Downregulating miRNA-199a-5p exacerbates fluorouracil-induced cardiotoxicity by activating the ATF6 signaling pathway.

BACKGROUND: Fluorouracil (5-FU) might produce serious cardiac toxic reactions. miRNA-199a-5p is a miRNA primarily expressed in myocardial cells and has a protective effect on vascular endothelium. Under hypoxia stress, the expression level of miRNA-199a-5p was significantly downregulated and is closely related to cardiovascular events such as coronary heart disease, heart failure, and hypertension. We explored whether 5-FU activates the endoplasmic reticulum stress ATF6 pathway by regulating the expression of miRNA-199a-5p in cardiac toxicity. METHODS: This project established a model of primary cardiomyocytes derived from neonatal rats and treated them with 5-FU in vitro. The expression of miRNA-199a-5p and its regulation were explored in vitro and in vivo. RESULTS: 5-FU decreases the expression of miRNA-199a-5p in cardiomyocytes, activates the endoplasmic reticulum stress ATF6 pathway, and increases the expression of GRP78 and ATF6, affecting the function of cardiomyocytes, and induces cardiac toxicity. The rescue assay further confirmed that miRNA-199a-5p supplementation can reduce the cardiotoxicity caused by 5-FU, and its protective effect on cardiomyocytes depends on the downregulation of the endoplasmic reticulum ATF6 signaling pathway. CONCLUSIONS: 5-FU can down-regulate expression of miRNA-199a-5p, then activate the endoplasmic reticulum stress ATF6 pathway, increase the expression of GRP78 and ATF6, affect the function of cardiomyocytes, and induce cardiac toxicity.

Is cryoablation still suitable for advanced non-small cell lung cancer after failure of first-line chemotherapy? A multicenter, prospective, randomized-controlled trial of eighty-seven patients.

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

Compound Kushen injection attenuates angiotensin II­mediated heart failure by inhibiting the PI3K/Akt pathway.

Compound Kushen injection (CKI) is a type of traditional Chinese medicine that has previously been studied for the treatment of various types of cancer. Previous studies have reported that CKI regulates cell apoptosis by downregulating the PI3K/Akt pathway. The present study aimed to determine whether CKI alleviates heart failure (HF) by attenuating cardiomyocyte apoptosis via the inhibition of the PI3K/Akt pathway. Angiotensin II (Ang II) was used to elicit HF, and osmotic minipumps with either Ang II (2 µg/kg/day) or phosphate­buffered saline (PBS; 200 µl) were subcutaneously implanted into 6­week­old male C57BL/6 mice for 3 weeks. In addition, PBS or CKI (25 mg/kg/day) were subcutaneously infused once a day for 3 weeks. Echocardiography was used to examine hemodynamics. The myocardial injury biomarkers, cardiac troponin I and N­terminal (NT)­pro hormone B­type natriuretic peptide, were assessed using enzyme­linked immunosorbent assay. Transmission electron microscopy was used to determine the morphology of the myocardium. The rate of apoptosis was detected using TUNEL staining and flow cytometry (FCM), and the expression levels of apoptosis­related proteins were measured using western blot (WB) analysis. Moreover, H9C2 cells were treated with CKI (2 mg/ml) or LY294002 (an inhibitor of the PI3K/Akt pathway; 25 µmol/l) in combination with Ang II (1 µmol/l) for 48 h. Cell Counting Kit­8 assay, FCM and WB analysis were performed in the H9C2 cells to examine cell viability, cell cycle distribution and representative signaling proteins. It was found that CKI promoted healthy cardiac function, reduced myocardial structural damage and reduced the rate of cardiomyocyte apoptosis. CKI markedly attenuated the expression of apoptosis­related proteins in the PI3K/Akt pathway. The results of the in vitro experiments indicated that CKI promoted cardiomyocyte proliferation and inhibited apoptosis, similar to LY294002. On the whole, the present study demonstrates that CKI reduces cardiomyocyte apoptosis, promotes healthy cardiac function and attenuates Ang II­mediated HF. These ameliorative effects may be associated with the inhibition of the PI3K/Akt pathway.

Effects of image-guided adaptive radiotherapy combined with hepatic artery chemoembolization in primary liver cancer patients.

OBJECTIVE: The study aimed to explore the effects of image-guided adaptive radiotherapy combined with hepatic artery chemoembolization on the immune function of primary liver cancer patients. METHODS: The study included 84 primary liver cancer patients who received treatment at our hospital between April 2018 and January 2020. They were divided into the control group (n=42, hepatic artery chemoembolization) and the study group (n=42, image-guided adaptive radiotherapy combined with hepatic artery chemoembolization) using the random number table method. AFP, ALT, AST, CA724, CA242 and immune function before and after treatment were compared in the two groups and the short-term efficacy and adverse events (AEs) were statistically analyzed. The two groups were followed up. RESULTS: After treatment, the study group had a higher ORR and DCR compared to the control group, and the difference was statistically significant (P < 0.05). There was no statistical difference in the levels of AFP, ALT, AST, CA724 and CA242 between the two groups before treatment (P > 05). After treatment, the study group had lower levels of AFP, ALT, AST, CA724 and CA242 than the control group, and the difference was statistically significant (P < 0.05). There was no statistical difference in the levels of CD4+, CD8+, and CD4+/CD8+ before treatment in the two groups (P > 05). After treatment, the study group had higher levels of CD4+ and CD4+/CD8+ but lower levels of CD8+ compared to the control group, and the difference was statistically significant (P < 0.05). In the study group, 2 patients developed radiation-induced liver disease, and the incidence was 4.76% (2/42), which occurred at 4 and 6 weeks after the end of radiotherapy, respectively. The patients mainly had elevated transaminases, ascites, and liver enlargement and hepatoprotection and nutritional support were provided, and the patients gradually recovered after treatment. There was no statistical difference in the incidence of AEs between the two groups (p > 0.05). All patients in the study completed follow up and the follow up completion rate was 100%. The median duration of follow up was 22.5 months. In the study group, 12 of 42 patients (28.57%) died and 21 cases (50.00%) had recurrence. In the control group, 21 of 42 cases (50.00%) died and 27 cases (64.29%) recurred. At 1 year, there was no statistical difference in ORR and DCR between the two groups (P > 0.05) and at 2 years, the study group had a higher ORR and DCR than the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Image-guided adaptive radiotherapy combined with hepatic artery chemoembolization may improve the immune function of primary liver cancer patients and is of important clinical application value.

Assessment of shallow aquifer vulnerability to fluoride contamination using modified AHP-DRASTICH model as a tool for effective groundwater management, a case study in Yuncheng Basin, China.

Vulnerability assessment is an effective tool for the precaution of groundwater quality to specific pollutants. Groundwater fluoride pollution is severe and universal in the world, however, the method of groundwater risk assessment to fluorine is never built. The objective of this study was to establish an effective method to assess the potential level of groundwater vulnerability to fluoride by a modification of the typical DRASTIC model. The hydrogeochemical (H) factor (pH and TDS) was designed as a complementary parameter in the DRASTICH model. The weights of the parameters were revised by Analytical Hierarchy Process (AHP) method. The built AHP-DRASTICH model was applied to evaluate the groundwater vulnerability to fluoride contamination in Yuncheng basin, northern China, where groundwater with high fluoride concentration occurred extensively. The assessment result indicates that about 40 percent of the area belonged to relatively high and high vulnerability zones, which mainly distributed at the central part of the basin with strong evaporation and longer water-rock interaction time. The AHP-DRASTICH model shows a stronger positive correlation between risk scores and F concentration, giving better vulnerability assessment to F pollution compared with DARSTIC and DRASTICH models. The AHP-DRASTICH model is reliable and useful for guiding government and policy maker to take effective actions protecting groundwater from specific pollution.

Effect of camrelizumab plus transarterial chemoembolization on massive hepatocellular carcinoma.

OBJECTIVE: To investigate the efficacy of camrelizumab plus transarterial chemoembolization (TACE) on massive hepatocellular carcinoma (HCC) patients. METHODS: A total of 92 cases with massive HCC from October 2019 to January 2021 were prospectively enrolled and randomly divided into the study group (n = 46) and the control group (n = 46). The control group received TACE while the study group were treated with camrelizumab plus TACE. The primary end points were clinical efficacy and adverse events. And the secondary end points were liver function, and alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) levels before and after treatment. RESULTS: All participants were followed-up for 7 to 24 months, with a median of 12 months. Patients in the study group received TACE for 1-3 times, with an average of (2.01 ± 0.09) times, while patients in the control group receive TACE for 2-4 times, with an average of (3.78 ± 0.12) times, and the control group received significantly more TACEs (χ2 = 5.518, P = 0.019). During the follow-up, the response rate and disease control rate of the study group were significantly higher than those of the control group (χ2 = 5.518, P = 0.019; χ2 = 4.467, P = 0.041). Before treatment, the levels of total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), CEA, and CA19-9 were comparable between the groups (P > 0.05). After treatment, the levels of TBIL, ALT, AST, AFP, CEA, and CA19-9 decreased, and the above indicators in the study group were significantly lower than those in the control group (P < 0.05). All patients showed transient liver damage, vomiting, nausea, fever and abdominal pain after surgery, and their symptoms were relieved after symptomatic treatment. Adverse events occurred in 9 cases in the study group, and 3 cases in the control group (χ2 = 3.419, P = 0.064). CONCLUSION: Compared with TACE alone, camrelizumab plus TACE treatment can significantly improve the liver function of patients with massive HCC and enhance the treatment effect, which is worthy of clinical promotion.

Long non-coding RNA ILF3-AS1 facilitates hepatocellular carcinoma progression by stabilizing ILF3 mRNA in an m6A-dependent manner.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Increasing evidences have demonstrated that ILF3 antisense RNA 1 (ILF3-AS1) acts as an oncogenic long noncoding RNA (lncRNA) in several types of human cancers. However, the expression pattern, functional role and underlying mechanism of ILF3-AS1 in HCC remains largely unclear. Here, we found that ILF3-AS1 expression was significantly elevated in HCC tissues and also associated with prognosis of patients with HCC. Functional assays demonstrated that knockdown of ILF3-AS1 expression resulted in the suppression of proliferation, migration and invasion in HCC cells, whereas overexpression of ILF3-AS1 exerted opposite effects. Additionally, knockdown of IFL3-AS1 attenuated HCC tumorigenesis and metastasis in vivo. Mechanistically, ILF3-AS1 associated with ILF3 mRNA and inhibited its degradation. ILF3-AS1 increased ILF3 m6A level via recruiting N6-methyladenosine (m6A) RNA methyltransferase METTL3. Moreover, IFL3-AS1 enhanced the interaction between ILF3 mRNA and m6A reader IGF2BP1. Overall, our study revealed the function and mechanism of ILF3-AS1 in the malignant phenotypes of HCC cells, which provides a novel therapeutic target for HCC.

Comparison of stereotactic body radiation therapy versus fractionated radiation therapy for primary liver cancer with portal vein tumor thrombus.

BACKGROUND: To compare the clinical outcomes of stereotactic body radiation therapy (SBRT) and fractionated radiation therapy (FRT) for primary liver cancer with portal vein tumor thrombus (PVTT). METHODS: This retrospective study included 36 patients who underwent SBRT and 36 patients who underwent FRT from August 2016 to June 2018. Patients were evaluated for short-term efficacy, long-term efficacy, AEs, and quality of life before and after treatment. RESULTS: With a median follow-up of 28.8 months (26-36 months), 27 patients survived in the SBRT group while 19 patients survived in the FRT group. The survival rate in the SBRT group was statistically higher than that of the FRT group after 6 months (80.56% vs. 58.33%; P = 0.041), 12 months (77.78% vs. 55.56%; P = 0.046) and 24 months 75.00% vs. 52.78%; P = 0.049). The median whole survival time of the SBRT group was 13.3 months (95% CI 12.83-13.97), which was statistically longer than 9.8 months in the FRT group (95% CI 8.83-10.97, P < 0.05) based on the Kaplan-Meier method. The SBRT group had better survival quality and fewer adverse events than the FRT group. CONCLUSION: SBRT had better clinical outcomes than FRT for primary liver cancer with PVTT.

A fatal multiple-lesion, inflammatory, pseudotumor in the lung: a rare case report.

An inflammatory pseudotumor is considered a benign form of lesion marked by a proliferation of myofibroblasts with different degrees of inflammatory infiltrates. Pulmonary inflammatory pseudotumors (PIPs) are extremely rare in middle-aged adults. Normally, a PIP has a single lesion, and can be controlled constantly by surgery and drugs. In this paper, we report a case study of a 51-year-old male patient who presented with multiple inflammatory pseudotumors in lungs, thoracic spine, ribs, left humerusl, derived from PIPs throughout his body, which indicated a long disease term and significant recrudescence. After 6 surgeries (a wedge resection of the right lower lobe, a removal of three thoracic vertebral lesions, a removal of left humeral tumor lesion, a right lower lobe resection, local cryoablation of right lung, debridement of left upper-arm osteomyelitis and soft tissue infection), radiotherapy for lesions of left humerus destruction at a total dose of 20 Gy/10 F, and systematic treatments (30 mg prednisone acetate daily for 6 weeks, 50 mg compound cyclophosphamide tablets for 2 weeks; antibiotics, blood transfusions, nutritional support), his symptoms improved but reoccurred. The patient ultimately died of septic shock. Our case report highlights that the progression of a PIP to a malignant form requires further research. A multiple-lesion PIP that does not respond to systemic treatment can be highly dangerous.

Co-ablation versus cryoablation for the treatment of stage III-IV non-small cell lung cancer: A prospective, noninferiority, randomized, controlled trial (RCT).

BACKGROUND: This study compared a co-ablation (CA) system, which is a novel ablation device, with an argon-helium cryoablation (AHC) system. We aimed to compare the efficacy and safety of CA and AHC for the treatment of stage III-IV non-small cell lung cancer (NSCLC). METHODS: We conducted a multicenter randomized controlled trial (RCT) to determine whether CA was noninferior to AHC. The primary efficacy endpoints were the iceball coverage rate (ICR) and the disease control rate (DCR) one month after treatment. Noninferiority was declared if the lower limit of two-sided 95% confidence interval (CI) was less than 10%. The ICR and DCR were identified by logistic regression. Treatment safety was assessed. RESULTS: A total of 81 patients underwent randomization (41 assigned to the CA and 40 assigned to the AHC groups)and transthoracic ablation. The ICRs in the CA and AHC groups were 99.24% ± 2.18% and 98.66% ± 3.79%, respectively. Central lesions were associated with an increased risk of an incomplete ICR. The DCRs in the CA and AHC groups were 97.6% and 95%, respectively. A smaller lesion area in the CA group was significantly correlated with a better DCR. The rate of complications was 29.26% in the CA group and 30% in the AHC group. (P = 0.943). There was less probe usage per patient in the CA group. CONCLUSIONS: We determined that CA is noninferior to AHC in terms of efficacy and safety for the treatment of stage III-IV NSCLC. A smaller lesion area in the CA group was significantly correlated with a better DCR. KEY POINTS: CA was noninferior to AHC for stage III-IV NSCLC.

Efficacy of argon-helium cryoablation and its effects on immune function of patients with neck malignant tumours.

OBJECTIVES: Our study aimed to investigate the clinical efficacy of argon-helium cryoablation and its effects on the immune function of patients with neck malignant tumours. DESIGN: Retrospective study. SETTING: Single-institution academic tertiary care centre. METHODS: Totally, 180 patients harbouring head and neck malignant tumours were divided into the argon-helium cryoablation group (n = 150) and the radiotherapy group (n = 50). The efficacy of the two groups was compared, and the immune function was observed. RESULTS: The short-term clinical effect of the argon-helium cryoablation group was significantly higher than that of the radiotherapy group (P < .05). After treatment, the CD3+, CD4+, CD8+ and CD4+/CD8+ of the argon-helium cryoablation group were significantly better than those of the radiotherapy group (P < .001). The results of TNF-α, IL-1 ß and CRP in the argon-helium cryoablation group were significantly better than that in the radiotherapy group (P < .001). CONCLUSION: Argon-helium cryoablation could effectively improve the immune function, 5-year survival rate and local remission rate.

A novel long noncoding RNA HHIP-AS1 suppresses hepatocellular carcinoma progression through stabilizing HHIP mRNA.

Aberrant expression of long non-coding RNAs (lncRNAs) has been observed in hepatocellular carcinoma (HCC) and confirmed to participate in the initiation and progression of HCC. In the present study, we identified a novel functional lncRNA, hedgehog-interacting protein antisense RNA 1 (HHIP-AS1). The expression levels of HHIP-AS1 were significantly decreased in HCC tissues. Downregulation of HHIP-AS1 expression correlated with larger tumor size, metastasis, and advanced TNM stage, and also predicted worse overall survival rate of HCC patients. Through performing overexpression and knockdown experiments, the biological function of HHIP-AS1 was identified to suppress HCC cell proliferation, migration and invasion, while promote apoptosis. Further investigation showed that HHIP-AS1 interacted with and positively regulated the stability of HHIP mRNA in a HuR-dependent manner. HHIP-AS1 exerted its suppressive effects through HHIP. Taken together, our findings demonstrate that HHIP-AS1 represses HCC progression by promoting HHIP expression, and indicate that the use of HHIP-AS1 may offer a promising treatment for HCC patients.

Novel contrast media based on the liquid metal gallium for in vivo digestive tract radiography: a feasibility study.

The barium sulfate has been playing an important role as the contrast medium in gastrointestinal radiography and disease diagnosis. However, its application has been gradually reduced due to the limitation of its imaging effect and the progress of other imaging techniques. Here, the liquid metal gallium was proposed as an improved contrast agent, which was applied in the in vivo digestive tract radiography of the mice for the first time. Under the CT scanning, the gallium produced excellent contrast effect intuitively. According to the records of discharge time, the tissue sections of organs, the survival state and body weight, the liquid metal was proven to be capable and safe for gastrointestinal radiography. Further, the mixture of the gallium and the barium sulfate has been tested, which showed better performance in both contrast and detail. Therefore, with the characteristics of better imaging contrast effect and acceptable safety, the gallium and its mixture with the barium sulfate might be useful as potential candidates for digestive tract contrast agent in animal experiments, even possibly as alternative contrast agents for clinical use.

NaK alloy-induced in vivo tumor ablation therapy.

PURPOSE: Alkali metal ablation is newly emerging as an effective, economic and minimally invasive ablation therapy. This study is dedicated to demonstrate the high efficiency of NaK alloy ablation on in vivo tumors with different stages in mice. MATERIAL AND METHODS: Panc02 tumor cells were injected into 21 female C57B/L mice, which were divided into three groups. Two experimental groups of mice received the same percutaneous NaK alloy injection for a week apart. The inner temperature response and surface temperature distribution were measured using a thermal couple and an infrared camera. After each ablation experiment, two mice in each group were chosen randomly to make pathological sections. The tumor volumes were measured once every two days. At the end, all tumors were cut off to calculate the tumor inhibition rates. RESULTS: The NaK alloy-induced ablation therapy produced an obvious temperature increase (85 °C) in the ablation region and the high temperature distribution was relatively concentrated. The histopathology sections showed that developing stage tumors received incomplete destruction of the malignant cells compared with early stage tumors. The tumor inhibition rate in the early and developing tumor treatment groups were 88.5% and 67.6%, respectively. CONCLUSIONS: This technology provides a nearly thorough ablation treatment for early stage tumors and also a palliative treatment for developing tumors.

Characteristics of Modic changes in cervical kyphosis and their association with axial neck pain.

BACKGROUND: The purpose of this study was to evaluate characteristics of Modic changes in cervical kyphosis (CK) and their association with axial neck pain. METHODS: Study participants included 286 asymptomatic or symptomatic patients with CK (mean age = 54.2 ± 12.2 years) who were consecutively enrolled from March 2009 to October 2015. Clinical and radiographic evaluations were performed at a university outpatient department. CK was classified as global type, reverse sigmoid type, or sigmoid type. RESULTS: There were 138 participants with global type CK, 103 with reverse sigmoid type CK, and 45 with sigmoid type CK. Of the 286 participants, 102 had Modic changes (Modic-1 in 38 segments and Modic-2 in 75 segments). Spinal cord compression grade and disc degeneration occurred more frequently in the group with axial neck pain compared to the group without pain. Angular motion was decreased in those with axial neck pain (mean ± standard deviation [SD] 7.8°±4.6°) compared to those who were asymptomatic (mean ± SD 8.9°±5.1°; P<0.001). In multivariate logistic regression analysis, Modic changes were associated with axial neck pain (odds ratio =5.356; 95% confidence interval =1.314-12.800; P<0.001). CONCLUSION: Modic changes occur most commonly in association with CK global type and less commonly with reverse sigmoid type and sigmoid type. Modic changes are associated with axial neck pain in patients with CK.

Incidence and risk factors of axial symptoms after cervical disc arthroplasty: a minimum 5-year follow-up study.

BACKGROUND: The purpose of this study was to investigate whether uncovertebral joint ossification was a risk factor for axial symptoms (AS) after cervical disc arthroplasty (CDA). METHODS: This retrospective study included 52 consecutive patients who underwent CDA for single-level cervical disc disease. To examine possible risk factors for AS after CDA, univariate and multivariate logistic regression analyses were conducted to compare data from the patients with and without AS (the AS and no-AS groups, respectively). RESULTS: Among the 52 patients examined, AS were observed in 24 patients (46.2 %), including a stiff neck (n = 11), neck pain and dullness (n = 10), and shoulder pain (n = 3). Uncovertebral joint ossification was detected in 22 (42.3 %) patients, including 17 patients in the AS group and 5 patients in the no-AS group. Clinical outcome improved during the follow-up period for the AS group. According to multivariate logistic regression analysis, uncovertebral joint ossification, cervical kyphosis, and range of motion (ROM) at the index level were identified as significant risk factors for AS after CDA. CONCLUSIONS: Satisfactory clinical outcomes were observed following CDA for the treatment of single-level cervical disc disease in the present cohort. In addition, uncovertebral joint ossification, cervical kyphosis, and ROM at the index level were found to affect the incidence of AS after CDA.

Long noncoding RNA uc.338 promotes cell proliferation through association with BMI1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common human cancers all over the world. Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in malignant transformation, tumor growth and metastasis in HCC. Among lncRNAs, ultraconserved RNAs (ucRNAs) containing an ultraconserved region have been report to contribute to human cancers. lncRNA ultraconserved element 338 (uc.338) was first found to be upregulated in HCC and promote cell growth. However, the exact mechanism by which uc.338 modulates cell growth remains unclear. In the present study, we demonstrated that uc.338 promotes HCC cell proliferation and induces cell cycle progression. RNA-immunoprecipitation and RNA pull-down assays showed that uc.338 associated with BMI1. We found that uc.338 promotes HCC cell proliferation and induces cell cycle progression through association with BMI1. uc.338 also modulated the transcription of CDKN1A. The oncogenic activity of uc.338 is partially due to its repression of p21. uc.338 may be a potential target for HCC therapy.

Effects of Temozolomide and Radiotherapy on Brain Metastatic Tumor: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate safety and efficacy of temozolomide plus radiotherapy in the treatment of brain metastasis. METHODS: Literature was searched in the following databases: Cochrane Controlled Trials Register (CENTRAL), PubMed (1994-2015.10), CBM (1978-2015.10), CNKI (1994-2015.10), VIP (1994-2015.10), and WANFANG (1994-2015.10). Randomized clinical trials (RCTs) of temozolomide plus radiotherapy in comparison with radiotherapy alone were included in this review and meta-analysis. The quality of included literatures was assessed by the international Cochrane collaboration method, and meta-analysis was performed using RevMan 5.0 software. RESULTS: Total 19 publications of RCTs were included, and there was no allocation concealment or blinding in any of them. Six of the 19 were multicenter RCTs. Overall response rate (ORR) was in favor of radiotherapy plus temozolomide (risk ratio [RR] = 1.35, 95% CI: 1.23-1.47). Subgroup analysis of non-small cell lung cancer (NSCLC) metastasis brain tumor also showed that ORR was in favor of radiotherapy plus temozolomide (RR = 1.38; 95% CI: 1.17-1.63). Progression-free survival (PFS) or overall survival rate, however, was not significantly different between the 2 treatment groups. In addition, incidence of side effect was significantly higher in the group of radiotherapy plus temozolomide than that of radiotherapy alone (HR = 2.03, 95% CI: 1.56-2.64). CONCLUSION: Addition of temozolomide to radiotherapy could increase ORR in brain metastatic tumors. However, it did not significantly improve PFS or OS in the patients with brain metastases but increased risk of drug-related toxicity.

Occurrence and hydrogeochemical characteristics of high-fluoride groundwater in Xiji County, southern part of Ningxia Province, China.

High-F(-) groundwater is widely distributed in Xiji County, which endangers the safety of drinking water. In order to evaluate the key factors controlling the origin and geochemical mechanisms of F(-) enrichment in groundwater at Xiji County, one hundred and five groundwater samples and sixty-two sediment samples were collected. Fluoride concentration in the groundwater samples ranged from 0.2 to 3.01 mg/L (mean 1.13 mg/L), with 17 % exceeding the WHO drinking water guideline value of 1.5 mg/L and 48 % exceeding the Chinese drinking water guideline value of 1.0 mg/L. High-F(-) groundwaters were characterized by hydrochemical types of Na-HCO3 and Na-SO4·Cl, which were found in Quaternary sediment aquifer and in Tertiary clastic aquifer, respectively. Conditions favorable for F(-) enrichment in groundwater included weakly alkaline pH (7.2-8.9), low concentration of Ca(2+), and high concentrations of HCO3 (-) and Na(+). Calcite and fluorite were the main minerals controlling F(-) concentration in groundwaters. The hydrolysis of F-bearing minerals in aquifer sediments was the more important process for F(-) release in Tertiary clastic aquifer, which was facilitated by long residence time of groundwater, in comparison with Quaternary sediment aquifer. Cation exchange would also play important roles, which removed Ca(2+) and Mg(2+) and led to more free mobility of F(-) in groundwater and permitted dissolution of fluorite, especially in Tertiary clastic aquifer. However, evapotranspiration and competing adsorption of B and HCO3 (-) were the more important processes for F(-) enrichment in Quaternary groundwater. Groundwater in Lower Cretaceous aquifer had relatively low F(-) concentration, which was considered to be the potential drinking water resource.