The neurocognitive mechanism linking temperature and humidity with miners' alertness: an fNIRS study.

As the depth of coal mining increases, the temperature and humidity of the underground environment also rise, which can negatively impact the physiological health of miners, and may even pose a threat to their safety and lives. However, studies on the neurocognitive mechanisms underlying the relationship between temperature, humidity, and miners' alertness are scant. This study investigates several research objectives: (A) the differences in reaction time and error rate in different temperature and humidity conditions, which factor has a greater impact; (B) the differences in the levels of Oxy-Hb in different conditions and which factor has a greater impact; (C) the differences of activation degree between different regions of interest; and (D) the differences in the shape of Oxy-Hb time course between different conditions between different regions of interests. The fNIRS was used to measure the activity in 100 participants' prefrontal cortex in this study. The results showed that both temperature and humidity would lead to decreased alertness of miners, which would not only prolong the reaction time, increase the error rate, and increase the Oxy-Hb concentration, but also lead to increased activation of the prefrontal cortex and greater activation of the right side than that of the left side, the Oxy-Hb time course was different on both sides, and temperature has a greater effect on alertness than humidity.

Zeta Potential and Size Analysis of Zeolitic Imidazolate Framework-8 Nanocrystals Prepared by Surfactant-Assisted Synthesis.

The crystal nucleation and growth mechanism of monodispersed metal-organic framework nanoparticles were studied using time-resolved light dynamic, electrokinetic, and powder X-ray diffraction methods. We confirmed that zeolitic imidazolate framework-8 (ZIF-8) nanocrystals follow a nonclassical crystal growth pathway, where a fast nucleation occurs with dense liquid clusters or nanocrystals forming spontaneously when two precursors are mixed. We also explored the zeta potential and solvodynamic size changes of ZIF-8 prepared by a surfactant-assisted synthesis. Three modulators, including 1-methylimidazole (1-mIm), tris(hydroxymethyl)aminomethane (THAM), and (1-hexadecyl)trimethylammonium bromide (CTAB), were studied. We found that 1-mIm dramatically increases the rate of nucleation of ZIF-8. With an increasing amount of 1-mIm, which functions as a coordination modulator, the size increases, and the zeta potential of ZIF-8 decreases. Whereas THAM, as both a coordination and a deprotonation modulator, increases the size and zeta potential of ZIF-8 simultaneously, CTAB, as a long alkyl cationic surfactant, mainly adsorbs on the surface of ZIF-8, and the zeta potential of the formed ZIF-8 is controlled by the amount of CTAB in solution compared with its critical micelle concentration. Overall, we reveal that the modulator type and concentration can be used to control the size and zeta potential of the dispersed ZIF-8 nanocrystals in a colloid system. The experiments also enable identification of the nucleation and crystal growth processes of ZIF-8. The findings will be applicable to other nanocrystals in colloid systems, which are used for heterogeneous catalysis and guest molecular loadings.

Evaluation of oral small molecule drugs for the treatment of COVID-19 patients: a systematic review and network meta-analysis.

INTRODUCTION: At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral small molecule drug treatment for COVID-19. METHODS: RCTs were identified through systematic searches of PubMed, Embase, and Cochrane Central Register of Controlled Trials through 1 April 2023. A total of nine RCTs were included, including 30,970 COVID-19 patients comparing five treatments (azvudine, molnupiravir, paxlovid, VV116, and placebo). The Cochrane risk of bias tool for randomized trials (RoB) was used to assess the bias risk of the included studies. The direct and indirect evidence were combined using a Bayesian network meta-analysis (PROSPERO Code No: CRD42023397837). RESULTS: Direct analysis showed that paxlovid was associated with a reduced risk of mortality (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.06-0.25) and hospitalization (OR = 0.04, 95% CI: 0.00-0.67) compared with placebo. Network meta-analysis showed that paxlovid had the highest probability of being the best management strategy in patients with COVID-19, reducing mortality (OR = 0.11, 95% CI: 0.01-1.99; surface under the cumulative ranking curve [SUCRA]: 0.77) and hospitalization (OR = 0.06, 95% CI: 0.00-1.03; SUCRA: 0.95). For prespecified safety outcomes, SUCRA values ranked VV116 (OR = 0.09, 95% CI: 0.00-2.07: SUCRA 0.86) as the most beneficial intervention for the prevention of serious adverse events. CONCLUSIONS: When compared to other antiviral medications, paxlovid can reduce the mortality and hospitalization of COVID-19 patients.

Polypharmacy, potentially inappropriate medications, and drug-drug interactions in older COVID-19 inpatients.

OBJECTIVES: The purpose of this study was to assess the impact of polypharmacy, potentially inappropriate medications, and drug-drug interactions on in-hospital mortality in older COVID-19 inpatients. METHODS: A cross-sectional study was conducted using electronic medical data from a tertiary hospital in Chengdu from December 2022 to January 2023. The 2019 AGS/Beers criteria was used to evaluate the potentially inappropriate mediation (PIM) status of older COVID-19 inpatients (age ≥ 65 years), the drug-drug interactions were evaluated on Medscape, and multivariate logistic regression was used to identify the risk factors associated with in-hospital mortality. RESULTS: A total of 206 older COVID-19 inpatients were included in the study. The mean number of drugs per day was 13.04. The prevalence of PIM use based on the 2019 AGS Beers Criteria was 66.99%. The prevalence of drug-drug interactions was 61.65%. Logistic regression demonstrated that age ≥ 80 (OR: 10.321, 95% CI: 1.649, 64.579, P = 0.013), renal insufficiency (OR: 4.740, 95% CI: 1.366, 16.447, P = 0.014), long-term hospitalization (OR: 6.637, 95% CI: 1.030, 42.779, P = 0.046), severe pneumonia (OR: 50.230, 95% CI: 5.180, 487.041, P = 0.001) were influencing factors associated with in-hospital mortality in older COVID-19 inpatients. CONCLUSIONS: The polypharmacy, potentially inappropriate medications, and drug-drug interactions were seen in many older COVID-19 inpatients.

Screening, identification and control of unknown estrogen-like compounds in Maillard reaction products of glucose-arginine/lysine model systems.

It was speculated that estrogen-like compounds may be produced by chemical reactions during food processing, such as Maillard reaction, which would disrupt the endocrine system of organisms. Herein, the Maillard reaction in the process of high temperature for long time was simulated by using model system, and unknown estrogen-like compounds produced during Maillard reaction were screened by colorimetric assay based on dual estrogen receptor (ER)-gold nanoparticles (AuNPs) and enzyme-linked immunosorbent assay (ELISA). Possible structures of estrogen-like compounds were inferred by ultra-performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS) in combination with a mass database, and finally the structure of estrogen-like compound, 2, 4-dihydroxy-1, 4-benzoxazin-3-one-2-o-ß-D-glucopyranoside (DIBOA-glc), was identified by high resolution orbitrap mass spectrometry (Orbitrap HRMS). This is the first study of the screening and identification of unknown estrogen-like compounds produced in Maillard reaction. Additionally, strategy of controlling the formation of DIBOA-glc by adding vitamin B6 in Maillard reaction was proposed, providing effective proposals for the safety control in actual food processing.

Efficacy and safety of azvudine in patients with COVID-19: A systematic review and meta-analysis.

Introduction: Azivudine has undergone a few randomized controlled trials (RCTs) as of late. This study aimed to assess the COVID-19 treatment with azvudine's efficacy and safety. Methods: Through January 20, 2023, systematic searches of PubMed, Embase, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials (CENTRAL), and MedRxiv were conducted to find the RCTs. The included studies' bias risk was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was performed using Revman 5.4 (PROSPERO Code: CRD42023395022). Results: A total of five RCTs with 1142 COVID-19 patients, 575 of whom received azvudine, were included. Additionally, seven RCTs are currently being conducted. In terms of clinical improvement and PT-PCR (reverse transcription polymerase chain reaction) negativity, the azvudine group had a greater patient percentage than the usual treatment or placebo group. It also took less time for the PT-PCR to become negative. In comparison to the placebo or standard treatment groups, the frequency of adverse events was reduced in the azvudine group (risk ratio [RR] = 0.89, 95% confidence interval [CI]: 0.80 to 0.99) and major adverse events (RR = 0.63, 95% CI: 0.22 to 1.79) groups. Conclusions: Without the burden of side effects, azvudine can hasten the clinical symptoms of COVID-19 patients and PT-PCR negative. It will take more extensive research to confirm these conclusions.

Global prevalence of polypharmacy and potentially inappropriate medication in older patients with dementia: a systematic review and meta-analysis.

Background: Older patients with dementia always need multiple drugs due to comorbidities and cognitive impairment, further complicating drug treatment and increasing the risk of potentially inappropriate medication. The objective of our study is to estimate the global prevalence of polypharmacy and potentially inappropriate medication (PIM) and explore the factors of PIM for older patients with dementia. Methods: We searched PubMed, Embase (Ovid), and Web of Science databases to identify eligible studies from inception to 16 June 2023. We conducted a meta-analysis for observational studies reporting the prevalence of potentially inappropriate medication and polypharmacy in older patients with dementia using a random-effect model. The factors associated with PIM were meta-analyzed. Results: Overall, 62 eligible studies were included, of which 53 studies reported the prevalence of PIM and 28 studies reported the prevalence of polypharmacy. The pooled estimate of PIM and polypharmacy was 43% (95% CI 38-48) and 62% (95% CI 52-71), respectively. Sixteen studies referred to factors associated with PIM use, and 15 factors were further pooled. Polypharmacy (2.83, 95% CI 1.80-4.44), diabetes (1.31, 95% CI 1.04-1.65), heart failure (1.17, 95% CI 1.00-1.37), depression (1.45, 95% CI 1.14-1.88), history of cancer (1.20, 95% CI 1.09-1.32), hypertension (1.46, 95% CI 1.05-2.03), ischemic heart disease (1.55, 95% CI 0.77-3.12), any cardiovascular disease (1.11, 95% CI 1.06-1.17), vascular dementia (1.09, 95% CI 1.03-1.16), chronic obstructive pulmonary disease (1.39, 95% CI 1.13-1.72), and psychosis (1.91, 95% CI 1.04-3.53) are positively associated with PIM use. Conclusion: PIM and polypharmacy were highly prevalent in older patients with dementia. Among different regions, the pooled estimate of PIM use and polypharmacy varied widely. Increasing PIM in older patients with dementia was closely associated with polypharmacy. For other comorbidities such as heart failure and diabetes, prescribing should be cautioned.

Antifungal activity of compounds from Gordonia sp. WA8-44 isolated from the gut of Periplaneta americana and molecular docking studies.

Invasive fungal infections are on the rise, leading to a continuous demand for antifungal antibiotics. Rare actinomycetes have been shown to contain a variety of interesting compounds worth exploring. In this study, 15 strains of rare actinobacterium Gordonia were isolated from the gut of Periplaneta americana and screened for their anti-fungal activity against four human pathogenic fungi. Strain WA8-44 was found to exhibit significant anti-fungal activity and was selected for bioactive compound production, separation, purification, and characterization. Three anti-fungal compounds, Collismycin A, Actinomycin D, and Actinomycin X2, were isolated from the fermentation broth of Gordonia strain WA8-44. Of these, Collismycin A was isolated and purified from the secondary metabolites of Gordonia for the first time, and its anti-filamentous fungi activity was firstly identified in this study. Molecular docking was carried out to determine their hypothetical binding affinities against nine target proteins of Candida albicans. Chitin Synthase 2 was found to be the most preferred antimicrobial protein target for Collismycin A, while 1,3-Beta-Glucanase was the most preferred anti-fungal protein target for Actinomycin D and Actinomycin X2. ADMET prediction revealed that Collismycin A has favorable oral bioavailability and little toxicity, making it a potential candidate for development as an orally active medication.

Prevalence of Use of Potentially Inappropriate Medications Among Older Adults Worldwide: A Systematic Review and Meta-Analysis.

Importance: The use of potentially inappropriate medications (PIMs) is widespread yet continues to receive little attention in outpatient services. Objective: To estimate the overall prevalence of PIM use in outpatient services. Data Sources: PubMed, Embase, and Web of Science were searched to identify relevant studies published from January 1, 1990, to November 21, 2022. Study Selection: Observational studies that reported the prevalence of PIM use among older patients in outpatient services were screened. Data Extraction and Synthesis: Two reviewers independently selected eligible articles, extracted data, and assessed the risk of bias. A random-effects meta-analysis was conducted to pool the prevalence estimates. Main Outcomes and Measures: The global patterns in the prevalence of PIM use among older patients in outpatient services were estimated, and the temporal trends and regional differences in PIM use were investigated. Results: A total of 94 articles with 132 prevalence estimates were analyzed, including nearly 371.2 million older participants from 17 countries. Overall, the pooled prevalence of PIM use was 36.7% (95% CI, 33.4%-40.0%). Africa had the highest prevalence of PIM use (47.0%; 95% CI, 34.7%-59.4%), followed by South America (46.9%; 95% CI, 35.1%-58.9%), Asia (37.2%; 95% CI, 32.4%-42.2%), Europe (35.0%; 95% CI, 28.5%-41.8%), North America (29.0%; 95% CI, 22.1%-36.3%), and Oceania (23.6%; 95% CI, 18.8%-28.8%). In addition, the prevalence of PIM use is highest in low-income areas. Use of PIMs among older patients has become increasingly prevalent in the past 2 decades. Conclusions and Relevance: This study of patterns of PIM use by different groups, such as geographic regions and World Bank countries, suggests noticeable geographic environment and economic income differences in the burden of PIMs in outpatient services. Furthermore, the high prevalence trend in the past 2 decades indicates that the global burden of PIM use continues to be worthy of attention.

Deprescribing Interventions for Older Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Deprescribing reduces polypharmacy in older adults. A thorough study of the effect of deprescribing interventions on clinical outcomes in older adults is presently lacking. As a result, we evaluated the impact of deprescribing on clinical outcomes in older patients. DESIGN: Meta-analysis and systematic review of randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane Library were searched from the time of creation to March 2023. SETTING AND PARTICIPANTS: Randomized controlled trial with participants at least 60 years old. MEASURES: Mortality, falls (number of fallers), hospitalization rates, emergency department visits, medication adherence, HRQoL (health-regulated quality of life), incidence of ADR (adverse drug reactions), PIM (potentially inappropriate medication), and PPO (potentially prescription omission) were evaluated in the meta-analysis. RESULTS: A total of 32 RCTs (18,670 patients) were included. Deprescribing interventions significantly reduced proportions of older adults with PIM, PPO, and the incidence of ADRs. The interventions group also improved medication compliance. CONCLUSIONS AND IMPLICATIONS: Compared to routine care, deprescribing interventions significantly improve clinical outcome indicators for older adults.

Prophylactic use amphotericin B use in patients with hematologic disorders complicated by neutropenia: a systematic review and meta-analysis.

The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched the PubMed, EMBASE, The Cochrane Library, CBM, CNKI, VIP and WanFang Data database and the China Clinical Trials Registry ( www.chictr.org.cn ) to collect randomized controlled trials (RCTs) of amphotericin B for patients with hematologic disorders complicated by neutropenia from inception to May 2023. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. The meta-analysis was performed using RevMan 5.3 software. A total of 6 studies with a total of 1019 patients were included. The results of the meta-analysis showed that the treatment group was superior to the control group in terms of the fungal infection rate, and the differences were statistically significant [RR = 0.47, 95% CI (0.32, 0.69), P < 0.0001]. There was no significant difference between the two groups in terms of the mortality [RR = 0.87, 95% CI (0.61, 1.23), P = 0.43] and the incidence of colonization [OR = 0.51, 95% CI (0.25, 1.03), P = 0.06]. The evidence shows that amphotericin B prophylactic use for patients with hematologic disorders complicated by neutropenia can decrease the fungal infection rate. However, there was no significant difference in reducing mortality or the incidence of colonization. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.

Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics.

Introduction: Vibrio parahaemolyticus is a foodborne pathogen commonly found in seafood, and drug resistance poses significant challenges to its control. This study aimed to identify novel drug targets for antibacterial drug discovery. Methods: To identify drug targets, we performed a pan-genome analysis on 58 strains of V. parahaemolyticus genomes to obtain core genes. Subsequently, subtractive proteomics and physiochemical checks were conducted on the core proteins to identify potential therapeutic targets. Molecular docking was then employed to screen for anti-V. parahaemolyticus compounds using a in-house compound library of Streptomyces parvus, chosen based on binding energy. The anti-V. parahaemolyticus efficacy of the identified compounds was further validated through a series of experimental tests. Results and Discussion: Pangenome analysis of 58 V. parahaemolyticus genomes revealed that there were 1,392 core genes. After Subtractive proteomics and physiochemical checks, Flagellar motor switch protein FliN was selected as a therapeutic target against V. parahaemolyticus. FliN was modeled and docked with Streptomyces parvus source compounds, and Actinomycin D was identified as a potential anti-V. parahaemolyticus agent with a strong binding energy. Experimental verification confirmed its effectiveness in killing V. parahaemolyticus and significantly inhibiting biofilm formation and motility. This study is the first to use pan-genome and subtractive proteomics to identify new antimicrobial targets for V. parahaemolyticus and to identify the anti-V. parahaemolyticus effect of Actinomycin D. These findings suggest potential avenues for the development of new antibacterial drugs to control V. parahaemolyticus infections.

Nirmatrelvir-ritonavir compared with other antiviral drugs for the treatment of COVID-19 patients: A systematic review and meta-analysis.

At present, there are some differences in the research results of nirmatrelvir-ritonavir compared with other antiviral drugs for the treatment of COVID-19 patients. We aimed to evaluate the efficacy and safety of nirmatrelvir-ritonavir compared with other antiviral drugs and the impact of different antiviral drugs on the short- and long-term effects of COVID-19. PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, Google Scholar, and MedRxiv were searched to identify relevant studies from inception to March 30, 2023. We conducted a meta-analysis to estimate the effects of nirmatrelvir-ritonavir compared with other antiviral drugs for the treatment of COVID-19 patients and safety outcomes. The RoB1 and ROBINS-I were used to assess the bias risk of the included studies. Revman 5.4 software was used for meta-analysis (PROSPERO Code No: CRD42023397816). Twelve studies were included, including 30 588 COVID-19 patients, of whom 13 402 received nirmatrelvir-ritonavir. The meta-analysis results showed that the nirmatrelvir-ritonavir group had a lower proportion of patients than the control group in terms of long-term mortality (odds ratio [OR] = 0.29, 95% confidence interval [CI]: 0.13-0.66), hospitalization (OR = 0.44, 95% CI: 0.37-0.53, short term; OR = 0.52, 95% CI: 0.36-0.77, long term), and disease progression (OR = 0.56, 95% CI: 0.38-0.83, short term; OR = 0.60, 95% CI: 0.48-0.74, long term), and nirmatrelvir ritonavir showed little difference in safety compared to the control group. Nirmatrelvir-ritonavir can reduce the mortality and hospitalization of COVID-19 patients compared with other antiviral drugs. Further large-scale studies remain to validate these findings.

Efficacy and Safety of Molnupiravir Treatment for COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: There are currently some differences in the research results of molnupiravir. This study aimed to evaluate the efficacy and safety of molnupiravir in the treatment of COVID-19. METHODS: PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), ClinicalTrials.gov, ICTRP (International Clinical Trials Registry Platform) and medRxiv were searched to identify relevant randomised controlled trials (RCTs) from inception to 1 January 2023. The Cochrane risk of bias tool for randomised trials was used to assess the bias risk of the included studies. Revman 5.4 software was used for meta-analysis. RESULTS: Nine RCTs were included, including 31 573 COVID-19 patients, of whom 15 846 received molnupiravir. The meta-analysis results showed that the molnupiravir group had a higher proportion in terms of clinical improvement (Day 5 RR 2.41, 95% CI 1.18-4.92; Day 10 RR 1.45, 95% CI 1.04-2.01) and real-time polymerase chain reaction negativity (Day 5 RR 2.78, 95% CI 1.38-5.62; Day 10 RR 1.18, 95% CI 1.07-1.31). However, no significant difference was observed between the two groups in terms of mortality, hospitalisation, adverse events and serious adverse events. CONCLUSIONS: Molnupiravir can accelerate the rehabilitation of COVID-19 patients, but it does not significantly reduce mortality and hospitalisation.

Developing a Warning Model of Potentially Inappropriate Medications in Older Chinese Outpatients in Tertiary Hospitals: A Machine-Learning Study.

Due to multiple comorbid illnesses, polypharmacy, and age-related changes in pharmacokinetics and pharmacodynamics in older adults, the prevalence of potentially inappropriate medications (PIMs) is high, which affects the quality of life of older adults. Building an effective warning model is necessary for the early identification of PIMs to prevent harm caused by medication in geriatric patients. The purpose of this study was to develop a machine learning-based model for the warning of PIMs in older Chinese outpatients. This retrospective study was conducted among geriatric outpatients in nine tertiary hospitals in Chengdu from January 2018 to December 2018. The Beers criteria 2019 were used to assess PIMs in geriatric outpatients. Three problem transformation methods were used to tackle the multilabel classification problem in prescriptions. After the division of patient prescriptions into the training and test sets (8:2), we adopted six widely used classification algorithms to conduct the classification task and assessed the discriminative performance by the accuracy, precision, recall, F1 scores, subset accuracy (ss Acc), and Hamming loss (hm) of each model. The results showed that among 11,741 older patient prescriptions, 5816 PIMs were identified in 4038 (34.39%) patient prescriptions. A total of 41 types of PIMs were identified in these prescriptions. The three-problem transformation methods included label power set (LP), classifier chains (CC), and binary relevance (BR). Six classification algorithms were used to establish the warning models, including Random Forest (RF), Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting (XGBoost), CatBoost, Deep Forest (DF), and TabNet. The CC + CatBoost model had the highest accuracy value (97.83%), recall value (89.34%), F1 value (90.69%), and ss Acc value (97.79%) with a good precision value (92.18%) and the lowest hm value (0.0006). Therefore, the CC + CatBoost model was selected to predict the occurrence of PIM in geriatric Chinese patients. This study's novelty establishes a warning model for PIMs in geriatric patients by using machine learning. With the popularity of electronic patient record systems, sophisticated computer algorithms can be implemented at the bedside to improve medication use safety in geriatric patients in the future.

Development and validation of a nomogram to predict the risk of potentially inappropriate medication use in older lung cancer outpatients with multimorbidity.

BACKGROUND: At present, there is no predictive model that can predict the prevalence of potentially inappropriate medication (PIM) use in older lung cancer outpatients. RESEARCH DESIGN AND METHODS: We measured PIM by the 2019 Beers criteria. Significant factors were identified to develop the nomogram using logistic regression. We validated the nomogram internally and externally in two cohorts. The discrimination, calibration, and clinical practicability of the nomogram were verified using receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow test, and decision curve analysis (DCA), respectively. RESULTS: A total of 3300 older lung cancer outpatients were divided into a training cohort (n = 1718) and two validation cohorts, including an internal validation cohort (n = 739) and an external validation cohort (n = 843). A nomogram for predicting PIM use patients was developed using six significant factors. ROC curve analysis showed that the area under the curve was 0.835 in the training cohort and 0.810 and 0.826 in the internal validation and external validation cohorts, respectively. The Hosmer‒Lemeshow test yielded P = 0.180, 0.779 and 0.069, respectively. The nomogram demonstrated a high net benefit in DCA. CONCLUSIONS: The nomogram could be a convenient, intuitive, and personalized clinical tool for assessing the risk of PIM in older lung cancer outpatients.

Cardiotoxicity with human epidermal growth factor receptor-2 inhibitors in breast cancer: Disproportionality analysis of the FDA adverse event reporting system.

BACKGROUND: The cardiotoxicity induced by human epidermal growth factor receptor-2 (HER-2) inhibitors in patients with breast cancer has been reported widely. However, these data sources were largely limited to fewer patients in clinical trials and case reports, lacking more comprehensive analysis from real-world data. METHODS: The cases diagnosed with breast cancer from January 2004 to December 2021 were extracted from the FDA adverse event database and further divided into 3 groups (the HER-2 inhibitor group, the positive control group, and the control group). The association between HER-2 inhibitors and cardiovascular adverse events was evaluated using the reporting odds ratio (ROR), a disproportionality method. RESULTS: A total of 167,639 breast cancer patients were included, including 18,615 cases in the HER-2 inhibitor drug group, 2568 cases in the positive control group, and 146,456 cases in the control group. A total of 2529 cases (13.5%) treated with HER-2 inhibitors experienced cardiovascular adverse events, mainly reported by health professionals (81.5%). The disproportionality analysis showed that cardiomyopathy was observed in all HER-2 inhibitors except trastuzumab deruxtecan. Trastuzumab-related CVAEs were most frequently reported (N =2075), and the median time was 80.50 days (IQR: 8.00 to 206.75 days). CONCLUSION: Based on real-world data analysis, our study demonstrated a significant association between HER-2 inhibitors and cardiovascular toxicity. Cardiac function in patients with breast cancer should be monitored early during anti-HER therapy, especially within six months.

Electrodeposition of Ag/ZIF-8-Modified Membrane for Water Remediation.

Metal-organic framework (MOF)-based membranes have been widely used in gas and liquid separation due to their porous structures and tunable compositions. Depending on the guest components, heterostructured MOFs can exhibit multiple functions. In the present work, we report a facile and rapid preparation of zeolitic imidazolate framework-8 (ZIF-8) and silver nanoparticle incorporated ZIF-8 (Ag/ZIF-8)-based membranes on stainless-steel mesh (SSM) through a "green" electrodeposition method. The SSM was first coated with a Zn-plated layer which contains mainly zinc hydroxide nitrate (Zn5(OH)8(NO3)2·2H2O) with a "leaf-like" morphology, providing anchoring points for the deposition of ZIF-8 and Ag/ZIF-8. It takes only 10 min to prepare a uniform coating of Zn5(OH)8(NO3)2·2H2O in aqueous conditions without the use of a strong base; this is by far the most efficient way of making zinc hydroxide nitrate nanocrystals. Following a similar electrodeposition approach, ZIF-8 and Ag/ZIF-8-coated SSM can be prepared within 20 min by applying a small current. The encapsulation of Ag does not alter the chemical composition nor the crystal structure of ZIF-8. The resulting ZIF-8 and Ag/ZIF-8-coated SSM have been tested for their effectiveness for rhodamine B dye removal in a fast vacuum filtration setting. Additionally, growth of E. coli was significantly inhibited after overnight incubation with Ag/ZIF-8-coated SSM. Overall, we demonstrate a fast synthesis procedure to make ZIF-8 and Ag/ZIF-8-coated SSM membranes for organic dye removal with excellent antimicrobial activity.

pH-Responsive Metal-Organic Framework Thin Film for Drug Delivery.

In this work, surface-supportive MIL-88B(Fe) was explored as a pH-stimuli thin film to release ibuprofen as a model drug. We used surface plasmon resonance microscopy to study the pH-responsive behaviors of MIL-88B(Fe) film in real time. A dissociation constant of (6.10 ± 0.86) × 10-3 s-1 was measured for the MIL-88B(Fe) film in an acidic condition (pH 6.3), which is about 10 times higher than the dissociation of the same film in a neutral pH condition. MIL-88B(Fe) films are also capable of loading around 6.0 µg/cm2 of ibuprofen, which was measured using a quartz crystal microbalance (QCM). Drug release profiles were compared in both acidic and neutral pH conditions (pH 6.3 and 7.4) using a QCM cell to model the drug release in healthy body systems and those containing inflammatory tissues or cancerous tumors. It was found that the amount of drug released in acidic environments had been significantly higher compared to that in a neutral system within 55 h of testing time. The pH-sensitive chemical bond breaking between Fe3+ and the carboxylate ligands is the leading cause of drug release in acidic conditions. This work exhibits the potential of using MOF thin films as pH-triggered drug delivery systems.