Yinhuang buccal tablet alters airway microbiota composition and metabolite profile in healthy humans.

ETHNOPHARMACOLOGICAL RELEVANCE: Perturbations in airway microbiota composition and disruption of microbe-metabolite interactions have been observed in respiratory infectious diseases (RIDs). The Yinhuang (YH) buccal tablet, as an ancient Chinese medicinal formula, has been traditionally employed for the management of upper RIDs. However, there is a lack of evidence for the effects of YH buccal tablets on upper respiratory tract microbiota and circulating metabolites. AIM OF THE STUDY: The aim of this study was to analyze the changes in respiratory microbiota composition and circulating metabolite profile after YH buccal tablets administration. MATERIALS AND METHODS: Throat swab samples and serum samples were collected from 60 healthy subjects for high-throughput 16S ribosomal RNA gene (16S rRNA) sequencing and non-targeted Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. RESULTS: Airway microbial composition changed significantly after YH administration. The abundance of Actinomyces and Prevotella_7 increased, while the abundance of potentially pathogenic Pseudomonas and Corynebacterium decreased. A total of 168 significant HMDB taxonomic metabolites were identified in serum samples, of which lipid metabolites accounted for the largest proportion. Correlation analysis showed that circulatory metabolites were significantly correlated with changes in airway microbiota composition. CONCLUSIONS: YH buccal tablets can inhibit opportunistic pathogens, increase beneficial microorganisms in the upper respiratory tract, and regulate the body's metabolic pathways. These findings provide insights into the mechanism of action of YH buccal tablets in the treatment and prevention of respiratory diseases.

Spatial-Temporal Dynamic Evolution of Land Deformation Driven by Hydrological Signals around Chaohu Lake.

The frequent occurrence of extreme climate events has a significant impact on people's lives. Heavy rainfall can lead to an increase of regional Terrestrial Water Storage (TWS), which will cause land subsidence due to the influence of hydrological load. At present, regional TWS is mostly obtained from Gravity Recovery and Climate Experiment (GRACE) data, but the method has limitations for small areas. This paper used water level and flow data as hydrological signals to study the land subsidence caused by heavy rainfall in the Chaohu Lake area of East China (June 2016-August 2016). Pearson's correlation coefficient was used to study the interconnection between water resource changes and Global Navigation Satellites System (GNSS) vertical displacement. Meanwhile, to address the reliability of the research results, combined with the Coefficient of determination method, the research findings were validated by using different institutional models. The results showed that: (1) During heavy rainfall, the vertical displacement caused by atmospheric load was larger than non-tidal oceanic load, and the influence trends of the two were opposite. (2) The rapidly increasing hydrologic load in the Chaohu Lake area resulted in greater subsidence displacement at the closer CORS station (CHCH station) than the more distant CORS station (LALA station). The Pearson correlation coefficients between the vertical displacement and water level were as high as -0.80 and -0.64, respectively. The phenomenon confirmed the elastic deformation principle of disc load. (3) Although there was a systematic bias between the different environmental load deformation models, the deformation trends were generally consistent with the GNSS monitoring results. The average Coefficients of determination between the different models and the GNSS results were 0.63 and 0.77, respectively. The results demonstrated the effectiveness of GNSS in monitoring short-term hydrological load. This study reveals the spatial-temporal evolution of land deformation during heavy rainfall around Chaohu Lake, which is of reference significance for water resource management and infrastructure maintenance in this area.

Effect of high-flow nasal cannula versus non-invasive ventilation after extubation on successful extubation in obese patients: a retrospective analysis of the MIMIC-IV database.

BACKGROUND: The pathophysiological characteristics of the respiratory system of obese patients differ from those of non-obese patients. Few studies have evaluated the effects of high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) on the prognosis of obese patients. We here compared the effects of these two techniques on the prevention of reintubation after extubation for obese patients. METHODS: Data were extracted from the Medical Information Mart for Intensive Care database. Patients who underwent HFNC or NIV treatment after extubation were assigned to the HFNC or NIV group, respectively. The reintubation risk within 96 hours postextubation was compared between the two groups using a doubly robust estimation method. Propensity score matching was performed for both groups. RESULTS: This study included 757 patients (HFNC group: n=282; NIV group: n=475). There was no significant difference in the risk of reintubation within 96 hours after extubation for the HFNC group compared with the NIV group (OR 1.50, p=0.127). Among patients with body mass index ≥40 kg/m2, the HFNC group had a significantly lower risk of reintubation within 96 hours after extubation (OR 0.06, p=0.016). No significant differences were found in reintubation rates within 48 hours (15.6% vs 11.0%, p=0.314) and 72 hours (16.9% vs 13.0%, p=0.424), as well as in hospital mortality (3.2% vs 5.2%, p=0.571) and intensive care unit (ICU) mortality (1.3% vs 5.2%, p=0.108) between the two groups. However, the HFNC group had significantly longer hospital stays (14 days vs 9 days, p=0.005) and ICU (7 days vs 5 days, p=0.001) stays. CONCLUSIONS: This study suggests that HFNC therapy is not inferior to NIV in preventing reintubation in obese patients and appears to be advantageous in severely obese patients. However, HFNC is associated with significantly longer hospital stays and ICU stays.

Stratification of lymph node metastasis improves diagnostic efficiency in thoracic esophageal squamous cell carcinoma.

INTRODUCTION: Difference of the short diameter of lymph nodes in the main regions of esophageal squamous cell carcinoma (ESCC) and its value in the diagnosis of lymph nodes need to explore. METHODS: The clinical data of patients with thoracic ESCC who underwent surgical treatment in our hospital were collected. The short diameters of the largest lymph node in each region of the patient were measured by preoperative enhanced computed tomography (CT) and were compared with the postoperative pathology. RESULTS: A total of 477 patients with thoracic ESCC who did not receive neoadjuvant therapy were enrolled in this study. The receiver operating characteristic curve suggested that the short diameters of the paracardial nodes, the left gastric nodes, the right recurrent laryngeal nerve nodes, and the left recurrent laryngeal nerve nodes could well predict the postoperative pathology of the lymph nodes, with area under curve (AUC) of 0.958, 0.937, 0.931, and 0.915, the corresponding cut-off values of 5.7 mm, 5.7 mm, 5.5 mm, and 4.8 mm, the corresponding sensitivities of 94.7%, 85.4%, 88.7%, and 79.4%, and the corresponding specificities of 93.7%, 96.3%, 86.2%, and 95.0%, respectively. The AUC of the thoracic paraesophageal lymph nodes, the subcarinal nodes and all regional lymph nodes were 0.845, 0.688, and 0.776, respectively. CONCLUSION: Region-based criterion for lymph node metastasis of thoracic ESCC is beneficial to improve the diagnostic efficiency of preoperative CT.

Nontargeted metabolomic analysis to unravel alleviation mechanisms of carbon nanotubes on inhibition of alfalfa growth under pyrene stress.

Carbon nanotubes have displayed great potential in enhancing phytoremediation of PAHs polluted soils. However, the response of plants to the coexistence of carbon nanotubes and PAHs and the associated influencing mechanisms remain largely unknown. Here, the effect of carbon nanotubes on alfalfa growth and pyrene uptake under exposure to pyrene was evaluated through sand culture experiment and gas chromatography time-of-flight mass spectrometer (GC-TOF-MS) based metabolomics. Results showed that pyrene at 10 mg kg-1 obviously reduced the shoot fresh weight of alfalfa by 18.3 %. Multiwall carbon nanotubes (MWCNTs) at 25 and 50 mg kg-1 significantly enhanced the shoot fresh weight in a dose-dependent manner, nearly by 80 % at 50 mg kg-1. Pyrene was mainly accumulated in alfalfa roots, in which the concentration was 35 times as much as that in shoots. MWCNTs greatly enhanced the accumulation of pyrene in alfalfa roots, almost by two times at 50 mg kg-1, while decreased pyrene concentration in shoots, from 0.11 mg kg-1 to 0.044 mg kg-1 at MWCNTs concentration of 50 mg kg-1. Metabolomics data revealed that pyrene at 10 mg kg-1 trigged significant metabolic changes in alfalfa root exudates, downregulating 27 metabolites. MWCNTs generated an increase in the contents of some downregulated metabolites caused by pyrene stress, which were restored to the original level or even higher, mainly including organic acids and amino acids. MWNCTs significantly enriched some metabolic pathways positively correlated with shoot growth and pyrene accumulation in shoots under exposure to pyrene, including TCA cycle, glyoxylate and dicarboxylate metabolism, cysteine and methione metabolism as well as alanine, aspartate and glutamate metabolism. This work highlights the regulation effect of MWCNTs on the metabolism of root exudates, which are helpful for alfalfa to alleviate the stress from pyrene contamination.

Cangma Huadu granules attenuate H1N1 virus-induced severe lung injury correlated with repressed apoptosis and altered gut microbiome.

Severe influenza A virus infection leads to overwhelming inflammatory responses and cellular apoptosis, which causes lung injury and contributes to high mortality and morbidity. The gut microbiome altered in response to the infection might influence the disease progression and the treatment outcome. Cangma Huadu (CMHD) granules, an in-hospital preparation of traditional Chinese medicine, have been shown to be favorable in the clinical treatment of influenza. However, the effects and mechanisms of CMHD granules on severe influenza pneumonia and its mechanisms are not well-known. In this study, a lethal influenza A (H1N1) A/Puerto Rico/8/34 virus (PR8)-infected mice model was established, and the 16S ribosomal RNA (16S rRNA) V3-V4 region sequencing of the intestinal microbiome was conducted. We revealed that the oral administration of CMHD granules protects mice against higher mortality, enhanced weight loss, overwhelmed interferon-γ concentration, lung viral titers, and severe lung pathological injury in PR8-infected mice. CMHD granules' administration downregulated the levels of interleukin (IL)-1ß, tumor necrosis factor-α, and malondialdehyde, while it upregulated the levels of IL-10, superoxide dismutase, and glutathione peroxidase. Subsequently, it decreased the protein ratio of B-cell lymphoma-2/Bcl-2-associated X and the expression of cleaved caspase-3. The diversity and compositions of the gut microbes were altered profoundly after the administration of CMHD granules in PR8-infected mice. A higher abundance of Bifidobacterium, Parasutterella, Bacteroides, and Faecalibaculum was observed in the CMHD group, and a higher abundance of Lactobacillus and Turicibacter was observed in the positive drug Ribavirin group. The linear discriminant analysis effect size also revealed a higher proportion of Bacteroides and Bifidobacterium_pseudolongum characterized in the CMHD group. These results demonstrated that CMHD granules are a promising strategy for managing severe influenza and attenuating severe lung damage via reducing viral titer, inflammatory responses, and oxidative stress. The mechanisms are involved in repressed Bcl-2-regulated apoptosis and altered composition and diversity of the gut microbiome.

A comparative evaluation of lasers and photodynamic therapy in the nonsurgical treatment of peri-implant diseases: A Bayesian network meta-analysis.

PURPOSE: We conducted this Bayesian network meta-analysis (NMA) to evaluate the safety and efficacy of different lasers and PDT compared to conventional mechanical debridement (CMD) for peri-implant treatment. METHODS: The Web of Science, Cochrane Library and PubMed databases were searched for randomized clinical trials (RCTs) assessing the clinical effectiveness of adjunctive PDT, different lasers, and CMD until January 1st, 2022. Clinical outcomes were the changes in pocket probing depth (PPD), marginal bone loss (MBL), and clinical attachment level (CAL). RESULTS: Twenty-three studies, including 4 types of lasers, were included. Compared to that with CMD alone, PPD reduction was significantly more efficient in the diode laser (LD)+CMD groups (MD, 0.53; 95%CI, 0.13-0.93) and the PDT+CMD groups (MD, 0.83; 95%CI, 0.32-1.34) than in the CMD group in the follow-up period. Moreover, PDT+CMD treatment also showed a significantly better marginal bone level gain (MD, 0.32; 95%CI, 0.06-0.57). No significant effect on ΔCAL was observed among the different treatment strategies. Despite no differences in PPD reduction, MBL and CAL gains were found among the adjunctive laser treatment groups, PDT+CMD had the highest ranking probability of the most effective treatment in these clinical indices of periodontitis. The certainty of evidence for all outcomes was judged as very low to moderate. CONCLUSIONS: Within the limits of this NMA, we found that adjunctive PDT achieved a small additional benefit on PPD reduction and MBL gain compared with CMD alone and had the highest probability of being ranked first on the changes in PPD, MBL and CAL. PDT+CMD may represent an alternative method for peri­implant treatment. Further high-quality RCTs are needed to assess the influence of potential confounders on the efficacy of lasers and PDT.

Dispose waste liquor of fresh biomass of a hyperaccumulator Sedum plumbizincicola in phytoextraction process.

Sedum plumbizincicola has been widely employed to remove cadmium (Cd) and zinc (Zn) from contaminated soils and harvested biomass is used to recover valuable metals. While chopping and compacting are efficient methods to rapidly reduce the volume and moisture of fresh biomass, the resulting waste liquor containing metals needs treatment. Two types of contaminated soils were cropped with S. plumbizincicola and top-dressed with this liquor to study metals migration in soil profile and their uptake by plants. There were three treatments: planting and adding liquor (PL), planting without liquor (P) and adding liquor without planting (L). The results showed that Cd and Zn from liquor were mainly retained at top soil 0-10 cm under L treatment. Compared with L treatment, soil Cd and Zn under PL treatment decreased significantly in soil profile due to the extraction of S. plumbizincicola. Moreover, the amount of Cd and Zn extracted by plants was greater than that applied in soils. The metal removal rate by S. plumbizincicola in acid clay loam soil was higher than that in neutral sandy soil. To sum up, metal retaining in soil and uptake by S. plumbizincicola can be used to treat waste liquor from its fresh biomass. Novelty StatementRapid and efficient treatment of harvested fresh biomass is still a challenge although phytoextraction using hyperaccumulator Sedum plumbizincicola has been widely employed. Chopping and compacting fresh biomass are efficient methods for rapid dehydration, however, a large amount of waste liquor that contains of Cd and Zn is produced and needs treatment. In the present study, a simple and low-cost method was tested to dispose the liquor, i. e. irrigating it onto the surface of contaminated soils where grown S. plumbizincicola. It was found that Cd and Zn applied in soils from liquor were mainly retained at top 0-10 cm soil depth where S. plumbizincicola root system was widespread, and the amount of Cd and Zn extracted by plants was greater than that applied in soils. Therefore, it is technically feasible to dispose the waste liquor dewatering from fresh biomass of S. plumbizincicola in its phytoextraction process. This study is helpful for the rapid, efficient and low-cost treatment of harvested fresh biomass in the large-scale application of phytoremediation.

[Thinking and practice of key links in design of clinical trial scheme for treatment of influenza with traditional Chinese medicine].

To sort out the key points in "PICOS" design of clinical trial scheme for influenza, and optimize the clinical trial scheme of Chinese patent medicine in the treatment of influenza by strictly following the principle of evidence-based medicine, focusing on the clinical practice of the disease, and highlighting the characteristics of traditional Chinese medicine. "The design of a randomized, double-blind, positive parallel control study of a certain herbal preparation for the treatment of non-severe influenza" was taken as an example in this study, and the key points in the clinical trial design of Chinese patent medicine for the treatment of influenza were specifically discussed from six aspects, including the type of study, object of study, intervention measures, control measures, outcome indicators and frequently asked questions in test design. From methodological suggestions, in the design scheme of clinical trial on efficacy and safety of Chinese patent medicine in the treatment of influenza, the randomized controlled study should be the first choice for type of study; the inclusion criteria should define both the diagnostic criteria of Western medicine and the syndromes of traditional Chinese medicine(TCM); the exclusion criteria should include a comprehensive list of confounding factors and special circumstances lea-ding to bias in the study results; the interventions should be based on a well-defined dosing programme; internationally recognized positive drugs or guidelines should be used as control measures, with median antipyretic time as the main outcome indicator. For the evalua-tion of curative effect, disease symptom scale can be set, and the TCM syndrome scoring scale was carefully used in this study, with time nodes set for the efficacy evaluation standard. The full name of the drugs should be written in the regulations on combined drug use and prohibited drug use.

A phase III study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909).

BACKGROUND: Neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACR) are the standard treatments for esophageal squamous cell carcinoma (ESCC). However, the 5-year overall survival (OS) rate is still far from satisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in Henan Cancer Hospital. ICIs combined with NAC may usher in a new era and may benefit locally advanced, resectable ESCC patients. METHODS: A two-arm phase III trial was launched in April 2020 in Henan Cancer Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. DISCUSSION: This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment. TRIAL REGISTRATION: NCT04280822 (https://www.clinicaltrials.gov/ct2/show/NCT04280822). Registered title: "A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination with Chemotherapy versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma". Version 1.0/Nov. 21, 2019.

Liu Shen Capsule Alters Airway Microbiota Composition and Metabolite Profiles in Healthy Humans.

Alteration in airway microbiota composition and perturbations in microbe-metabolites interactions have been proposed as markers of many diseases. Liu Shen (LS) capsule, a traditional Chinese medicine, was proved as favorable in treating respiratory diseases. However, the effects of the LS capsule in terms of regulating human microorganisms and metabolite profiles are not well known. This study aimed to define and compare the respiratory microbiota composition and circulating and fecal metabolite profiles before and after LS capsule administration. A total of 30 healthy volunteers were recruited. The pharyngeal swab samples were collected for 16S rRNA gene sequencing. The serum and fecal samples were collected to analyze the non-targeted ultra-performance liquid chromatography-tandem mass spectrometry metabolomics. The airway microbial compositions were profoundly altered after LS capsule administration, as evidenced by increased microbial diversity and altered microbial taxa distribution. The increasing abundance of bacterial Bifidobacteria, and Lactobacillus characterized the after-administration groups, and the increasing of abundance bacterial Proteobacteria, Veillonella, Prevotella, Neisseria, and Actinomyces characterized the before-administration groups. Significant discriminations were observed in both serum and fecal metabolic profiles between the before- and after-administration groups. A total number of 134 and 71 significant HMDB taxonomic metabolites including glycerophospholipids, fatty acyls, and prenol lipids in the serum and fecal samples were identified respectively between the before- and after-administration groups. The integrated analysis showed that some altered airway microbiota phylum, such as Bacteroidetes and Proteobacteria, significantly correlated with metabolites in serum and fecal. Hence, our study reported the alternations in the composition and functions of the airway microbial community and the changes in circulating and fecal metabolite profiles after LS capsule administration in healthy humans, thus providing a novel insight into the mechanisms underlying the role of LS capsule treating and preventing related diseases.

A phase II, single-centre trial of neoadjuvant toripalimab plus chemotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains a challenging malignancy with poor prognosis and limited therapeutic methods. However, recent clinical trials of immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of lethal malignancies. The second-line treatment of late-stage ESCC was approved based on the results of KEYNOTE-180, KEYNOTE-181 and ATTRACTION-1, ATTRACTION-3. Combining ICIs with chemotherapy in neoadjuvant therapy may benefit patients with locally advanced, resectable ESCC. METHODS: A two-arm phase II trial was launched in July 2019 in Henan Cancer Hospital. The primary outcome measure will be completed within 21 months. The pathological complete response (pCR) rate is the primary endpoint, and the secondary endpoints include overall survival (OS), disease-free survival (DFS), the toxicities of the neoadjuvant toripalimab plus chemotherapy, the relationship between combined positivity score (CPS) of specimen and the treatment response, the relationship between lymphocyte infiltration and the treatment response, the progression-free survival (PFS) rate, and adverse events (AEs). It was assumed that the pCR rate of this trial might be 25%. Therefore, the 30 enrolled patients could reject the hypothesis at 75% (α=0.1). DISCUSSION: The study will determine the safety and efficacy of neoadjuvant immunochemotherapy for ESCC and provide enough evidence for phase III clinical trials. TRIAL REGISTRATION: Clinical Trials.gov, NCT03985670, Registered: October 24, 2019, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0008Z9D&selectaction=Edit&uid=U0002MIY&ts=2&cx=-i71o4q. Registry name: "Teripalimab Plus Chemotherapy in Local Advanced Esophageal Cancer".

Clinical evaluation of right recurrent laryngeal nerve nodes in thoracic esophageal squamous cell carcinoma.

BACKGROUND: The accuracy of clinical N staging of esophageal squamous cell carcinoma is suboptimal. As an important station of lymph node metastasis, station C201 (right recurrent laryngeal nerve nodes) has rarely been evaluated alone. We aimed to explore an effective way to evaluate the right recurrent laryngeal nerve nodes in thoracic esophageal squamous cell carcinoma. METHODS: We retrospectively analyzed 628 thoracic esophageal squamous cell carcinoma patients who underwent radical resection without neoadjuvant therapy from two Chinese cancer centers. The diameter of the short axis of the largest right recurrent laryngeal nerve node (DC201) was measured on contrast-enhanced multi-slice computed tomography (MSCT). Right recurrent laryngeal nerve nodes were examined by postoperative pathologic results. The receiver operating characteristic (ROC) curve was generated to assess the diagnostic capabilities of DC201 to determine the right recurrent laryngeal nerve nodes status. RESULTS: ROC curve analysis revealed that the optimal cut-off point of DC201 was 6 mm, with an area under curve (AUC), sensitivity, specificity, and Youden index of 0.896, 71.9%, 88.8%, and 0.607 respectively. When the cut-off point of DC201 was set to 10 mm, sensitivity, specificity and the Youden index were 14.1%, 99.6% and 0.137 respectively. Among 128 patients with right recurrent laryngeal nerve node metastasis, 71 and 108 patients had the largest right recurrent laryngeal nerve node located above the suprasternal notch level and in the tracheoesophageal groove respectively. CONCLUSIONS: When DC201 ≥6.0 mm instead of DC201 ≥10 mm was used to dictate the right recurrent laryngeal nerve nodes metastasis, contrast-enhanced MSCT could evaluate the status of right recurrent laryngeal nerve nodes with high sensitivity and specificity. The largest right recurrent laryngeal nerve nodes were mainly located in the tracheoesophageal groove and/or above the suprasternal notch.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a single-Centre, open-label, randomized, controlled, clinical trial (HCHTOG1903).

BACKGROUND: Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. METHODS: This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. DISCUSSION: This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. TRIAL REGISTRATION: NCT04138212, date of registration: October 24, 2019.

Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126.

Mesenchymal stem cells (MSCs) show protective effects on ischemia/reperfusion- (I/R-) induced endothelial cell (EC) injury and vascular damage. Stem cell-released exosomes (EXs) could modulate target cell functions by delivering their cargos, and exert therapeutic effects as their mother cells. miR-126 is an important regulator of EC functions and angiogenesis. In this study, we determined whether EXs released from MSC-EXs provided beneficial effects on hypoxia/reoxygenation- (H/R-) injured ECs by transferring miR-126. MSCs were transfected with a miR-126 mimic or miR-126 short hairpin RNA to obtain miR-126-overexpressing MSC-EXs (MSC-EXsmiR-126) and miR-126 knockdown MSC-EXs (MSC-EXsSimiR-126). For functional studies, H/R-injured ECs were coincubated with various MSC-EXs. The viability, migration, tube formation ability, and apoptosis of ECs were measured. miR-126 and proangiogenic/growth factor (VEGF, EGF, PDGF, and bFGF) expressions were detected by qRT-PCR. Akt, p-Akt, p-eNOS, and cleaved caspase-3 expressions were examined by western blot. The PI3K inhibitor (LY294002) was used in pathway analysis. We found that overexpression/knockdown of miR-126 increased/decreased the proliferation of MSCs, as well as miR-126 expression in their derived MSC-EXs. MSC-EXsmiR-126 were more effective in promoting proliferation, migration, and tube formation ability of H/R-injured ECs than MSC-EXs. These effects were associated with the increase in p-Akt/Akt and p-eNOS, which could be abolished by LY294002. Besides, MSC-EXsmiR-126 were more effective than MSC-EXs in reducing the apoptosis of ECs, coupled with the decrease in cleaved caspase-3. Moreover, compared to MSC-EXs, MSC-EXsmiR-126 significantly upregulated the level of VEGF, EGF, PDGF, and bFGF in H/R-injured ECs. Downregulation of miR-126 in MSC-EXs inhibited these effects of MSC-EXs. The results suggest that MSC-EXs could enhance the survival and angiogenic function of H/R-injured ECs via delivering miR-126 to ECs and subsequently activate the PI3K/Akt/eNOS pathway, decrease cleaved caspase-3 expression, and increase angiogenic and growth factors.

A Novel Dual Successive Projection-Based Model-Free Adaptive Control Method and Application to an Autonomous Car.

In this paper, a novel model-free adaptive control (MFAC) algorithm based on a dual successive projection (DuSP)-MFAC method is proposed, and it is analyzed using the introduced DuSP method and the symmetrically similar structures of the controller and its parameter estimator of MFAC. Then, the proposed DuSP-MFAC scheme is successfully implemented in an autonomous car "Ruilong" for the lateral tracking control problem via converting the trajectory tracking problem into a stabilization problem by using the proposed preview-deviation-yaw angle. This MFAC-based lateral tracking control method was tested and demonstrated satisfactory performance on real roads in Fengtai, Beijing, China, and through successful participation in the Chinese Smart Car Future Challenge Competition held in 2015 and 2016.

Phosphate adsorption and precipitation on calcite under calco-carbonic equilibrium condition.

Phosphate (PO43-) removal on calcite often entails two processes: adsorption and precipitation. Separating these two processes is of great importance for assessment of PO43- stability after removal. Thus, this study was aimed at finding a critical range of conditions for separating these two processes in calco-carbonic equilibrium, by adjusting PO43- concentration, reaction time and pH. PO43- removal kinetic results showed that: (I) At pH7.7, PO43- removal was mainly by adsorption at initial PO43- concentration ≤2.2 mg L-1 and reaction time ≤24 h, with dominant precipitation occurring at initial PO43- concentration ≥3 mg L-1 after 24 h reaction; (II) At pH8.3, adsorption was the key removal process at initial PO43- concentration ≤7.5 mg L-1 and reaction time ≤24 h, whereas precipitation was observed at initial PO43- concentration of 10 mg L-1 after 24 h reaction, (III) At pH 9.1 and 10.1, PO43- removal mechanism was mainly by adsorption at initial PO43- concentration ≤10 mg L-1 within 24 h reaction. Based on the kinetic results, it is suggested that PO43- precipitation will occur after 24 h reaction when saturation index of amorphous calcium phosphate is between 1.97 and 2.19. Besides, increasing PO43- concentration does not cause a continuous decline of PO43- removal percentage. Moreover, experimental removal data deviated largely from the theoretical adsorption value by CD-MUSIC model. These indicate occurrence of precipitation which is in agreement with the kinetic result. Therefore our study will provide fundamental reference information for better understanding of phosphorous stabilization after removal by calcite.

Comparative study of phosphorus adsorption behaviors in lake sediments over short and long periods of time: implication for the prediction of the release of phosphorus by CaCl2 and NaHCO3 extraction.

Ten sediments were collected from the northern part of Taihu Lake, China. They were incubated for 24 h and 80 days to analyze the adsorption characteristics. After adsorption, the residual sediments were extracted with 0.01 M CaCl2 and 0.5 M NaHCO3 separately. Maximum buffer capacities of the Langmuir and Freundlich functions of 80-day incubation were highly correlated with 24 h (R 2 = 0.97). A longer time would enhance the resistance of the sediments to P changes in the water. Adsorption and NaHCO3-P were highly linearly related with R 2 > 0.969, but the relationships between 24 h and 80 days were different. The relationships between adsorption and CaCl2-P could be better explained (97 %) by segmented line models, but the fitting results were affected by incubation time. An interesting finding is that when we plotted the NaHCO3-P and CaCl2-P together by a segmented line model, the data showed a uniform trend unrelated to the incubation time. NaHCO3-P is seldom used to evaluate P status in sediments in comparison with soils. Yet, our results suggested NaHCO3-P is a good bridge to link the sediments P retention ability and P release risk. Due to its simplicity, NaHCO3-P has promising potential in predicting the transfer of P from sediments.

Graphene oxide/chitin nanofibril composite foams as column adsorbents for aqueous pollutants.

A novel graphene oxide/chitin nanofibrils (GO-CNF) composite foam as a column adsorbent was prepared for aqueous contaminant disposal. The structures, morphologies and properties of composite foams supported by nanofibrils were characterized. As a special case, the adsorption of methylene blue (MB) on GO-CNF was investigated regarding the static adsorption and column adsorption-desorption tests. Results from equilibrium adsorption isotherms indicated that the adsorption behavior was well-fitted to Langmuir model. The composite foams reinforced by CNF were dimensionally stable during the column adsorption process and could be reused after elution. The removal efficiency of MB was still nearly 90% after 3 cycles. Furthermore, other inorganic or organic pollutants adsorbed by composite foams were also explored. Therefore, this novel composite foam with remarkable properties such as dimensional stability, universal adsorbent for cationic pollutants, high adsorption capacity, and ease of regeneration was a desirable adsorbent in the future practical application of water pollutant treatment.

[Sorption of o-Phthalate onto Calcite in Open-System].

The batch sorption methods were deployed to study the sorpti of p-phthalate on calcite in open-system. Results show that: (1) The o-phthalate sorption reached the equilibrium within 3 hours. Both pseudo first-order and pseudo second-order models described the kinetic characteristics well; (2) The o-phthalate sorption rate decreased with pH (7. 7-9.7). This phenomenon was due to the competition effect of HCO3- and CO(3)2-, and the electrostatic effect on the surface; (3) The o-phthalate sorption rate also decreased with the increase in ionic strength. This was due to the rise in concentration of HCO3- and CO(3)2- induced by salt effect; (4) Compared with m-phthalate and p-phthalate, o-phthalate sorption rate was much higher due to the proximity of its two carboxyl groups which easily formed a chelate ring of surface complex. By studying the factors that influence o-phthalate sorption onto calcite, the sorption mechanism can be well understood. This mechanism can be applied in the removal of o-phthalate from the environment.