Longer Time Interval from Neoadjuvant Chemoradiation to Surgery is Associated with Poor Survival for Patients Without Clinical Complete Response in Oesophageal Cancer.

BACKGROUND: The optimal interval between neoadjuvant therapy and oesophagectomy for oesophageal cancer remains controversial. METHODS: Patients with locally advanced oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy followed by oesophagectomy between June 2017 and December 2020 were prospectively enrolled and retrospectively analysed. Patients were divided into two groups: timely (group A; < 10 weeks) and delayed (group B; ≥ 10 weeks) surgery groups. Survival was the primary outcome, and tumour response and post-operative complications were the secondary outcomes. RESULTS: Overall, 224 patients were recruited; 116 patients (51.8%) underwent timely surgery within 10 weeks (group A), and 108 patients (49.2%) underwent delayed surgery over 10 weeks (group B) after chemoradiotherapy. In patients with clinical complete response (cCR), two groups had no significant difference of survival benefit (P = 0.618). However, in patients without cCR, delayed surgery was associated with poor survival (P = 0.035) and cancer progression (P = 0.036). A total of 40 patients (34.5%) in group A and 54 patients (50.0%) in group B achieved pCR (P = 0.019). pCR rates were significantly different across the four groups and increased over time (P = 0.006). CONCLUSIONS: Patients with a prolonged time interval from neoadjuvant chemoradiation to surgery had higher pCR rates. For patients with cCR to neoadjuvant chemoradiation, the time interval to surgery can be safely prolonged for at least 10 weeks. However, for patients with non-cCR to neoadjuvant chemoradiation, delayed surgery is associated with poor survival, and surgery should be performed within 10 weeks of neoadjuvant chemoradiation.

The comparisons of neoadjuvant chemoimmunotherapy versus chemoradiotherapy for oesophageal squamous cancer.

OBJECTIVES: The aim of this study was to evaluate the short-term outcomes of neoadjuvant chemoimmunotherapy (NACI) followed by oesophagectomy for locally advanced oesophageal squamous carcinoma. METHODS: Patients receiving NACI or chemoradiotherapy between September 2019 and September 2021 were identified. The primary outcomes were tumour response and survival. Secondary outcomes were toxic effects and postoperative complications. The propensity score matching for enrolled patients was performed. RESULTS: Data of 149 patients with clinical stage II-IV oesophageal squamous cancer, including 55 receiving NACI and 94 receiving neoadjuvant chemoradiotherapy (NACR), were analysed after propensity score matching. With regard to tumour response score, 24 (43.6%) and 59 (62.8%) patients were scored 0/1 in the NACI and NACR groups, respectively (P = 0.023). Of note, 17 (30.9%) patients in the NACI group achieved pathological complete response (CR) (ypT0N0), while 48 (51.1%) patients in NACR group achieved pathological CR (P = 0.026). NACR was associated with the higher risk of postoperative pneumonia (P = 0.034) and less lymph nodes and stations dissected (P ≤ 0.001). The 1-year cumulative overall survival rate was 94.5% and 86.2% in the NACI and NACR groups, respectively (P = 0.170). CONCLUSIONS: We found that NACI compared with NACR was associated with lower pneumonia rate and was safe and feasible for locally advanced oesophageal squamous cancer. However, the tumour regression score and the pathological CR rate of patients treated with neoadjuvant immunotherapy were lower than those of patients treated with NACR. The short-term follow-up results were comparable between 2 treatment modalities.

Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments.

Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide, and effective biomarkers are still lacking for early detection and prognosis prediction. Here, based on gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA), 806 long non-coding RNAs (lncRNAs), 122 microRNAs (miRNAs) and 1269 mRNAs associated with CDK1 were identified. The regulatory axis of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT was determined according to the correlation between gene expression and patient prognosis. The abnormal up-regulation of FAM111B/ZWINT in LUAD was related to hypomethylation. Furthermore, immune infiltration analysis suggested FAM111B/ZWINT could affect the development and prognosis of cancer by regulating the LUAD immune microenvironment. EMT feature analysis suggested that FAM111B/ZWINT promoted tumor spread through the EMT process. Functional analysis showed FAM111B/ZWINT was involved in cell cycle events such as DNA replication and chromosome separation. We analyzed the HERB and GSCALite databases to identify potential target medicines that may play a role in the treatment of LUAD. Finally, the expression of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT axis was verified in LUAD cells by RT-qPCR, and these results were consistent with bioinformatics analysis. Overall, we constructed a CDK1-related ceRNA network and revealed the LINC00460/LINC00525-hsa-mir-338-FAM111/ZWINT pathways as potential diagnostic biomarkers or therapeutic targets of LUAD.

Progress in traditional Chinese medicine and natural extracts for the treatment of lupus nephritis.

Lupus nephritis (LN) is an autoimmune disease with multiple system involvement and is also one of the most serious forms of organ damage in systemic lupus erythematosus (SLE), which is mainly caused by the formation and deposition of immune complexes in glomeruli. More than 50% of SLE patients have clinical manifestations of renal damage. At present, the treatment of lupus nephritis is mainly based on glucocorticoids and immunosuppressants. However, due to adverse drug reactions and frequent recurrence or aggravation after drug reduction or withdrawal, the prognosis remains poor; thus, it is still one of the most important causes of end-stage renal failure. Therefore, new treatment strategies are urgently needed. This article aims to review the application of traditional Chinese medicine and natural extracts in the treatment of lupus nephritis to provide the basic mechanisms of treatment and a new treatment strategy with clear effects and high safety performance.

Biosafety risk assessment of nanoparticles: Evidence from food case studies.

Nanotechnology provides a wide range of benefits in the food industry in improving food tastes, textures, sensations, quality, shelf life, and food safety. Recently, potential adverse effects such as toxicity and safety concerns have been associated with the increasing use of engineered nanoparticles in food industry. Additionally, very limited information is known concerning the behavior, properties and effects of food nano-materials in the gastrointestinal tract. There is explores the current advances and provides insights of the potential risks of nanoparticles in the food industry. Specifically, characteristics of food nanoparticles and their absorption in the gastrointestinal tract, the effects of food nanoparticles against the gastrointestinal microflora, and the potential toxicity mechanisms in different organs and body systems are discussed. This review would provide references for further investigation of nano-materials toxicity effect in foods and their molecular mechanisms. It will help to develop safer foods and expand nano-materials applications in safe manner.

Unravelling the Role of LncRNA WT1-AS/miR-206/NAMPT Axis as Prognostic Biomarkers in Lung Adenocarcinoma.

Lung cancer is the world's highest morbidity and mortality of malignant tumors, with lung adenocarcinoma (LUAD) as a major subtype. The competitive endogenous RNA (ceRNA) regulative network provides opportunities to understand the relationships among different molecules, as well as the regulative mechanisms among them in order to investigate the whole transcriptome landscape in cancer pathology. We designed this work to explore the role of a key oncogene, MYC, in the pathogenesis of LUAD, and this study aims to identify important long noncoding RNA (lncRNA)-microRNA (miRNA)- transcription factor (TF) interactions in non-small cell lung cancer (NSCLC) using a bioinformatics analysis. The Cancer Genome Atlas (TCGA) database, containing mRNA expression data of NSCLC, was used to determine the deferentially expressed genes (DEGs), and the ceRNA network was composed of WT1-AS, miR-206, and nicotinamide phosphoribosyltransferase (NAMPT) bashing on the MYC expression level. The Kaplan-Meier univariate survival analysis showed that these components may be closely related prognostic biomarkers and will become new ideas for NSCLC treatment. Moreover, the high expression of WT1-AS and NAMPT and low expression of miR-206 were associated with a shortened survival in NSCLC patients, which provided a survival advantage. In summary, the current study constructing a ceRNA-based WT1-AS/miR-206/NAMPT axis might be a novel important prognostic factor associated with the diagnosis and prognosis of LUAD.

A Novel Multiresolution-Statistical Texture Analysis Architecture: Radiomics-Aided Diagnosis of PDAC Based on Plain CT Images.

Early screening of PDAC (pancreatic ductal adenocarcinoma) based on plain CT (computed tomography) images is of great significance. Therefore, this work conducted a radiomics-aided diagnosis analysis of PDAC based on plain CT images. We explored a novel MSTA (multiresolution-statistical texture analysis) architecture to extract texture features and built machine learning models to classify PDACs and HPs (healthy pancreases). We also performed significance tests of differences to analyze the relationships between histopathological characteristics and texture features. The MSTA architecture originates from the analysis of histopathological characteristics and combines multiresolution analysis and statistical analysis to extract texture features. The MSTA architecture achieved better experimental results than the traditional architecture that scales the coefficient matrices of the multiresolution analysis. In the validation of the classifications, the MSTA architecture achieved an accuracy of 81.19% and an AUC (area under the ROC (receiver operating characteristic) curve) of 0.88 (95% confidence interval: 0.84-0.92). In the test of the classifications, it achieved an accuracy of 77.66% and an AUC of 0.79 (95% confidence interval: 0.71-0.87). Moreover, the significance tests of differences showed that the extracted texture features may be relevant to the histopathological characteristics. The MSTA architecture is beneficial for the radiomics-aided diagnosis of PDAC based on plain CT images. Its texture features can potentially enhance radiologists' imaging interpretation abilities.

Timing of surgery after neoadjuvant chemoradiotherapy affects oncologic outcomes in patients with esophageal cancer.

BACKGROUND: The optimal time interval between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy in esophageal cancer has not been defined. AIM: To evaluate whether a prolonged time interval between the end of nCRT and surgery has an effect on survival outcome in esophageal cancer patients. METHODS: We searched PubMed, Embase, Web of Science, the Cochrane Library, Wanfang and China National Knowledge Infrastructure databases for relevant articles published before November 16, 2019, to identify potential studies that evaluated the prognostic role of different time intervals between nCRT and surgery in esophageal cancer. The hazard ratios and 95% confidence intervals (95%CI) were merged to estimate the correlation between the time intervals and survival outcomes in esophageal cancer, esophageal squamous cell carcinoma and adenocarcinoma using fixed- and random-effect models. RESULTS: This meta-analysis included 12621 patients from 16 studies. The results demonstrated that esophageal cancer patients with a prolonged time interval between the end of nCRT and surgery had significantly worse overall survival (OS) [hazard ratio (HR): 1.107, 95%CI: 1.014-1.208, P = 0.023] than those with a shorter time interval. Subgroup analysis showed that poor OS with a prolonged interval was observed based on both the sample size and HRs. There was also significant association between a prolonged time interval and decreased OS in Asian, but not Caucasian patients. In addition, a longer wait time indicated worse OS (HR: 1.385, 95%CI: 1.186-1.616, P < 0.001) in patients with adenocarcinoma. CONCLUSION: A prolonged time interval from the completion of nCRT to surgery is associated with a significant decrease in OS. Thus, esophagectomy should be performed within 7-8 wk after nCRT.

Preparation of Nano-Silver-Containing Polyethylene Composite Film and Ag Ion Migration into Food-Simulants.

Nano-composite films were developed between silver nanoparticles (Ag NPs) and a low-density polyethylene (LDPE) using master batches by melt extruding and melt compounding. The Ag/PE composite film showed decreased gas permeability, moisture permeability coefficient, the tear strength, the longitudinal and transverse elongation to that of commercial LDPE. Although stiffness increased at high Ag (40 ppm) concentration, but the longitudinal and transverse tensile strength enhance comparing with commercial PE. Light transmittance and haze were comparable. Both Nano-silver and composite films are effective against Escherichia coli (E. coli). Antibacterial activity of nano-silver for E. coli was determined by diameter of the inhibition zone and the minimum inhibitory concentration of nano-silver is detected by tube double dilution method reaching 15.63 ppm. The composite films are effective inhibition of E. coli at concentrations of 40 ppm Ag nanoparticles. Moreover, Nano-silver migration occurs in composite film. One-side migration was conducted to detect under three food simulants (3% acetic acid, 50% ethanol and distilled water) at three degree of temperature (25 °C, 40 °C and 70 °C) on different period of time (2, 4, 6, 8, 10 and 12 hours). These results indicated that the highest migration amount was obtained with 3% acetic acid following distilled water and finally 50% ethanol under same conditions. The migration level is dependent upon time and temperature and high migration time and temperature can enhance migration level. These findings demonstrate that nano-silver-containing polyethylene composite film may have a great potential for developing antibacterial and acid food packaging system.

Down-regulation of microRNA-200b is a potential prognostic marker of lung cancer in southern-central Chinese population.

MicroRNAs (miRNAs) may regulate diverse biological processes and play an important role in cancer. And MiRNAs have been proposed as a useful tool for lung cancer diagnosis and therapeutics in cancer. The purpose of the present study was to investigate the association among the expression level of mature miR-200b-5p in peripheral blood and the risk of lung cancer and clinic pathological characteristics. This case-control study included 24 patients with lung cancer and 12 healthy controls. MiR-200b expression was deleted using real-time PCR. and the miR-200b expression of normal controls was significantly higher than that in lung cancer patients (1732.13 pg/mL vs 881.67 pg/mL, P < 0.05), no difference with age, sex, tissue type and clinical stage of lung cancer patients (P > 0.05). Furthermore, miR-200b expression level fluctuated with tumor progression in lung cancer, and there was highly significant for clinical stage II compared with the clinical stage III (P < 0.05). In addition, the down-regulation of miR-200b showed a highly discriminative receiver operating characteristic (ROC) curve profile, clearly distinguishing cancer patients from cancer-free subjects with an area under the ROC curve (AUROC) of 0.87. The detection of miR-200b expression yielded 83.30% sensitivity and 100.00% specificity in the diagnosis of lung cancer. Therefore, these findings suggested that miR-200b may be used as a marker for the detection and diagnosis of lung cancer in peripheral blood.

Isolation, genetic identification and degradation characteristics of COD-degrading bacterial strain in slaughter wastewater.

Contamination of water by meat production is an important and extensive environmental problem and even threat to human health. Biodegradation is a major mechanism which removes the pollutants from the environment. Therefore, the present study aimed to isolate and characterize a COD degrading bacteria which can effectively degrade slaughter wastewater. Six COD degrading bacteria were isolated from slaughtering waste water and sludge in Hunan a meat product Co., Ltd. And the COD degradation rate of each strain was determined by potassium permanganate method. Through observing morphologically and analyzing sequence to 16S rDNA, the highest COD degradation strain was Bacillus velezensis by preliminarily identified and classified, reaching 11.80%. The suitable conditions of the growth of Bacillus velezensis strain were 37 °C, pH 7.0, the peptone concentration 1.5%, and the yeast extract concentration 0.8%.

Modified Double-Layer Anastomosis for Minimally Invasive Esophagectomy: An Effective Way to Prevent Leakage and Stricture.

BACKGROUND: Anastomotic leakage and stricture contribute to a large number of mortality and morbidity after esophagectomy. The aim of this work is to evaluate the outcome of modified double-layer hand-sewn esophagogastric anastomosis during minimally invasive esophagectomy for esophageal cancer. METHODS: The clinicopathological data of 176 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using modified double-layer hand-sewn technique after radical esophagectomy were retrospectively reviewed. Total minimally invasive approach, including thoracoscopic surgery for thoracic procedure and laparoscopic approach for abdominal procedure, was implemented during the radical Mckeown esophagectomy. Patients were followed up for the assessment of postoperative anastomotic complications including anastomotic leakage and stricture, being the primary outcome measures for this study. RESULTS: Anastomotic leakage occurred in 2 of 176 patients (1.1%); both of the patients experienced only minor leakage and were treated conservatively. There was no significant difference in leakage between patients with and without major comorbidity (p = 0.331). After a mean follow-up of 21.3 months, four patients (4/176, 2.3%) developed benign anastomotic strictures, including those 2 patients experienced postoperative leakage. Symptoms for stricture were improved by endoscopic dilatations in all 4 patients. Besides, there was one case (1/176, 0.6%) of gastric necrosis in this cohort, who was also successfully managed by conservative therapy with no operative mortality. CONCLUSION: This modified double-layer hand-sewn anastomosis is a highly safe and stable technique for esophagogastrostomy, which is an effective way to prevent both anastomotic leakage and stricture.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

BACKGROUND: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. METHODS: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). RESULTS: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). CONCLUSIONS: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

Optimization for extracellular biosynthesis of silver nanoparticles by Penicillium aculeatum Su1 and their antimicrobial activity and cytotoxic effect compared with silver ions.

The present study addresses an eco-friendly and energy-saving method for extracellular biosynthesis of silver nanoparticles (AgNPs) using a cell free filtrate of the fungus strain Penicillium aculeatum Su1 as a reducing agent. Parametric optimization of the biosynthesis process demonstrated different effects on the size, distribution, yield, and synthesis rate of biosynthesized AgNPs. The transmission electron microscopy (TEM) measurements demonstrated that AgNPs were spherical or approximately spherical, with a size between 4 and 55nm. High-resolution transmission electron microscopy (HR-TEM) and X-ray diffraction (XRD) analyses indicated that AgNPs were nanocrystalline by nature, with the character of a face-centered cubic (fcc). Fourier transform infrared spectroscopy (FTIR) analysis confirmed the existence of protein molecules that acted as a reducing agent and a capping agent during the biosynthesis process. Furthermore, the biosynthesized AgNPs exhibited higher antimicrobial activity than silver ions against Gram negative bacteria, Gram positive bacteria and fungi. Compared with silver ions, the biosynthesized AgNPs presented higher biocompatibility toward human bronchial epithelial (HBE) cells and high cytotoxicity in a dose-dependent manner with an IC50 of 48.73µg/mL toward A549 cells. These results demonstrate that Penicillium aculeatum Su1 is a potential bioresource that can be used to produce low-cost and eco-friendly AgNPs as efficient antimicrobial agent, drug delivery vehicle or anticancer drug for clinic treatment.

Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling.

BACKGROUND: Esophagectomy with gastric interposition could serve as a good human reflux model to study the molecular pathogenesis of esophageal mucosal damage induced by gastroesophageal reflux. This study was to investigate the role of Notch signaling in reflux injury of esophageal mucosa. METHODS: Patients undergoing Ivor-Lewis esophagectomy for early stage esophageal squamous cell carcinoma were included. Follow-ups were scheduled at 6, 18, 36 and 48 months postoperatively, including reflux symptom assessment, endoscopic and histological evaluation of esophageal mucosal damage. The expressions of Notch1 and its downstream target gene Hes1 were evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). RESULTS: Forty-four out of 48 patients completed four follow-ups. Injuries of esophageal remnant confirmed by endoscopical and histological examinations were both more often with a longer postoperative period (P<0.05). The mRNA expression levels of Notch1 and Hes1 were decreased in a time-dependent manner after operation (P<0.001). Notch1 and Hes1 mRNA levels were significantly higher in normal squamous mucosa than in esophagitis, and higher in esophagitis than in metaplasia (P<0.05). Immunohistochemical study also demonstrated a similar protein expression pattern. Samples with endoscopic evidence of mucosal damage exhibited lower expression of Notch1 mRNA levels as compared to biopsies without visualized damage (P=0.035). CONCLUSIONS: This is the first longitudinal study on Notch signaling in human esophagectomy model, our preliminary findings suggest decreased Notch signaling might be involved in the development of mucosa damage caused by gastroesophageal reflux.

Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease.

BACKGROUND: Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD). We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e., ACEI/ARB + CCB) with ACEI/ARB monotherapy in patients with hypertension and CKD. METHODS: Publications were identified from PubMed, Embase, Medline, and Cochrane databases. Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered. The outcomes of end-stage renal disease (ESRD), cardiovascular events, BP, urinary protein measures, estimated glomerular filtration rate (GFR), and adverse events were extracted. RESULTS: Based on seven RCTs with 628 patients, ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] = 0.84; 95% confidence interval [CI]: 0.52-1.33) and cardiovascular events (RR = 0.58; 95% CI: 0.21-1.63) significantly, compared with ACEI/ARB monotherapy. There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] = -1.28 mmHg; 95% CI: -3.18 to -0.62), proteinuria (standard mean difference = -0.55; 95% CI: -1.41 to -0.30), GFR (WMD = -0.32 ml/min; 95% CI: -1.53 to -0.89), and occurrence of adverse events (RR = 1.05; 95% CI: 0.72-1.53). However, ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD = -4.46 mmHg; 95% CI: -6.95 to -1.97), compared with ACEI/ARB monotherapy. CONCLUSION: ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.