Salidroside attenuates cerebral ischemia/reperfusion injury by regulating TSC2-induced autophagy.

Salidroside (SAL), an antioxidant derived from Rhodiola rosea, exerts neuroprotective effects in cerebral ischemia/reperfusion (I/R) injury; however, the mechanisms have not been fully elucidated. The present study established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R) to explore the roles and mechanisms of SAL in cerebral I/R injury. The rat model of MCAO/R was established and rats were treated with different doses of SAL. The Zea-Longa scoring system and 2,3,5-triphenyltetrazolium chloride (TTC) staining showed that SAL reduced neurological deficit scores and cerebral infarct volumes in MCAO/R rats. The results of Morris water maze (MWM) test showed that SAL reduced memory impairment in MCAO/R rats. In addition, SAL significantly reduced oxidative stress and suppressed inflammatory response. Next, the OGD/R model was established with PC12 cells and treated with SAL. The results of flow cytometry and 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays showed that SAL reduced apoptosis, enhanced cell viability and protected neuronal cells from damage by decreasing lactate dehydrogenase (LDH) activity. SAL increased the expression of TSC complex subunit 2 (TSC2), and activated the 5'-AMP-activated protein kinase (AMPK) and inhibited the mammalian target of rapamycin (mTOR) signaling pathways. It was verified that SAL alleviated cerebral I/R injury by regulating the AMPK/TSC2/mTOR pathway to induce autophagy. In conclusion, SAL reduces the inflammatory response and oxidative stress in a concentration-dependent manner, and protects against cerebral I/R injury by modulating TSC2-induced autophagy. These findings suggest SAL may prove to be a potential therapeutic agent for ischemic stroke.

Iterative Approach of Experiment-Machine Learning for Efficient Optimization of Environmental Catalysts: An Example of NOx Selective Reduction Catalysts.

An iterative approach between machine learning (ML) and laboratory experiments was developed to accelerate the design and synthesis of environmental catalysts (ECs) using selective catalytic reduction (SCR) of nitrogen oxides (NOx) as an example. The main steps in the approach include training a ML model using the relevant data collected from the literature, screening candidate catalysts from the trained model, experimentally synthesizing and characterizing the candidates, updating the ML model by incorporating the new experimental results, and screening promising catalysts again with the updated model. This process is iterated with a goal to obtain an optimized catalyst. Using the iterative approach in this study, a novel SCR NOx catalyst with low cost, high activity, and a wide range of application temperatures was found and successfully synthesized after four iterations. The approach is general enough that it can be readily extended for screening and optimizing the design of other environmental catalysts and has strong implications for the discovery of other environmental materials.

Microscopic insights into the variations of antibiotics sorption to clay minerals.

Understanding the adsorption behavior of antibiotic molecules on minerals is crucial for determining the environmental fate and transport of antibiotics in soils and waters. However, the microscopic mechanisms that govern the adsorption of common antibiotics, such as the molecular orientation during the adsorption process and the conformation of sorbate species, are not well understood. To address this gap, we conducted a series of molecular dynamics (MD) simulations and thermodynamics analyses to investigate the adsorption of two typical antibiotics, tetracycline (TET) and sulfathiazole (ST), on the surface of montmorillonite. The simulation results indicated that the adsorption free energy ranged from - 23 to - 32 kJ·mol-1, and - 9 to - 18 kJ·mol-1 for TET and ST, respectively, which was consistent with the measured difference of sorption coefficient (Kd) for TET-montmorillonite of 11.7 L·g-1 and ST-montmorillonite of 0.014 L·g-1. The simulations also found that TET was adsorbed through dimethylamino groups (85% in probability) with a molecular conformation vertical to the montmorillonite's surface, while ST was adsorbed through sulfonyl amide group (95% in probability) with vertical, tilted and parallel conformations on the surface. The results confirmed that molecular spatial orientations could affect the adsorption capacity between antibiotics and minerals. Overall, the microscopic adsorption mechanisms revealed in this study provide critical insights into the complexities of antibiotics adsorption to soil and facilitate the prediction of adsorption capacity of antibiotics on minerals and their environmental transport and fate. This study contributes to our understanding of the environmental impacts of antibiotic usage and highlights the importance of considering molecular-level processes when assessing the fate and transport of antibiotics in the environment.

A Retrospective Study on the Effect of Empowerment Psychological Intervention Led by Specialist Nurses on Post-traumatic Stress Disorder in ICU Patients.

BACKGROUND: Many patients in the intensive care unit (ICU) suffer from post-traumatic stress disorder (PTSD), which seriously affects the treatment, recovery, and prognosis of patients. OBJECTIVE: To observe the effect of empowerment psychological intervention on the status of PTSD in ICU patients. METHODS: A total of 86 patients with PTSD who were treated in ICU from July 2019 to December 2021 were divided into two groups according to the intervention method. The control group (n = 43) used routine psychological intervention, while the intervention group (n = 43) used empowerment psychological intervention led by specialist nurses. The Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality of the patients. The Resilience Questionnaire (CD-RISC) was used to evaluate the resilience of the patients, and the Post Traumatic Stress Disorder Self-Rating Scale (PTSD-SS) was used to assess the severity of the symptoms. The Hamilton Anxiety and Depression Inventory (HAMA and HAMD) was adapted to assess the degree of anxiety and depression, and the Post-Traumatic Growth Inventory (PTGI) was adapted to evaluate the post-traumatic growth of the patients. RESULTS: After the intervention, the total CD-RISC score and its tenacity, self-improvement, and optimism scores in the two groups were all higher than before, and the total PSQI score and its sleep quality, time, efficiency and impairment, as well as hypnotic drugs, daytime dysfunction and time to sleep were lower than before, and the CD-RISC score in the intervention group was higher than that in the control group, PSQI score was lower than that in the control group (p < 0.05). After the intervention, PTSD-SS scores and anxiety-depression scores were lower, and PTGI scores were higher in both groups than before (p < 0.05). CONCLUSION: The empowerment psychological intervention led by specialist nurses applied to ICU patients with PTSD can improve their psychological resilience and sleep quality, reduce negative emotions, alleviate clinical symptoms, and promote post-traumatic growth.

Dynamic Changes in Biofilm Structures under Dynamic Flow Conditions.

Quantitative assessment of the responses of biofilm structure to external hydrodynamics is critical for understanding biofilm detachment mechanisms. This study used multidimensional imaging and numerical simulation approaches to elucidate the complex relationships between biofilm detachment and hydrodynamics with Shewanella oneidensis MR-1. By integrating real-time confocal laser scanning microscopy (CLSM) images with image analysis tools, the three-dimensional structural changes occurring in thin MR-1 biofilms (<10 µm) under hydrodynamic treatment at a flow velocity of 0.42 × 10-3 to 3.3 × 10-3 m/s in the laminar flow regime were visualized in situ and quantified with single-cell resolution. Analyses of the imaging results revealed high spatial heterogeneity in the degree and intensity of biofilm detachment. Spots with thick and rough biofilm surfaces or high flow rates had high detachment rates, indicating that local biofilm morphology, including thickness and roughness, and hydrodynamic flow conditions collectively controlled the detachment rate. Numerical simulations revealed a significant correlation between local detachment events and the shear stress induced by hydraulic flow at the three-dimensional level. Compared to the even or thin biofilm, a thick or rough structure might induce a 2-fold increase in shear stress over local biofilm surfaces at a microscale dimension. The results provide quantitative and microscopic insights into biofilm detachment processes in subsurface environments, especially in domains under dynamic flow conditions, such as those in hyporheic zones. The relationship between biofilm detachment and hydrodynamics and biofilm structural factors can be integrated into reactive transport models used to describe microbial growth and transport in porous media. IMPORTANCE Detachment is an important process determining the structure and function of bacterial biofilm, which has significant implications for biogeochemical cycling of elements, biofilm application, and infection control in clinical settings. Quantifying the responses of biofilm structure to hydrodynamics is crucial for understanding biofilm detachment mechanisms in aquatic environments. In this work, the spatial and temporal changes occurring in biofilm structures in response to different hydrodynamic conditions were studied by using flow cell reactors. We established the quantitative relationships among detachment, biofilm morphology, and shear stress induced by changes in hydrodynamic conditions. This work provides a quantitative understanding of the complex relationship between biofilm detachment and hydrodynamics in natural environments.

Low pretreatment serum globulin may predict favorable prognosis for gastric cancer patients.

An elevated serum albumin (ALB) and albumin/globulin ratio (AGR) have been reported to be associated with a favorable prognosis for several types of cancer. However, little is known about prognostic significance of globulin (GLB) in gastric cancer patients. The purpose of this study was to evaluate whether GLB, ALB, and AGR analysis could predict the prognosis of patients with gastric cancer. A retrospective cohort of 186 patients with gastric cancer followed by radical surgery was recruited between January 2007 and December 2010. Levels for preoperative GLB and ALB were obtained and used to calculate the AGR. Survival analysis was used to evaluate the predictive value of GLB, ALB, and AGR. X-tile program determined 37.6, 33.4, and 1.33 as the optimal cutoff value for ALB, GLB, and AGR in terms of survival. Univariate analysis revealed that low GLB levels were significantly associated with favorable survival (P = 0.045). Conversely, low ALB levels were associated with a significantly worse survival (P = 0.000). In conclusion, low preoperative GLB level may serve as a valuable marker to predict the prognosis of gastric cancer patients.

Effect of phosphate on ferrihydrite transformation and the associated arsenic behavior mediated by sulfate-reducing bacterium.

Although PO43- is commonly found in association with iron (oxyhydr)oxide, the effect of PO43- on ferrihydrite reduction, mineralogical transformation, and associated As behavior in sulfate-reducing bacteria (SRB)-rich environments remains unclear. In this study, batch experiments, together with geochemical, mineralogical, and biological analyses, were conducted to elucidate these processes. The results showed that SRB can reduce ferrihydrite via direct and indirect processes, and PO43- promoted ferrihydrite reduction by supporting SRB growth at low and medium PO43- loadings. However, at high loadings, PO43- stabilized the ferrihydrite. PO43- shifted the transformation of ferrihydrite from magnetite and mackinawite to vivianite, which scavenges As effectively by incorporating As into its particle. In systems with 0.5 mM SO42-, PO43- exerted a weak effect on As mobilization. However, in systems with 10 mM SO42-, substantial amounts of As were released into the solution, and PO43- impacted As behavior strongly. Low PO43- loadings increased the mobilization of As because of the competitive adsorption of PO43- on mackinawite. Medium and high PO43- loadings were beneficial for As immobilization because of the substitution of mackinawite by vivianite. These findings have important implications for understanding the biogeochemistry of iron (oxyhydr)oxide and As behavior in SRB-containing sediments.

The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials.

Objectives: Vitamin C deficiency is common among patients with sepsis and has been associated with poor clinical outcomes. Nevertheless, the effect of intravenous (IV) vitamin C for the treatment of sepsis remains controversial. The purpose of this meta-analysis was to evaluate the effect of IV vitamin C in patients with sepsis or septic shock. Methods: Electronic databases (PubMed, Embase, Scopus, and Cochrane Library) were searched from inception through May 25, 2022 for randomized controlled trials evaluating the effect of IV vitamin C treatment in patients with sepsis. The primary outcome was short-term mortality, and secondary outcomes including the duration of vasopressor, length of intensive care unit (ICU) stay, and Sequential Organ Failure Assessment (SOFA) score after vitamin C treatment. Subgroup analyses were performed based on the type of disease, dose and duration of IV vitamin C. Results: A total of 10 studies were included, with a total sample of 755 septic patients. The IV vitamin C was associated with a significant reduction in the short-term mortality (OR 0.51, 95% CI 0.37-0.69, I 2 = 0%) and duration of vasopressor (MD -27.88, 95% CI -49.84 to -5.92, I 2 = 95%). The length of ICU stay (MD -0.68, 95% CI -2.13 to 0.78, I 2 = 74%) and SOFA score (MD -0.05, 95% CI -1.69 to 1.58, I 2 = 86%) were not significantly different between two groups. Conclusion: In patients with sepsis or septic shock, the IV vitamin C reduced the short-term mortality rate and duration of vasopressor, with no effect on the length of ICU stay and SOFA score. Further trials are required to explore the optimal dosage and duration of IV vitamin C. Systematic Review Registration: https://inplasy.com/inplasy-2022-6-0013/, identifier INPLASY202260013.

Mechanistic and modeling insights into the immobilization of Cd and organic carbon during abiotic transformation of ferrihydrite induced by Fe(II).

Iron (Fe) oxides and fulvic acid (FA) are the key components affecting the fate of cadmium (Cd) in soil. The presence of FA influences Fe mineral transformation, and FA may complicate phase transformation and dynamic behavior of Cd. How varying Fe minerals and FA affect Cd immobilization during the ferrihydrite transformation induced by various Fe(II) concentrations, however, is still lack of quantitative understanding. In this study, we built a model for Cd species quantification during phase transformation based on mechanistic insights obtained from batch experiments. Spectroscopic analysis showed that Fe(II) concentrations affected secondary Fe minerals formation under the condition of co-existence of Cd and FA, and ultimately changed the distribution of Cd and FA. Microscopic analysis revealed that besides surface adsorption, part of Cd was sequestrated by magnetite, whereas FA was able to diffuse into lepidocrocite defects. The model revealed that adsorbed Cd was mainly controlled by FA and ferrihydrite, and direct complexation of Cd by FA had a strong impact on the continuous change in Cd at lower Fe(II) concentration. The results contribute to an in-depth understanding of the mobility of Cd in the environment and provide a method for quantifying the dynamic behavior of heavy metals in multi-reactant systems.

Prevalence of left iliac vein compression in an asymptomatic population and patients with left iliofemoral deep vein thrombosis: A multicenter cross-sectional study in southern China.

OBJECTIVE: Population-based epidemiological data on left common iliac vein (LCIV) compression is scarce. This study aimed to investigate the prevalence of LCIV compression in an asymptomatic population and patients with left iliofemoral deep vein thrombosis (IF-DVT). MATERIALS AND METHODS: Nonprobability sampling method was used in this multicenter cross-sectional study. The minimum diameter of LCIV and right common iliac vein minimum were measured. The percentage of LCIV compression (LCIV-CP) was calculated. Compression severity (CS) was classified as mild (CP ≤ 50%), moderate (50% < CP ≤ 70%), and severe (CP > 70%). RESULTS: In all, 896 subjects constituted the asymptomatic population and 93 patients constituted the IF-DVT population. In the asymptomatic population, LCIV-CP ranged from 1.1% to 89.9% (mean 44.0%), and people with mild, moderate, and severe CS accounted for 62.3%, 28.2%, and 9.5%, respectively. In the IF-DVT population, the mean LCIV-CP was 71.1% (range 42.2%-95.2%), and patients with severe CS accounted for 75.3%. Gender and age differences in LCIV-CP and CS distribution were observed in the asymptomatic population. Females, the young- and middle-aged group had higher LCIV-CPs. In the population with moderate-severe CS, the middle-aged group accounted for a larger proportion. Middle-aged females comprised the highest percentage of patients with moderate or severe CS. Sex and age affected the LCIV-CP and CS distribution. No gender and age differences were observed in the IF-DVT population. CONCLUSIONS: LCIV compression is common in population. Middle-aged females are the predominant population with moderate-severe compression. Overlapping of LCIV-CP in the asymptomatic and IF-DVT population is significant and other risk factors should be integrated into the consideration when assessing the risk of IF-DVT secondary to LCIV compression.

Effect of humic acid on bioreduction of facet-dependent hematite by Shewanella putrefaciens CN-32.

Interfacial reactions between iron (Fe) (hydr)oxide surfaces and the activity of bacteria during dissimilatory Fe reduction affect extracellular electron transfer. The presence of organic matter (OM) and exposed facets of Fe (hydr)oxides influence this process. However, the underlying interfacial mechanism of facet-dependent hematite and its toxicity toward microbes during bioreduction in the presence of OM remains unknown. Herein, humic acid (HA), as typical OM, was selected to investigate its effect on the bioreduction of hematite {100} and {001}. When HA concentration was increased from 0 to 500 mg L-1, the bioreduction rates increased from 0.02 h-1 to 0.04 h-1 for hematite {100} and from 0.026 h-1 to 0.05 h-1 for hematite {001}. Since hematite {001} owned lower resistance than hematite {100} irrespective of the HA concentration, and hematite {100} was less favorable for reduction. Microscopy-based analysis showed that more hematite {001} nanoparticles adhered to the cell surface and were bound more closely to the bacteria. Moreover, less cell damage was observed in the HA-hematite {001} treatments. As the reaction progressed, some bacterial cells died or were inactivated; confocal laser scanning microscopy showed that bacterial survival was higher in the HA-hematite {001} treatments than in the HA-hematite {100} treatments after bioreduction. Spectroscopic analysis revealed that facet-dependent binding was primarily realized by surface complexation of carboxyl functional groups with structural Fe atoms, and that the binding order of HA functional groups and hematite was affected by the exposed facets. The exposed facets of hematite could influence the electrochemical properties and activity of bacteria, as well as the binding of bacteria and Fe oxides in the presence of OM, thereby governing the extracellular electron transfer and concomitant bioreduction of Fe (hydr)oxides. These results provide new insights into the interfacial reactions between OM and facet-dependent Fe oxides in anoxic, OM-rich soil and sediment environments.

Simultaneous vs. staged resection for synchronous colorectal liver metastases: a metaanalysis.

PURPOSE: The optimal timing of surgical resection for synchronous colorectal liver metastases (SCLMs) remains controversial. The aim of this metaanalysis was to compare outcomes between simultaneous resection and staged resection from all published comparative studies in the literature. MATERIALS AND METHODS: Databases, including PubMed, Embase, Cochrane Library, Ovid, and Web of Science, were searched to identify studies comparing outcomes following simultaneous resection with staged resection for SCLM. The metaanalysis was performed by RevMan 4.2. RESULTS: Fourteen comparative studies comprising 2,204 patients were identified. Patients undergoing simultaneous resection were found to have similar operative time (weighted mean difference [WMD], -34.19; 95% confidence interval [CI], -81.32-12.95, P = .16) and intraoperative blood loss (WMD, -161.33; 95% CI, -351.45-28.79, P = .10). Shorter hospital stay (WMD, -4.77; 95% CI, -7.26-2.28, P < .01) and lower morbidity rate (odds ratio [OR], 0.71; 95% CI, 0.57-0.88, P = .002) were observed in simultaneous resection group. The survival rate in the simultaneous resection group did not statistically differ with that in the staged resection group at 1 year (OR, 0.77; 95% CI, 0.51-1.16, P = .21), 3 years (OR, 1.12; 95% CI, 0.85-1.47, P = .43), and 5 years (OR, 1.14; 95% CI, 0.86-1.50, P = .37) postresection, respectively. CONCLUSIONS: Simultaneous resection is safe and efficient in the treatment of patients with SCLM while avoiding a second major operation. In appropriately selected patients, simultaneous resection might be considered as the preferred treatment. Since heterogeneity was detected, caution is needed in interpretation of the results. Better designed, adequately powered studies are required for addressing this issue.

Survival after anatomic resection versus nonanatomic resection for hepatocellular carcinoma: a meta-analysis.

BACKGROUND AND OBJECTIVES: To compare the effect on survival of anatomic resection (AR) versus nonanatomic resection (NAR) in patients with hepatocellular carcinoma (HCC) from all published comparative studies in the literature. METHODS: Databases, including Pubmed, Embase, the Cochrane Library, Ovid, and Web of Science, were searched to identify studies comparing AR with NAR for HCC. In this meta-analysis, primary end points were the overall survival and disease-free survival; the secondary end point was local recurrence rate. The meta-analysis was performed by use of RevMan 4.2. RESULTS: Nine comparative studies comprising 1,503 patients (833 AR and 670 NAR) were identified. In the combined results, disease-free survival was significantly higher in the AR group than in the NAR group (OR 1.78, 95% CI 1.22-2.59, P = 0.003; heterogeneity P = 0.08). Overall survival (OR 1.31, 95% CI 0.92-1.85, P = 0.13; heterogeneity P = 0.04) did not suggest any significant difference between AR and NAR. No statistically significant difference was found for local recurrence rate between the two resection methods (OR 0.55, 95% CI 0.25-1.23, P = 0.15; heterogeneity P = 0.010). CONCLUSIONS: Anatomic resection is associated with better disease-free survival than nonanatomic resection. Because heterogeneity was detected, caution is needed in interpretation of the results. Better designed, adequately powered studies are required to address this issue.

Clinicopathologic features and prognostic factors in alpha-fetoprotein-producing gastric cancers: analysis of 104 cases.

BACKGROUND AND OBJECTIVES: There were no comprehensive studies on the clinicopathologic features and prognosis of alpha-protein-producing gastric cancer. The aim of this study was to elucidate the clinicopathologic characteristics and prognostic factors of alpha-fetoprotein (AFP)-producing gastric cancer. METHODS: Among 4,426 gastric cancer patients receiving surgery in the Cancer Hospital of Fudan University from 1996 to 2007, there were 111 patients with elevated serum level of AFP preoperatively after excluding chronic hepatitis, hepatocirrhosis, and hepatocellular carcinoma. Primary lesions of 104 patients were stained positively for AFP. The clinicopathologic characteristics and prognostic factors of AFP-producing gastric cancer were analyzed. Additionally, 208 stage-matched AFP-negative gastric cancer patients were selected as control. RESULTS: There was a significantly higher incidence of vascular invasion, lymph node metastasis, and liver metastasis in AFP-positive group than in the negative group. The overall 5-year survival rates of AFP-positive and negative groups were 28% and 38%, respectively. The AFP-positive group had a significantly poorer survival in comparison to the stage-matched negative group. The independent prognostic factors of AFP-positive group included liver metastasis and pathological stage. CONCLUSIONS: AFP-positive gastric cancer had more aggressive behavior than that of AFP-negative gastric cancer. In addition to surgery, multimodal therapy should be considered.

Prognostic significance of tumor size in T3 gastric cancer.

BACKGROUND: Clinical significance of tumor size remains elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of tumor size in T3 gastric cancer. METHODS: A total of 273 patients with T3 gastric cancer who underwent curative D2 gastrectomy between 1996 and 2005 were evaluated. In terms of average value of tumor size, patients were divided into two groups according to tumor size: small-size group (SSG, tumor 6 cm). The prognostic value of tumor size and the correlation between tumor size and other clinicopathologic factors were investigated. RESULTS: LSG accounted for 34.8% in all patients. Tumor size was correlated with histological type, lymphatic invasion, venous invasion, and resection type. The prognosis of LSG patients was worse than that of SSG patients. Multivariate analysis showed that type of resection, status of lymph nodes, metastatic lymph node ratio, and tumor size were defined as independent prognostic factors for patients with T3 gastric cancer. A comparison between LSG patients and SSG patients showed differences in the survival of those with stage IIIB and IV disease. CONCLUSIONS: Tumor size is a simple and reliable prognostic factor for patients with T3 gastric cancer; it might be a candidate for the gastric cancer staging system.

Effects of lysophosphatidylcholine on beta-amyloid-induced neuronal apoptosis.

AIM: We have investigated the effects of lysophosphatidylcholine (LPC), a product of lipid peroxidation, on Abeta(1-42)-induced SH-SY5Y cell apoptosis. METHODS: The viability of cultured SH-SY5Y cells was measured using a CCK-8 kit. Apoptosis was determined by Chip-based flow cytometric assay. The mRNA transcription of Bcl-2, Bax, and caspase-3 were detected by using reverse transcription and real-time quantitative PCR and the protein levels of Bax and caspase-3 were analyzed by Western blotting. The cytosolic calcium concentration of SH-SY5Y cells was tested by calcium influx assay. G2A expression in SH-SY5Y cells was silenced by small interfering RNA. RESULTS: Long-term exposure of SH-SY5Y cells to LPC augmented the neurotoxicity of Abeta(1-42). Furthermore, after LPC treatment, the Bax/Bcl-x(L) ratio and the expression levels, as well as the activity of caspase-3 were, elevated, whereas the expression level of TRAF1 was reduced. Because LPC was reported to be a specific ligand for the orphan G-protein coupled receptor, G2A, we investigated LPC-mediated changes in calcium levels in SH-SY5Y cells. Our results demonstrated that LPC can enhance the Abeta(1-42)-induced elevation of intracellular calcium. Interestingly, Abeta(1-42) significantly increased the expression of G2A in SH-SY5Y cells, whereas knockdown of G2A using siRNA reduced the effects of LPC on Abeta(1-42)-induced neurotoxicity. CONCLUSION: The effects of LPC on Abeta(1-42)-induced apoptosis may occur through the signal pathways of the orphan G-protein coupled receptor.

Baseline platelet counts and derived inflammatory biomarkers: prognostic relevance in metastatic melanoma patients receiving Endostar plus dacarbazine and cisplatin.

Background: The clinical efficacy and safety of Endostar combined with chemotherapy in the treatment of metastatic malignant melanoma (MM) were analyzed and the indicators capable of predicting the efficacy of the regimen were identified to guide clinical practice. Patients and methods: The clinical data of 55 patients with metastatic MM without gene mutations who were treated with Endostar combined with dacarbazine and cisplatin were retrospectively analyzed. Efficacy was assessed using RECIST 1.1, and adverse events (AEs) were graded according to NCI-CTCAE 4.0. The log-rank test was used to compare the survival curves of patients in different subgroups, and stepwise multivariate Cox regression analysis was used to determine significant prognostic factors. Differences were considered statistically significant at P<0.05. Results: Of the 55 patients, seven showed a partial response, 20 showed stable disease, and 28 showed progressive disease. The median progression-free survival was 17.9 months. AEs were controllable. Univariate analysis identified biotherapy, clinical stage, clinical classification, low baseline platelet count, platelet to albumin ratio (PAR), and platelet to globulin ratio (PGR) as factors affecting drug efficacy. Multivariate Cox regression analysis identified clinical stage and PAR as independent factors predicting the efficacy of the regimen. Conclusions: Endostar combined with chemotherapy showed a curative effect on metastatic MM without gene mutations, and AEs were controllable. The baseline platelet count and derived PAR and PGR values were associated with the efficacy of the regimen. The potential value of efficacy prediction remains to be further verified by prospective random experiments.

[Clinical analysis of 168 cases of multiple primary colorectal carcinoma].

OBJECTIVE: To study the incidence rate of multiple primary colorectal carcinomas (MPCC) in colorectal carcinoma and to evaluate its clinical and pathological characteristics. METHODS: One hundred and sixty-eight (4.6%) patients from 3663 cases with colorectal carcinoma were diagnosed with MPCC from January 1985 to December 2003. The clinical data of the patients were collected retrospectively to investigate the diagnosis and treatment of MPCC. RESULTS: Of the 168 patients, 81 were diagnosed as synchronous colorectal carcinoma (SC), 72 with metachronous colorectal carcinoma (MC), 15 with both SC and MC. The median age at time of diagnosis of colorectal carcinoma was 58 years old (range from 20 to 82 years old). Three hundred and ninety-three cancer lesions were detected in these 168 cases (mean, 2.3 lesions/case). The rectum and sigmoid colon were the most involved sites (61.6%). Eighteen cases (10.7%) were verified with hereditary non-polyposis colorectal cancer (HNPCC) while another 9 cases were highly suspected. Fourteen patients (8.3%) were found with other malignancies out of large intestine, 41 patients (24.4%) with colorectal adenomas, 72 (42.9%) with adenoma carcinogenesis. Among the 96 SC patients, 91 were given preoperative colonoscopy and 65 (71.4%) got the diagnosis. All the MC patients were diagnosed by postoperative colonoscopy. The overall 5-year survival rate of the 168 patients was 69.8%. CONCLUSIONS: MPCC should be paid more attention in colorectal cancer management. Colonoscopic surveillance is much more important in diagnosis and follow-up of MPCC for reducing the misdiagnosis of SC and detecting more MC in time. Prompt treatment of adenoma can reduce the occurrence of MPCC, and active and standard surgical treatment should be done for MPCC.

Apatinib mesylate tablet in the treatment of advanced malignant melanoma.

BACKGROUND: Observing and studying clinical efficacy and safety of apatinib mesylate tablet in the treatment of advanced malignant melanoma (MM). METHODS: Retrospectively analyzing the clinical data of 22 patients with metastatic MM who had failed conventional chemotherapy from June 2016 to January 2018. All patients took 500 mg of apatinib mesylate tablets per day. The efficacy should be evaluated according to RECIST 1.1 criteria. Adverse events (AEs) should be graded according to NCI-CTCAE 4.0. RESULTS: There were two cases of partial remission (PR), 11 of stable disease (SD) and nine of progressive disease (PD) in the 22 patients with advanced MM, where the objective remission rate (ORR) was 9.1% and the disease control rate (DCR) was 59.1%. The median progression-free survival (PFS) was 7.5 months, and the 6-month progression-free survival rate (PFR) was 54.7%. Six patients died and the overall survival (OS) was not reached. AEs were controllable and all were in Grade 1-3. CONCLUSION: Apatinib mesylate tablets have a certain curative effect on patients with malignant melanomas of Stage IV who failed conventional chemotherapy. Apatinib mesylate tablets at a daily dose of 500 mg are well tolerated by most patients.

Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer.

Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. Here we identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in gastric cancer (GC) tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene and termed it as circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in GC.