Multi-MSIProcessor: Data Visualizing and Analysis Software for Spatial Metabolomics Research.

Mass spectrometry imaging (MSI) has emerged as a revolutionary analytical strategy in biomedical research for molecular visualization. By linking the characterization of functional metabolites with tissue architecture, it is now possible to reveal unknown biological functions of tissues. However, due to the complexity and high dimensionality of MSI data, mining bioinformatics-related peaks from batch MSI data sets and achieving complete spatially resolved metabolomics analysis remain a great challenge. Here, we propose novel MSI data processing software, Multi-MSIProcessor (MMP), which integrates the data read-in, MSI visualization, processed data preservation, and biomarker discovery functions. The MMP focuses on the AFADESI-MSI data platform but also supports mzXML and imzmL data input formats for compatibility with data generated by other MSI platforms such as MALDI/SIMS-MSI. MMP enables deep mining of batch MSI data and has flexible adaptability with the source code opened that welcomes new functions and personalized analysis strategies. Using multiple clinical biosamples with complex heterogeneity, we demonstrated that MMP can rapidly establish complete MSI analysis workflows, assess batch sample data quality, screen and annotate differential MS peaks, and obtain abnormal metabolic pathways. MMP provides a novel platform for spatial metabolomics analysis of multiple samples that could meet the diverse analysis requirements of scholars.

Unveiling the hidden: identification and management of overlooked blood vessels in laparoscopic left hemicolectomy for splenic flexure cancer.

BACKGROUND: During laparoscopic left hemicolectomy procedures, a previously overlooked consistently thick blood vessel within the gastrocolic ligament near the splenic hilum may contribute to post-operative bleeding complications. The purpose of this study was to investigate the identification and management of the previously overlooked blood vessel. METHODS: This is a retrospective descriptive study of patients undergoing laparoscopic left colectomy for splenic fexure cancer conducted at a national gastrointestinal surgery centre in China. Consecutive patients with splenic fexure cancer who underwent laparoscopic left colectomy using our"five-step process"(n = 34) between January 2021 and July 2023 were included. RESULTS: The vessels can be effectively exposed using the aforementioned "five-step process." It was observed that the overlooked vessels consistently present in all patients were identified as the omental branch of the left gastroepiploic artery and vein. CONCLUSION: We have identified the origin of previously overlooked blood vessels and recommended a safe method for their management. This may offer advantages to colorectal surgeons performing laparoscopic left colectomy for splenic flexure cancer.

Optimizing the algae-bacteria biofilm reactor for imidacloprid wastewater treatment: An evaluation of hydraulic retention times for enhanced efficiency and energy savings.

Recent observations have highlighted the rapidly growing prevalence of emerging contaminants such as Imidacloprid (IMI) within our environment. These insecticidal pollutants, coexisting with more traditional contaminants, have become predominant in aquatic systems, posing risks to both human and ecological well-being. Among the various wastewater treatment approaches tested, biofilm reactors are currently gaining prominence. In this study, we employed an Algae-Bacteria Biofilm Reactor (ABBR) to concurrently address both conventional and emergent contaminants, specifically IMI, over an extended timeframe. Following a 60-day assessment, the ABBR consistently demonstrated removal efficiencies exceeding 85% for total dissolved nitrogen, ammonia nitrogen, and total dissolved phosphorus, and also achieved removal efficacy for the soluble chemical oxygen demand (sCOD). Despite the removal efficiency of IMI (with initial concentration is 1.0 mg/L) in ABBR showed a gradual decline over the extended period, it remained consistently effective over 50% due to the microalgae-mediated free radical reactions, indicating the ABBR's sustained efficiency in long-duration operations. Additionally, applying some non-conventional modifications, like aeration removal and reducing light exposure, demonstrated minimal impact on the reactor's pollutant removal efficiencies, achieving comparable results to the control group (which utilized aeration with a 14:10 light/dark ratio), 0.92 kW h/L/d of electricity can be saved economically, which accentuated the potential for energy conservation. An in-depth analysis of the treated effluents from the ABBRs, using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique, uncovered four potential transformation pathways for IMI. Overall, our findings suggest that these optimized processes did not influence the transformation products of IMI, thereby reaffirming the viability of our proposed optimization.

Identification of lignans and quality assessment in Dendrobium officinale under different cultivation modes.

RATIONALE: Lignans have attracted much attention from researchers because of their wide distribution and industrial applications in plants, as well as the remarkable diversity of their biological activities. As the literature has mainly focused on the extraction and identification of monomeric compounds of lignans, most lignans in Dendrobium officinale, a traditional Chinese medicine with a long cultivation history and rich sources, have not been detected using quality control methods. The aim of this study was to identify the lignans in Dactilon officinale. METHODS: High-performance liquid chromatography (HPLC) coupled with diode array detection and HPLC multiple-stage tandem mass spectrometry was used to identify the chemical constituents of D. officinale. Simultaneously, the characteristic chromatograms of D. officinale were established. Additionally, a method was established to determine the content of syringaresinol-4,4'-di-O-ß-D-glucoside, syringaresinol-4-O-ß-D-glucoside and syringaresinol. RESULTS: Thirty-three lignans, including 17 tetrahydrofuran lignans, two dibenzylbutane lignans, three aryl tetrahydronaphthalene lignans and 11 8-O-4'-neolignans, were tentatively identified from the methanol extract of the stems of D. officinale. This is the first report of 8-O-4'-neolignans from D. officinale. In addition, a total of eight characteristic peaks were marked in characteristic chromatograms, which were identified as lyoniresinol-9'-O-ß-D-glucoside, syringaresinol-4,4'-di-O-ß-D-glucoside, 8-hydroxy-syringaresinol-4-O-ß-D-glucoside, 5,5'-dimethoxy-lariciresinol-4-O-ß-D-glucoside, syringaresinol-4-O-ß-D-glucoside, 4-hydroxy-3,3',5,5'-tetramethoxy-8,4'-oxyneoligna-7'-ene-9,9'-diol-9-O-ß-D-glucoside, 4-hydroxy-3,3',5,5'-tetramethoxy-8,4'-oxyneoligna-7'-ene-9,9'-diol-4-O-ß-D-glucoside and syringaresinol. Our results showed that no significant difference occurred in lignan composition among the 99 batches of D. officinale from different sources. However, the peak areas of the lignans of D. officinale planted under simulated wild culture were generally higher than those in greenhouses, and showed an upward trend with the increase in growth years. The average contents of syringaresinol-4,4'-di-O-ß-D-glucoside, syringaresinol-4-O-ß-D-glucoside and syringaresinol were 10.112-179.873, 51.227-222.294 and 6.368-120.341 µg/g, respectively. CONCLUSIONS: This study provided a basis for improving the quality control of D. officinale and could provide references for the identification of lignans in other Dendrobium species.

Efficient removal of thiamethoxam by freshwater microalgae Scenedesmus sp. TXH: Removal mechanism, metabolic degradation and application.

Neonicotinoids, as the most widely used pesticides in the world, help improve the production of crops. Meanwhile, it also brings potential threats to surrounding environments and other organisms because of its wide use and even abuse. In this study, Scenedesmus sp. TXH isolated from a wastewater treatment plant was used to remove the neonicotinoid pesticide thiamethoxam (THIA). The removal efficiency, degradation pathway, metabolite fate of THIA and physicochemical effects on microalgae cells were studied. Meanwhile, the feasibility of using microalgal technology to remove THIA from municipal wastewater was also explored. The results showed that 5-40 mg/L of THIA slightly promoted the growth of microalgae, while 60 mg/L THIA severely inhibited microalgal growth. It was observed that malondialdehyde content and superoxide dismutase activity in 60 mg/L THIA group increased significantly (p < 0.05) in the early stage of the experiment, indicating that THIA caused oxidative damage to microalgae. Scenedesmus sp. TXH showed high-efficient degradation ability and high resistance to THIA, with 100% removal of THIA at 5, 20 and 40 mg/L groups and 97.5% removal of THIA at 60 mg/L group on day 12. THIA was mainly removed by biodegradation, accounting for 78.18%, 93.50%, 96.81% and 91.35% under 5, 20, 40 and 60 mg/L on day 12, respectively. Six degradation products were identified, and four potential degradation pathways were proposed. In practical wastewater, the removal efficiency of total dissolved nitrogen, total dissolved phosphorus, ammonia nitrogen and THIA reached 85.68%, 90.00%, 98.43% and 100%, respectively, indicating that Scenedesmus sp. TXH was well adapted to the wastewater and effectively removed THIA and conventional pollutants.

Unveiling the mechanisms of peracetic acid activation by iron-rich sludge biochar for sulfamethoxazole degradation with wide adaptability.

Advanced oxidation processes (AOPs) based on peracetic acid (PAA) has been extensively concerned for the degradation of organic pollutants. In this study, metallic iron-modified sludge biochar (Fe-SBC) was employed to activate PAA for the removal of sulfamethoxazole (SMX). The characterization results indicated that FeO and Fe2O3 were successfully loaded on the surface of the sludge biochar (SBC). Fe-SBC/PAA system achieved 92% SMX removal after 30 min. The pseudo-first-order kinetic reaction constant of the Fe-SBC/PAA system was 7.34 × 10-2 min-1, which was 2.4 times higher than the SBC/PAA system. The degradation of SMX was enhanced with increasing the Fe-SBC dosage and PAA concentration. Apart from Cl-, NO3- and SO42- had a negligible influence on the degradation of SMX. Quenching experiments and electron paramagnetic resonance (EPR) techniques identified the existence of reactive species, of which CH3C(O)OO•, 1O2, and O2•- were dominant reactive species in Fe-SBC/PAA system. The effect of different water matrices on the removal of SMX was investigated. The removal of SMX in tap water and lake water were 79% and 69%, respectively. Four possible pathways for the decay of SMX were presented according to the identification of oxidation products. In addition, following the ecological structure-activity relationship model (ECOSAR) procedure and the germination experiments with lettuce seeds to predict the toxicity of the intermediates. The acute and chronic ecotoxicity of SMX solution was dramatically diminished by processing with Fe-SBC/PAA system. In general, this study offered a prospective strategy for the degradation of organic pollutants.

Changes of bacterial community structure,monosaccharide composition and CO2 exchange along the successional stages of biological soil crusts.

Biological soil crusts (BSCs) are a dominant ecological landscape of drylands, which have a significant impact on global biogeochemical flux. However, it is unclear how bacterial community and physiological characteristics vary along the BSCs successional stages. In this study, bacterial community composition, physiological characteristics, and monosaccharide composition of extracellular polysaccharides (EPSs) were compared among different successional stages. Our findings demonstrated that besides the dominant bacterial species, the bacterial communities also showed considerable differences between these two stages. Cyanobacteria were keystone taxa in the early stage, while heterotrophic bacteria (Proteobacteria, Actinobacteria and Acidobacteria) were keystone taxa in the later stages. According to the results of CO2 exchange, cyanobacterial crusts accumulated net carbon faster than moss crusts, while moss crusts had a significantly higher respiration rate. The monosaccharide analysis indicated that the EPSs components also varied depending on BSCs' successional stages. Specifically, the contents of rhamnose and arabinose were higher in the cyanobacterial crusts than other types of crusts, while the contents of fucose, xylose, mannose and glucose were the highest in cyanobacterial-lichen crusts, and galactose content was highest in the moss crusts. Altogether, our results stress the heterogeneous variation of BSCs along with succession, and this work offered a fresh viewpoint for a deeper comprehension of the interactions between the monosaccharide components of EPS and the networks of bacterial communities in BSCs.

Spatiotemporal distribution, sources apportionment and ecological risks of PAHs: a study in the Wuhan section of the Yangtze River.

This study investigated the sources, contamination and ecological risks of polycyclic aromatic hydrocarbons (PAHs) based on their spatiotemporal distribution in aquatic environment in the Wuhan section of the Yangtze River (WYR). The fugacity ratio evaluation indicated that sediment was secondary release sources of two- and three-ring PAHs and sinks of four- and five-ring PAHs. The total concentrations of PAHs (Σ16PAHs) ranged from 2.51 to 102.5 ng/L in water with the dominant contribution of 47.8% by two-ring PAHs. Σ16PAHs in sediments varied from 5.90 to 2926 ng/g with the contribution of 35.4% by four-ring PAHs. The higher levels of PAHs occurred around developed industrial areas during the wet season, which was related to local industrial emissions and influenced by rainfall/runoff. Annual flux of Σ16PAHs was estimated of 28.77 t. The PMF model analysis revealed that petroleum and industrial emissions were the dominant sources in water accounting for 58.5% of the total pollution, although traffic emission was the main source for sediment accounting for 44.6%. Risk assessments showed that PAHs in water were at low risks, whereas about 44% of the sediments were identified as medium risks. Therefore, energy structure adjustment and further implement of regulation and monitoring are necessary to reduce PAH emissions.

Genomic evolution and diverse models of systemic metastases in colorectal cancer.

OBJECTIVE: The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing. DESIGN: Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells. RESULTS: Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2, which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells. CONCLUSION: Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.

The significance of recent diversification in the Northern Hemisphere in shaping the modern global flora revealed from the herbaceous tribe of Rubieae (Rubiaceae).

The global herbaceous flora is probably shaped by both ancient and/or recent diversification, companied with the impacts from geographic differences between the Northern and Southern Hemispheres. Therefore, its biogeographic pattern with respect to temporal and spatial divergence is far from full understanding. Tribe Rubieae, the largest herbaceous tribe in the woody-dominant Rubiaceae, provides an excellent opportunity for studying the macroevolution of worldwide colonization. Here, we aim to reconstruct the evolutionary history of Rubieae with regard to climate fluctuation and geological history in the Cenozoic. A total of 204 samples of Rubieae representing all the distribution areas of the tribe were used to infer its phylogenetic and biogeographic histories based on two nrDNA and six cpDNA regions. The ancestral area of Rubieae was reconstructed using a time-calibrated phylogeny in RASP and diversification rates were inferred using Bayesian analysis of macroevolutionary mixtures (BAMM). Our results show Rubieae probably originated in European region during the middle Oligocene, with the two subtribes separating at 26.8 million years ago (Ma). All the genera in Rubieae formed separate clades between 24.79 and 6.23 Ma. The ancestral area of the subtribe Rubiinae was the Madrean-Tethyan plant belt and the North Atlantic land bridge (NALB) provided passage between North America and Europe for Rubiinae. The subtribe Galiinae clade originated in Europe/central Asia during the late Oligocene. Two diversification shifts were detected within Rubieae in the late Neogene. Most extant Rubieae species diverged recently during the Neogene within clades that generally were established during the late Paleogene. The tribe shows complex migration/dispersal patterns within the North Hemisphere combined with multiple recent dispersals into Southern Hemisphere. Our results highlighted the important role of recent biogeographic diversification in the Northern Hemisphere in shaping the modern global herbaceous flora during the latest and rapid worldwide expansion in the Neogene.

Brivaracetam prevents the development of epileptiform activity when administered early after cortical neurotrauma in rats.

OBJECTIVES: There is no effective therapy to prevent the development of posttraumatic epilepsy (PTE). Recently, we reported that administration of the antiseizure medication (ASM) levetiracetam (LEV) shortly after trauma prevented the development of epileptiform activity in two experimental models of neurotrauma. However, the time window for effective intervention with LEV may be too narrow for most clinical settings. Using the controlled cortical impact (CCI) injury model, the current study tested whether early administration of brivaracetam (BRV), an ASM with 20 times the affinity of LEV for the SV2A synaptic vesicle protein, could improve upon the antiepileptogenic action observed with LEV. METHODS: Rats (postnatal day [P] 24-32) subjected to CCI injury were given a single dose of BRV (21 or 100 mg/kg, i.p.) at one of three post-injury time points: immediately (0-2 minutes), 30 minutes, or 60 minutes. Control animals received only vehicle (0.9% saline). Posttraumatic electrographic epileptiform activity was assayed ex vivo from coronal neocortical slices collected proximal to the injury (four per rat) 3-4 weeks after injury. In this model, ictal-like burst discharges occur spontaneously or can be evoked in an "all or none" manner with applied electrical stimulation within the first 2 weeks after injury. RESULTS: A single dose of BRV administered to rats up to 60 minutes after traumatic brain injury (TBI) significantly reduced the development of posttraumatic epileptiform activity by (1) inhibiting the development of both evoked and spontaneous epileptiform activity, (2) raising the threshold for stimulus-evoked epileptiform discharges, and (3) reducing the intensity of epileptiform bursts that arise after cortical neurotrauma. SIGNIFICANCE: Clinically there has been little success preventing the development of posttraumatic epilepsy. The results of this study support the hypothesis that early intervention with BRV has the potential to prevent or reduce posttraumatic epileptogenesis, and that there may be a limited time window for successful prophylactic intervention.

Endoscopic stent versus diverting stoma as a bridge to surgery for obstructive colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Self-expandable metallic stent (SEMS), an alternative to diverting stoma (DS), has been used as a "bridge to surgery" (BTS) to decompress acute obstruction of colorectal cancer (CRC) for decades. However, whether SEMS is a safe technique for obstruction of CRC without compromising the long-term survival of patients remains unidentified compared to those of DS. The aim of the present study was to elucidate the safety and survival outcomes of SEMS and DS. METHODS: Embase, PubMed, and Medline were searched for qualified studies published until October, 2020, in which SEMS or DS was performed as a BTS without resection at the same stage. The last search was on December 5th, 2020. The Newcastle-Ottawa scale (NOS) was used to assess the quality of included studies. The major complication rate, mortality, 3-year overall survival (OS), and permanent stoma rate were estimated as outcomes. RESULTS: The present study was registered on INPLASY (No. 2020100079). Seven eligible studies were included, involving 646 and 712 patients who underwent SEMS and DS treatments, respectively. The Clavien-Dindo I/II grade complication rate was significantly lower in the SEMS group than in the DS group (8.68 vs. 16.85%; RR, 0.59; 95% confidence interval (CI) 0.41-0.84; P = 0.004). The Clavien-Dindo III/IV grade complication rate was comparable in two groups (7.69 vs. 8.79%; RR, 0.82; 95% CI 0.54-1.27; P = 0.37). There were no statistical differences in the short-term mortality (5.16 vs. 4.53%; RR, 1.25; 95% CI 0.75-2.08; P = 0.39), 3-year OS (71.91 vs. 76.60%; RR, 0.93; 95% CI 0.86-1.01; P = 0.10), and permanent stoma rate (22.08 vs. 27.54%; RR, 0.84; 95% CI 0.67-1.06; P = 0.14) between the two groups. CONCLUSIONS: To some extent, SEMS is a safe BTS technique for acute obstructive CRC, without significant adverse effect on the survival of patients. Given the advantage of minimal invasion, SEMS may be a better alternative to DS for obstructive CRC. However, the conclusions remain to be discussed because of lacking high-quality randomized controlled trails.

Comparison of the extraperitoneal and transperitoneal routes for permanent colostomy: a meta-analysis with RCTs and systematic review.

AIM: To assess the efficacy of extraperitoneal colostomy (EPC) in preventing stoma-related complications. BACKGROUND: Transperitoneal colostomy (TPC) is a widely used surgical approach. However, TPCs have been reported to have increased risks of stoma-related complications, such as parastomal hernias, stomal retraction, and stomal prolapse. The purpose of EPC is to reduce these complications. However, there is still a lack of evidence-based studies. MATERIALS AND METHODS: MEDLINE, EMBASE, Web of Science, Scopus, MOOSE, PubMed, Google Scholar, Baidu Scholar, and the Cochrane Library were searched to conduct a systematic review and meta-analysis with RCTs. The meta-analysis was performed with RevMan 5.4 software. RESULTS: This study included 5 eligible RCTs. Compared with the TPC group, the EPC group had lower incidence rates of parastomal hernias (RR, 0.14; 95% CI, 0.04-0.52, P = 0.003, I2 = 0%) and stomatal prolapse (RR, 0.27; 95% CI, 0.08-0.95, P = 0.04, I2 = 0%), but a higher rate of defecation sensation (RR, 3.51; 95% CI, 2.47-5.0, P < 0.00001, I2 = 37%). No statistically significant differences were observed in stoma retraction, colostomy construction time, stoma ischemia, or stoma necrosis. CONCLUSION: Extraperitoneal colostomies are associated with lower rates of postoperative complications than transperitoneal colostomies. A randomized controlled trial meta-analysis found that permanent colostomies after abdominoperineal resection resulted in better outcomes.

Actional Mechanisms of Active Ingredients in Functional Food Adlay for Human Health.

Medicinal and food homologous adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional mechanism of functional ingredients in adlay to promote human health, based on the PubMed, CNKI, Google, and ISI Web of Science databases from 1988 to 2022. Adlay and its extracts are rich in 30 ingredients with more than 20 health effects based on human and animal or cell cultures: they are anti-cancer, anti-inflammation, anti-obesity, liver protective, anti-virus, gastroprotective, cardiovascular protective, anti-hypertension, heart disease preventive, melanogenesis inhibiting, anti-allergy, endocrine regulating, anti-diabetes, anti-cachexia, osteoporosis preventive, analgesic, neuroprotecting, suitable for the treatment of gout arthritis, life extending, anti-fungi, and detoxifying effects. Function components with anti-oxidants are rich in adlay. These results support the notion that adlay seeds may be one of the best functional foods and further reveal the action mechanism of six major functional ingredients (oils, polysaccharides, phenols, phytosterols, coixol, and resistant starch) for combating diseases. This review paper not only reveals the action mechanisms of adding adlay to the diet to overcome 17 human diseases, but also provides a scientific basis for the development of functional foods and drugs for the treatment of human diseases.

Effects of Adjuvant Therapy Compliance and Anastomotic Leakage on the Oncologic Outcomes of Patients With Rectal Cancer After Curative Resection.

BACKGROUND: Anastomotic leakage might be directly or indirectly related to the prognosis of patients with rectal cancer. OBJECTIVE: This study aimed to investigate whether anastomotic leakage affects the oncologic outcomes in patients with rectal cancer. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a teaching hospital between January 2009 and December 2013. PATIENTS: Patients who underwent curative resection for primary rectal cancer were included. MAIN OUTCOME AND MEASURE: Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival. RESULTS: The overall incidence of anastomotic leakage was 2.7% (107/3865). Local recurrence was more frequent in patients with anastomotic leakage than in those without (14.0% vs 6.7%; p = 0.007). By multivariate analysis, anastomotic leakage was associated with increased local recurrence rate (p = 0.014) and poorer overall survival (p = 0.011). In subgroup analysis, compared with other pathologic risk factors, anastomotic leakage was associated with higher occurrence of local and distant recurrence in patients with stage II rectal cancer (p = 0.031 and <0.001). In patients with stage III rectal cancers, adjuvant therapy was more likely to be delayed or canceled in those experiencing anastomotic leakage (63 vs 39 d, p < 0.001; 37.3% vs 66.7%, p < 0.001). In addition, this patient group had the worst survival outcome when compared with those without anastomotic leakage and those with timely adjuvant therapy (5-year disease-free survival rate, p = 0.013; 5-year overall survival rate, p = 0.001). LIMITATIONS: This study is limited by its retrospective nature. CONCLUSIONS: There was a robust association between anastomotic leakage and local recurrence, while also potentially affect long-term survival of the patient group. Delayed or cancelled adjuvant therapy administration because of anastomotic leakage may partly account for the poorer survival in those patients with advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B459. EFECTOS DE OBSERVANCIA DE TERAPIA ADYUVANTE Y FUGA ANASTOMTICA, EN RESULTADOS ONCOLGICOS DE PACIENTES CON CNCER RECTAL, DESPUS DE UNA RESECCIN CURATIVA: ANTECEDENTES:La fuga anastomótica podría estar relacionada directa o indirectamente, con el pronóstico de los pacientes con cáncer de recto.OBJETIVO:El estudio tuvo como objetivo investigar si la fuga anastomótica afecta los resultados oncológicos, en pacientes con cáncer de recto.DISEÑO:Fue un análisis retrospectivo de datos recolectados prospectivamente.AJUSTE:El estudio se realizó en un hospital universitario entre enero de 2009 y diciembre de 2013.PACIENTES:Pacientes sometidos a resección curativa por cáncer rectal primario.PRINCIPALES MEDIDAS DE RESULTADO:Se utilizaron análisis de Kaplan-Meier para evaluar la supervivencia libre de enfermedad y supervivencia general.RESULTADOS:La incidencia global de fuga anastomótica fue del 2,7% (107/3865). La recurrencia local fue más frecuente en pacientes con fuga anastomótica, que en aquellos sin ella (14,0% frente a 6,7%, p = 0,007). Por análisis multivariado, la fuga anastomótica se asoció con una mayor tasa de recurrencia local (p = 0,014) y una peor supervivencia general (p = 0,011). En el análisis de subgrupos, en comparación con otros factores de riesgo patológicos, la fuga anastomótica se asoció con una mayor incidencia de recidiva local y a distancia en pacientes con cáncer rectal en estadio II (p = 0,031 y <0,001, respectivamente). En pacientes con cáncer rectal estadio III, la terapia adyuvante tuvo más probabilidades de retrasarse o cancelarse en aquellos que sufrían fuga anastomótica (63 vs 39 días, p <0,001; 37,3% vs 66,7%, p <0,001). Y este grupo de pacientes tuvo el peor resultado de supervivencia en comparación con aquellos sin fuga anastomótica y aquellos con terapia adyuvante oportuna (tasa de supervivencia libre de enfermedad a 5 años, p = 0,013; tasa de supervivencia global a 5 años, p = 0,001).LIMITACIONES:El estudio está limitado por su naturaleza retrospectiva.CONCLUSIONES:Hubo una sólida asociación entre la fuga anastomótica y la recurrencia local, mientras que también afecta potencialmente la supervivencia a largo plazo, del grupo de pacientes. La administración de terapia adyuvante retrasada o cancelada debido a una fuga anastomótica, puede explicar en parte, la menor supervivencia en aquellos pacientes con cáncer rectal avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B459.

Characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with idiopathic membranous nephropathy.

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection in idiopathic membranous nephropathy (IMN) patients, who are treated with immunosuppressive drugs. However, the risk factors of infection and their prognosis are rarely investigated. We aimed to characterize the clinical manifestations of PCP in patients with IMN, and to understand their risk factors, so that we can provide early warnings to patients with high risk and potential poor prognosis. We conducted a retrospective observational study of IMN patients in a referral center in China, from Jan 2012 to Dec 2018. Clinical and laboratory data were collected separately at the time of IMN and PCP diagnosis. Patients with PCP were matched to those without by gender and age at a ratio of 1:4. The risk factors and prognostic factors were determined by univariate and multivariate logistic regression analysis. A total of 879 patients with IMN were included, with a median follow-up of 267 (interquartile range (IQR) 64,842) days. In total, 26 (2.96%) of them were diagnosed with PCP. The infection rate increased to 3.87% among patients who received corticosteroids, and it further increased to 5.49% in those received over 0.5mg/kg prednisone. Univariate analysis indicated that initial usage of corticosteroids, use of cyclophosphamide, reduced estimated glomerular filtration rate (eGFR), and higher 24-h proteinuria were related to the PCP susceptibility. Multivariate analysis revealed that corticosteroid treatment and reduced eGFR increased the risk of the Pneumocystis jirovecii infection. The case fatality rate of the PCP patients was 23.08%, and increased to 75% among patients requiring invasive ventilation. Univariate analysis indicated that pulmonary insufficiency, invasive ventilation, decreased eGFR, and increased lactate dehydrogenase at presentation were linked to poor prognosis. PCP is not rare in patients with IMN, especially those on corticosteroids, and presented with decreased eGFR. Considering the high case fatality rate, further studies are in need for prevention and management of these patients.

Expression of FOXA1 gene regulates the proliferation and invasion of human gastric cancer cells.

Forkhead box (FOX) transcription factors regulate the development of several human cancers. However, the role and therapeutic potential of FOXA1 in gastric cancer is still largely unexplored. The results showed a significant (P < 0.05) upregulation of FOXA1 in gastric cancer tissues and cell lines. Silencing of FOXA1 in gastric cells significantly (P < 0.05) decreased their viability through induction of apoptosis. The induction of apoptosis was associated with upregulation of Bax and downregulation of Bcl-2. Additionally, FOXA1 silencing caused activation of caspase-3 and 9 with no apparent effects on the expression of caspase-8 suggestive of intrinsic apoptosis. The transwell cell invasion revealed significant (P < 0.05) decline of cell invasion of gastric cancer cells upon FOXA1 silencing. The FOXA1 knockdown further inhibited the in vivo tumor growth suggestive of its therapeutic potential. Taken together, the findings of the present revealed that FOXA1 regulates the proliferation and development of gastric cancer and may exhibit therapeutic implications in gastric cancer treatment.

Nomograms for predicting cancer-specific and overall survival in patients with invasive extramammary Paget's disease.

Aim: To develop nomograms for predicting cancer-specific survival (CSS) and overall survival (OS) in patients with invasive extramammary Paget's disease (iEMPD). Patients & methods: Retrospective data of 1955 patients with iEMPD were collected from the Surveillance, Epidemiology, and End Results database. Nomograms for predicting CSS and OS were established using competing risk regression and Cox regression, respectively, and were internally validated. Results: Five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) clinicopathological factors were utilized to construct nomograms for predicting CSS and OS, respectively. The concordance indices of the nomograms for predicting CSS and OS were 0.78 and 0.73, respectively. The validation of the nomograms showed good calibration and discrimination. The decision curve analyses confirmed the clinical utility of these nomograms. Conclusion: The nomograms can be a reliable tool for treatment design and prognostic evaluation of iEMPD.

Lay abstract Invasive extramammary Paget's disease (iEMPD) is a rare type of cutaneous malignancy with a heterogeneous prognosis. The prognostic factors remain poorly described, resulting in unclear risk stratification of the patients with iEMPD. The purpose of this study is to identify the prognostic factors associated with cancer-specific and overall survival rates in iEMPD and to develop accurate risk stratification models to guide the design of individualized treatment regimens. Clinicopathological data of 1955 patients pathologically diagnosed with iEMPD were retrospectively collected from the Surveillance, Epidemiology, and End Results database, and were utilized for analysis and construction of models for predicting the long-term survival in patients with iEMPD. Eventually, five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) factors were chosen to develop models for predicting cancer-specific and overall survival, respectively. The prediction accuracy and clinical utility of the established models were confirmed in subsequent evaluation. Because iEMPD is an extremely rare disease that a lot of clinical practitioners might not be familiar with, the availability of these quantifiable predictive models will provide convenience in daily practice.

Inoculation concentration modulating the secretion and accumulation pattern of exopolysaccharides in desert cyanobacterium Microcoleus vaginatus.

Cyanobacterial exopolysaccharides (EPS) accumulated during microalgal cultivation have significant application potential in antioxidation, pharmaceutical products, and so on. Inoculation concentration strongly affects the cultivation cost, biomass, and EPS accumulation. In this study, a high-EPS-excreted desert cyanobacterium Microcoleus vaginatus was isolated, and the effects of inoculation concentration on biomass, photosynthetic activity, and EPS accumulation were explored. The results showed that the original fluorescence (Fo ) provided a good indication to cyanobacterial biomass, when Chl-a concentration was lower than 10 mg L-1 . Inoculation concentration significantly affected cyanobacterial biomass and EPS concentration (P < 0.001), whereas did not affect photosynthetic activity (Fv /Fm ; P > 0.05). The two fractions of EPS, capsular exopolysaccharides (CPS) and released exopolysaccharides (RPS) were strongly affect by inoculation concentration. Other than forming thick sheath (CPS) surrounded the filaments, M. vaginatus excreted higher proportions of RPS to culture medium, and the ratio of RPS to CPS ranged from 1.08 to 1.58 depending on the inoculation concentration. Additionally, although the biomass and EPS accumulation increased with inoculation concentration, the increasing inoculation concentration did not bring to the proportionate increase of the final biomass and EPS yield. Altogether, comprehensively considering the EPS yield and productivity, inoculation concentration of 0.04 mg Chl-a L-1 is recommended for M. vaginatus to produce EPS, with an EPS yield of 94.32 mg L-1 and EPS productivity of 184.86 mg (mg Chl-a)-1  L-1  d-1 at the end of experiment.

Synergistic heat/UV activated persulfate for the treatment of nanofiltration concentrated leachate.

Nanofiltration concentration leachate is a high concentration organic wastewater with low biodegradability and high toxicity. To explore the feasibility of a combined Heat/UV activated persulfate process on nanofiltration concentrated leachate, the effects of persulfate concentration, initial solution pH before reaction, UV-lamp power and reaction temperature on the removal of organic pollutant were systematically investigated. Results indicated that the maximum rate of chemical oxygen demand (COD), ammonia-nitrogen (NH3-N) and absorbance of organic matter under UV light at 254 nm (UV254) removal from the leachate were 65.4%, 51.4% and 98.1%, respectively, at a persulfate concentration of 18 g L-1, initial solution pH before reaction of 9.0, UV-lamp power of 60 W and temperature of 80 °C. The results of three-dimensional fluorescence and UV254 showed that the removal rates of humic substances contained in the nanofiltration concentrated leachate were over 98%. In addition, the results of free radical scavenging showed that hydroxyl radicals were dominant under alkaline conditions. The results of this study demonstrated that coupling heat and ultraviolet activated persulfate oxidation is a promising technique for the treatment of nanofiltration concentrated leachate.