Safety and efficacy of apatinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma after the failure of two or more lines of chemotherapy (AHEAD): a prospective, single-arm, multicenter, phase IV study.

BACKGROUND: Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. METHODS: Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. RESULTS: Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1). CONCLUSIONS: The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Effective removal of methylene blue with zero-valent iron/tea residual biochar composite: Performance and mechanism.

Zero-valent iron (Fe0)-modified biochar (BFN) was prepared via low-temperature pyrolysis of tea residue (TR) and ferric nitrate hexahydrate (FN) coupled with NaOH activation for the removal of methylene blue (MB). BFN exhibited a specific surface area of 382.66 m2·g-1, an average pore diameter of 4.97 nm and an equilibrium adsorption capacity as high as 452.5 mg·g-1 of 0.33 g·L-1 toward 150 mg·L-1 MB within 60 min at 30 °C and pH 7.0. The recovered MB is far below of the removal rate in each of adsorption-desorption cycle because the removal mechanism is that MB molecular was firstly chemically adsorbed, then it was reduced and mineralized by BFN with the formation of nitrate, sulfate, CO2 and H2O.

Case report: Conversion therapy for advanced intrahepatic cholangiocarcinoma using PD-1 inhibitor plus S-1 and nab-paclitaxel.

Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant hepatobiliary tumor with a high rate of advanced disease at initial presentation. Conversion into resectable iCCA is important for improving the prognosis. Immunotherapy-based regimens are being increasingly used for treating advanced iCCA in recent years. However, the use of combined chemotherapy and immunotherapy for conversion has rarely been reported. The aim of this report was to present the outcomes of a 52-year-old female patient with IIIB iCCA. The patient was treated with a programmed cell death protein-1 inhibitor plus S-1 and nab-paclitaxel. The postoperative histopathological results indicated pathologic complete response after six cycles of systematic treatment. The patient is currently disease-free for one year.

Effect of underdilated transjugular intrahepatic portosystemic shunt on prognosis in patients with prior splenectomy: a propensity score-matched case-control study.

PURPOSE: This study aimed to investigate whether underdilated transjugular intrahepatic portosystemic shunt (TIPS) could reduce the risk of hepatic encephalopathy (HE) and ameliorate impaired hepatic function in patients with a history of splenectomy. METHODS: A retrospective case-control study was conducted with 96 patients who had prior splenectomy and TIPS placement from August 2016 to May 2022. All patients were divided into two groups based on the diameter of expansion balloon catheters, the underdilated group (6-mm balloon catheter, n = 60) and a control group (8-mm balloon catheter, n = 36). Following the 1:1 propensity score matching (PSM), 33 patients in the underdilated group and 33 patients in the control group were included. RESULTS: During a median follow-up of 36 months, a quicker recovery in liver function after TIPS placement was showed in the underdilated group. The mean TBIL content (16.562 ± 6.549 µmol/L vs 23.871 ± 11.609 µmol/L, P = 0.019) and the mean CLIF-C AD score (41.108 ± 5.223 vs 45.100 ± 4.429, P = 0.033) in the underdilated group were significantly lower than those in the control group during 6 to 12 months after the procedure. In line with the control group, the ability to reduce portal pressure gradient (PPG) and achieve a significantly clinical remission of PVT and ascites severity was showed in the underdilated group 3 months after TIPS creation (P < 0.001). The Kaplan-Meier analysis demonstrated that no statistically significant differences were found in the cumulative incidence of no overt HE (OHE) (log-rank P = 0.383), cumulative incidence without shunt dysfunction (log-rank P = 0.283), cumulative incidence of no variceal rebleeding (log-rank P = 0.696), and survival (log-rank P = 0.341) (log-rank P = 0.341) between the two groups during the follow-up period. CONCLUSION: For patients with prior splenectomy, it is safe to employ underdilated TIPS, as the stents will eventually self-expand to 8 mm. The present study has shown some degree of liver function preservation in the underdilated group, which may be related to slower progressive changes in the portal hemodynamics.

Association between clinical characteristics and CT findings in patients with coronavirus disease-2019.

ABSTRACT: This retrospective study was to investigate the association between clinical characteristics and computerized tomography (CT) findings in patients with coronavirus disease-2019 (COVID-19). The clinical data of COVID-19 patients were retrospectively analyzed. Spearman correlation analysis was used to identify the correlation. Totally 209 consecutive COVID-19 patients were eligible for the study, with the mean age of 47.53 ±â€Š13.52 years. At onset of the disease, the most common symptoms were fever (85.65%) and cough (61.24%). The CT features of COVID-19 included pulmonary, bronchial, and pleural changes, with the significant pulmonary presentation of ground-glass opacification (93.30%), consolidation (48.80%), ground-glass opacification plus a reticular pattern (54.07%), telangiectasia (84.21%), and pulmonary fibrotic streaks (49.76%). Spearman analysis showed that the CT findings had significantly inverse associations with the platelets, lymphocyte counts, and sodium levels, but were positively related to the age, erythrocyte sedimentation rate, D-dimer, lactic dehydrogenase, α-hydroxybutyrate dehydrogenase, and C-reactive protein levels (P < .05). In conclusion, the severity of lung abnormalities on CT in COVID-19 patients is inversely associated with the platelets, lymphocyte count, and sodium levels, whereas positively with the age, erythrocyte sedimentation rate, D-dimer, lactic dehydrogenase, hydroxybutyrate dehydrogenase, and C-reactive protein levels.

The Clinical Value of Multislice Spiral Computed Tomography in the Diagnosis of Upper Digestive Tract Diseases.

Imaging methods for gastrointestinal diseases were based on X-ray imaging until the 1970s, but the development of fiberoptic endoscopy in the 1980s has replaced X-ray imaging. Endoscopy can directly observe the location, size, scope, and color of lesions and obtain pathological results through biopsy, while ligation and other treatments can be performed on polyps and other lesions. Studies have shown that multilayer spiral computed tomography (CT) examination after standardized gastrointestinal preparation and full use of the advantages of various 3D postprocessing reconstruction techniques are of great clinical value in the detection of gastrointestinal diseases, determination of the nature of lesions, localization of lesions, and staging of gastrointestinal malignancies and can make up for the shortcomings of fiberoptic endoscopy, and various 3D postprocessing reconstruction modes have their own advantages and disadvantages. Among them, conventional CT cross-sectional images are the basic images for the diagnosis of various gastric testicular lesions. Axial images, especially thin-layer axial images, can detect the absolute majority of lesions, but there are limitations in observing the anatomical position of lesions, invasion of surrounding tissues, lymph node metastasis, vascularity, and determination of the stage of malignant tumors.

Long non­coding RNA CASC19 promotes glioma progression by modulating the miR­454­3p/RAB5A axis and is associated with unfavorable MRI features.

Glioma is one of the most common malignancies of the nervous system. Long non­coding RNAs (lncRNAs) are regulators involved in the progression of tumors. The present study aimed to determine the role of lncRNA cancer susceptibility 19 (CASC19) in glioma and its underlying molecular mechanism. Reverse transcription­quantitative PCR was performed to detect CASC19 and microRNA (miR)­454­3p expression in glioma and normal brain tissues. Ras­related protein in brain 5A (RAB5A) expression in glioma cells was also analyzed via western blotting. The relationship between CASC19 expression, clinicopathological parameters and MRI characteristics in patients with glioma was analyzed. Cell Counting Kit­8, BrdU, wound healing and Transwell assays were adopted to detect glioma cell proliferation, migration and invasion, respectively. The dual­luciferase reporter gene and RNA immunoprecipitation experiments were conducted to verify the targeting relationship between CASC19 and miR­454­3p, and between miR­454­3p and RAB5A. The results revealed that CASC19 expression was significantly upregulated in glioma tissues and cell lines. CASC19 expression was also positively associated with tumor diameter and pathological grade. Additionally, its high expression was closely associated with tumor MRI signal heterogeneity and peritumoral edema. CASC19 upregulation promoted glioma cell proliferation and metastasis, while CASC19­knockdown demonstrated the opposite effect. CASC19 sponged miR­454­3p, which indirectly increased RAB5A expression. The results demonstrated that the CASC19/miR­454­3p/RAB5A axis is involved in the promotion of glioma progression.

IL-17 predicts the effect of TACE combined with apatinib in hepatocellular carcinoma.

OBJECTIVE: IL-17 is considered to be a cancer-promoting gene in hepatocellular carcinoma (HCC). Here, we explored the effect of IL-17 in predicting the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with apartinib in patients with HCC in this study. METHODS: Established of IL-17 knockdown SK-Hep1 cells for studying the effects of IL-17 expression on the invasion and migration of human HCC cells in vitro by transwell assay and tumor angiogenesis in nude mouse. Immunohistochemistry was used to detect the expression of IL-17, E-cadherin, Vimentin and CD34 protein in 175 cases of human HCC tumor tissues. Kaplan-Meier was used to analyze the prognostic significance of TACE combined with apatinib treatment in HCC patients. RESULTS: n SK-Hep1 cells, IL-17 knockdown could increase E-cadherin protein expression, reduce vimentin protein expression, inhibit cell invasion and migration in vitro, and inhibit angiogenesis of tumor and decrease plasma VEGF level in nude mouse. In tumor tissues of HCC patients, IL-17 protein expression was negatively correlated with E-cadherin protein expression (r = -0.622, P < 0.001), positively correlated with Vimentin protein expression (r = 0.540, P < 0.001), and was positively correlated with MVD of HCC tumor tissues (r = 0.564, P < 0.001). Compared with adjuvant TACE alone, patients with low-expression of IL-17 treated combined with apatinib have a higher 5-year overall survival. However, additional apatinib treatment did not significantly improve 5-year overall survival in HCC patients with high IL-17 expression. CONCLUSION: IL-17 had a pivotal role in the invasion and angiogenesis of HCC and contribute to the selection of patients who may benefit from adjuvant TACE combined with apatinib.

Insights on the structure and digestibility of sweet potato starch: Effect of postharvest storage of sweet potato roots.

To unravel changes in the structures and digestibility of sweet potato starch in the roots during postharvest storage (0 to 20 days), starches are isolated and characterized in terms of amylose content, polyphenols amount, molecular molar mass (Mw), molecular reassociation and multi-scale reassociated structures after cooking. Results reveal that starch digestibility decreases with a concomitant increase on resistant starch (RS) fraction during the first 10 days. These changes are associated with an increase of ordered structures, amylose and polyphenols content as well as the starch fractions with molecular weight of (2.0-2.5) × 107 g/mol. However these trends get reversed at higher postharvesting periods. Correlation matrices reveal that the short-range ordered structures and starch molecular reassociation behavior of starch paste and polyphenol content are the key factors in determining the RS content. Besides, the short-range ordered structures, specific starch molecular weight distribution and amylose of starch paste can be tailored for modulating the digestibility by controlling the postharvest storage time. This study opens a promising pathway to tailor starch digestibility via simply controlling the postharvest storage time of starch-containing crops.

One-pot bottom-up fabrication of biocompatible PEGylated WS2 nanoparticles for CT-guided photothermal therapy of tumors in vivo.

BACKGROUND: Tungsten disulfide (WS2), which enjoyed a good potential to be a promising clinical theranostic agent for cancer treatment, is still subject to the tedious synthesis procedure. METHODS: Here, we reported a one-pot 'bottom-up' hydrothermal strategy for the fabrication of PEGylated WS2 nanoparticles (NPs). The WS2-PEG nanoparticles were characterized systematically. The CT imaging and photothermal therapy against tumor as well as biosafety in vitro and in vivo were also investigated. RESULTS: The obtained WS2-PEG NPs enjoyed obvious merits of good solubility and favorable photothermal performance. WS2-PEG NPs exhibited desirable photothermal ablation ability against cancer cells and cancer cell-bearing mice in vitro and in vivo. MTT assay and histological analysis demonstrated the low cytotoxicity and biotoxicity of WS2-PEG NPs, providing a valid biosafety guarantee for the coming biomedical applications. In addition, thanks to the obvious X-ray attenuation of W atom, the WS2-PEG NPs can also be served as a favorable contrast agent for CT imaging of tumors. CONCLUSION: WS2-PEG NPs has enjoyed a good potential to be a promising clinical CT-guided photothermal therapeutic agent against cancers.

The role of adenosine in up-regulation of p38 MAPK and ERK during limb ischemic preconditioning-induced brain ischemic tolerance.

Our previous studies have demonstrated that limb ischemic preconditioning (LIP) induced brain ischemic tolerance and up-regulated the expression of p38 MAPK and ERK in the hippocampal CA1 region in rats. The present study was undertaken to investigate the role of adenosine in brain protection and up-regulation of p38 MAPK and ERK induced by LIP. It was found that adenosine A1 receptor antagonist DPCPX dose-dependently inhibited the protective effect of LIP. The up-regulation of p38 MAPK and ERK induced by LIP could be blocked by DPCPX. Furthermore, we observed the effect of adenosine on the brain ischemia. The results showed that pre-administration of adenosine could partly mimic the neuroprotective effect on the brain, up-regulate the expression of p38 MAPK and ERK. Based on the above results, it can be concluded that adenosine participated in brain protection and up-regulation of the expression of p38 MAPK and ERK during the induction of brain ischemic tolerance after LIP.

The clinical application value of MR diffusion-weighted imaging in the diagnosis of rectal cancer: A retrospective study.

The present study evaluated the clinical potential of magnetic resonance (MR) diffusion-weighted imaging (DWI) in the diagnosis of rectal cancer.A total of 84 patients confirmed with rectal cancer were used as study subjects in the present study. All patients received conventional sequence MR T1WI, T2WI, and DWI examination as well as operative pathological examination. The differences between the MRI results and operative pathological results were analyzed.The diagnosis accordance rates of conventional sequence examination in stage T1, T2, T3, and T4 were 60.00%, 82.75%, 62.85%, and 80.00%, respectively. The diagnosis accordance rates of conventional sequence combined with DWI examination in stages T1, T2, T3, and T4 were 100.00%, 100.00%, 82.85%, and 100.00% respectively. The total diagnosis accordance rates in the T staging of rectal cancer with conventional (Routinely or generally applied) sequence examination and conventional sequence combined with DWI examination were 71.42% and 92.85%, respectively.The analysis on consistency of MR conventional sequence examination suggested that the conventional sequence combined with DWI examination is more consistent with pathological staging when compared with the convention sequence examination alone. MR DWI combined with conventional sequences reveals quite good accuracy in the T staging of rectal cancer.

Clinical Characteristics and Surgical Treatment of Intraorbital Foreign Bodies in a Tertiary Eye Center.

PURPOSE: Intraorbital foreign body is relatively rare and therefore is often misdiagnosed in clinical practice. The purpose of this report is to summarize the clinical features of intraorbital foreign bodies and their surgical management. METHODS: A retrospective study of clinical cases. Clinical manifestations, imaging findings, and surgical treatments in patients with intraorbital foreign bodies, who were seen at the Zhongshan Ophthalmic Center of Sun Yat-sen University between January 2002 and July 2013, were retrospectively reviewed. RESULTS: Of the 22 cases reviewed, 19 were men and 3 women with a mean age of 22.2 years. Patients ≤14 years of age accounted for 45.5% of the cases. The right orbit was affected in 10 patients and the left in 12 patients. Organic intraorbital foreign bodies comprised 72.7% of the patients. Foreign body locations within the orbit were superior (40.9%), medial (27.3%), lateral (18.2%), and inferior (9.1%). Half of the patients presented with preoperative visual impairments and 45.5% with limited motility/strabismus and ptosis. Orbital imaging revealed that organic foreign bodies consisted of a strip, rod-like high-density image surrounding soft tissue on CT scan and hypointense on both T1WI and T2WI with MRI images. Complete removal of the intraorbital foreign body was accomplished by anterior orbitotomy in 21 patients and lateral orbitotomy in the remaining patients. Removal was achieved in a single surgery for 21 patients whereas 2 surgeries were required for the remaining patients. No postoperative complications were reported in any of the patients. CONCLUSIONS: Intraorbital foreign bodies requiring surgical removal mostly involved organic foreign bodies. These were most commonly found in male children. Orbital imaging played a critical role for an accurate presurgical diagnosis. Anterior orbitotomy provided the best surgical outcomes.

Photo-catalyzed p-nitrophenol degradation in aqueous dispersions of ferrihydrite and H2O2.

Nitrophenols are hazardous and toxic to living organisms. For this study, ferrihydrite was prepared to test its capabilities for p-nitrophenol degradation. A ferrihydrite particle prepared in neutral environmental conditions is sphere-like with a diameter of 2-4 nm and its total surface area is approximately 229 m2 x g(-1). The combination of ferrihydrite and trace H2O2 is effective for the degradation of p-nitrophenol under simulated sunlight irradiation. Hydroquinone, the initial intermediate of p-nitrophenol decomposition, autocatalyses the subsequent degradation of p-nitrophenol because it accelerates the photo-reductive dissolution of ferrihydrite. The effect of key operating parameters such as ferrihydrite dosage, initial solution pH and H2O2 dosage were also studied on the photocatalytic degradation of p-nitrophenol. The results indicate that the combination of 0.2 g x L(-1) ferrihydrite, 0.45 mmol x L(-1) H2O2 is highly efficient for the degradation of p-nitrophenol (0.15 mmol x L(-1)) at pH 2.5-3.0. A ferrihydrite was reused several times, still keeping its original photocatalysis.

Reductive transformation of p-nitrophenol by Fe(II) species: the effect of anionic media.

Electron exchange between aqueous Fe(II) and structural Fe(III) of iron minerals has been illustrated for understanding the reduction of nitroaromatic compounds (NAC). However, factors influencing Fe(II)-induced the reduction of NAC still remain elusive. In this paper, p-nitrophenol (1.5mM) was selected to explore the effects of pH, the stabilizing ligands (Cl(-), SO4(2-)) of ferrous ions and the extra addition of iron hydroxide on the reduction of NAC via Fe(II) species. The results indicate that the reduction degree of is much lower in SO4(2-) medium than that in Cl(-) medium at pH 7.6. p-Nitrophenol reduction increased in SO4(2-) medium and slightly decreased in Cl(-) medium when Fe hydroxide was extra added. Cl(-) strength (0.01-0.1 mol L(-1)) has no obvious effect on p-NP reduction. SO4(2-) species and its dosage have markedly inhibitory effect on p-NP reduction due to the selective adsorption of SO4(2-) and the formation of sulphated surface complexes on the fresh Fe hydroxide.

[Clinical Observation of Erlotinib in the Treatment of Elderly Patients with Advanced Non-small Cell Lung Cancer.].

BACKGROUND: About 80% lung cancer is non-small cell lung cancer (NSCLC) and more than 70% are in advanced stage. The aim of this study is to evaluate the clinical efficacy and the side effects of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer. METHODS: Twenty-nine patients with advanced non-small cell lung cancer were treated with erlotinib 150 mg/d, then the adverse reaction and clinical efficacy were recorded during 3 months. RESULTS: Total 29 patients were evaluated for efficacy. The total rate of effect was 20.69%, including 1 case CR, 5 cases PR, 9 cases SD and 14 cases PD. We compared the effective rate of stage III with IV. There were no significant difference between the effective rate of stage III and IV (P=0.337). The main side effects were rash (37.93%), diarrhea (17.24%) and vomiting (6.9%) and most side effects were grade I and II. CONCLUSIONS: Erlotinib for elderly patients with advanced non-small cell lung cancer have better effective and less toxic effects and the further clinical study should be warranted.

[A Retrospective Analysis of Erlotinib and TP/GP Regimen in the Treatment of Advanced Non-small Cell Lung Cancer.].

BACKGROUND: About 80% lung cancers belong to non-small cell lung cancer (NSCLC) and more than 70% are in advanced stage. The aim of this study was to evaluate the clinical efficacy and toxicity of erlotinib and GP/TP regimen on advanced non-small cell lung cancer. METHODS: Ninety-one advanced NSCLC patients with different treatments from January 2007 to April 2009 in our hospital were retrospectively analyzed. Ninety-one patients were divided into the erlotinib and TP/GP group. Erlotinib group: received erlotinib 150 mg/dl TP/GP group: the original chemotherapy for advanced non-small cell lung cancer. The cycles were repeated for 21 days. The patients were given docetaxel (80 mg/m(2), d1) or gemcitabine (1 000 mg/m(2), d1, 8) +cisplatin (70 mg/m(2), d2); then the adverse reaction and clinical efficacy were recorded during 3 months. RESULTS: Total 91 patients were evaluated for efficacy. The total rate of effect was 23.33% in erlotinib group. The side effects were erythra, diarrhea and vomiting. Pulmonary fibrosis was found in one patient after 21 days. TP/GP group: the total rate of effect was 27.78% and 28% and the side effects were bone marrow depression and reaction of gastrointestinal tract. There were no significantly difference between the two groups in the total rate of effect (P>0.05). But the side effects were less in erlotinib group, and there were significantly difference between the two groups. CONCLUSIONS: Erlotinib on advanced non-small cell lung cancer shows more effectiveness and adverse reactions are tolerable. The further clinical study should be warranted.