Enhanced recovery after surgery (ERAS) in sacral tumour surgery and comprehensive description of a multidisciplinary program: a prospective study in a specialized hospital in China.

PURPOSE: There were fewer data to guide the application of enhanced recovery after surgery (ERAS) theory into sacral tumour surgery. In the present study, we were aiming to describe a multidisciplinary program of ERAS and evaluate the availability in sacral tumour surgery. METHODS: This was a prospective study of patients with sacral tumour between March 2021 and September 2021 at a single centre. We proposed a multidisciplinary program of ERAS for pre-admission, preoperative, intraoperative, postoperative, and post-discharge clinical care which positively influenced outcomes of patients with sacral tumour. All patients were prospectively assigned into two groups, ERAS group in which patients received ERAS protocols (n = 63), No-ERAS group in which patients had conventional clinical pathways (n = 62). Patient data were collected which included demographics, preoperative preparation, detailed information of surgical procedure, 60-day reoperation rate, 60-day readmission, postoperative length of stay (PLOS), time to first ambulation and flatus after surgery, time to removal of last drainage tube, and visual analogue scale (VAS) score at first ambulation and discharge. Complications referred to ones that occurred within 60 days after surgery. The above parameters were compared between ERAS group and No-ERAS group. RESULTS: Time to first ambulation after surgery in ERAS group (mean 20.9 h) was significantly shorter than that in No-ERAS group (mean 104.3 ho). Meanwhile, time to first flatus after surgery in ERAS group (mean 26.7 h) was also significantly shorter than that in No-ERAS group (mean 37.3 h). Patients in ERAS group had statistically shorter PLOS (10.7 days) as compared to that in No-ERAS group (13.8 days). In ERAS group, 19 of 63 patients (30.2%) were discharged within seven days after surgery as compared to seven of 62 patients (11.3%) in No-ERAS group. VAS score at first ambulation in ERAS group was not obviously higher than that in No-ERAS group though the time of first ambulation in ERAS group was statistically earlier than one in No-ERAS group. Furthermore, VAS score at discharge in ERAS group was significantly lower than that in No-ERAS group. The rate of postoperative incision necrosis was 6.3% (4/63) in ERAS group and 8.1% (5/62) in No-ERAS group and all of these nine patients underwent reoperation before discharge. The difference was not statistically significant in the wound complication of incision necrosis and 60-day reoperation rate. Only one readmission occurred in No-ERAS group due to the surgical site infection and also there was no significant difference of 60-day readmission rate between these two groups. Furthermore, there was no statistical difference of complications of femoral artery thrombosis and rectal rupture between ERAS group and No-ERAS group. CONCLUSIONS: Our proposed ERAS pathway for sacral tumour surgery and early walking facilitate safe and prompt discharge. ERAS protocols of sacral tumour surgery could decrease PLOS without significantly increasing postoperative complications, 60-day readmission rate and 60-day reoperation rate. The application of ERAS pathway in the field of sacral tumour surgery should have personalized feature with regard to resection type.

Lifestyle is associated with thyroid function in subclinical hypothyroidism: a cross-sectional study.

BACKGROUND: Few studies have focused on the association between lifestyle and subclinical hypothyroidism (SCH). The purpose of this study was to investigate the association between lifestyle and thyroid function in SCH. METHODS: This study was a part of a community-based and cross-sectional study, the Epidemiological Survey of Thyroid Diseases in Fujian Province, China. A total of 159 participants with SCH (81 males and 78 females) and 159 euthyroid (87 males and 72 females) participants without any missing data were included in the analysis. General information and lifestyle information including sleep, exercise, diet and smoking habits of the participants was collected by questionnaire and Pittsburgh sleep quality index scale (PSQI) was collected. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urine iodine concentration (UIC) were tested. Thyroid homeostasis parameter thyroid' s secretory capacity (SPINA-GT), Jostel's TSH index (TSHI), thyrotroph T4 sensitivity index (TTSI) were calculated. Logistic regression and multiple linear regression were performed to assess associations. RESULTS: Compared with euthyroid subjects, patients with SCH were more likely to have poor overall sleep quality (15.1 vs.25.8 %, P = 0.018) and l less likely to stay up late on weekdays (54.7 vs. 23.9 % P < 0.001). In SCH group, exercise was the influencing factor of TSH (ß= -0.224, P = 0.004), thyroid secretory capacity (ß = 0.244, P = 0.006) and thyrotropin resistance (ß = 0.206, P = 0.009). Iodine excess was the influencing factor of thyroid secretory capacity (ß = 0.209, P = 0.001) and pituitary thyroid stimulating function (ß = 0.167, P = 0.034). Smoking was the influencing factor of pituitary thyroid stimulating function (ß = 0.161, P = 0.040). Staying up late on weekends was the influencing factor of thyroid secretory capacity (ß = 0.151, P = 0.047). After adjusting for possible confounders, logistic regression showed that those with poor overall sleep quality assessed by PSQI and iodine excess had an increased risk of SCH (OR 2.159, 95 %CI 1.186-3.928, P = 0.012 and OR 2.119, 95 %CI 1.008-4.456, P = 0.048, respectively). CONCLUSIONS: Lifestyle including sleep, smoking, diet and exercise was closely related to thyroid function especially thyroid homeostasis in SCH.

Accumulative occlusion time correlates with postoperative pulmonary complications in patients undergoing pelvic and sacrum tumor resection assisted by abdominal aortic balloon occlusion: a retrospective cohort study.

BACKGROUND: Postoperative pulmonary complications (PPCs) seems to be high in patients undergoing pelvic and sacrum tumor resection assisted by abdominal aortic balloon occlusion. We hypothesized that the accumulative occlusion time (AOT) of the abdominal aortic balloon may be predictive of PPCs. The objective of the study was to identify the influence of AOT on PPCs. METHODS: Retrospectively analyzed perioperative factors of 584 patients who underwent pelvic and sacrum tumor resection assisted by abdominal aortic balloon occlusion in our hospital from January 1, 2016 to December 31, 2018. PPCs including suspected pulmonary infection, atelectasis, pulmonary edema, pleural effusion, respiratory failure were clinically diagnosed. Perioperative parameters among patients with and without PPCs were compared. A receiver operating characteristic (ROC) analysis was conducted to evaluate the discriminative power of AOT with regard to PPCs. A multivariate logistic-regression model was finally established to identify independent risk factors for PPCs. RESULTS: The incidence of PPCs was 15.6% (91 patients). The median AOT in PPCs group was significantly higher than that in non-PPCs group (P <  0.001). The hospital stay was significantly prolonged in PPCs group (P <  0.001). The ROC analysis showed an AOT of 119 min as the threshold value at which the joint sensitivity (88.60%) and specificity (31.87%) was maximal. Finally, AOT ≥ 119 min (P = 0.046; odds ratio (OR) = 2.074), age (P < 0.001; OR = 1.032), ASA grade III (P = 0.015; OR = 3.264), and estimated blood loss (P = 0.022; OR = 1.235) were independent risk factors of PPCs by multivariate logistic regression analysis. CONCLUSION: The incidence of PPCs in patients undergoing the pelvic and sacrum tumor surgery assisted by abdominal aortic balloon occlusion was 15.6%. AOT ≥ 119 min was an independent predictor for PPCs. Surgeons should strive to minimize the AOT within 2 h.

Realizing the Haldane Phase with Bosons in Optical Lattices.

We analyze an experimentally realizable model of bosons in a zigzag optical lattice, showing that, by rapidly modulating the magnetic field, one can tune interaction parameters and realize an analog of the Haldane phase. We explain how quantum gas microscopy can be used to detect this phase's nonlocal string order and its topological edge states. We model the detection process. We also find that this model can display supersolid correlations, but argue that they only occur at parameter values which would be challenging to realize in an experiment.

Determination of chlorine ions in raw milk by pulsed amperometric detection in a flow injection system.

Chloride ion concentration in milk was determined by pulsed amperometric detection in a flow injection system. Results showed that the Au electrode lost 3 electrons at 1.10 V and formed chloroaurate ions (AuCl4-) by combining with chloride ions, after which AuCl4- was partly reduced to Au at 0.6 V. Based on the electrochemical process, a triple waveform with detection potential of 1.15 V, detection time of 150 ms, oxidation potential of 1.4 V, oxidation time of 550 ms, reduction potential of 0 V, and reduction time of 400 ms was applied to the Au electrode for detecting chloride ion concentration in milk. The approach is rapid and automatic and features a detection limit of 0.005 g/L. The relative standard deviation obtained by 60 repetitive injections reached 1.48% at 2 g/L of NaCl. The method developed using the Au electrode without modification was used to analyze the chloride ion concentration in raw milk without preprocessing. The method showed good agreement with potentiometric titration.

Neighborhood Environmental Health and Premature Death From Cardiovascular Disease.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in the United States and disproportionately affects racial/ethnic minority groups. Healthy neighborhood conditions are associated with increased uptake of health behaviors that reduce CVD risk, but minority neighborhoods often have poor food access and poor walkability. This study tested the community-driven hypothesis that poor access to food at the neighborhood level and poor neighborhood walkability are associated with racial disparities in premature deaths from CVD. METHODS: We examined the relationship between neighborhood-level food access and walkability on premature CVD mortality rates at the census tract level for the city of Atlanta using multivariable logistic regression models. We produced maps to illustrate premature CVD mortality, food access, and walkability by census tract for the city. RESULTS: We found significant racial differences in premature CVD mortality rates and geographic disparities in food access and walkability among census tracts in Atlanta. Improved food access and walkability were associated with reduced overall premature CVD mortality in unadjusted models, but this association did not persist in models adjusted for census tract population composition and poverty. Census tracts with high concentrations of minority populations had higher levels of poor food access, poor walkability, and premature CVD mortality. CONCLUSION: This study highlights disparities in premature CVD mortality and neighborhood food access and walkability at the census tract level in the city of Atlanta. Improving food access may have differential effects for subpopulations living in the same area. These results can be used to calibrate neighborhood-level interventions, and they highlight the need to examine race-specific health outcomes.

Adherence to combination antiretroviral treatment and clinical outcomes in a Medicaid sample of older HIV-infected adults.

The adherence threshold for combination antiretroviral therapy (cART) has historically been set at 95% or greater. We examined whether different levels of cART adherence (≥95% [optimal adherence], 90-94%, 80-89%, and <80%) were associated with different clinical outcomes (emergency department visits [ED visits] and duration of hospital admission) in a sample of older (50-64 years) persons living with HIV (PLWH). Medicaid data from 29 US states (n = 5177) were used for this study. cART adherence was measured and data regarding relevant covariates, such as race, sex, age, urbanicity, and comorbidity were obtained. Descriptive statistics were conducted to characterize study participants. We conducted univariate and multivariable regression analyses to evaluate the association between cART adherence and ED visits and duration of hospital admission while adjusting for covariates (race, sex, age, urbanicity, and comorbidity). Approximately 32% of all participants (n = 5177) reported optimal cART adherence (≥95%). After adjusting for covariates, only participants who reported <80% adherence were more likely to have an ED visit (adjusted odds ratio = 1.34, 95% CI = 1.08-1.48, p < .0001) and a longer duration of hospital admission (regression coefficient = 1.24, 95% CI = 0.53-1.96, p = .0007) when compared to participants who reported ≥95% adherence. There were no significant differences in likelihood of having an ED visit and longer duration of hospital admission between participants who reported ≥95% adherence and participants who reported 90-94% adherence and 80-89% adherence. Significant differences by covariates were observed. Adverse clinical outcomes were associated with low cART adherence (<80%) among older PLWH, though they did not differ between optimal and moderate cART adherence (90-94% and 80-89%). Although optimal cART adherence is an important goal, clinical outcomes in older PLWH may not differ between moderate and optimal cART adherence.

Individual and county level predictors of asthma related emergency department visits among children on Medicaid: A multilevel approach.

OBJECTIVE: Disparities in asthma outcomes are well documented in the United States. Interventions to promote equity in asthma outcomes could target factors at the individual and community levels. The objective of this analysis was to understand the effect of individual (race, gender, age, and preventive inhaler use) and county-level factors (demographic, socioeconomic, health care, air-quality) on asthma emergency department (ED) visits among Medicaid-enrolled children. This was a retrospective cohort study of Medicaid-enrolled children with asthma in 29 states in 2009. Multilevel regression models of asthma ED visits were constructed utilizing individual-level variables (race, gender, age, and preventive inhaler use) from the Medicaid enrollment file and county-level variables reflecting population and health system characteristics from the Area Resource File (ARF). County-level measures of air quality were obtained from Environmental Protection Agency (EPA) data. RESULTS: The primary modifiable risk factor at the individual level was found to be the ratio of long-term controller medications to total asthma medications. County-level factors accounted for roughly 6% of the variance in the asthma ED visit risk. Increasing county-level racial segregation (OR=1.04, 95% CI=1.01-1.08) was associated with increasing risk of asthma ED visits. Greater supply of pulmonary physicians at the county level (OR=0.81, 95% CI=0.68-0.97) was associated with a reduction in risk of asthma ED visits. CONCLUSIONS: At the patient care level, proper use of controller medications is the factor most amenable to intervention. There is also a societal imperative to address negative social determinants, such as residential segregation.

Impact of Comorbidities Among Medicaid Enrollees With Chronic Obstructive Pulmonary Disease, United States, 2009.

INTRODUCTION: Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD). Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs. We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders. METHODS: We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients. We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index. Elixhauser comorbidity counts were clustered from 0 to 7 or more. We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence. RESULTS: Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased. ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black). Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders. Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD. Female sex was associated with COPD-related and non-COPD-related ED visits. CONCLUSION: Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD. Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team.

Correlates of Combination Antiretroviral Adherence Among Recently Diagnosed Older HIV-Infected Adults Between 50 and 64 years.

Optimal adherence to combination antiretroviral therapy is essential to the health of older people living with HIV (PLWH), however, the literature on adherence and aging is limited. Using Medicaid data from 29 states (N = 5177), we explored correlates of optimal adherence among older PLWH. The prevalence of optimal adherence was low (32 %) in this study. Males were more adherent than females (APR = 1.11, 95 % CI 1.02-1.21, P = 0.0127); persons with three or more co-morbidities (APR = 0.67, 95 % CI 0.60-0.74, P < 0.001), two co-morbidities (APR = 0.86, 95 % CI 0.75-0.98, P = 0.0319) and one co-morbidity (APR = 0.82, 95 % CI 0.73-0.92, P = 0.0008) were less adherent than those without any co-morbidity; and residents of rural areas (APR = 0.90, 95 % CI 0.63-0.98, P = 0.0385) and small metropolitan areas (APR = 0.82, 95 % CI 0.72-0.94, P = 0.0032) were less adherent than residents of large metropolitan areas. There were no racial differences in optimal adherence. Targeted interventions that provide adherence support, case management, and peer navigation services may be of benefit in achieving optimal adherence in this population.

The association between combination antiretroviral adherence and AIDS-defining conditions at HIV diagnosis.

Combination antiretroviral therapy (cART) has changed the clinical course of HIV. AIDS-defining conditions (ADC) are suggestive of severe or advanced disease and are a leading cause of HIV-related hospitalizations and death among people living with HIV/AIDS (PLWHA) in the USA. Optimal adherence to cART can mitigate the impact of ADC and disease severity on the health and survivability of PLWHA. The objective of this study was to evaluate the association between ADC at HIV diagnosis and optimal adherence among PLWHA. Using data from the 2008 and 2009 Medicaid data from 29 states, we identified individuals, between 18 and 49 years, recently infected with HIV and with a cART prescription. Frequencies and descriptive statistics were conducted to characterize sample. Univariate and multivariable Poisson regression analyses were employed to evaluate the association optimal cART adherence (defined as ≥ 95% study days covered by cART) and ADC at HIV diagnosis (≥1 ADC) were assessed. Approximately 17% of respondents with ADC at HIV diagnosis reported optimal cART adherence. After adjusting for covariates, respondents with an ADC at HIV diagnosis were less likely to report optimal cART adherence (adjusted prevalence ratio (APR) = 0.64, 95% confidence intervals (CI), 0.54-0.75). Among the covariates, males (APR=1.10, 95% CI, 1.02-1.19) compared to females were significantly more likely to report optimal adherence while younger respondents, 18-29 years (APR=0.67, 95% CI, 0.57-0.77), 30-39 years (APR=0.86, 95% CI, 0.79-0.95) compared to older respondents were significantly less likely to report optimal adherence. PLWHA with ADC at HIV diagnosis are at risk of suboptimal cART adherence. Multiple adherence strategies that include healthcare providers, case managers, and peer navigators should be utilized to improve cART adherence and optimize health outcomes among PLWHA with ADC at HIV diagnosis. Targeted adherence programs and services are required to address suboptimal adherence in this population.

SNX14 inhibits autophagy via the PI3K/AKT/mTOR signaling cascade in breast cancer cells.

BACKGROUND: Sorting nexin 14 (SNX14) is a member of the sorting junction protein family. Its specific roles in cancer development remain unclear. Therefore, in this study, we aimed to determine the effects and underlying mechanisms of SNX14 on autophagy of breast cancer cells to aid in the therapeutic treatment of breast cancer. METHODS: In this study, we performed in vitro experiments to determine the effect of SNX14 on breast cancer cell growth. Moreover, we used an MCF7 breast cancer tumor-bearing mouse model to confirm the effect of SNX14 on tumor cell growth in vivo. We also performed western blotting and quantitative polymerase chain reaction to identify the mechanism by which SNX14 affects breast cancer MCF7 cells. RESULTS: We found that SNX14 regulated the onset and progression of breast cancer by promoting the proliferation and inhibiting the autophagy of MCF7 breast cancer cells. In vivo experiments further confirmed that SNX14 knockdown inhibited the tumorigenicity and inhibited the growth of tumor cells in tumor tissues of nude mice. In addition, western blotting analysis revealed that SNX14 modulate the autophagy of MCF7 breast cancer cells via the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signaling pathway. CONCLUSION: Our findings indicate that SNX14 is an essential tumor-promoting factor in the development of breast cancer.

Application of Northern Goshawk Back-Propagation Artificial Neural Network in the Prediction of Monohydroxycarbazepine Concentration in Patients with Epilepsy.

INTRODUCTION: A northern goshawk back-propagation artificial neural network (NGO-BPANN) model was established to predict monohydroxycarbazepine (MHD) concentration in patients with epilepsy. METHODS: The data were collected from 108 Han Chinese patients with epilepsy on oxcarbazepine monotherapy. The results of 14 genotype variates were selected as the input layer in the first BPANN model, and the variables that had a more significant impact on the plasma concentration of MHD were retained. With demographic characteristics and clinical laboratory test results, the genotypes of SCN1A rs2298771 and SCN2A rs17183814 were used to construct the BPANN model. The BPANN model was comprehensively validated and used to predict the MHD plasma concentration of five patients with epilepsy in our hospital. RESULTS: The model demonstrated favorable fitness metrics, including a mean squared error of 0.00662, a gradient magnitude of 0.00753, an absence of validation tests amounting to zero, and a correlation coefficient of 0.980. Sex, BMI, and the genotype SCN1A rs2298771 were ranked highest by the absolute mean impact value (MIV), which is primarily associated with the concentration of MHD. The test group exhibited a range of - 20.84% to 31.03% bias between the predicted and measured values, with a correlation coefficient of 0.941 between the two. With BPANN, the MHD nadir concentration could be predicted precisely. CONCLUSION: The NGO-BPANN model exhibits exceptional predictive capability and can be a practical instrument for forecasting MHD concentration in patients with epilepsy. CLINICAL TRIAL REGISTRATION: www.chiCTR-OOC-17012141 .

Building a Hospital Pharmacist Workforce by a Diversified and Position-Oriented Learning System.

Background: The role of hospital pharmacists has shifted from primarily ensuring drug supply to providing comprehensive pharmaceutical care. To accommodate this shift, new positions are needed. The traditional training model for hospital pharmacists is no longer sufficient for the evolving demands of pharmaceutical care and these new roles. This study aimed to describe the development of a position-oriented learning system explicitly tailored for hospital pharmacists and to assess its impact on workforce development and pharmacy service. Methods: The position-oriented learning system for hospital pharmacists, aimed at enhancing training and workforce development, was evaluated based on two critical criteria: the completion rate of learning modules and the subsequent improvement in pharmaceutical care at the hospital. The completion rate assessed the engagement and effectiveness of the training content. At the same time, the improvement in pharmaceutical care evaluated practical outcomes such as percentages of patients who received pharmaceutical care and percentages of inappropriate medication orders intercepted. Results: In 2021, 218 employees participated in the learning system. The pharmacy department has identified 22 pharmacists for various positions through this system. The quantity and quality of pharmaceutical care have improved significantly. Conclusion: The position-oriented diversified learning system achieves the perfect combination of department development direction and individual career planning of employees. The learning system can significantly improve the learning efficiency of pharmacists, enhance the quality of various pharmaceutical care, and promote the development of disciplines.

The cost-effectiveness of targeted screening for congenital cytomegalovirus in newborns compared to clinical diagnosis in the US.

OBJECTIVE: Congenital cytomegalovirus (cCMV) is the leading environmental cause of hearing loss (HL) among children, affecting four in one thousand newborns. cCMV testing in the US is currently based on clinical diagnosis which does not consistently identify cCMV cases and precludes early intervention to prevent and reduce the severity of HL. We estimated the cost-effectiveness of targeted newborn screening and cCMV testing among newborns compared to clinical diagnosis. METHODS: We use a decision-analytic model to estimate the costs of preventing HL progression, of additional cases of severe HL, of identifying a case of HL one year earlier, and of identifying an additional case of cCMV, through targeted screening and cCMV testing for infants failing two newborn hearing screens with follow-up to age five. We also estimate the costs of nationwide implementation of a newborn screening and testing program. Model pathways were based on best practices for screening, testing, and treatment. Probabilities were drawn from the published literature; costs were estimated based on Medicare reimbursement rates. Probabilistic and scenario analyses were conducted to determine the robustness of results. RESULTS: Targeted testing and cCMV screening, compared to standard of care, cost an additional $2.96 (±2.26) per infant screened and identified 0.00038 (±0.00022) cases of HL, 3.8 in 10000 children, at a cost of $8197 (±4217) per case of HL identified. Implementing targeted screening for all children in the US was estimated to cost $193,229. CONCLUSIONS: Although cases numbers are small, our model shows that targeted newborn screening and cCMV testing reduced cases of HL progression. Adoption of newborn targeted screening as standard of care should be considered given it may prevent disability at very low cost.

Research progress of E3 ubiquitin ligase regulating biological behavior of human placental trophoblast cells.

E3 ubiquitin ligases are important components of the ubiquitin protease system. This family includes many proteins, which can catalyze the ubiquitination of a variety of protein substrates and promote the degradation of them by the proteasome system. Recent studies have shown that E3 ubiquitin ligase plays a key role in the process of fetal development and placental formation. It affects the biological behavior of placental trophoblast cells, leading to a series of pregnancy complications that threaten mothers and babies greatly. This review focuses on the regulation, target and mechanism of E3 ubiquitin ligase on the biological behavior of human placental trophoblast cells.

A 3D "sandwich" co-culture system with vascular niche supports mouse embryo development from E3.5 to E7.5 in vitro.

BACKGROUND: Various methods for ex utero culture systems have been explored. However, limitations remain regarding the in vitro culture platforms used before implanting mouse embryos and the normal development of mouse blastocysts in vitro. Furthermore, vascular niche support during mouse embryo development from embryonic day (E) 3.5 to E7.5 is unknown in vitro. METHODS: This study established a three-dimensional (3D) "sandwich" vascular niche culture system with in vitro culture medium (IVCM) using human placenta perivascular stem cells (hPPSCs) and human umbilical vein endothelial cells (hUVECs) as supportive cells (which were seeded into the bottom layer of Matrigel) to test mouse embryos from E3.5 to E7.5 in vitro. The development rates and greatest diameters of mouse embryos from E3.5 to E7.5 were quantitatively determined using SPSS software statistics. Pluripotent markers and embryo transplantation were used to monitor mouse embryo quality and function in vivo. RESULTS: Embryos in the IVCM + Cells (hPPSCs + hUVECs) group showed higher development rates and greater diameters at each stage than those in the IVCM group. Embryos in the IVCM + Cells group cultured to E5.5 morphologically resembled natural egg cylinders and expressed specific embryonic cell markers, including Oct4 and Nanog. These features were similar to those of embryos developed in vivo. After transplantation, the embryos were re-implanted in the internal uterus and continued to develop to a particular stage. CONCLUSIONS: The 3D in vitro culture system enabled embryo development from E3.5 to E7.5, and the vascularization microenvironment constructed by Matrigel, hPPSCs, and hUVECs significantly promoted the development of implanted embryos. This system allowed us to further study the physical and molecular mechanisms of embryo implantation in vitro.

Unraveling the Plasma Protein Corona by Ultrasonic Cavitation Augments Active-Transporting of Liposome in Solid Tumor.

Ligand/receptor-mediated targeted drug delivery has been widely recognized as a promising strategy for improving the clinical efficacy of nanomedicines but is attenuated by the binding of plasma protein on the surface of nanoparticles to form a protein corona. Here, it is shown that ultrasonic cavitation can be used to unravel surface plasma coronas on liposomal nanoparticles through ultrasound (US)-induced liposomal reassembly. To demonstrate the feasibility and effectiveness of the method, transcytosis-targeting-peptide-decorated reconfigurable liposomes (LPGLs) loaded with gemcitabine (GEM) and perfluoropentane (PFP) are developed for cancer-targeted therapy. In the blood circulation, the targeting peptides are deactivated by the plasma corona and lose their targeting capability. Once they reach tumor blood vessels, US irradiation induces transformation of the LPGLs from nanodrops into microbubbles via liquid-gas phase transition and decorticate the surface corona by reassembly of the lipid membrane. The activated liposomes regain the capability to recognize the receptors on tumor neovascularization, initiate ligand/receptor-mediated transcytosis, achieve efficient tumor accumulation and penetration, and lead to potent antitumor activity in multiple tumor models of patient-derived tumor xenografts. This study presents an effective strategy to tackle the fluid biological barriers of the protein corona and develop transcytosis-targeting liposomes for active tumor transport and efficient cancer therapy.

An interpretable ensemble learning model facilitates early risk stratification of ischemic stroke in intensive care unit: Development and external validation of ICU-ISPM.

Ischemic stroke (IS) is a common and severe condition that requires intensive care unit (ICU) admission, with high mortality and variable prognosis. Accurate and reliable predictive tools that enable early risk stratification can facilitate interventions to improve patient outcomes; however, such tools are currently lacking. In this study, we developed and validated novel ensemble learning models based on soft voting and stacking methods to predict in-hospital mortality from IS in the ICU using two public databases: MIMIC-IV and eICU-CRD. Additionally, we identified the key predictors of mortality and developed a user-friendly online prediction tool for clinical use. The soft voting ensemble model, named ICU-ISPM, achieved an AUROC of 0.861 (95% CI: 0.829-0.892) and 0.844 (95% CI: 0.819-0.869) in the internal and external test cohorts, respectively. It significantly outperformed the APACHE scoring system and was more robust than individual models. ICU-ISPM obtained the highest performance compared to other models in similar studies. Using the SHAP method, the model was interpretable, revealing that GCS score, age, and intubation were the most important predictors of mortality. This model also provided a risk stratification system that can effectively distinguish between low-, medium-, and high-risk patients. Therefore, the ICU-ISPM is an accurate, reliable, interpretable, and clinically applicable tool, which is expected to assist clinicians in stratifying IS patients by the risk of mortality and rationally allocating medical resources. Based on ICU-ISPM, an online risk prediction tool was further developed, which was freely available at: http://ispm.idrblab.cn/.