The exploration of perioperative hypotension subtypes: a prospective, single cohort, observational pilot study.

Background: Hypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension. Methods: This is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored. Results: Sixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1-23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury. Conclusion: Perioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.

A CuCo Bimetal Confined Hollow SiC Hybrid Photothermal Nanoreactor for the Integration of Pollutant Mineralization and Solar-Powered Water Evaporation.

Growing attention has been paid to the rational treatment of antibiotics-bearing medical wastewater. However, the complexity of polluted wastewater makes the later comprehensive treatment difficult only by the Advanced Oxidation Process technique. Therefore, the coupled water treatment techniques including contaminant mineralization and regeneration of cleanwater become very attractive. A bimetallic functional hollow nanoreactor defined as (Co@SiO2/Cu-X) was successfully constructed by coating a Cu-doped silica layer on the metal-organic framework (ZIF-67) followed by programmed calcination in nitrogen. The nanoreactor was endowed with a hollow configuration composed of mesoporous N-doping C-Silica hybrid shell encapsulated ultrafine Cu and Co metallic species. Such a configuration allows for the efficient diffusion and open reaction space of big contaminant molecules. The catalytic synergy of exposed Co-Cu bimetals and the easy accessibility of electron-rich contaminants by polar N doping sites triggered surface affinity make the optimal Co@SiO2/Cu-6 afford an excellent catalytic norfloxacin mineralization activity (7 min, kabs=0.744 min-1) compared to Cu-free Co@SiO2-6 (kabs=0.493 min-1) and Co-6 (kabs=0.378 min-1) Benefiting from the above unique advantages, Co@SiO2/Cu-6 show excellent removal performance in degrading different pollutants (carbamazepine, oxytetracycline, tetracycline, and bisphenol A) and persistent recycled stability in removing NFX. In addition, by virtue of the excellent photothermal properties, interfacial solar water evaporation application by Co@SiO2/Cu-6 was further explored to reach the regeneration of cleanwater (1.595 kg m-2 h-1, 97.51 %). The integration of pollutant mineralization and solar water evaporation by creating the monolith evaporation by anchoring the Co@SiO2/Cu-6 onto the tailored melamine sponge allows the regeneration of cleanwater (1.6 kg⋅m-2⋅h-1) and synchronous pollutant removal (NFX, 95 %, 60 min), which provides potential possibility the treatment of complicated wastewater.

Drug Discovery for Adult Cardiomyocyte Regeneration: Opportunities and Challenges.

Significance: Cardiovascular disease is a major contributor to human mortality and morbidity. The cardiac tissue undergoes fibrotic healing after injury because of the limited regenerative capacity of adult mammalian cardiomyocyte (CM). Extensive research has been performed to identify therapeutic targets for CM regeneration, as the success of promoting adult human CM regeneration to repair the injured heart is considered the Holy Grail in the field. Recent Advances: To date, more than 30 target genes have been shown to regulate adult mammalian CM proliferation. More than 20 targets have been validated in adult mouse myocardial infarction (MI) model in a therapeutic setting. In this review, the translational efficacy readouts from 17 selected pharmaceutical targets are summarized, among which the Hippo-yes-associated protein (Yap) pathway is the most extensively investigated and fits the criteria for a promising target for pro-CM-regeneration therapy development. Critical Issues and Future Directions: As the pro-CM-regeneration potential of current drug treatment for cardiovascular patients is limited, to help identify and fill the gap between basic research and drug discovery in this specific field, details regarding target identification, validation in mouse MI models, high-throughput screening assay development, and preclinical in vivo efficacy model optimization are discussed. Finally, suggestions and recommendations are also provided to help establish a common guideline for in vivo translational studies for drug discovery focusing on CM regeneration. Antioxid. Redox Signal. 39, 1070-1087.

The exhaustion of lymphocytes is the main factor that decreases the sensitivity of QFT-GIT detection in silicosis.

BACKGROUND: Tuberculosis infection is a major complication of silicosis, but there is no study on whether silicosis can affect the sensitivity of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. This study will analyze the relationship between silicosis and QFT-GIT, determine the main factor of the QFT-GIT sensitivity decrease in silicosis and explore the methods to increase the sensitivity. METHODS: Silicosis patients with positive tubercle bacillus cultures were collected. The QFT-GIT, flow cytometry and blocking antibodies were used. RESULTS: The sensitivity of QFT-GIT in silicosis patients (58.46%) was significantly decreased and the expression of PD-1 on T cells and CD56+NK cells in pulmonary tuberculosis combined with silicosis were higher than normal tuberculosis patients and silicosis only patients. Further analysis found that the ratio of PD-1+CD4+T and IFN-γwere negatively correlated and blockaded the PD-1 pathway with antibodies can restore the sensitivity of QFT-GIT in silicosis. CONCLUSIONS: This is the first study to analyze the relationship between immune exhaustion and QFT-GIT in silicosis and found that the sensitivity of QFT-GIT was decreased by the expression of PD-1 on lymphocytes. Antibody blocking experiments increased the expression of IFN-γ and provided a new method to improve the sensitivity of QFT in silicosis. The study also found that silicosis can increase PD-1 expression. As PD-1 functions in infectious diseases, it will promote immune exhaustion in silicosis and lead to tuberculosis from latent to active infection. The study provided theoretical evidence for the diagnosis and immunotherapy of silicosis complications, and it has great value in clinical diagnostics and treatment.

New insight into the analgesic recipe: A cohort study based on smart patient-controlled analgesia pumps records.

Purpose: Intravenous patient-controlled analgesia (IV-PCA) has been widely used; however, regimen criteria have not yet been established. In China, the most often used opioid is sufentanil, for which repeated doses are a concern, and empirical flurbiprofen axetil (FBP) as an adjuvant. We hypothesized that hydromorphone would be a better choice and also evaluated the effectiveness of FBP as an adjuvant. Methods: This historical cohort study was conducted in two tertiary hospitals in China and included 12,674 patients using hydromorphone or sufentanil for IV-PCA between April 1, 2017, and January 30, 2021. The primary outcome was analgesic insufficiency at static (AIS). The secondary outcomes included analgesic insufficiency with movement (AIM) and common opioid-related adverse effects such as postoperative nausea and vomiting (PONV) and dizziness. Results: Sufentanil, but not the sufentanil-FBP combination, was associated with higher risks of AIS and AIM compared to those for hydromorphone (OR 1.64 [1.23, 2.19], p < 0.001 and OR 1.42 [1.16, 1.73], p < 0.001). Hydromorphone combined with FBP also decreased the risk of both AIS and AIM compared to those for pure hydromorphone (OR 0.74 [0.61, 0.90], p = 0.003 and OR 0.80 [0.71, 0.91], p < 0.001). However, the risk of PONV was higher in patients aged ≤35 years using FBP (hydromorphone-FBP vs. hydromorphone and sufentanil-FBP vs. hydromorphone, OR 1.69 [1.22, 2.33], p = 0.001 and 1.79 [1.12, 2.86], p = 0.015). Conclusion: Hydromorphone was superior to sufentanil for IV-PCA in postoperative analgesia. Adding FBP may improve the analgesic effects of both hydromorphone and sufentanil but was associated with an increased risk of PONV in patients <35 years of age.

Distribution and clinical significance of circulating CD8+CD28- regulatory T cells in the peripheral blood of patients with pulmonary tuberculosis.

BACKGROUND: Regulatory T cells (Treg cells) in the peripheral blood of patients with pulmonary tuberculosis (PTB) may be closely related to the progression of PTB. In this study, the distribution characteristics and clinical importance of CD8+CD28- Treg cells in patients with tuberculosis were systematically analyzed, and the role and importance of CD8+CD28- Treg cells in influencing the immune response and progression of tuberculosis were discussed, which will provide immunological indices and reference values for the clinical diagnosis of tuberculosis. METHODS: Flow cytometry, sputum smears and computed tomography imaging were used to analyze the distribution characteristics of CD8+CD28- Treg cells in the peripheral blood of patients with PTB and the correlation between CD8+CD28-Treg cells and clinical and immune indices. RESULTS: The percentages of CD4+CD25high and CD8+CD28- Treg cells in the peripheral blood of patients with PTB were significantly higher than those in the healthy control (HC) group. Further analysis showed that the percentage of CD4+CD25highTreg cells in the Stage II group was significantly higher than that in the HC group. The percentages of CD4+CD25high and CD8+CD28- Treg cells increased significantly in patients in the Stage II group. The proportion of CD8+CD28- Treg cells was directly proportional to the degree of positivity in sputum smears, while CD4+CD25highTreg cells did not exhibit this trend. The correlations between the percentage of CD4+CD25high and CD8+CD28- Treg cells and the percentage of lymphocyte subsets were examined. The percentage of CD8+CD28- Treg cells was negatively correlated with the percentage of CD4+T cells and positively correlated with the CD8+T cell percentage in the HC and PTB groups. The percentage of CD4 + CD25highTreg cells was positively correlated with the percentage of CD4+T cells only in the PTB group. CONCLUSIONS: This study was the first to show that the proportion of CD8+CD28- Treg cells in the peripheral blood of patients with PTB was significantly increased, and the increase in CD8+CD28- Treg cells was related to the progression of PTB, which may affect the proportion of immune cell subsets by inhibiting the immune response, resulting in the progression of PTB.

Exploring the growth patterns of medical demand for eye care: a longitudinal hospital-level study over 10 years in China.

BACKGROUND: The increasing demand for eye care inflicts a heavy burden on the eye care system. The uneven distribution of demand dynamically exacerbates the supply-demand imbalance. Systematic explorations of the growth patterns of the demand for eye care are needed to detect potential influences on the safety and quality of medical services. METHODS: This is an observational longitudinal study at the hospital level. We exported 8 million outpatient visit records over 10 years from the electronic health record (EHR) system of Zhongshan Ophthalmic Center (ZOC). The total visits to all levels of medical institutions in China were collected from the websites of the China National Statistics Bureau. The target 10-year period was from Jan 1, 2008, to Dec 31, 2017. Revisit intervals were analysed to assess the stickiness of patient demand. The proportions of non-local patients (from cities other than Guangzhou in Guangdong Province, or provinces other than Guangdong Province in China) were analysed to assess flowing demand liquidity. RESULTS: Visits to medical institutions continuously increased over the examined period (2008-2017) in China. Increasing patient visits and corresponding supplementation of doctors broke the supply-demand balance at ZOC. In terms of the temporal aspect, uneven distributions over cycles of weeks and years, referred to as Monday peaks and vacation peaks, became more evident during the examined period. With respect to geography, the coverage of demand sources expanded to the whole nation, and the flowing demand accounted for higher proportions at both the city and province levels. Subdepartments of ophthalmology had diverse growth speeds and proportions of flowing demand. Patients presented higher stickiness with shorter revisit intervals, and non-locals had higher stickiness than local patients. CONCLUSIONS: The growth patterns of demand for eye care indicate potential challenges for ophthalmologists at the hospital level, including regular workload peaks, a wider range of patients with diverse cultural backgrounds, and higher stickiness of patients.

Phytochemical Curcumin-Coformulated, Silver-Decorated Melanin-like Polydopamine/Mesoporous Silica Composites with Improved Antibacterial and Chemotherapeutic Effects against Drug-Resistant Cancer Cells.

The devastating occurrence of drug resistance such as antimicrobial resistance has aroused global concerns for public health, which has propelled a continuous pursuit of safe and effective therapeutic agents. In this study, silver nanoparticles were decorated in mesoporous silica of SBA-15 coated with melanin-like polydopamine (PDA) as nanocarriers. Meanwhile, the constructed mesopore was loaded with phytochemical curcumin (CCM) through its noncovalent interactions with PDA coatings. The obtained CCM@SBA-15/PDA/Ag composites were characterized by physicochemical methods and exhibited desirable biocompatibility and low hemolytic activity. The dual-stimuli-responsive (pH and ROS) release of curcumin and/or silver nanoparticles from the CCM@SBA-15/PDA/Ag composites was achieved to reduce the side effects of noncontrolled drug leakage under physiological conditions. Additionally, compared with that of SBA-15/PDA/Ag and CCM@SBA-15/PDA, CCM@SBA-15/PDA/Ag combination showed a prolonged inhibitory effect on bacterial growth of G- E. coli (72 h) and G+ S. aureus (24 h), attributing to the enhanced effect of the bactericide of silver nanoparticles and curcumin. Furthermore, through the utilization of the nanoformulation of curcumin, improved chemotherapeutic efficiency against human cervical cancer cells (HeLa) and Taxol-resistant nonsmall cell lung cells (A549/TAX) was identified in comparison with that of free curcumin. Thus, our study rationalized the combinational design of the natural compound and silver nanoparticles as an integrated dual-responsive nanoplatform in dealing with infectious bacteria and drug resistance in cancers for enhanced therapy.

Encapsulating insoluble antifungal drugs into oleic acid-modified silica mesocomposites with enhanced fungicidal activity.

Recently, with increasing medical practices, including organ transplantation and tumor chemotherapy, fungal infections, particularly the occurrence of drug-resistant fungal strains, remain a severe problem for the public health, which cause worse complications in the immunocompromised patients. The search for efficacious yet safe antifungal agents is in high demand in precision medicine. However, fungicides are often poorly water soluble for oral absorption, which is difficult for pharmaceutical efficacy evaluation. In this study, lipophilic oleic acid (OA)-grafted mesoporous silica (SBA-15) was facilely modified by cetyltrimethylammonium bromide (CTAB), which acts as an efficient antifungal drug matrix of itraconazole (ITZ). Characterized by physicochemical methods, the rod-like SBA-15-OA-CTAB/ITZ composite with retained mesostructural regularity shows that the loading amount of ITZ in the mesopore is ∼18%, contributing to the enhanced antifungal activity against Aspergillus fumigatus (A. fumigatus) and Candida albicans (C. albicans). The antimicrobial mechanism study suggests that the reactive oxygen species (ROS) were formed when fungal cells were incubated with the formulated ITZ, while there was no ROS formation in the presence of pure ITZ, which may result from the quaternary ammonium moieties of CTAB in the nanocomposites. Due to the potential toxicity of CTAB on mammalian cells, the as-synthesized mesoporous SBA-15-OA-CTAB/ITZ provides an alternative molecular design for the formulation improvement of a lipophilic antifungal drug applicable for external uses such as topical therapy.

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19.

In this study, we collected a total of 610 hospitalized patients from Wuhan between February 2, 2020, and February 17, 2020. We reported a potentially high false negative rate of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 in the 610 hospitalized patients clinically diagnosed with COVID-19 during the 2019 outbreak. We also found that the RT-PCR results from several tests at different points were variable from the same patients during the course of diagnosis and treatment of these patients. Our results indicate that in addition to the emphasis on RT-PCR testing, clinical indicators such as computed tomography images should also be used not only for diagnosis and treatment but also for isolation, recovery/discharge, and transferring for hospitalized patients clinically diagnosed with COVID-19 during the current epidemic. These results suggested the urgent needs for the standard of procedures of sampling from different anatomic sites, sample transportation, optimization of RT-PCR, serology diagnosis/screening for SARS-CoV-2 infection, and distinct diagnosis from other respiratory diseases such as fluenza infections as well.

Dual-Responsive Dual-Drug-Loaded Bioinspired Polydopamine Nanospheres as an Efficient Therapeutic Nanoplatform against Drug-Resistant Cancer Cells.

Multidrug resistance evoked by overusing pharmaceuticals of poor water solubility has posed a serious threat to public health, which urges the development of safe and efficacious therapeutic formulations. In this study, biomimetic nanospherical polydopamine (PDA) formed under mild conditions was modified using methoxypolyethylene glycol amine (m-PEG-NH2) to produce a polydopamine-based drug delivery platform. As characterized by various physicochemical methods, the PEGylated PDA with a uniform size distribution showed superior biocompatibility and efficient load capability for two hydrophobic anticancer drugs of paclitaxel and phytochemical curcumin, which exhibited synergistic cytotoxicity and a pH/ROS-responsive release behavior. Significantly, an enhanced effect of the encapsulated paclitaxel and curcumin was identified toward the drug-resistant A549/TAX cancer cells, which was correlated with the improved cellular internalization of hyperbranched PDA composites and distinctive cell cycle arrest of loaded drugs. The dual-drug-loaded spherical PDA nanocomposites hold enormous potential to tackle drug resistance from a chemotherapy perspective.

Applying deep learning in recognizing the femoral nerve block region on ultrasound images.

BACKGROUND: Identifying the nerve block region is important for the less experienced operators who are not skilled in ultrasound technology. Therefore, we constructed and shared a dataset of ultrasonic images to explore a method to identify the femoral nerve block region. METHODS: Ultrasound images of femoral nerve block were retrospectively collected and marked to establish the dataset. The U-net framework was used for training data and output segmentation of region of interest. The performance of the model was evaluated by Intersection over Union and accuracy. Then the predicted masks were highlighted on the original image to give an intuitive evaluation. Finally, cross validation was used for the whole data to test the robust of the results. RESULTS: We selected 562 ultrasound images as the whole dataset. The training set intersection over union (IoU) was 0.713, the development set IoU is 0.633 and the test set IoU is 0.638. For the single image, the median and upper/lower quartiles of IoU were 0.722 (0.647-0.789), 0.653 (0.586-0.703), 0.644 (0.555-0.735) for the training set, development set and test set respectively. The segmentation accuracy of the test set was 83.9%. For 10-fold cross validation, the median and quartiles of the 10-iteration sum IoUs was 0.656 (0.628-0.672); for accuracy, they were 88.4% (82.1-90.7%). CONCLUSIONS: We provided a dataset and trained a model for femoral-nerve region segmentation with U-net, obtaining a satisfactory performance. This technique may have potential clinical application.

Comparison of Cytotoxicity Evaluation of Anticancer Drugs between Real-Time Cell Analysis and CCK-8 Method.

Critical cytotoxicity evaluation of pharmaceuticals is necessary for the clinical practice of chemotherapy. To quantitatively evaluate cell viability, currently there are two main types of sensitive methods including real-time cell analysis (RTCA) and CCK-8 assay, in which RTCA records electrochemical signal changes around an incubated cell, whereas CCK-8 is based on the colorimetric method. Despite the different detection principles adopted for the cytotoxicity assessment, the comparison of the two methods in terms of the application scope is lacking. In this study, comparison studies were conducted between the RTCA and CCK-8 assays using anticancer drugs including doxorubicin hydrochloride, curcumin, irinotecan (CPT-11), taxol, and oxaliplatin, which are classified into two groups of drug molecules in the absence and presence of additives. The cytotoxicity evaluation of these drugs on cancer cells revealed that the physicochemical properties of drug formulations such as optical and electrochemical properties are closely linked with the readout of cytotoxic methods. The experimental results suggested that the preselection of cytotoxic assay is critical for the quantitative measurement of cytotoxicity of anticancer drugs, which is of clinical importance for their therapeutic usage.

Dexmedetomidine versus midazolam and propofol for sedation in critically ill patients: Mining the Medical Information Mart for Intensive Care data.

BACKGROUND: The benefits of dexmedetomidine on reducing mortality and length of intensive care unit (ICU) stay are still controversial. We aimed to evaluate the superiority of dexmedetomidine by comparing it with midazolam and propofol. METHODS: Subjects who were given dexmedetomidine, midazolam and propofol exclusively as sedatives in the Beth Israel Deaconess Medical Center between 2001 and 2012 were identified from the Medical Information Mart for Intensive Care (MIMIC) III database. Univariate, multivariate and stratified analysis was performed to compare the mortality and length of ICU stay between the dexmedetomidine, midazolam and propofol groups. To compare the depth of sedation between the midazolam and propofol group, we used propensity score matching (PSM) to create comparable units and their Richmond Agitation Sedation Score (RASS) were analyzed. RESULTS: A total of 1,542 unique ICU records were identified in the MIMIC-III database, among which 163 belonged to the dexmedetomidine group and 531 belonged to the midazolam group and 848 belonged to the propofol group. Mortality was decreased in dexmedetomidine group compared with midazolam group (OR 15.25; 95% CI, 5.29-64.80, P<0.001) and propofol group (OR 5.51; 95% CI, 1.91-23.45, P=0.006). In patients with high Simplified Acute Physiologic Score (SAPS) II (>52), midazolam was related to a higher mortality (~50%). But competing risk analysis revealed that dexmedetomidine was associated with longer ICU stay (P<0.001). There was no significant difference in the RASS between propofol and midazolam group (P=0.300). CONCLUSIONS: Dexmedetomidine was significantly related to lower mortality when compared with midazolam and propofol. Midazolam had a comparably higher mortality than propofol and dexmedetomidine in patients with high SAPS II. Propofol and midazolam were equivalent in sedative efficacy. Further evaluation is needed.

Epsilon-poly-l-lysine decorated ordered mesoporous silica contributes to the synergistic antifungal effect and enhanced solubility of a lipophilic drug.

The emergence of drug-resistant fungal strains remains a severe threat for the public health, which prompts strict restrictions on the uses of antifungal drugs. However, the majority of lipophilic fungistatic agents are poorly water soluble with a low oral adsorption characteristic posing challenges for the precise prescriptions. In this study, a natural antimicrobial cationic peptide of epsilon-poly-l-lysine (EPL) decorated ordered mesoporous silica (SBA-15) was facilely prepared for the efficient loading of antifungal itraconazole (ITZ) drugs. The characterized mesoporous SBA-15/EPL/ITZ composite exhibited remarkable antifungal performance against Aspergillus fumigatus as a model mold, which was attributed to synergistic antifungal activities of ITZ and EPL in the mesopores. Moreover, the in vitro release behaviors of ITZ in the composite nanoexcipients both in simulated gastric fluid and fasted state simulated intestinal fluid were studied. The observed release kinetics of ITZ demonstrated a contributing role of SBA-15/EPL to enhance the solubility of ITZ and thereby may promote its flux across the gastrointestinal epithelium, which is beneficial for the absorption of drugs. Additionally, SBA-15/EPL/ITZ composites showed desirable biocompatibility toward mammalian red blood cells, human cervical cancer cells (Hela) and human embryonic kidney cells (HEK-293T). Furthermore, the pharmacokinetic profiles of obtained nano-formulations were assessed in rats, among which the improved adsorption of SBA-15/EPL/ITZ composites (AUC0-24h sum: 8381.7 nM·h) was identified compared with that of pure ITZ (525.1 nM·h) and the commercial drug of Sporanox (7516.6 nM·h). Collectively, the prepared SBA-15/EPL/ITZ provides an ecofriendly and integrated nanocomposite with enhanced solubility of lipophilic drugs to combat proliferations of infectious fungi.

GSH-responsive curcumin/doxorubicin encapsulated Bactrian camel serum albumin nanocomposites with synergistic effect against lung cancer cells.

The aim of this study was to prepare camel serum albumin (CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin (CCM) and doxorubicin (Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian ( Camelus bactrianus) CSA. The constructed CSA nanoparticles (CSA-NPs) with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite (CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione (GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drug-delivery matrix to exert synergistic effects.

Multiple Machine Learnings Revealed Similar Predictive Accuracy for Prognosis of PNETs from the Surveillance, Epidemiology, and End Result Database.

Background: Prognosis prediction is indispensable in clinical practice and machine learning has been proved to be helpful. We expected to predict survival of pancreatic neuroendocrine tumors (PNETs) with machine learning, and compared it with the American Joint Committee on Cancer (AJCC) staging system. Methods: Data of PNETs cases were extracted from The Surveillance, Epidemiology, and End Result (SEER) database. Statistic description, multivariate survival analysis and preprocessing were done before machine learning. Four different algorithms (logistic regression (LR), support vector machines (SVM), random forest (RF) and deep learning (DL)) were used to train the model. We used proper imputations to manage missing data in the database and sensitive analysis was performed to evaluate the imputation. The model with the best predictive accuracy was compared with the AJCC staging system using the SEER cases. Results: The four models had similar predictive accuracy with no significant difference existed (p = 0.664). The DL model showed a slightly better predictive accuracy than others (81.6% (± 1.9%)), thus it was used for further comparison with the AJCC staging system and revealed a better performance for PNETs cases in SEER database (Area under receiver operating characteristic curve: 0.87 vs 0.76). The validity of missing data imputation was supported by sensitivity analysis. Conclusions: The models developed with machine learning performed well in survival prediction of PNETs, and the DL model have a better accuracy and specificity than the AJCC staging system in SEER data. The DL model has potential for clinical application but external validation is needed.

Prolonged dexmedetomidine infusion in critically ill adult patients: a retrospective analysis of a large clinical database Multiparameter Intelligent Monitoring in Intensive Care III.

BACKGROUND: There is no conclusive evidence for the effects of prolonged infusion of dexmedetomidine in critically ill patients. We aimed to investigate the safety of long-term dexmedetomidine infusion in a large critically ill patients cohort from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. METHODS: We retrospectively extracted records from MIMIC-III database. Dexmedetomidine administration time was the basis for group. Variables were compared by chi-square tests, and Mann-Whitney U test as appropriate. We used logistic regression model for multivariate analysis. Contour maps were drawn to measure rebound of heart rate (HR) and blood pressure (BP). RESULTS: We finally got 1,946 records including 1,368 distinct individuals. Age, body mass index (BMI), length of stay in hospital, accumulated doses of dexmedetomidine and Sequential Organ Failure Assessment (SOFA) score were independent risk factors of in-hospital mortality (P<0.05). But prolonged dexmedetomidine infusion (≥24 h) and abrupt cessation did not increase in-hospital mortality. Furthermore, the rebound of HR and BP was more likely to occur in patients with prolonged infusion of dexmedetomidine. CONCLUSIONS: Prolonged dexmedetomidine infusion is not related to an increased in-hospital mortality, but it is associated with the rebound effect of HR and BP. Further prospective studies are needed.

Multifunctional Bismuth Oxychloride/Mesoporous Silica Composites for Photocatalysis, Antibacterial Test, and Simultaneous Stripping Analysis of Heavy Metals.

The increasing complexity of environmental pollution nowadays poses a severe threat to the public health, which attracts considerable attentions in searching for nanomaterials of multiproperty. In this study, mesoporous silica of KIT-6-encapsulated bismuth oxychloride (BiOCl), an intrinsically multifunctional material exhibiting bunched structure in the composites, are facilely prepared under hydrothermal conditions. Subsequently, the produced materials of multifunctionality were applied for photocatalysis, antibacterial test, and simultaneous determination of heavy metals including lead and cadmium. A combination of physiochemical characterizations have revealed that the BiOCl-KIT-6 composites exhibit enlarged yet refined surface morphology contributing to the improved photocatalytic ability with a band gap of 3.06 eV at a molecular ratio of 8Bi-Si. Moreover, the antibacterial activities of our BiOCl-KIT-6 composites were explored, and possible antimicrobial mechanism related to the production of reactive oxygen species was discussed. Furthermore, a sensitive electrochemical determination of heavy metals of lead and cadmium using square-wave anodic stripping voltammetry was also achieved. The composites-modified glassy carbon electrode displays a linear range of calibration curve from 0.2 to 300 µg/L with a detection limit of 0.05 µg/L (Pb2+) and 0.06 µg/L (Cd2+), respectively.

Bioinformatic Analysis of Potential Biomarkers for Spinal Cord-injured Patients with Intractable Neuropathic Pain.

BACKGROUND: Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting individuals' quality of life. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and microRNAs (miRNAs) related to neuropathic pain by the bioinformatics method. METHODS: Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from individuals with or without neuropathic pain after SCI were collected. Twelve samples from individuals with neuropathic pain and 13 samples from individuals without pain as controls were included in the downloaded microarray. Differentially expressed genes (DEGs) between the neuropathic pain group and the control group were detected using the GEO2R online tool. Functional enrichment analysis of DEGs was performed using the DAVID database. Protein-protein interaction network was constructed from the STRING database. MiRNAs targeting these DEGs were obtained from the miRNet database. A merged miRNA-DEG network was constructed and analyzed with Cytoscape software. RESULTS: In total, 1134 DEGs were identified between individuals with or without neuropathic pain (case and control), and 454 biological processes were enriched. We identified 4 targeted miRNAs, including mir-204-5p, mir-519d-3p, mir-20b-5p, mir-6838-5p, which may be potential biomarkers for SCI patients. CONCLUSION: Protein modification and regulation of the biological process of the central nervous system may be a risk factor in SCI. Certain genes and miRNAs may be potential biomarkers for the prediction of and potential targets for the prevention and treatment of neuropathic pain after SCI.