Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression. RESULTS: Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients. CONCLUSION: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.

The RhoA GTPase regulates Type I Interferon Signaling in Systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. Methods: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to asssess the biologic function of RhoA. An Enzyme-Linked Immunoassay (ELISA) measured C-X-C motif chemokine ligand 10(CXCL10)protein expression. Results: Our studies demonstrated that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1(OAS1). Finally,we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in PBMCs of SLE patients. Conclusion: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.

[Chemical Composition Characteristics and Source Apportionment of PM2.5 During the Heating Period of 2016-2017 in the Eastern Part of the North China Plain].

To study the composition characteristics and source apportionment of PM2.5 in the eastern part of the North China Plain, manual samples during the two-year heating period of 2016 and 2017 were collected in seven cities, including Hengshui, Cangzhou, Ji'nan, Dezhou, Binzhou, Zibo, and Liaocheng. The results showed that the average values of ρ(PM2.5) during the observation periods were 137.23 µg·m-3 and 111.83 µg·m-3, respectively, which exceeded the daily average secondary standard limit of GB 3095-2012 "Environmental Air Quality Standard" by 1.8 and 1.5 times, respectively. The mean mass of water-soluble ions accounted for 53.32% and 47.04% of ρ(PM2.5), respectively, of which SNA (NO3-, SO42-, and NH4+) were the main ions. During the 2016 and 2017 observation periods, NO3-/SO42- increased from 1.35 to 1.60, while the concentration of Cl- decreased, indicating a decrease in the impact of coal burning. The proportions of secondary organic carbon (SOC) in organic carbon (OC) were 71.63% and 55.35%, respectively, indicating the source of secondary organic carbon had decreased. Analysis of characteristic elements Fe/Al and Ba/Ni showed that dust sources and vehicle sources had increased significantly. The backward trajectories of air mass results showed that the polluted air mass mainly came from the northwest direction during the observation period. However, the PM2.5 concentration was highest when the air mass came from the Anhui and Jiangsu provinces.

LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma.

We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients.

[The prevention of denhong injection on contrast-induced renal impairment after percutaneous coronary intervention].

OBJECTIVE: To investigate the prevention of Danhong Injection (DHI) on contrast-induced renal impairment after percutaneous coronary intervention (PCI). METHODS: Eighty patients receiving PCI were randomly assigned to the control group and the treatment group, 40 in each. All patients used loperamide injection as the contrast media, and received routine medicines such as enteric coated aspirin and Betaloc, as well as routine rehydration therapy. As for patients in the treatment group, 20 mL DHI was intravenously dripped by adding in 250 mL 0.9% sodium chloride injection from 2 -3 days before PCI to 3 days after PCI, once daily. The levels of serum creatinine (SCr), cystatin C (CysC), urine micro-albumin (mAlb), and beta2-microglobulin (beta2-MG) were measured before PCI, and 24, 48, 72 h after PCI. The occurrence of radio contrast-induced nephropathy (RCIN) of the two groups was observed. RESULTS: The serum SCr and CysC levels of the two groups reached the peak 24 h after PCI (P < 0.05, P < 0.01). But they respectively restored to the pre-PCI levels at 48 and 72 h after PCI in the treatment group. In the control group the serum SCr level basically restored to the pre-PCI level at 72 h after PCI. The urinary mAlb and beta2-MG levels of the two groups reached the peak at 24 and 48 h after PCI (P < 0.05, P < 0.01), and basically restored to the pre-PCI level at 72 h after PCI. But they did not restore in the control group (P < 0.05). Seven patients suffered from RCIN in the two groups, of them 5 (12.5%) in the control group and 2 (5.0%) in the treatment group, with no statistical difference (P > 0.05). CONCLUSIONS: DHI could effectively prevent contrast-induced renal impairment and shorten the recovery time of renal impairment. It was worth further studies.

[Detection and prognostic significance of micrometastasis in peripheral blood of patients with non-small cell lung cancer treated by chemo-radiation therapy].

OBJECTIVE: To investigate the prognostic significance of micrometastasis (MM) in peripheral blood of patients with non-small cell lung cancer (NSCLC) treated by chemo-radiation therapy. METHODS: Peripheral blood was taken from 67 NSCLC patients before and after definitive chemo-radiation therapy. CK19 mRNA of the peripheral blood was measured by nested RT-PCR and both their relationship with clinicopathological features and prognostic significance were further investigated. RESULTS: The micrometastasis-positive rates were 65.7% (44/67) and 32.8% (22/67), respectively, before and after the treatment. The micrometastasis-positive rate before treatment was closely in correlation with N-stage (P = 0.014). In contrast, it turned out to be more closely related with histological types (P = 0.019), weight loss (P = 0.01), KPS status (P = 0.027) as well as N-stage (P = 0.032) after chemo-radiation therapy. 4-yr distant metastasis rates (DMR) for micrometastasis-positive and -negative patients were 78.3% and 70.4%, respectively, before the treatment (P = 0.544) while they were 100% and 62.9%, respectively, after the chemoradiation (P < 0.001). The median survival time (MST) and 4-yr overall survival rate (OSR) for pretreatment micrometastasis-positive and -negative patients were 13.8 months and 17.6 months, and 18.2% and 17.4%, respectively (P = 0.619), while for post-treatment micrometastasis-positive and -negative patients they were 7.8 months and 27.6 months and 0 and 26.4%, respectively (P < 0.001). Multivariate analysis showed that the post-treatment positive micrometastasis was an independent unfavorable prognostic factor (P = 0.000). CONCLUSION: Detection of micrometastasis in peripheral blood may possess a prognostic significance after definitive chemo-radiation therapy. Micrometastasis-negative patients have better prognosis compared to those with positive micrometastasis.

Staging of nasopharyngeal carcinoma investigated by magnetic resonance imaging.

BACKGROUND AND PURPOSE: To investigate the American Joint Commission on Cancer (AJCC) sixth edition staging system of nasopharyngeal carcinoma (NPC) by Magnetic Resonance Imaging (MRI). PATIENTS AND METHODS: One hundred and fifty-nine non-disseminated biopsy-proven NPC patients were studied with MRI before treatment. Retrieval of MRI information enabled us to restage all patients accurately according to the sixth edition of the AJCC staging system. Splitting the respective T and N stages by the significant defining factors identified, the cancer death hazard ratios were modeled by the Cox model in SPSS 10.0 for windows (SPSS Inc, Chicago, IL). RESULTS: Single site of skull base abnormality (HR = 3.91, 95% CI: 0.74-20.56) has a superior result to others involved in T3 (HR = 5.83, 95% CI: 1.24-27.29). Involvement of either anterior or posterior cranial nerves solely (HR = 6.02, 95% CI: 1.55-35.60) was not found to be as a poor prognostic indicator as others involved in T4 (HR = 7.81, 95% CI: 1.81-33.63). Less than or equal to 3 cm of N1 (HR = 4.01, 95% CI: 0.48-33.83) and N2 (HR = 4.72, 95% CI: 0.62-35.78) have a better result than >3 cm of N1 (HR = 8.09, 95% CI: 0.95-68.97) and N2 (HR = 10.58, 95% CI: 1.32-84.62), respectively. CONCLUSIONS: Perhaps, it is better to down-stage single site of skull base abnormality from T3 to T2, and involvement of either anterior or posterior cranial nerves solely from T4 to T3, meanwhile, < or =3 cm of N2 down-stage to N1, >3 cm of N1 up-stage to N2.

Influence of MRI abnormality in skull base bone on prognosis of nasopharyngeal carcinoma.

PURPOSE: To evaluate the influence of skull base bone (SBB) abnormality showed by MRI on prognosis of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: From March 1993 to December 1998, 122 NPC patients received prime radiotherapy treatment. All of them were proved pathologically and checked by magnetic resonance imaging (MRI). Every patient received radiation through conjoint facio-cervical field and conventional dose-fractionation schedules. The total dose to the primary tumor was 60-75 Gy (median, 70 Gy). The Kaplan-Meier method, the Log-rank test and the Cox regression model were used to evaluate the significance of prognostic factors on NPC patient survival. RESULTS: The overall median survival period was 50 (6-92) months, and the 1, 3 and 5 year-survival rates were, respectively, 99.2%, 87.9%, and 73.3%. The 1, 3, and 5 year-survival rates of abnormality and normality of the SBB on MRI were 98.9%, 87.2%, 71.9%, and 100.0%, 89.8%, 77.0%, respectively (P = 0.4233). Gender, age, head pain, SBB abnormality, cranial nerve palsy, cervical lymphadenopathy and primary tumor extent were analyzed with the Cox regression model and SBB abnormality on MRI did not prove to have statistical significance (P = 0.6934). According to the analysis of regrouping, patients with SBB abnormalities > or =2 sites have a worse prognosis (P = 0.0427). Then, the above seven factors are analyzed by Cox regression model and the result had statistical significance (P = 0.0385). CONCLUSION: The SBB abnormality on MRI is of no obvious influence on prognosis of NPC. However, when SBB abnormality sites were > or =2, there is obvious statistical significance on the prognosis.

[Changes of taste bud and fungiform papillae after 60Co radiation in rat].

OBJECTIVE: To observe the morphological changes and the regenerating ability of the fungiform papillae and taste buds after 60Co radiation with clinical doses in rats. METHODS: The heads, faces and necks of 30 SD rats were radiated with a large dose and one time of 60Co in the clinical radiation. The general living condition and the number and shape of the fungiform papillae and taste buds of the tongues were observed after the radiation in rats. RESULTS: In the group of 60Co radiation, the animals had wilting, decreasing appetite, losing weight. The heads, faces and necks of animals appeared redness, peeling of hair, increasing of secretions in 5 days after the 60Co radiation. The changes reached the summit in 10 days and the general living condition of the animals recovered in 60 days. The fungiform papillae and taste buds of the animals appeared degeneration, atrophy and collapsing in 5 days after the 60Co radiation. The injuries reached the summit in 10-20 days and the fungiform papillae and taste buds regenerated partially, and the some atrophied fungiform papillae and taste buds were not regenerated in 60 days. CONCLUSION: The damage to fungiform papillae and taste buds of tongue following the 60Co radiation with the clinical doses was very serious. The damaged fungiform papillae and taste buds can regenerate partially, but not completely.