and the antioxidant activities of TMP may also contribute to its antitumor effect. These data provide new insight into the mechanisms underlying the antitumor effect of TMP.

Synuclein γ protects Akt and mTOR and renders tumor resistance to Hsp90 disruption.

Heat shock protein (Hsp)90 regulates many key pathways in oncogenesis, including Akt and mammalian target of rapamycin (mTOR). The strengths of disruption of Hsp90 in cancer therapy include their versatility in inhibiting a wide range of oncogenic pathways. The present study demonstrated that synuclein γ (SNCG) protects the functions of Akt and mTOR in the condition when the function of Hsp90 is blocked. Disruption of Hsp90 abolished Akt activity and mTOR signaling. However, expression of SNCG restored Akt activity and mTOR signaling. SNCG bound to Akt and mTOR in the presence and absence of Hsp90. Specifically, the C-terminal (Gln106-Asp127) of SNCG bound to the loop connecting αC helix and ß4 sheet of the kinase domain of Akt. SNCG renders resistance to 17-AAG-induced apoptosis both in vitro and in tumor xenograft. A clinical follow-up study indicates that patients with an SNCG-positive breast cancer have a significantly shorter disease-free survival and overall survival than patients with SNCG-negative tumors. The present study indicates that SNCG protects Hsp90 client proteins of Akt and mTOR, and renders drug resistance to Hsp90 disruption.

Pathological implication and function of Bcl2-inhibitor of transcription in ovarian serous papillary adenocarcinomas.

The Bit-1 protein appears to be a part of the integrin-specific signaling pathway involved into anoikis. When Bit1 is released from the mitochondria into the cytoplasm it can elicit caspase-independent apoptosis. The expression of Bit1 in 78 serous papillary adenocarcinomas and 78 normal epithelial ovarian tissue specimens was analyzed by immunohistochemistry. We also investigate Bit1 function by transfection. Bit1 was expressed in 100% and 33.3% of ovarian cancers and normal epithelial tissues, respectively, and its expression was significantly correlated with histologic grade and overall survival. However, Bit1 expression was not associated with age. We also confirmed that Bit1 overexpression in cytosol of Caov-3 cells induced apoptosis. Bit1 may be a useful pathological marker and a prognostic marker for serous papillary adenocarcinomas outcome. Its pro-apoptotic property also makes it a potential gene medicine for ovarian cancers therapy.

Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2.

Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A(4) (LXA(4)) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA(4), ANXA1, SAA and LL-37 were dependent on the activation of their mutual cell-surface receptor formyl peptide receptor-2 (FPR2) and subsequent ROS-MAPK-NF-kB signalings. Furthermore, our results indicated that LPS switched macrophages into an IL-10(low)IL-12(high) M1 profile, whereas M-CSF+MCP-1 and FPR2 agonists skewed them into M2 (IL-10(high)IL-12(low)). In that respect, through modulating the phosphorylation of signal transducer and activator of transcription-3 (STAT3), LXA(4) and ANXA1 induced monocyte differentiation into M2a+M2c-like cells and showed antitumorigenetic activities, whereas SAA, LL-37 and M-CSF+MCP-1 led to M2b- or M2d-like polarization, which exacerbated HCC invasion in vitro and in vivo, respectively. Our results suggest that FPR2 has an appreciable pleiotropic regulator role in tumor immunoediting.

Recombinant Mycobacterium smegmatis expressing an ESAT6-CFP10 fusion protein induces anti-mycobacterial immune responses and protects against Mycobacterium tuberculosis challenge in mice.

The currently used vaccine against tuberculosis, Bacille Calmette-Guérin (BCG), has variable efficacy, so new vaccine development is crucial. In this study, we evaluated a recombinant vaccine prepared from non-pathogenic Mycobacterium smegmatis (rMS) that expresses a fusion of early secreted antigenic target 6-kDa antigen (ESAT6) and culture filtrate protein 10 (CFP10). C57BL/6 mice were immunized with the rMS expressing the ESAT6-CFP10 fusion protein (rM.S-e6c10) or with BCG. The mice in the rM.S-e6c10 group had a significantly higher titre of anti-ESAT6-CFP10 antibodies than did animals in the BCG or saline groups. Spleen cells from rM.S-e6c10-immunized mice exhibited a cytotoxic response to ESAT6 and CFP10-expressed target cells, but spleen cells from animals in the other groups did not. Levels of IFN-γ and IL-2 production by purified T cells from spleens were significantly higher in rM.S-e6c10 group than in BCG group. Finally, after M. tuberculosis (MTB)-challenged mice, dramatic reduction in the numbers of MTB colony-forming units (CFUs) in the lungs was observed for the mice immunized with the rMS. The protective efficacy of rM.S-e6c10 and BCG vaccination was similar based on measures of MTB burden and lung pathology. Our data indicate that the recombinant M. smegmatis vaccine expressing the ESAT6-CFP10 fusion protein has potential in clinic application.

Overexpression of the PDCD2-like gene results in inhibited TNF-alpha production in activated Daudi cells.

Both PDCD2 and PDCD2-like proteins have PDCD2_C terminal domains, but their functions are still unclear. After analysis of their expression in Gene Expression Omnibus, we hypothesized that they played a role in inflammation. In Daudi cells exposed to lipopolysaccharides, PDCD2-like RNA was upregulated, whereas PDCD2 was downregulated. Overexpression of PDCD2-like gene effectively attenuated tumor necrosis factor (TNF)-alpha release but elevated interleukin (IL)-6 and PDCD2 expression induced by lipopolysaccharide (LPS). It is possible that both proteins have anti-inflammatory effects like IL-6. The results have implications for understanding the function of PDCD2/PDCD2-like proteins and may help in the development of novel anti-inflammatory drugs.

Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine.

In Europe, swainsonine has been studied widely for prevention of metastasis and cancer therapy. In order to investigate the effects and mechanisms of swainsonine on the human gastric carcinoma SGC-7901 cell, we carried out in vivo and in vitro experiments. After treatment with swainsonine, an effective dose and IC50 value of swainsonine for SGC-7901 cells were examined by MTT assay. Cell-cycle distribution and apoptotic rates were analyzed using FCM, and [Ca2+]i was measured using LSCM. The expression of p53, c-myc and Bcl-2 were determined using an immunocytochemical method. Simultaneously, 50 mice were divided randomly into five groups. Three groups were administrated swainsonine at dose of 3, 6 and 12 mg/kg body wt., two control groups were administrated N.S. 20 ml/kg body wt. and 5-Fu 20 mg/kg body wt., respectively, by intraperitoneal injection. The inhibition rate was calculated and pathological sections were observed. The growth of SGC-7901 cell is inhibited by swainsonine in vitro, with an IC50 value at 24 h of 0.84 microg/ml, and complete inhibition concentration is 6.2 microg/ml. After treatment with swainsonine at the concentrations of 0.5, 1.5 and 4.5 microg/ml for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreases, and the apoptotic trigger gene c-myc increases markedly (p<0.05), as well as [Ca2+]i overloading, SGC-7901 cell is induced to apoptosis in the end. It is also found that the percentages of S phase are 38.8%, 39.7% and 29.6%, respectively (20.0% in control group and 23.2% in 5-Fu group). The rates of inhibition were 13.2%, 28.9%, 27.3%, respectively, when the nude mice were administered swainsonine (p<0.05 or 0.01). The structure of the tumor showed hemorrhage, necrosis and inflammatory cell infiltration. We therefore conclude that swainsonine could inhibit cell proliferation in vitro and the growth of human gastric carcinoma in vivo. The mechanisms of swainsonine-induced apoptosis may relate to [Ca2+]i overloading and the expression of apoptosis-related genes.

Discovery of a novel series of inhibitors of human cytomegalovirus primase.

Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible people throughout the world. We have discovered a series of imidazolyl-pyrimidine compounds, which were found to be irreversible inhibitors of the hCMV UL70 primase based on results from radiolabeling and SAR studies. Two promising analogs are described that rival ganciclovir and cidofovir in antiviral potency and possess improved cytotoxicity profiles.