Facile activation of natural calcium-rich sepiolite with oxalic acid for selective Pb(II) removal: Highly-efficient performance, mechanisms and site energy distribution.

The design and development of adsorbents with high efficiency, selectivity, and economy for Pb(II) are essential to environmental governance and ecological safety. Herein, an oxalic acid (OA) activated natural sepiolite (nSEP) composite for highly efficient Pb(II) removal was prepared by a facile impregnation strategy. The OA activated nSEP nanocomposite (OA-nSEP) was characterized by various instrumental techniques and its adsorption performance towards Pb(II) was further evaluated through a series of static and dynamic experiments under various environmental conditions. Results revealed that OA reacted with the calcium impurities in nSEP to form calcium oxalate, causing mesoporous structure and larger specific surface area of OA-nSEP. The obtained OA-nSEP possessed super high Pb(II) adsorption capacities (858.4-1252 mg/g), which were much higher than that of most modified clays or conventional materials. The average adsorption site energy and the standard deviation of the site energy distribution were analyzed to investigate the strength of Pb(II) binding onto OA-nSEP and the adsorption site heterogeneity. Mechanism studies confirmed that oxalate groups exerted a primary role in the adsorption process. X-ray diffraction and X-ray photoelectron spectrometry (XPS) unveiled that the coordination of oxalate with Pb(II) and precipitation of lead oxalate was responsible for the high efficiency and selectivity. Distinguishing feature of high adsorption capacity, specific selective adsorption, abundant availability, and splendid reusability make the OA-nSEP a promising candidate for eliminating Pb(II) in practical scenarios.

Efficacy and safety of toripalimab with fruquintinib in the third-line treatment of refractory advanced metastatic colorectal cancer: results of a single-arm, single-center, prospective, phase II clinical study.

Background: The most effective treatment with immune checkpoint inhibitors (ICIs) is limited to the microsatellite instability high (MSI-H) subgroup of advanced colorectal cancer. ICIs are completely ineffective in microsatellite stabilized (MSS) patients with advanced colorectal cancer. Fruquintinib, a tyrosine kinase inhibitor (TKI) domestically made in China that specifically inhibits vascular endothelial growth factor receptors, is used to treat refractory metastatic colorectal cancer (mCRC). Researches showed that anti-angiogenic therapy combined with immunotherapy induces a long-lasting antitumor immune response. Here, we aimed to evaluate antitumor efficacy and safety of fruquintinib with anti-programmed death-1 (PD-1) antibody toripalimab in Chinese patients with non-MSI-H/mismatch repair proficient (pMMR) mCRC. Methods: This was a single-arm, single-center, prospective, phase II clinical trial. A total of 19 MSS patients with refractory or advanced mCRC were enrolled They received fruquintinib (5 mg, orally, once daily for 3 weeks followed by 1 week off in 4-week cycles) and toripalimab (240 mg, intravenously administered on day 1 once every 3 weeks) until disease progression or unacceptable toxicity. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), 1-year PFS rate, disease control rate (DCR), and toxicity were reviewed and evaluated. The Cox regression model was used to analyze the influence on OS and PFS. Results: Among the 19 patients, the median age was 52 years (range, 30-71 years); 4 patients (21.05%) achieved partial response, 10 patients (52.63%) experienced stable disease, and 4 patients (21.05%) experienced progressive disease. The ORR was 21.05%. The median PFS and OS were 5.98 months and 11.10 months, respectively. Patients with peritoneal metastasis received greater benefit from combination therapy, with a longer PFS (P=0.043) in the univariate analysis. The most common treatment-related adverse reactions were fatigue (57.89%), hepatic dysfunction (42.11%) and hypertension (36.84%). No serious adverse effects or adverse effect-related deaths were reported. Conclusions: Our study provides evidence supporting fruquintinib combined with an anti-PD-1 monoclonal antibody have the better effect than fruquintinib alone in the third-line setting for Chinese patients with MSS advanced colorectal cancer. Primary lesion excision and peritoneal metastasis were independent prognostic factors of PFS. Further well-designed, prospective, large-scale studies are needed to validate this outcome.

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

Application of computed tomographic angiography and echocardiography in predicting left atrial appendage thrombosis in patients with non-valvular atrial fibrillation.

AIM: We aimed to explore the application of computed tomographic angiography (CTA) and echocardiography in predicting left atrial appendage (LAA) thrombosis in patients with non-valvular atrial fibrillation. METHODS: The clinical data of 164 atrial fibrillation patients receiving cardiac CTA and real-time three-dimensional transoesophageal echocardiography (RT-3D-TEE) were retrospectively analysed. The patients were divided into group A (anticoagulant treatment group, n = 112) and group B (selective anticoagulant treatment group, n = 52) according to the CHA2DS2-VASc score, which scored for the presence or absence of congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischaemic attack, vascular disease, age 65-74 years and gender (female). The CHA2DS2-VASc score was used to predict risk of thromboembolism from atrial fibrillation. The correlations of CHA2DS2-VASc score with CTA-based LAA classification and RT-3D-TEE measurement parameters were explored using Spearman's analysis. Receiver operating characteristic (ROC) curves were plotted to explore the predictive value of CTA and RT-3D-TEE for LAA thrombus. RESULTS: There were significant differences in age, disease course, hypertension, diabetes mellitus, coronary heart disease, heart failure, stroke/transient ischaemic attack/thromboembolism, vascular disease, B-type natriuretic peptide and serum uric acid levels, CHA2DS2-VASc score, LAA classification, left ventricular ejection fraction (LVEF), left atrial diameter (LAD), maximum diameter of LAA orifice, minimum diameter of LAA orifice and LAA length (p < 0.05). CHA2DS2- VASc score was positively correlated with cauliflower LAA, LAD, maximum diameter of LAA orifice, minimum diameter of LAA orifice and LAA length, and negatively correlated with LVEF (p < 0.001). ROC curve analysis indicated that CTA, RT-3D-TEE and CHA2DS2-VASc score had similar predictive values for risk of LAA thrombosis in atrial fibrillation patients, with the areas under the curve being 0.778, 0.814 and 0.792, respectively. CONCLUSIONS: Both CTA and RT-3D-TEE had high predictive values for LAA thrombosis in atrial fibrillation patients.

The effectiveness and safety of the rapid titration strategy of background controlled-release oxycodone hydrochloride for patients with moderate-to-severe cancer pain: A retrospective cohort study.

Background: Oxycodone hydrochloride is a semisynthetic narcotic analgesic agent. This study aimed to explore optimal titration strategy of controlled-release (CR) oxycodone hydrochloride in patients with cancer pain. Methods: 258 patients, who used regular strong opioids (morphine and CR oxycodone hydrochloride) for cancer pain across 25 three grade class hospitals in China during January 15th 2017 to April 30th 2017, were retrospectively studied. The patients were divided into 4 groups according to treatment regimens titrated. The pain remission rate and numeric rating scale (NRS) of cancer pain was recorded at 0, 12, 24, 36, 48, 60, 72 h after opioid titration. The incidence of adverse events (AEs) with therapy were also observed. Results: 12 h after treatment, pain remission rate of Group B, C and D was significantly higher (P < 0.001) than Group A. For the complete remission rate, there were also significant differences among the four groups (P < 0.001). No significant difference was found among four groups for pain remission rate at 24, 72 h after treatment. Multiple comparison of NRS scores showed that the both Group B and C varied significantly with Group D (P = 0.028, P = 0.05, respectively), showing superior analgesic effect over Group D. AEs were significantly different among groups (P < 0.01), with the most frequent AEs in Group A, lowest in Group B. Conclusion: The rapid titration strategy of background CR oxycodone hydrochloride was effectiveness and safety in patients with moderate-to-severe cancer pain.

Comparing the influence of humic/fulvic acid and tannic acid on Cr(VI) adsorption onto polystyrene microplastics: Evidence for the formation of Cr(OH)3 colloids.

Microplastics (MPs) can act as vectors for various contaminants in the aquatic environment. Although some research has investigated the adsorption characteristics and influencing factors of metals/organic molecules on MPs, the effects of dissolved organic matter (DOM) (which are ubiquitous active species in ecosystems) on metal oxyanions such as Cr(VI) capture by MPs are largely unknown. This study explored the adsorption behaviors and mechanisms of Cr(VI) oxyanions onto polystyrene (PS) MPs using batch adsorption experiments and multiple spectroscopic methods. The effects of representative DOM components (i.e., humic acid (HA), fulvic acid (FA) and tannic acid (TA)) on Cr(VI) capture by PS were particularly studied. Results revealed a significantly enhanced adsorption of Cr(VI) on PS in the presence of TA. The Cr(VI) adsorption capacity was increased from 2876 µg g-1 to 4259 µg g-1 and 5135 µg g-1 when the TA concentrations raised from 0 to 10 and 20 mg L-1, respectively. Combined microscopic and spectroscopic investigations revealed that Cr(VI) was reduced to Cr(III) by TA and formed stable Cr(OH)3 colloids on PS surfaces. Contrarily, HA and FA inhibited Cr(VI) adsorption onto PS, especially at pH > 2.0 and higher DOM concentrations, due to site competition and electrostatic repulsion. Increase in pH was found to reduce zeta potentials of MPs, resulting in inhibited Cr(VI) adsorption. The adsorbed Cr(VI) declined with increasing ionic strength, implying that outer-sphere surface complexation affected the adsorption process in the presence of DOM. These new findings improved our fundamental understanding of the fate of Cr(VI) and MPs in DOM-rich environmental matrices.

Treatment mechanism of matrine in combination with irinotecan for colon cancer.

The inhibitory effect of matrine (MA) was studied in combination with irinotecan (CPT-11) on proliferation of human colon carcinoma cell line HT29. We also explored the mechanism of cell apoptosis induction in HT29. HT29 cells were treated with different concentrations of MA and CPT-11 alone and in combination. The growth inhibition in HT29 cells was evaluated using MTT assay. Apoptosis was detected using AV-PI double staining flow cytometry. Transmission electron microscopy was used to detect structural changes in cells. Topoisomerase (TOPO) I, Bax and Caspase-3 expression levels were evaluated using western blot analysis. MA and CPT-11 alone and in combination, inhibited the proliferation of HT29 cells, whereas the combination treatment exhibited higher inhibitory effect (P<0.01). This suggests the existence of synergistic cytotoxicity. Compared with each treatment alone, the combination treatment caused more significant damage to cell structure, and caused a significantly higher apoptosis rate (P<0.01). Additionally, the combination treatment increased TOPO I, Bax and Caspase-3 expression levels (P<0.01). In conclusion, MA in combination with CPT-11 synergistically inhibited HT29 cell proliferation and induced apoptosis in these cells. The mechanism may be related to upregulation of the TOPO I, Bax and Caspase-3 protein expression.

Association between the ERCC1 rs11615 polymorphism and clinical outcomes of oxaliplatin-based chemotherapies in gastrointestinal cancer: a meta-analysis.

PURPOSE: The relationship between the excision repair cross-complementing 1 (ERCC1) rs11615 polymorphism (C/T) and responses to oxaliplatin-based chemotherapy for gastric cancer (GC) and colorectal cancer (CRC) patients is controversial. Therefore, we performed a meta-analysis to assess this relationship. METHOD: Relevant studies were retrieved by searching the PubMed database. A systematic review and meta-analysis was performed to evaluate the predictive value of the ERCC1 rs11615 polymorphism for the clinical outcomes of GC and CRC patients receiving oxaliplatin-based chemotherapy. Therapeutic response to chemotherapy, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: A total of 22 studies were included in this meta-analysis, including 1,242 cases of GC and 1,772 cases of CRC. For the ERCC1 rs11615 polymorphism, the T allele was associated with a reduced response to chemotherapy in Asians and GC patients (P<0.05). On the other hand, the T allele was associated with a significant increase in the risk for shorter PFS and OS in all patients (PFS: hazard ratio [HR] =1.22, P<0.001, 95% confidence interval [CI] =0.93-1.51 and OS: HR =1.12, P<0.001, 95% CI =0.85-1.40). CONCLUSION: The ERCC1 rs11615 polymorphism was closely associated with the clinical outcomes of GC and CRC patients treated with oxaliplatin-based chemotherapy.

[MODEL ESTABLISHMENT, MRI AND PATHOLOGICAL FEATURES OF EARLY STEROID-INDUCED AVASCULAR NECROSIS OF FEMORAL HEAD IN RABBIT].

OBJECTIVE: To establish an rabbit model of early steroid-induced avascular necrosis of the femoral head (SANFH) and evaluate its validity with MRI and pathological examination. METHODS: Twenty 6-month-old rabbits (weighing, 2-3 kg) were randomly divided into 2 groups (control group and model group), 10 rabbits in each group. Dexamethasone sodium phosphate solution (10 mg/kg) was injected into bilateral gluteus in model group, and the same amount of saline was injected in control group, every 3 days for 14 times. General observation was done after modelling. Osteonecrosis was verified by pathological observation and MRI findings at 6 weeks. RESULTS: After 6 weeks, rabbits did not show obvious changes in control group; increased hair removal, decreased food intake, and slight limp were observed in model group. The MRI results showed normal shape of the bilateral femoral head and no abnormal signals in control group; irregular shape of the bilateral femoral head and a slice of irregular abnormal signals were observed, and necrosis and cystolization of the subchondral bone and sparse changes of trabecular bone were shown in model group. General observation from coronal section of femoral head showed smooth red cartilage surface in control group; on the contrary, the cartilage surface of the femoral head became dull, thin even visible hemorrhage under articular cartilage and necrosis of the femoral head were observed. The histopathological examination indicated that trabecular bone of the femoral head in control group was massive, thick, and close and osteocytes in the bone lacunae had normal shapes. The osseous trabecular became thinner and broken; karyopyknosis of osteocytes and bone empty lacunae could be obviously seen in model. group. The rates of empty lacunae were 8.0% ± 0.5% in control group and 49.0% ± 0.3% in model group, showing significant difference (t = 21.940, P = 0.000). CONCLUSION: Establishing a model of early SANFH through injecting short-term, shock, and high dose of dexamethasone, and it can been evaluated effectively with MRI and pathological examination.

Lack of association between the XPD Lys751Gln polymorphism and colorectal cancer risk: a meta-analysis.

BACKGROUND: The xeroderma pigmentosum complementary group D (XPD) gene has been linked to the development of colorectal cancer (CRC) through disruption of DNA repair. Several studies have suggested that the XPD polymorphism Lys751Gln is associated with an increased risk of developing CRC. However, previous results remain inconclusive. Herein, we performed a meta-analysis to evaluate the potential for this relationship. METHODS: Relevant studies were retrieved from the PubMed database. Strict selection and exclusion criteria were determined, and the odds ratio with a 95% confidence interval was used to assess the strength of associations. The fixed or random effects model was selected on the basis of heterogeneity tests among studies. Publication bias was estimated using funnel plots and Egger's regression test. RESULTS: The meta-analysis included 2,961 cases and 4,539 controls from eleven studies. The results indicated that the XPD Lys751Gln polymorphism had no association with CRC risk for all genetic models (Gln-Gln versus Lys-Lys, P=0.477; Lys-Gln versus Lys-Lys, P=0.283; Lys-Gln + Gln-Gln versus Lys-Lys, P=0.562), even when compared within subgroups based on ethnicity and source of controls. CONCLUSION: Based on the results of our meta-analysis, there is no evidence of a link between the XPD Lys751Gln polymorphism and risk of CRC.

The prognostic value of osteopontin expression in non-small cell lung cancer: a meta-analysis.

To investigate the association of Osteopontin (OPN) expression in tumor tissue with clinicopathological features of non-small cell lung carcinoma (NSCLC) patients. Publications assessing the clinicopathological characteristics and prognostic significance of OPN in expression NSCLC were identified up to March 2014. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between OPN expression and these clinical parameters. A total of eleven studies met the inclusion criteria, and included 1536 cases of NSCLC tumor tissue and 340 cases of normal lung tissue. The OPN expression rate in NSCLC tissue was higher than normal tissue [Odds ratio (OR) 6.427; 95% confidence interval (CI) 4.689-8.808; P = 0.000]. Simultaneously, we also found that OPN expression was positively associated with stage (OR 0.332; 95% CI 0.250-0.440; P = 0.000), lymph node metastasis (OR 3.094; 95% CI 2.295-4.172; P = 0.000), tumor size (tumor size <3 cm vs. ≥3 cm; OR 0.484; 95% CI 0.303-0.773; P = 0.002) and pathology (OR 0.611; 95% CI 0.466-0.800; P = 0.000). It was unrelated that OPN expression in NSCLC tissue with and degree of differentiation and other clinical features (P > 0.05). Experimental findings indicate that, OPN plays a crucial role in the development of NSCLC.