Nanoparticle albumin-bound paclitaxel-based neoadjuvant regimen: A promising treatment option for HER2-low-positive breast cancer.

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.

Integrated analysis identifies oxidative stress-related lncRNAs associated with progression and prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. Oxidative stress reactions have been reportedly associated with oncogenesis and tumor progression. By analyzing mRNA expression data and clinical information from The Cancer Genome Atlas (TCGA), we aimed to construct an oxidative stress-related long noncoding RNA (lncRNA) risk model and identify oxidative stress-related biomarkers to improve the prognosis and treatment of CRC. RESULTS: Differentially expressed oxidative stress-related genes (DEOSGs) and oxidative stress-related lncRNAs were identified by using bioinformatics tools. An oxidative stress-related lncRNA risk model was constructed based on 9 lncRNAs (AC034213.1, AC008124.1, LINC01836, USP30-AS1, AP003555.1, AC083906.3, AC008494.3, AC009549.1, and AP006621.3) by least absolute shrinkage and selection operator (LASSO) analysis. The patients were then divided into high- and low-risk groups based on the median risk score. The high-risk group had a significantly worse overall survival (OS) (p < 0.001). Receiver operating characteristic (ROC) and calibration curves displayed the favorable predictive performance of the risk model. The nomogram successfully quantified the contribution of each metric to survival, and the concordance index and calibration plots demonstrated its excellent predictive capacity. Notably, different risk subgroups showed significant differences in terms of their metabolic activity, mutation landscape, immune microenvironment and drug sensitivity. Specifically, differences in the immune microenvironment implied that CRC patients in certain subgroups might be more responsive to immune checkpoint inhibitors. CONCLUSIONS: Oxidative stress-related lncRNAs can predict the prognosis of CRC patients, which provides new insight for future immunotherapies based on potential oxidative stress targets.

Effects of Urban and Rural Resident Basic Medical Insurance on Healthcare Utilization Inequality in China.

Objectives: This study aims to evaluate the effects of Urban and Rural Resident Basic Medical Insurance (URRBMI) integration on healthcare utilization and explore the contribution of URRBMI to healthcare utilization inequality among middle-aged and older adults. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS) 2011-2018. The difference-in-difference model, concentration index (CI), and decomposition method were adopted. Results: The results suggested that the probability of outpatient visits and the number of outpatient visits had decreased by 18.2% and 10.0% respectively, and the number of inpatient visits had increased by 3.6%. However, URRBMI had an insignificant effect on the probability of inpatient visits. A pro-poor inequality for the treatment group was observed. The decomposition revealed that the URRBMI contributed to the pro-poor inequality in healthcare utilization. Conclusion: The findings suggest that URRBMI integration has decreased outpatient care utilization and improved the number of inpatient visits. While the URRBMI has improved healthcare utilization inequality, some challenges still exist. Comprehensive measures should be taken in the future.

Microporous PdCuB nanotag-based electrochemical aptasensor with Au@CuCl2 nanowires interface for ultrasensitive detection of PD-L1-positive exosomes in the serum of lung cancer patients.

Programmed cell death ligand 1 protein-positive (PD-L1+) exosomes have been found to be a potential biomarker for the diagnosis of non-small cell lung cancer (NSCLC). However, the development of highly sensitive detection technique for PD-L1+ exosomes is still a challenge in clinical applications. Herein, a sandwich electrochemical aptasensor based on ternary metal-metalloid palladium-copper-boron alloy microporous nanospheres (PdCuB MNs) and Au@CuCl2 nanowires (NWs) was designed for the detection of PD-L1+ exosomes. The excellent peroxidase-like catalytic activity of PdCuB MNs and the high conductivity of Au@CuCl2 NWs endow the fabricated aptasensor with intense electrochemical signal, thus enabling the detection of low abundance exosomes. The analytical results revealed that the aptasensor maintained favorable linearity over a wide concentration range of 6 orders of magnitude and reached a low detection limit of 36 particles/mL. The aptasensor is successfully applied to the analysis of complex serum samples and achieves the accurate identification of clinical NSCLC patients. Overall, the developed electrochemical aptasensor provides a powerful tool for early diagnosis of NSCLC.

Recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors.

Background: Hepatocellular carcinoma (HCC) frequently relapses after minimally invasive treatment. This study aimed to observe the influencing factors of different recurrence patterns after radiofrequency ablation (RFA) for the treatment of recurrence. Methods: The medical records of HCC patients who underwent RFA between January 2010 and January 2019 were retrospectively reviewed. HCC recurrence is classified into three types: local tumour progression (LTP), intrahepatic distant metastasis, and extrahepatic metastasis. Risk factors, overall survival (OS), and disease-free survival (DFS) were assessed for each modality. Among the risk factors are age, gender, liver function tests, blood tests, and tumour size. The OS and DFS curves were measured by the Kaplan-Meier method. Results: 406 patients who had undergone RFA were included in the study. The median survival for OS and DFS were 120 and 43.6 months. During follow-up, 39, 312, and 55 patients developed LTP, intrahepatic distant metastasis, and extrahepatic metastatic recurrence, respectively. The independent risk factors for each type were as follows: WBC > 5.55*109/L was an independent risk factor for local recurrence. Multiple tumours, extrahepatic metastases, and AFP > 200 ng/ml were used for intrahepatic metastases. Age (P = 0.030), recurrence pattern (P < 0.001) and Child-Pugh class B (P = 0.015) were independent predictors of OS. Conclusions: According to our classification, each pattern of recurrence has different risk factors for recurrence, OS, and DFS.

A study on predicting the length of hospital stay for Chinese patients with ischemic stroke based on the XGBoost algorithm.

BACKGROUND: The incidence of stroke is a challenge in China, as stroke imposes a heavy burden on families, national health services, social services, and the economy. The length of hospital stay (LOS) is an essential indicator of utilization of medical services and is usually used to assess the efficiency of hospital management and patient quality of care. This study established a prediction model based on a machine learning algorithm to predict ischemic stroke patients' LOS. METHODS: A total of 18,195 ischemic stroke patients' electronic medical records and 28 attributes were extracted from electronic medical records in a large comprehensive hospital in China. The prediction of LOS was regarded as a multi classification problem, and LOS was divided into three categories: 1-7 days, 8-14 days and more than 14 days. After preprocessing the data and feature selection, the XGBoost algorithm was used to build a machine learning model. Ten fold cross-validation was used for model validation. The accuracy (ACC), recall rate (RE) and F1 measure were used to evaluate the performance of the prediction model of LOS of ischemic stroke patients. Finally, the XGBoost algorithm was used to identify and remove irrelevant features by ranking all attributes based on feature importance. RESULTS: Compared with the naive Bayesian algorithm, logistic region algorithm, decision tree classifier algorithm and ADaBoost classifier algorithm, the XGBoot algorithm has higher ACC, RE and F1 measure. The average ACC, RE and F1 measure were 0.89, 0.89 and 0.89 under the 10-fold cross-validation. According to the analysis of the importance of features, the LOS of ischemic stroke patients was affected by demographic characteristics, past medical history, admission examination features, and operation characteristics. Finally, the features in terms of hemiplegia aphasia, MRS, NIHSS, TIA, Operation or not, coma index etc. were found to be the top features in importance in predicting the LOS of ischemic stroke patients. CONCLUSIONS: The XGBoost algorithm was an appropriate machine learning method for predicting the LOS of patients with ischemic stroke. Based on the prediction model, an intelligent medical management prediction system could be developed to predict the LOS based on ischemic stroke patients' electronic medical records.

Multifunctional Droplets Formed by Interfacially Self-Assembled Fluorinated Magnetic Nanoparticles for Biocompatible Single Cell Culture and Magnet-Driven Manipulation.

The ability to encapsulate and manipulate droplets with a picoliter volume of samples and reagents shows great potential for practical applications in chemistry, biology, and materials science. Magnetic control is a promising approach for droplet manipulation due to its ability for wireless control and its ease of implementation. However, it is challenged by the poor biocompatibility of magnetic materials in aqueous droplets. Moreover, current droplet technology is problematic because of the molecule leakage between droplets. In the paper, we propose multifunctional droplets with the surface coated by a layer of fluorinated magnetic nanoparticles for magnetically actuated droplet manipulation. Multifunctional droplets show excellent biocompatibility for cell culture, nonleakage of molecules, and high response to a magnetic field. We developed a strategy of coating the F-MNP@SiO2 on the outer surface of droplets instead of adding magnetic material into droplets to enable droplets with a highly magnetic response. The encapsulated bacteria and cells in droplets did not need to directly contact with the magnetic materials at the outer surface, showing high biocompatibility with living cells. These droplets can be precisely manipulated based on magnet distance, the time duration of the magnetic field, the droplet size, and the MNP composition, which well match with theoretical analysis. The precise magnetically actuated droplet manipulation shows great potential for accurate and sensitive droplet-based bioassays like single cell analysis.

Danlou tablet inhibits high-glucose-induced cardiomyocyte apoptosis via the miR-34a-SIRT1 axis.

Diabetic cardiomyopathy (DCM) is highly prevalent and increases the risk of heart failure and sudden death. Therefore, proper and effective treatments for DCM are in urgent demand. Danlou tablet (Dan) is reported to confer protective effects on several heart diseases. However, to our knowledge, whether Dan provides protection against DCM is unclear. In this study, we explored the effect of Dan on DCM with the in vitro DCM model using AC16 cardiomyocytes. We found that Dan treatment significantly reduced cardiomyocyte apoptosis and oxidative stress in high-glucose (HG)-treated cardiomyocytes, as evidenced by decreased Annexin V-FITC+ cardiomyocytes, intracellular reactive oxygen species (ROS) levels, Bax/Bcl2 ratio, and cleaved-Caspase3/Caspase3 ratio. Interestingly, Dan treatment caused a decreased level of microRNA-34a (miR-34a), which could enhance cardiomyocyte apoptosis. Furthermore, miR-34a mimic blocked Dan's effect in apoptosis prevention. Finally, we observed that the miR-34a mimic effectively decreased the level of sirtuin 1 (SIRT1), while the miR-34a inhibitor increased the level of SIRT1. And downregulation of SIRT1 effectively reversed the effect of miR-34a inhibitor on cardiomyocyte apoptosis. Taken together, our study showed that Dan prevented HG-induced cardiomyocyte apoptosis through downregulating miR-34a and upregulating SIRT1. Our study has provided experimental support for the potential use of Dan in treating DCM. Further detailed study of Dan and the underlying mechanisms may shed light on the prevention and treatment of DCM.

The effect of real-ambient PM2.5 exposure on the lung and gut microbiomes and the regulation of Nrf2.

The influence of air pollution on human health has sparked widespread concerns across the world. Previously, we found that exposure to ambient fine particulate matter (PM2.5) in our "real-ambient exposure" system can result in reduced lung function. However, the mechanism of organ-specific toxicity is still not fully elucidated. The balance of the microbiome contributes to maintaining lung and gut health, but the changes in the microbiome under PM2.5 exposure are not fully understood. Recently, crosstalk between nuclear factor E2-related factor 2 (Nrf2) and the microbiome was reported. However, it is unclear whether Nrf2 affects the lung and gut microbiomes under PM2.5 exposure. In this study, wild-type (WT) and Nrf2-/- (KO) mice were exposed to filtered air (FA) and real ambient PM2.5 (PM) in the " real-ambient exposure" system to examine changes in the lung and gut microbiomes. Here, our data suggested microbiome dysbiosis in lung and gut of KO mice under PM2.5 exposure, and Nrf2 ameliorated the microbiome disorder. Our study demonstrated the detrimental impacts of PM2.5 on the lung and gut microbiome by inhaled exposure to air pollution and supported the protective role of Nrf2 in maintaining microbiome homeostasis under PM2.5 exposure.

A novel method for assessing cardiac function in patients with coronary heart disease based on wrist pulse analysis.

BACKGROUND: The timely assessment of B-type natriuretic peptide (BNP) marking chronic heart failure risk in patients with coronary heart disease (CHD) helps to reduce patients' mortality. OBJECTIVE: To evaluate the potential of wrist pulse signals for use in the cardiac monitoring of patients with CHD. METHODS: A total of 419 patients with CHD were assigned to Group 1 (BNP < 95 pg/mL, n = 249), 2 (95 < BNP < 221 pg/mL, n = 85), and 3 (BNP > 221 pg/mL, n = 85) according to BNP levels. Wrist pulse signals were measured noninvasively. Both the time-domain method and multiscale entropy (MSE) method were used to extract pulse features. Decision tree (DT) and random forest (RF) algorithms were employed to construct models for classifying three groups, and the models' performance metrics were compared. RESULTS: The pulse features of the three groups differed significantly, suggesting different pathological states of the cardiovascular system in patients with CHD. Moreover, the RF models outperformed the DT models in performance metrics. Furthermore, the optimal RF model was that based on a dataset comprising both time-domain and MSE features, achieving accuracy, average precision, average recall, and average F1-score of 90.900%, 91.048%, 90.900%, and 90.897%, respectively. CONCLUSIONS: The wrist pulse detection technology employed in this study is useful for assessing the cardiac function of patients with CHD.

Transcranial low-intensity ultrasound stimulation for treating central nervous system disorders: A promising therapeutic application.

Transcranial ultrasound stimulation is a neurostimulation technique that has gradually attracted the attention of researchers, especially as a potential therapy for neurological disorders, because of its high spatial resolution, its good penetration depth, and its non-invasiveness. Ultrasound can be categorized as high-intensity and low-intensity based on the intensity of its acoustic wave. High-intensity ultrasound can be used for thermal ablation by taking advantage of its high-energy characteristics. Low-intensity ultrasound, which produces low energy, can be used as a means to regulate the nervous system. The present review describes the current status of research on low-intensity transcranial ultrasound stimulation (LITUS) in the treatment of neurological disorders, such as epilepsy, essential tremor, depression, Parkinson's disease (PD), and Alzheimer's disease (AD). This review summarizes preclinical and clinical studies using LITUS to treat the aforementioned neurological disorders and discusses their underlying mechanisms.

[Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial].

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION: Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Weakly acidic microenvironment of the wound bed boosting the efficacy of acidic fibroblast growth factor to promote skin regeneration.

The pH value within the wound microenvironment influences indirectly and directly all biochemical reactions taking place in the process of skin wound healing. Currently, it is generally believed that a low pH value, such as it is found on normal skin, is favorable for wound regeneration, while some investigations have shown that in fact alkaline microenvironments are required for some healing processes. The role of growth factors in promoting wound healing requires a specific microenvironment. In wound microenvironments of different pH, growth factors with different isoelectric points may have different effects. To explore whether the application of FGF with different isoelectric points in wounds with different pH values interferes with the healing process to different degrees, GelMA hydrogels with different pH values were prepared to maintain the wounds microenvironment with the same pH values, in which aFGF and bFGF were loaded as well. The results show that GelMA hydrogels of different pH values maintained the same pH of the wound microenvironment sustainably on the 4th day. Moreover, aFGF and bFGF promoted skin wound healing to varying degrees in different pH wound microenvironments. In particular, aFGF significantly promoted wound re-epithelialization in a weak acidic microenvironment, while bFGF promoted collagen synthesis and deposition in the early stage of weak acid wounds. In addition, aFGF plays a superior role in inhibiting inflammation in weak acidic wounds.

Towards an experimental system for the examination of protein mannosylation in Actinobacteria.

The actinobacterial species Cellulomonas fimi ATCC484 has long been known to secrete mannose-containing proteins, but a closer examination of glycoproteins associated with the cell has never been reported. Using ConA lectin chromatography and mass spectrometry we have surveyed the cell associated glycoproteome from C. fimi and collected detailed information on the glycosylation sites of 19 cell-associated glycoproteins. In addition, we have expressed a previously known C. fimi secreted cellulase, Celf_3184, (formerly CenA), a putative peptide prolyl-isomerase, Celf_2022, and a penicillin binding protein, Celf_0189, in the mannosylation capable host, Corynebacterium glutamicum. We found that the glycosylation machinery in C. glutamicum was able to use the recombinant C. fimi proteins as substrates and that the glycosylation matched closely that found in the native proteins when expressed in C. fimi. We are pursuing this observation as a prelude to dissecting the biosynthetic machinery and biological consequences of this protein mannosylation.

Development of the "hidden" multi-target-directed ligands by AChE/BuChE for the treatment of Alzheimer's disease.

Accumulation of evidences suggested that excessive amounts of AChE and BuChE in the brain of AD patients at the different stage of AD, which could hydrolyze ACh and accelerated Aß aggregation. To develop new "hidden" multifunctional agents through AChE/BuChE would be a promising strategy to treat AD. To this end, firstly, a series of chalcone derivatives with chelating property was designed and synthesized. The in vitro results showed that compound 3f indicated significant selective MAO-B inhibitory activity (IC50 = 0.67 µM) and remarkable anti-inflammatory property. It also significantly inhibited self-induced Aß1-42 aggregation and showed remarkable neuroprotective effects on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f was a selective metal chelator and could inhibit Cu2+-induced Aß1-42 aggregation. Based on this, the carbamate fragment was introduced to compound 3f to obtain carbamate derivatives. The biological activity results exhibited that compound 4b showed good BBB permeability, good AChE inhibitory potency (IC50 = 5.3 µM), moderate BuChE inhibitory potency (IC50 = 12.4 µM), significant MAO-B inhibitory potency, anti-inflammation potency on LPS-induced BV-2 cells and neuroprotective effects on Aß25-35-induced PC12 cell injury. Compared with 3f, compound 4b did not show obvious chelation property. Significantly, compound 4b could be activated by AChE/BuChE following inhibition of AChE/BuChE to liberate an active multifunctional chelator 3f, which was consistent with our original intention. More importantly, compounds 3f and 4b presented favorable ADME properties and good stability in artificial gastrointestinal fluid, blood plasma and rat liver microsomes. The in vivo results suggested that compound 4b (0.0195 µg/mL) could significantly improve dyskinesia and reaction capacity of the AlCl3-induced zebrafish AD model by increasing the level of ACh. Together our data suggest that compound 4b was a promising "hidden" multifunctional agent by AChE/BuChE, and this strategy deserved further development for the treatment of AD.

Transcranial magnetic stimulation cortical oscillations and improve cognition in obstructive sleep apnea patients.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive tool to improve cognition. Relevant clinical studies are mainly focused on neurological and psychiatric diseases. However, cognition decline and psychiatric disorders are popular in obstructive sleep apnea (OSA) patients. We aimed to investigate the effect of TMS over the left dorsolateral prefrontal cortex (DLPFC) on cognition test performance and to compare the changes in quantitative electroencephalogram (EEG) before and after stimulation for OSA. METHODS: This study recruited 42 OSA patients diagnosed with polysomnography according to American Academy of Sleep Medicine guidelines. TMS (intermittent theta-burst stimulation paradigm; 2 s on, 8 s off, 600 pulses*3, intermittent 15 min) was performed on the DLPFC. Cambridge Automated Neuropsychological Test Battery was used to assess cognitive performance. EEG oscillations were computed via power spectral density with MATLAB software. RESULTS: Real-TMS group displayed a significant improvement in visual memory, sustain attention performance, as well as the outcome of working memory. However, the executive function of latency was changed in both groups. Furthermore, TMS resulted in a significant increase in the relative power spectral density of the theta band and beta band in the parietal, temporal, and anterior regions, respectively. CONCLUSIONS: In summary, our findings indicate that TMS can safely modulate cortical oscillations and improve cognition in OSA patients. In the future, TMS can be utilized as an alternative treatment option to improve cognition in OSA patients.

High Performance Inverted RbCsFAPbI3 Perovskite Solar Cells Based on Interface Engineering and Defects Passivation.

Lead halide-based perovskites solar cells (PSCs) are intriguing candidates for photovoltaic technology due to their high efficiency, low cost, and simple fabrication processes. Currently, PSCs with efficiencies of >25% are mainly based on methylammonium (MA)-free and bromide (Br) free, formamide lead iodide (FAPbI3)-based perovskites, because MA is thermally instable due to its volatile nature and Br incorporation will induce blue shift in the absorption spectrum. Therefore, MA-free, Br-free formamidine-based perovskites are drawing huge research attention in recent years. The hole transporting layer (HTL) is crucial in fabricating highly efficient and stable inverted p-i-n structured PSCs by enhancing charge extraction, lowering interfacial recombination, and altering band alignment, etc. Here, this work employs a NiOx /PTAA bi-layer HTL combined with GuHCl (guanidinium hydrochloride) additive engineering and PEAI (phenylethylammonium iodide) passivation strategy to optimize the charge carrier dynamics and tune defects chemistry in the MA-free, Br-free RbCsFAPbI3-based perovskite absorber, which boosts the device efficiency up to 22.78%. Additionally, the device retains 95% of its initial performance under continuous 1 sun equivalent LED light illumination at 45 °C for up to 500 h.

A therapeutic regimen of ceftazidime-avibactam for a critical patient receiving prolonged intermittent renal replacement therapy.

The present report firstly described a critically ill patient receiving a dosing regimen of ceftazidime-avibactam (CAZ-AVI) (1.875g q24h) to eliminate multidrug-resistant Klebsiella pneumoniae and a scheduled time for prolonged intermittent renal replacement therapy (PIRRT) every 48h (6h-session beginning 12h after the previous dosage on hemodialysis day). This dosing regimen for CAZ-AVI and a scheduled time for PIRRT allowed pharmacodynamic parameters of ceftazidime and avibactam to have little difference on hemodialysis and non-hemodialysis days so that we can maintain a relatively stable drug concentration. Our report highlighted not only the importance of dosing regimens in patients with PIRRT but also the significance of hemodialysis time points during the dosing interval. The innovative therapeutic plan proved to be suitable for patients infected with Klebsiella pneumoniae when on PIRRT according to the trough plasma concentrations of ceftazidime and avibactam which were maintained above the minimum inhibitory concentration during the dosing interval.

The biological functions of maternal-derived extracellular vesicles during pregnancy and lactation and its impact on offspring health.

During pregnancy and lactation, mothers provide not only nutrients, but also many bioactive components for their offspring through placenta and breast milk, which are essential for offspring development. Extracellular vesicles (EVs) are nanovesicles containing a variety of biologically active molecules and participate in the intercellular communication. In the past decade, an increasing number of studies have reported that maternal-derived EVs play a crucial role in offspring growth, development, and immune system establishment. Hereby, we summarized the characteristics of EVs; biological functions of maternal-derived EVs during pregnancy, including implantation, decidualization, placentation, embryo development and birth of offspring; biological function of breast milk-derived EVs (BMEs) on infant oral and intestinal diseases, immune system, neurodevelopment, and metabolism. In summary, emerging studies have revealed that maternal-derived EVs play a pivotal role in offspring health. As such, maternal-derived EVs may be used as promising biomarkers in offspring disease diagnosis and treatment. However, existing research on maternal-derived EVs and offspring health is largely limited to animal and cellular studies. Evidence from human studies is needed.

Preoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma.

BACKGROUND AND AIMS: In recent years, more and more inflammatory indicators have been studied to predict the long-term survival of patients with ampullary carcinoma (AC) after radical resection, but these prognostic indicators are still controversial. Therefore, based on previous inflammation scores, this study established a novel, easily accessible, more feasible and more predictive prognostic marker [Carbohydrate antigen199 to gamma-glutamyltransferase ratio (CA19-9/GGT)] to better assess the prognostic significance in AC patients undergoing radical resection. METHODS: Overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox regression model. Correlation between CA19-9/GGT and clinicopathological variables were analyzed by Chi-squared test, Fisher ' s exact test, independent sample t test and Mann-Whitney U test. The performance of prognostic indexes is compared by the consistency index (C-index). The prediction accuracy of nomogram is further confirmed by calibration curve and decision curve analysis (DCA). RESULTS: CA19-9/GGT was an independent risk factor affecting OS [P = 0.001, hazard ratio (HR) 2.459, 95% confidence intervals (CI) 1.450-4.167] and RFS (P = 0.002, HR 2.333, 95% CI 1.371-3.971) in multivariate analysis. The optimal cut-off value of CA19-9/GGT was 0.14. In CA19-9/GGT correlation analysis, high risk group (> 0.14) was significantly associated with poor prognosis. The predictive performance of CA19-9/GGT (OS: C-index = 0.753, RFS: C-index = 0.745) was confirmed to be superior to other prognostic indicators according to the C-index. Compared with the simple AJCC staging system, the Nomogram prediction model (OS: C-index = 0.787, RFS: C-index = 0.795) established by the combination of CA19-9/GGT and AJCC 8th TNM staging system has higher prediction accuracy. CONCLUSIONS: CA19-9/GGT was an independent prognostic indicator after radical resection of AC. Incorporating CA19-9/GGT into the AJCC TNM staging system optimized the prediction accuracy of the TNM staging system, and further verified the predictive value of CA19-9/GGT.