Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Short-chain fatty acids: bridges between diet, gut microbiota, and health.

In recent years, gut microbiota has become a hot topic in the fields of medicine and life sciences. Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota produced by microbial fermentation of dietary fiber, play a vital role in healthy and ill hosts. SCFAs regulate the process of metabolism, immune, and inflammation and have therapeutic effects on gastrointestinal and neurological disorders, as well as antitumor properties. This review summarized the production, distribution, and molecular mechanism of SCFAs, as well as their mechanisms of action in healthy and ill hosts. In addition, we also emphasized the negative effects of SCFAs, aiming to provide the public with a more comprehensive understanding of SCFAs.

Bibenzyl and naphthalene derivatives from Dendrobium chrysanthum and their anti-hepatic-steatosis activities.

In this study, 16 new compounds, six bibenzyls (1-6) and 10 naphthalenes (7-13), including three pairs of naphthalene enantiomers and three known compounds (14-16), were isolated from Dendrobium chrysanthum. Structurally, compounds 1-5 are previously undescribed dimeric bibenzyls, uniquely linked by unusual carbon bonds. The structures of the compounds were determined using spectroscopy and X-ray crystallography. The screening results indicated that 1, 2, and 5 showed remarkable lipid-lowering activities in FFA-induced HepG2 cells, with EC50 values ranging from 3.13 to 6.57 µM. Moreover, 1, 2, and 5 significantly decreased both the mRNA and protein levels of the target SREBP-1c, and 5 also reduced PPARα mRNA and protein levels. Therefore, 1, 2, and 5 are potential drugs against hepatic steatosis by targeting PPARα or SREBP-1c.

Design of a dynamic target simulator optical system with a large FOV and long exit pupil distance.

According to new generation missile test and detection requirements, it is necessary to introduce hardware-in-the-loop (HIL) simulation technology to realize the performance test of the seeker. This paper introduces the concept of secondary imaging and uses the method of focal distance allocation so that the optical system field of view (FOV) can still be greater than 6°, under the condition that the exit pupil distance is larger than 800 mm and a high-quality lighting system is designed. The design results show that when the exit pupil distance of the system is 1000 mm and the FOV is 6.4°, the modulation transfer function (MTF) of the system is 60l p/m m>0.4, and the distortion is less than 0.1%. The uniformity of the illumination system is greater than 90%, meeting the requirements of the design index.

Genome sequencing and transcriptome analyses provide insights into the origin and domestication of water caltrop (Trapa spp., Lythraceae).

Humans have domesticated diverse species from across the plant kingdom; however, our current understanding of plant domestication is largely founded on major cereal crops. Here, we examine the evolutionary processes and genetic basis underlying the domestication of water caltrop (Trapa spp., Lythraceae), a traditional, yet presently underutilized non-cereal crop that sustained early Chinese agriculturalists. We generated a chromosome-level genome assembly of tetraploid T. natans, and then divided the allotetraploid genome into two subgenomes. Based on resequencing data from 57 accessions, representing cultivated diploid T. natans, wild T. natans (2x and 4x) and diploid T. incisa, we showed that water caltrop was likely first domesticated in the Yangtze River Valley as early as 6300 yr BP, and experienced a second improvement c. 800 years ago. We also provided strong support for an allotetraploid origin of T. natans within the past 230 000-310 000 years. By integrating selective sweep and transcriptome profiling analyses, we identified a number of genes potentially selected and/or differentially expressed during domestication, some of which likely contributed not only to larger fruit sizes but also to a more vigorous root system, facilitating nutrient uptake, environmental stress response and underwater photosynthesis. Our results shed light on the evolutionary and domestication history of water caltrop, one of the earliest domesticated crops in China. This study has implications for genomic-assisted breeding of this presently underutilized aquatic plant, and improves our general understanding of plant domestication.

Neuropilin1 silencing impairs the proliferation and migration of cells in pancreatic cancer.

BACKGROUND: Neuropilin1 (NRP1) participates in cancer cell proliferation, migration, and metastasis as a multifunctional co-receptor by interacting with multiple signal pathways, but few studies have addressed the precise function of NRP1 in pancreatic cancer (PACA) cells. We aimed to study whether NRP1 gene silencing involved in the proliferation and migration of PACA cells in vitro. METHODS: A lentiviral vector expressing NRP1 shRNA was constructed and transfected into human PACA cells (CFPAC-1 and PANC-1). The expression of NRP1 protein and mRNA was detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assay, respectively. CCK-8 assay, wound healing assay, and transwell assay were conducted to examine the effect of NRP1 silencing on cells proliferation and migration capability. RESULTS: Results of qRT-PCR and Western blot showed successfully established, stably transfected shRNA-NRP1 cells in PACA cells. The proliferation capacity of PACA cells in NRP1 shRNA group was lower significantly than that in the negative control (NC) group (P < .05). The invasion and migration capability of PACA cells in NRP1 shRNA group was lower significantly than that in the NC group (P < .01). CONCLUSIONS: NRP1-shRNA lentiviral interference vectors can effectively decrease NRP1 gene expression in PACA cells, thereby inhibiting cells proliferation and migration, which provides a basis for finding a valuable therapeutic target for PACA therapy.

Arterial stiffness in adults with steady-state bronchiectasis: association with clinical indices and disease severity.

BACKGROUND: Cardiovascular disease are common co-morbidities in bronchiectasis and contribute substantially to disease burden and mortality. Brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, has a strong predictive value for cardiovascular event. We hypothesized that baPWV would be increased in steady-state bronchiectasis patients, and correlates with the degree of systemic inflammation and disease severity assessed with Bronchiectasis Severity Index and FACED scores. METHODS: Eighty patients with steady-state bronchiectasis and 80 age- and sex-matched controls were enrolled. BaPWV was measured as an indicator of arterial stiffness. Demographic, clinical indices, radiology, spirometry, sputum bacteriology and systemic inflammatory mediators were also assessed. RESULTS: Bronchiectasis patients had significantly increased baPWV [median 1514 cm/s vs. 1352 cm/s, P = 0.0003] compared with control subjects. BaPWV significantly correlated with Bronchiectasis Severity Index (rho = 0.65, P < 0.001) and FACED (rho = 0.49, P < 0.001) scores. In multivariate regression analysis, age, Pseudomonas aeruginosa colonization, systolic blood pressure, body-mass index and exacerbation frequency in the last 12 months, but not systemic inflammatory markers, were independent factors influencing on baPWV in bronchiectasis patient after adjustment for other clinical variables. Reproducibility of baPWV measurement was good. CONCLUSION: Bronchiectasis patients have increased arterial stiffness compared with control subjects, which correlates with disease severity, but not systemic inflammatory markers. Age, Pseudomonas aeruginosa colonization, systolic blood pressure, body-mass index and exacerbation frequency in last 12 months might independently predict the severity of arterial stiffness in bronchiectasis. Therefore, arterial stiffness might have contributed to the increased risks of developing cardiovascular diseases in bronchiectasis.

Synthesis and antitumor evaluation of 2,3-diarylbenzofuran derivatives on HeLa cells.

2,2-Dihydroxyarylethanones, readily prepared from the commercially available aromatic ethyl ketones, were reacted with resorcinol, 3-methoxyphenol or 2-methoxyphenol in multi steps one-pot manner promoted by trifluoroacetic acid to furnish the 2,3-diarylbenzofuran derivatives in 22-95% yield. Sixteen targeted compounds were synthesized and characterized by 1H NMR, 13C NMR and HRMS. MTT assay indicated that most compounds possessed effectively inhibitory activities against the proliferation of HeLa cell. Among them, 4f had the highest inhibitory activities, with the IC50 being 13.40±2.04µmol/L. Cell cycle analysis, Annexin V-FITC/propidium iodide dual staining assay and western blotting analysis revealed that 4f inhibited the proliferation of Hela cell through apoptosis induction in a dose-dependent manner via obviously up-regulated the levels of Bak and Bim, while striking down-regulated the level of Bcl-2 and Bcl-xL protein.

Immunosuppressive Agents for the Treatment of Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Currently, there are no effective therapeutic agents for patients with primary sclerosing cholangitis (PSC). This study aimed to evaluate the safety and efficiency of immunosuppressive agents (IAs) for the treatment of PSC. METHODS: The literatures were searched using the following keywords singly or in combination: PSC, treatments, IAs. The primary outcome was defined as the need for liver transplantation or mortality. RESULTS: Two hundred sixty six patients from 7 eligible studies were analyzed. IAs had no remarkable effects on the rate of mortality or liver transplantation (relative risk, RR 1.02, 95% CI 0.58-1.62, p = 0.92). Subgroup analyses showed no significant effect of IAs co-administration therapy (IAs co-administered with ursodeoxycholic acid, IA co-administered with IA; RR 1.41, 95% CI 0.40-4.95, p = 0.60). IAs caused adverse events (AEs) such as diarrhea, abdominal pain, and pruritus (RR 1.81, 95% CI 1.07-3.07, p = 0.03). IAs therapy did not significantly improve markers of liver function except for aspartate transaminase (weighted mean difference -9.76, 95% CI -12.92 to -6.6, p < 0.001). CONCLUSION: IAs administrated as either monotherapy or combination therapy do not reduce the risk of mortality or liver transplantation. IAs monotherapy is associated with AEs.

MiR-143 Targeting TAK1 Attenuates Pancreatic Ductal Adenocarcinoma Progression via MAPK and NF-κB Pathway In Vitro.

BACKGROUND: Transforming growth factor (TGF)-ß-activated kinase 1 (TAK1) is one of the major regulators of inflammation-induced cancer cell growth and progression. MiR-143 dysregulation is a common event in a variety of human diseases including pancreatic ductal adenocarcinoma (PDA). AIMS: To identify the interaction between TAK1 and miR-143 in PDA. METHODS: Data mining of TAK1 expression in PDA patient gene profiling was conducted. QRT-PCR and western blot were performed to detect the expression of TAK1 in PDA tissues and cell lines. Ectopic miR-143 and TAK1 were introduced to PDA cells. Cell growth, apoptosis and migration were examined. Xenograft models were used to examine the function of TAK1 in vivo. Western blot and luciferase assay were carried out to investigate the direct target of miR-143. RESULTS: PDA patient gene profiling data (GSE15471 and GSE16515) showed that TAK1 mRNA was aberrantly up-regulated in PDA tissues. TAK1 protein levels were overexpressed in PDA tissues and cell lines. Overexpression of TAK1 was strongly associated with positive lymph node metastasis. Inhibition of TAK1 suppressed cell growth, migration, and induced cell apoptosis in vitro and in vivo. Further studies demonstrated that TAK1 was a direct target gene of miR-143. MiR-143 also inhibited PDA cells proliferation and migration, induced apoptosis and G1/S arrest. Moreover, TAK1 depletion inactivated MAPK and NF-κB pathway, mimicking the function of miR-143. CONCLUSIONS: The study highlights that miR-143 acts as a tumor suppressor in PDA through directly targeting TAK1, and their functional regulation may provide potential therapeutic strategies in clinics.

Use of ultrasonic and pepsin treatment in tandem for collagen extraction from meat industry by-products.

BACKGROUND: Relatively little attention is paid to collagen-rich cattle short tendons (musculus extensor communis, musculus flexor digitorum, musculus digitorum profundis) as a source of high content and relatively pure collagen, a meat-processing by-product that is used to a minimal extent. Thus, suitable extraction processes from a meat production by-product to gain intact collagen is promising, which thus become interesting from an economic and environmental point of view. RESULTS: Two extraction methods were compared: a 48 h pepsin treatment using 0.5 mol L⁻¹ acetic acid and an extraction using pepsin treatment after ultrasonic treatment in a 0.5 mol L⁻¹ acetic acid solution (the total ultrasonic and pepsin treatment time was 48 h). The results indicated that the optimal conditions for the extraction of collagen from cattle tendon with the ultrasonic-pepsin tandem method is: 4°C, tendon pre-swollen for 12 h in 0.5 mol L⁻¹ acetic acid, pepsin amount: 50 U mg⁻¹ of sample, ultrasonic-pepsin tandem treatment time for 18 h and 30 h, respectively. Extracted cattle tendon collagen using ultrasonic and pepsin treatment in tandem was characterised by amino acid analysis, SDS-PAGE, FT-IR, solubility and thermal denaturation temperature. The results show that the ultrasonic-pepsin tandem method can effectively improve the efficiency of pepsin extraction of natural collagen without any compromise of the resultant collagen quality. CONCLUSION: This study provides a favourable process to deal with poorly extractable residue by use of ultrasonic and pepsin treatment in tandem. Extracted collagen possesses an intact molecular structure, which is useful and particularly important for its biomedical applications, such as drug delivery systems, wound dressings, and scaffolds.

Malignancies of the anal canal: a multi-center retrospective analysis in South China population.

PURPOSE: Malignancies of the anal canal are rare diseases associated with limited reports and insufficient data. The purpose of this study was to evaluate the spectrum of pathological subtypes, therapeutic modalities and prognosis of patients in the Chinese population with anal canal malignancies. METHODS: A retrospective consecutive series of patients with malignancies of the anal canal at 4 institutions in China between January 1990 and December 2011 was studied. The patient demographic data, including age, gender, tumor stage, initial symptoms, pathological diagnosis, treatment and survival, were collected and analyzed from the hospitals' databases. RESULTS: A total of 180 patients (90 males, 90 females) with anal canal malignancies was identified. Their median age was 58 years (range 17-88). The 3 most common pathological subtypes were adenocarcinoma (N-129, 71.7%), squamous cell carcinoma (SCC; N=21, 11.7%) and melanoma (N7equals;15, 8.3%). Ninety-five adenocarcinoma patients and 10 SCC patients were managed with abdominoperineal resection (APR). With a median follow-up time of 28.9 months (range 1-173), the 5-year overall survival (OS) rates for all patients, adenocarcinoma patients, SCC patients and melanoma patients were 41.9, 40.6, 44.5 and 14.8% respectively, and the median OS time were 46.8, 50.1, 52.5 and 25.0 months, respectively (p=0.173). CONCLUSION: Adenocarcinoma was the major histological subtype in Chinese patients with anal canal malignancies. APR-based combined modality treatment was the first choice for the past two decades, whereas multidisciplinary treatment was not performed adequately. The management of SCC must be standardized in South China population. In the future, randomized clinical trials are warranted for the optimal treatment options of anal canal adenocarcinoma patients.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma.

BACKGROUND: Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM: To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS: The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS: CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION: This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

Primary malignant melanoma of the esophagus combined with squamous cell carcinoma: A case report.

BACKGROUND: Primary malignant melanoma of the esophagus is a rare malignant tumor of the esophagus, and its combination with squamous cell carcinoma is also rare. Here, we report the diagnosis and treatment of a case of primary esophageal malignant melanoma combined with squamous cell carcinoma. CASE SUMMARY: A middle-aged man underwent gastroscopy for dysphagia. Gastroscopy revealed multiple bulging esophageal lesions, and after pathologic and immunohistochemical analyses, the patient was finally diagnosed with "malignant melanoma with squamous cell carcinoma". This patient received comprehensive treatment. After one year of follow-up, the patient was in good condition, and the esophageal lesions seen on gastroscopy were controlled, but unfortunately, liver metastasis occurred. CONCLUSION: When multiple esophageal lesions are present, the possibility of multiple pathological sources should be considered. This patient was diagnosed with primary esophageal malignant melanoma combined with squamous cell carcinoma.

Is endoscopic mucosal ablation a valid option for treating colon polyps?

The present letter to editor is related to endoscopic mucosal ablation (EMA). EMA is safe and effective in the treatment of colonic polyps when endoscopic resection is not possible or available, but the indication of EMA should be determined for a further large number of studies. EMA should be used with caution for larger lesions.

Circularly polarized luminescence from helical N,O-boron-chelated dipyrromethene (BODIPY) derivatives.

We report N,O-boron-chelated dipyrromethene derivatives exhibiting circularly polarized luminescence (CPL) in the red/near-infrared region, both in solution and the aggregated state. The CPL is originated from the helical chirality through intramolecular substitution of fluorine by an alkenolic substituent. The self-assembly of the fluorophores significantly enhances the |glum| values from 10-4 to 10-2.

The Effects of the SARS-CoV-2 Virus on the Cardiovascular System and Coagulation State Leading to Cardiovascular Diseases: A Narrative Review.

The novel coronavirus pandemic has led to morbidity and mortality throughout the world. Until now, it is a highly virulent contagion attacking the respiratory system in humans, especially people with chronic diseases and the elderly who are most vulnerable. A majority of afflicted are those suffering from cardiovascular and coronary diseases. In this review article, an attempt has been made to discuss and thoroughly review the mode of therapies that alleviate cardiac complications and complications due to hypercoagulation in patients infected with the SARS-CoV-2 virus. Presently a host of thrombolytic drugs are in use like Prourokinase, Retelapse, RhTNK-tPA and Urokinase. However, thrombolytic therapy, especially if given intravenously, is associated with a serious risk of intracranial haemorrhage, systemic haemorrhage, immunologic complications, hypotension and myocardial rupture. The effects of the SARS-CoV-2 virus upon the cardiovascular system and coagulation state of the body are being closely studied. In connection to the same, clinical prognosis and complications of thrombolytic therapy are being scrutinized. It is noteworthy to mention that myocardial oxygen supply/demand mismatch, direct myocardial cells injury and acute plaque rupture are the multiple mechanisms responsible for acute coronary syndrome and cardiac complications in Covid-19 infection. However, this review has limitations as data available in this context is limited, scattered and heterogenous that questions the reliability of the same. So, more multi-centric studies involving representative populations, carried out meticulously, could further assist in responding better to cardiac complications among Covid-19 patients.

Isolation and characterization of endophytic huperzine A-producing fungi from Huperzia serrata.

Huperzia serrata is a producer of huperzine A (HupA), a cholinesterase inhibitor (ChEI). Over 120 endophytic fungi were recovered from this plant and screened for Hup-A and nine were found. These nine represented seven different fungal genera with the most significant producer being Shiraia sp. A total of 127 endophytic fungi isolates obtained from the root, stem, and leaf segments of H. serrata were grouped into 19 genera based on their morphological traits and sequence analysis of the internal transcribed spacers (ITS1-5.8S-ITS2), indicating endophytic fungi in H. serrata are diverse and abundant. Aspergillus, Podospora, Penicillium, Colletotrichum, and Acremonium were the frequent genera, whereas the remaining genera were infrequent groups. Overall, 39 endophytic fungi isolates showed acetylcholinesterase (AChE) inhibition in vitro. Nine endophytic fungi isolates from seven distinct genera were capable of producing HupA verified by thin-layer chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). Among the HupA-producing fungi, the yield of HupA produced by the Shiraia sp. Slf14 was 327.8 µg/l in potato dextrose broth, and the fungal HupA was further validated by mass spectrometry (ESI-MS). The present study demonstrated that H. serrata was a fascinating fungal reservoir for producing HupA and other ChEIs.

Assimilation of 17α-ethinylestradiol by sludge and its stress on microbial communities under aerobic and anaerobic conditions.

The efficiency of 2 common types sludge, activated sludge and digesting sludge, to biodegrade ethinylestradiol (EE2) under aerobic and anaerobic conditions, and the impacts of EE2 on microbial community structure were investigated. The results showed that 75%-88% EE2 were removed under aerobic conditions and the values were 75%-84% under anaerobic conditions. The diversity of microbial species in the tested sludge decreased when exposed to EE2 and the shift of microbial community structures was dependent on both sludge types and process conditions. Predominant bacteria were identified as Proteobacteria class which was considered to have EE2 degradation capacities. Twelve strains were found, 8 of them belonged to the Class of γ-proteobacterium, 1 of ß-proteobacterium, 1 of Actinobacterium, and 2 of unclassified strains.

Efficacy of the FOLFOX/CAPOX regimen for advanced small bowel adenocarcinoma: a three-center study from China.

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy, and most patients present with unresectable or metastatic disease. Thus far, no standard chemotherapeutic regimen has been established and related data are scarce, especially in Eastern countries. The purpose of this multicenter study was to evaluate the efficacy and toxicity of oxaliplatin combined with fluoropyrimidines in Chinese patients with advanced SBA. METHODS: Advanced SBA patients who received FOLFOX (5-fluorouracil/5-FU plus leucovorin and oxaliplatin)/ CAPOX (capecitabine plus oxaliplatin) as first-line chemotherapy between February, 2004 and October, 2010 were identified from 3 large medical centers in China. The response rate (RR), progression-free survival (PFS), overall survival (OS), and chemotherapy-associated toxicity were evaluated. Cox models were applied for multivariate analyses. RESULTS: Of 34 patients, with SBA 28 received FOLFOX and 6 CAPOX. The objective response (OR) and disease control (DC) rates were 32.3% and 61.7%, respectively. The median PFS and OS were 6.3 and 14.2 months, respectively. The toxicity was tolerable, grade 3-4 toxicity was rare. In multivariate analysis, only multi-organ metastasis reached borderline significance for shorter PFS (p=0.059), but the variables of age (>65 years; p=0.001), and multi-organ metastasis (p=0.001) were significantly associated with poor OS. CONCLUSION: To our knowledge, this multicenter retrospective study is the first and largest one among Asian studies at present estimating oxaliplatin combined with fluoropyrimidines as first-line chemotherapy for advanced SBA. FOLFOX/CAPOX is proved effective for advanced SBA in this study, but the results do not absolutely agree with previous studies from Western countries, showing that further studies are still needed.