Synthetic and theoretical investigation on the one-pot halogenation of ß-amino alcohols and nucleophilic ring opening of aziridinium ions.

Aziridinium ions are useful reactive intermediates for the synthesis of enantiomerically enriched building blocks. However, N,N-dialkyl aziridinium ions are relatively underutilized in the synthesis of optically active molecules as compared to other three-membered ring cogeners, aziridines and epoxides. The characterization of both optically active aziridinium ions and secondary ß-halo amines as the precursor molecules of aziridinium ions has been scarcely reported and is often unclear. In this paper, we report for the first time the preparation and experimental and theoretical characterization of optically active aziridinium ions and secondary ß-halo amines. Optically active secondary N,N-substituted ß-halo amines were efficiently synthesized from N,N-substituted alaninol via formation and ring opening at the more hindered carbon of aziridinium ions by halides. Optically active ß-halo amines and aziridinium ions were characterized by NMR and computational analyses. The structure of an optically active ß-chloro amine was confirmed via X-ray crystallographic analysis. The aziridinium ions derived from N,N-dibenzyl alaniol remained stable only for several hours, which was long enough for analyses of NMR and optical activity. The stereospecific ring opening of aziridinium ions by halides was computationally studied using DFT and highly-accurate DLPNO-CCSD(T) methods. The highly regioselective and stereoselective ring opening of aziridinium ions was applied for efficient one-pot conversion of ß-alaninols to enantiomerically enriched ß-amino alcohols, ß-amino nitriles, and vicinal diamine derivatives.

Novel (64)Cu-radiolabeled bile acid conjugates for targeted PET imaging.

A promising bifunctional chelate (N-NE3TA) was conjugated to bile acids, cholic acid (CA), deoxycholic acid (DCA), and chenodeoxycholic acid (CDCA) as tumor targeting vectors. Bile acid conjugates of N-NE3TA (CA-N-NE3TA, DCA-N-NE3TA, and CDCA-N-NE3TA) were comparatively evaluated for complexation with (64)Cu, an imaging probe for positron emission tomography (PET). N-NE3TA-bile acid conjugates were evaluated for radiolabeling kinetics with (64)Cu, and the corresponding (64)Cu-radiolabeled conjugates were screened for complex stability in human serum and EDTA solution. The NE3TA-bile acid conjugates instantly bound to (64)Cu with excellent radiolabeling efficiency at room temperature. All NE3TA-bile acid conjugates radiolabeled with (64)Cu remained inert in human serum for 2days without releasing a considerable amount of the radioactivity. The (64)Cu-radiolabeled complexes were further challenged by EDTA in a 100-fold molar excess. Bile acid-N-NE3TA conjugates radiolabeled with (64)Cu were quite stable with a minimal transfer of (64)Cu to EDTA at 4h time point. The in vitro data indicate that the bile acid-N-NE3TA conjugates deserve further biological evaluation for (64)Cu-based targeted PET imaging applications.

Synthesis and comparative biological evaluation of bifunctional ligands for radiotherapy applications of (90)Y and (177)Lu.

Zevalin® is an antibody-drug conjugate radiolabeled with a cytotoxic radioisotope ((90)Y) that was approved for radioimmunotherapy (RIT) of B-cell non-Hodgkin's lymphoma. A bifunctional ligand that displays favorable complexation kinetics and in vivo stability is required for effective RIT. New bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA for potential use in RIT were efficiently prepared by the synthetic route based on regiospecific ring opening of aziridinium ions with prealkylated triaza- or tetraaza-backboned macrocycles. The new bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA along with the known bimodal ligands 3p-C-NETA and 3p-C-DEPA were comparatively evaluated for potential use in targeted radiotherapy using ß-emitting radionuclides (90)Y and (177)Lu. The bifunctional ligands were evaluated for radiolabeling kinetics with (90)Y and (177)Lu, and the corresponding (90)Y or (177)Lu-radiolabeled complexes were studied for in vitro stability in human serum and in vivo biodistribution in mice. The results of the comparative complexation kinetic and stability studies indicate that size of macrocyclic cavity, ligand denticity, and bimodality of donor groups have a substantial impact on complexation of the bifunctional ligands with the radiolanthanides. The new promising bifunctional chelates in the DE4TA and NE3TA series were rapid in binding (90)Y and (177)Lu, and the corresponding (90)Y- and (177)Lu-radiolabeled complexes remained inert in human serum or in mice. The in vitro and in vivo data show that 3p-C-DE4TA and 3p-C-NE3TA are promising bifunctional ligands for targeted radiotherapy applications of (90)Y and (177)Lu.

Lateral arm microvascular free tissue reconstruction of a large neck keloid.

Keloid scars pose a surgical challenge in the region of the head and neck. We present a rare case of a large infected and recurrent neck keloid that failed multiple prior reconstructive attempts. Ultimately, the tissue was resected and the surgical bed was repaired with a lateral arm microvascular free flap. This repair emphasizes the need for adequate coverage of the defect while maintaining neck mobility, ease of swallowing, and cosmesis. This is the second report in the literature of free tissue transfer as treatment for a large keloid scar, and the first to show the feasibility of early post operative low dose irradiation of the surgical bed.

Maternal empowerment, feeding knowledge, and infant nutrition: Evidence from rural China.

Background: Maternal empowerment - the capacity to make decisions within households - is linked to better child feeding and nutritional outcomes, but few studies have considered the mediating role of caregiver knowledge. Further, existing literature centres primarily on the husband-wife dyad while overlooking grandmothers as important childcare decision-makers. Methods: We collected primary data through household surveys in 2019 and 2021 from 1190 households with infants zero to six months living in rural western China. We identified the primary and secondary caregivers for each infant and assessed their feeding knowledge and practices, as well as infant nutritional status. We constructed a maternal empowerment index using a seven-item decision-making questionnaire and examined the relationship between maternal empowerment in childcare and household decisions, caregivers' feeding knowledge, and infant feeding practices and nutritional outcomes. Results: Mothers had significantly higher levels of feeding knowledge than secondary caregivers (most were grandmothers, 72.7%), with average knowledge scores of 5.4 vs. 4.1, respectively, out of 9. Mothers and secondary caregivers with higher levels of feeding knowledge had significantly higher exclusive breastfeeding rates by 13-15 percentage points (P < 0.01) and 11-13 percentage points (P < 0.01), respectively. The knowledge of secondary caregivers was even more strongly associated with not feeding formula (15 percentage points, P < 0.01). Mothers empowered to make childcare decisions were more likely to exclusively breastfeed (12-13 percentage points, P < 0.01), less likely to formula feed (9-10 percentage points, P < 0.05), and more likely to have children with higher Z-scores for length-for-age (0.32-0.33, P < 0.01) and weight-for-age (0.24-0.25, P < 0.05). Effects remained after controlling for maternal feeding knowledge. Conclusions: While mothers' and grandmothers' feeding knowledge was both important for optimal infant feeding, grandmothers' knowledge was particularly critical for practicing exclusive breastfeeding. Given the disparity in feeding knowledge between the two caregivers, our study further shows that mothers empowered in childcare decision-making were more likely to exclusively breastfeed their infants. This implies that some mothers with adequate knowledge may not practice optimal feeding because of lower decision-making power. Overall, our study highlights the role of secondary caregivers (grandmothers) in infant care and suggests that future child nutritional interventions may benefit from involving secondary caregivers (grandmothers). Registration: Parent trial registration: ISRCTN16800789.

Gap in protective behaviors between Han and minority ethnicities during COVID-19 pandemic in rural western China: A decomposition analysis.

Understanding the ethnic gap in protective behavior and its explanatory factors is a promising step for reducing pandemic-induced disparities. However, no studies have endeavored to identify the factors contributing to a gap in protective behaviors between Han and minority ethnicities during COVID-19 pandemic in rural China. We aimed to analyze the gap in protective behaviors between Han and minority residents in rural China. We conducted cross-sectional studies in multi-ethnic rural China in 2020. A total of 1640 participants from Han and minority groups were invited to participate. The decomposition method was applied to analyze the gap in protective behaviors and its associated factors between the Han and minority groups. Participants in the Han group had a higher protective behavioral score (9.26 ± 1.20) than the minority group (8.97 ± 1.50), yielding a significant gap in protective behaviors between Han and minority ethnicities of 0.29. Socio-demographic characteristics, health status, the degree of knowledge held about COVID-19, and psychological responses to COVID-19 explained 79.3 % (0.23/0.29) of the behavioral gap between the Han and minority groups. The difference in household asset levels was the largest explained contributor to the behavioral gap (52.17 %) (0.12/0.23), followed by fear felt for COVID-19 (-21.74 %) (-0.05/0.23). Differences in educational attainment, degree of knowledge held about COVID-19, and self-efficacy in response to COVID-19 each explained 17.4 % (0.04/0.23) of the behavioral gap. In conclusion, Han group show greater protective behaviors than minority ethnic groups. To drive better protective behavior in the most vulnerable communities, targeted, group-specific COVID-19 preventative messages deployed in public health communication strategies is suggested to enhance individual confidence in coping with the pandemic while creating a healthy amount of fear for public health crisis.

Foreign body impaction of the vertebral canal.

Foreign body impactions in the aerodigestive tract are common, but have the potential for serious complications. A foreign body may disrupt the mucosal lining and migrate regionally thereby risking impingement or injury to critical neurovascular structures in the cervical region. It is important to recognize potential complications that may arise from luminal compromise. In such cases, expeditious surgical treatment is warranted.

What Links Chronic Kidney Disease and Ischemic Cardiomyopathy? A Comprehensive Bioinformatic Analysis Utilizing Bulk and Single-Cell RNA Sequencing Data with Machine Learning.

Chronic kidney disease (CKD) emerges as a substantial contributor to various cardiovascular disorders, including ischemic cardiomyopathy (ICM). However, the underlying molecular mechanisms linking CKD and ICM remain elusive. Our study aims to unravel these connections by integrating publicly available bulk and single-cell RNA sequencing (scRNA-seq) data. Expression profiles from two ICM datasets obtained from heart tissue and one CKD with Peripheral Blood Mononuclear Cell (CKD-PBMC) dataset were collected. We initiated by identifying shared differentially expressed genes (DEGs) between ICM and CKD. Subsequent functional enrichment analysis shed light on the mechanisms connecting CKD to ICM. Machine learning algorithms enabled the identification of 13 candidate genes, including AGRN, COL16A1, COL1A2, FAP, FRZB, GPX3, ITIH5, NFASC, PTN, SLC38A1, STARD7, THBS2, and VPS35. Their expression patterns in ICM were investigated via scRNA-seq data analysis. Notably, most of them were enriched in fibroblasts. COL16A1, COL1A2, PTN, and FAP were enriched in scar-formation fibroblasts, while GPX3 and THBS2 showed enrichment in angiogenesis fibroblasts. A Gaussian naïve Bayes model was developed for diagnosing CKD-related ICM, bolstered by SHapley Additive exPlanations interpretability and validated internally and externally. In conclusion, our investigation unveils the extracellular matrix's role in CKD and ICM interplay, identifies 13 candidate genes, and showcases their expression patterns in ICM. We also constructed a diagnostic model using 13 gene features and presented an innovative approach for managing CKD-related ICM through serum-based diagnostic strategies.

Increased plasma expression of a disintegrin and metalloproteinase with thrombospondin motifs like 4 in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can result in right heart failure. We aimed to evaluate the plasma protein levels of a disintegrin and metalloproteinase with thrombospondin motifs like 4 (ADAMTSL4) and its relationship with IPAH and CTEPH. Plasma ADAMTSL4 protein levels were measured using proteomics analysis in eight patients with IPAH and nine healthy controls. ADAMTSL4 levels in pulmonary tissues were assessed using bioinformatics tools. Protein expression of ADAMTSL4 in platelet-derived growth factor (PDGF)-BB-treated primary rat pulmonary arterial smooth muscle cells (PASMCs) was detected by Western blot. Plasma ADAMTSL4 concentrations were measured in 45 patients (15 with IPAH and 30 with CTEPH) using enzyme-linked immunosorbent assay (ELISA). Correlation between ADAMTSL4 levels and clinical parameters was evaluated. In patients with IPAH, the plasma levels of ADAMTSL4 protein were significantly higher than those in healthy controls (flod change [FC] 1.85, p < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, p < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup (p < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 ± 0.73 ng/mL, p < 0.01) and CTEPH (4.22 ± 0.66 ng/mL, p < 0.01) were higher than in healthy controls (3.01 ± 0.46 ng/mL). Plasma ADAMATL4 protein levels had a cutoff value of 3.55 ng/mL based on the receiver operator characteristic curve and were positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.305, p < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP.

Effect of the mHealth-supported Healthy Future programme delivered by community health workers on maternal and child health in rural China: study protocol for a cluster randomised controlled trial.

INTRODUCTION: Millions of young rural children in China still suffer from poor health and malnutrition, partly due to a lack of knowledge about optimal perinatal and child care among rural mothers and caregivers. Meanwhile, there is an urgent need to improve maternal mental health in rural communities. Comprehensive home visiting programmes delivered by community health workers (CHWs) can bridge the caregiver knowledge gap and improve child health and maternal well-being in low-resource settings, but the effectiveness of this approach is unknown in rural China. Additionally, grandmothers play important roles in child care and family decision-making in rural China, suggesting the importance of engaging multiple caregivers in interventions. The Healthy Future programme seeks to improve child health and maternal well-being by developing a staged-based curriculum that CHWs deliver to mothers and caregivers of young children through home visits with the assistance of a tablet-based mHealth system. This protocol describes the design and evaluation plan for this programme. METHODS AND ANALYSIS: We designed a cluster-randomised controlled trial among 119 rural townships in four nationally designated poverty counties in Southwestern China. We will compare the outcomes between three arms: one standard arm with only primary caregivers participating in the intervention, one encouragement arm engaging primary and secondary caregivers and one control arm with no intervention. Families with pregnant women or infants under 6 months of age are invited to enrol in the 12-month study. Primary outcomes include children's haemoglobin levels, exclusive breastfeeding rates and dietary diversity in complementary feeding. Secondary outcomes include a combination of health, behavioural and intermediate outcomes. ETHICS AND DISSEMINATION: Ethical approval has been provided by Stanford University, Sichuan University and the University of Nevada, Reno. Trial findings will be disseminated through national and international peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: ISRCTN16800789.

In-Hospital Formula Feeding Hindered Exclusive Breastfeeding: Breastfeeding Self-Efficacy as a Mediating Factor.

Breastfeeding self-efficacy (BSE), defined as a mother's confidence in her ability to breastfeed, has been confirmed to predict the uptake of exclusive breastfeeding (EBF). Early experiences during the birth hospital stay, especially in-hospital formula feeding (IHFF), can impact both EBF and maternal breastfeeding confidence. Therefore, our objective was to examine the association between IHFF and EBF outcomes and investigate whether this association is influenced by BSE. The study included 778 infants from a larger cohort study conducted in 2021, with a one-year follow-up in rural areas of Sichuan Province, China. We used a causal mediation analysis to estimate the total effect (TE), natural direct (NDE), and nature indirect effects (NIE) using the paramed command in Stata. Causal mediation analyses revealed that IHFF was negatively associated with EBF (TE odds ratio = 0.47; 95% CI, 0.29 to 0.76); 28% of this association was mediated by BSE. In the subgroup analysis, there were no significant differences in the effects between parity subgroups, as well as between infant delivery subgroups. Our study found that IHFF hindered later EBF and that BSE mediated this association. Limiting the occurrence of in-hospital formula feeding or improving maternal breastfeeding self-efficacy is likely to improve exclusive breastfeeding outcomes.

Synthesis and preclinical evaluation of bifunctional ligands for improved chelation chemistry of 90Y and 177Lu for targeted radioimmunotherapy.

We report a practical and high-yield synthesis of a bimodal bifunctional ligand 3p-C-NETA-NCS containing the isothiocyanate group for conjugation to a tumor targeting antibody. 3p-C-NETA-NCS was conjugated to a tumor-targeting antibody, trastuzumab, and the corresponding 3p-C-NETA-trastuzumab conjugate was evaluated and compared to trastuzumab conjugates of the known bifunctional ligands C-DOTA, C-DTPA, and 3p-C-DEPA for radiolabeling kinetics with (90)Y and (177)Lu. 3p-C-NETA-trastuzumab conjugate exhibited extremely rapid complexation kinetics with (90)Y and (177)Lu. (90)Y-3p-C-NETA-trastuzumab and (177)Lu-3p-C-NETA-trastuzumab conjugates were stable in human serum for 2 weeks. A pilot biodistribution study was conducted to evaluate in vivo stability and tumor targeting of (177)Lu-radiolabeled trastuzumab conjugate using nude mice bearing ZR-75-1 human breast cancer. (177)Lu-3p-C-NETA-trastuzumab conjugate displayed low radioactivity level at blood (1.6%), low organ uptake (<2.2%), and high tumor-to-blood ratio (6.4) at 120 h. 3p-C-NETA possesses favorable in vitro and in vivo profiles and is an excellent bifunctional chelator that can be used for targeted RIT applications using (90)Y and (177)Lu and has the potential to replace DOTA and DTPA analogues in current clinical use.

Hub Genes Identification, Small Molecule Compounds Prediction for Atrial Fibrillation and Diagnostic Model Construction Based on XGBoost Algorithm.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and engenders significant global health care burden. The underlying mechanisms of AF is remained to be revealed and current treatment options for AF have limitations. Besides, a detection system can help identify those at risk of developing AF and will enable personalized management. Materials and Methods: In this study, we utilized the robust rank aggregation method to integrate six AF microarray datasets from the Gene Expression Omnibus database, and identified a set of differentially expressed genes between patients with AF and controls. Potential compounds were identified by mining the Connectivity Map database. Functional modules and closely-interacted clusters were identified using weighted gene co-expression network analysis and protein-protein interaction network, respectively. The overlapped hub genes were further filtered. Subsequent analyses were performed to analyze the function, biological features, and regulatory networks. Moreover, a reliable Machine Learning-based diagnostic model was constructed and visualized to clarify the diagnostic features of these genes. Results: A total of 156 upregulated and 34 downregulated genes were identified, some of which had not been previously investigated. We showed that mitogen-activated protein kinase and epidermal growth factor receptor inhibitors were likely to mitigate AF based on Connectivity Map analysis. Four genes, including CXCL12, LTBP1, LOXL1, and IGFBP3, were identified as hub genes. CXCL12 was shown to play an important role in regulation of local inflammatory response and immune cell infiltration. Regulation of CXCL12 expression in AF was analyzed by constructing a transcription factor-miRNA-mRNA network. The Machine Learning-based diagnostic model generated in this study showed good efficacy and reliability. Conclusion: Key genes involving in the pathogenesis of AF and potential therapeutic compounds for AF were identified. The biological features of CXCL12 in AF were investigated using integrative bioinformatics tools. The results suggested that CXCL12 might be a biomarker that could be used for distinguishing subsets of AF, and indicated that CXCL12 might be an important intermediate in the development of AF. A reliable Machine Learning-based diagnostic model was constructed. Our work improved understanding of the mechanisms of AF predisposition and progression, and identified potential therapeutic avenues for treatment of AF.

Explaining the declining utilization of village clinics in rural China over time: A decomposition approach.

With a goal of improving health system quality and efficiency, reforms of China's health system over the past decade have sought to strengthen primary healthcare in lower-level clinics and health centers. Despite these wide-ranging reforms and initiatives, population-based studies have documented dramatic declines in patients' use of primary care facilities during this period. In this paper, we explore the determinants of this trend in China's rural areas using detailed longitudinal data following a nationally-representative sample of rural households and village clinics from 2011 to 2018. We estimate that between 2011 and 2018, the probability that individuals sought care at village clinics when ill dropped by 44%. At the same time, the utilization of outpatient services in county hospitals increased by 56% and patient self-treatment increased by 20%. Detailed Kitagawa-Oaxaca-Blinder decompositions suggest four primary drivers of this trend: the shifting burden of disease in rural areas, changes in how patients choose to seek care given different disease conditions, declining drug inventory in village clinics, and the decreasing importance of remoteness as a determinant of healthcare seeking behavior. Our results highlight the deteriorating role of village clinics in the rural healthcare system and the increasing importance of self-treatment and higher-tier primary care services.

Structural Determinants of Child Health in Rural China: The Challenge of Creating Health Equity.

Over the past two decades, the literature has shown a clear gradient between child health and wealth. The same health-wealth gradient is also observed among children in China, with a large gap in health between rural and urban children. However, there are still unanswered questions about the main causes of China's rural-urban child health inequality. This paper aims to review the major factors that have led to the relatively poor levels of health among China's rural children. In addition to the direct income effect on children's health, children in rural areas face disadvantages compared with their urban counterparts from the beginning of life: Prenatal care and infant health outcomes are worse in rural areas; rural caregivers have poor health outcomes and lack knowledge and support to provide adequate nurturing care to young children; there are large disparities in access to quality health care between rural and urban areas; and rural families are more likely to lack access to clean water and sanitation. In order to inform policies that improve health outcomes for the poor, there is a critical need for research that identifies the causal drivers of health outcomes among children. Strengthening the pediatric training and workforce in rural areas is essential to delivering quality health care for rural children. Other potential interventions include addressing the health needs of mothers and grandparent caregivers, improving parenting knowledge and nurturing care, improving access to clean water and sanitation for remote families, and most importantly, targeting poverty itself.

Chemerin Regulates the Proliferation and Migration of Pulmonary Arterial Smooth Muscle Cells via the ERK1/2 Signaling Pathway.

Pulmonary arterial hypertension (PAH) is an incurable disease with high mortality. Chemerin has been found to be associated with pulmonary hypertension (PH). However, the specific role of chemerin in mediating PH development remains unclear. This study aimed to elucidate the regulatory effects and the underlying mechanism of chemerin on PH and to investigate the expression levels of chemerin protein in plasma in PAH patients. In vivo, two animal models of PH were established in rats by monocrotaline (MCT) injection and hypoxia. We found that the expression levels of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), were significantly upregulated in the lungs of PH rats. Primary cultured pulmonary arterial smooth muscle cells [(PASMCs) (isolated from pulmonary arteries of normal healthy rats)] were exposed to hypoxia or treated with recombinant human chemerin, we found that CMKLR1 expression was upregulated in PASMCs in response to hypoxia or chemerin stimulation, whereas the exogenous chemerin significantly promoted the migration and proliferation of PASMCs. Notably, the regulatory effects of chemerin on PASMCs were blunted by PD98059 (a selective ERK1/2 inhibitor). Using enzyme linked immunosorbent assay (ELISA), we found that the protein level of chemerin was also markedly increased in plasma from idiopathic pulmonary arterial hypertension (IPAH) patients compared to that from healthy controls. Moreover, the diagnostic value of chemerin expression in IPAH patients was determined through receiver operating characteristic (ROC) curve analysis and the result revealed that area under ROC curve (AUC) for plasma chemerin was 0.949. Taken together, these results suggest that chemerin exacerbates PH progression by promoting the proliferation and migration of PASMCs via the ERK1/2 signaling pathway, and chemerin is associated with pulmonary hypertension.

The know-do gap in quality of health for chronic non-communicable diseases in rural China.

Proper management of non-communicable diseases (NCDs) is a severe challenge to China's rural health system. This study investigates what influences the poor medical treatment of NCDs (diabetes and angina) by evaluating the "know-do gap" between provider knowledge and practice. To determine whether low levels of provider knowledge low quality of patient care is the primary constraint on the quality of NCDs diagnosis and treatment in rural China. Providers from Village Clinics (VC) and Township Health Centers (THC), and Standardized Patients (SP) were selected by a multi-stage random sampling method. Clinical vignettes were administered to 306 providers from 103 VCs and 50 THCs in rural Sichuan Province. SPs presented diabetes symptoms completed 97 interactions with providers in 46 VCs and 51 THCs; SPs presented angina symptoms completed 100 interactions with providers in 50 VCs and 50 THCs. Process quality, diagnosis quality, and treatment quality were assessed against national standards for diabetes and angina. Two-tailed T-tests and tests of proportions for continuous outcomes and tests of proportions for binary dependent variables were used to compare vignette and SP results. Differences between vignette and SP data calculated the know-do gap. Regression analyses were used to examine the providers/facility characteristics and knowledge/practice associations. THC providers demonstrated significantly more knowledge in vignettes and better practices in SP visits than VC providers. However, levels of knowledge were low overall: 48.2% of THC providers and 28.2% of VC providers properly diagnosed type 2 diabetes, while 23.8% of THC providers and 14.7% of VC providers properly diagnosed angina. With SPs, 2.1% of THC providers and 6.8% of VC providers correctly diagnosed type 2 diabetes; 25.5% of THC providers and 12.8% of VC providers correctly diagnosed angina. There were significant know-do gaps in diagnosis process quality, diagnosis quality, and treatment quality for diabetes (p < 0.01), and in diagnosis process quality (p < 0.05) and treatment quality for angina (p < 0.01). Providers in rural China display low levels of knowledge when treating diabetes and angina. Despite low knowledge, evidence of the know-do gap indicates that low-quality healthcare is the primary constraint on the quality of NCD diagnosis and treatment in rural China. Our research findings provide a new perspective for the evaluation of the medical quality and a technical basis for the development of new standardized cases in the future.

Efficient bifunctional decadentate ligand 3p-C-DEPA for targeted α-radioimmunotherapy applications.

A new bifunctional ligand 3p-C-DEPA was synthesized and evaluated for use in targeted α-radioimmunotherapy. 3p-C-DEPA was efficiently prepared via regiospecific ring opening of an aziridinium ion and conjugated with trastuzumab. The 3p-C-DEPA-trastuzumab conjugate was extremely rapid in binding (205/6)Bi, and the corresponding (205/6)Bi-3p-C-DEPA-trastuzumab complex was stable in human serum. Biodistribution studies were performed to evaluate in vivo stability and tumor targeting of (205/6)Bi-3p-C-DEPA-trastuzumab conjugate in tumor bearing athymic mice. (205/6)Bi-3p-C-DEPA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low organ uptake and high tumor uptake. The results of the in vitro and in vivo studies indicate that 3p-C-DEPA is a promising chelator for radioimmunotherapy of (212)Bi and (213)Bi.

Multidisciplinary Team Managements and Clinical Outcomes in Patients With Pulmonary Arterial Hypertension During the Perinatal Period.

Background: Pulmonary arterial hypertension (PAH) patients with pregnancy have high maternal mortality. This study aimed to provide clinical evidence with multidisciplinary team (MDT) management and to evaluate the clinical outcomes in PAH patients during the perinatal period. Methods: We conducted a retrospective evaluation of PAH patients pregnant at the First Affiliated Hospital of Chongqing Medical University between May 2015 and May 2021. Results: Twenty-two patients (24 pregnancies) were included in this study and received MDT management, and 21 pregnancies chose to continue pregnancy with cesarean section. Nine (37.5%) were first-time pregnancies at 27.78 ± 6.16 years old, and 15 (62.5%) were multiple pregnancies at 30.73 ± 3.71 years old. The average gestational week at hospitalization and delivery were 29.38 ± 8.63 weeks and 32.37 ± 7.20 weeks, individually. Twenty-one (87.5%) pregnancies received single or combined pulmonary vasodilators. The maternal survival rate of PAH patients reached 91.7%. Fifteen (62.5%) pregnancies were complicated with severe adverse events. Patients with complicated adverse events showed lower percutaneous oxygen saturation (SpO2), lower albumin, lower fibrinogen, higher pulmonary artery systolic pressure (PASP), higher blood pressure, longer activated partial thromboplastin time, and longer coagulation time. Fourteen (66.7%) pregnancies with cesarean sections were prematurely delivered and 85.7% newborns who survived after the operation remained alive. Conclusion: The survival rate of parturients with PAH was improved in relation to MDT and pulmonary vasodilator therapy during the perinatal period compared with previous studies. SpO2, albumin, PASP, blood pressure, and coagulation function should be monitored carefully in PAH patients during pregnancy.

Pyridine-containing octadentate ligand NE3TA-PY for formation of neutral complex with 177Lu(III) and 90Y(III) for radiopharmaceutical applications: Synthesis, DFT calculation, radiolabeling, and in vitro complex stability.

Targeted radionuclide therapy is a developing therapeutic modality for cancer and employs a cytotoxic radionuclide bound to a chelating agent and a bioactive molecule with high binding affinity for a specific biomarker in tumors. An optimal chelator is one of the critical components to control therapeutic efficacy and toxicity of targeted radionuclide therapy. We designed a new octadentate ligand NE3TA-PY (7-[2-[(carboxymethyl)(2-pyridylmethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) for ß-particle-emitting 177Lu and 90Y with targeted radionuclide therapy applications. The pyridine-containing polyaminocarboxylate ligand was proposed to form a neutral complex with Lu(III) and Y(III). The new chelator NE3TA-PY was synthesized and experimentally and theorectically studied for complexation with 177Lu(III) and 90Y(III). DFT-optimized structures of Y(III)-NE3TA-PY and Lu(III)-NE3TA-PY complexes were predicted. NE3TA-PY displayed excellent radiolabeling efficiency with both 177Lu and 90Y. The new chelator (NE3TA-PY) bound to 177Lu was more stable in human serum and better tolerated when challenged by EDTA than 90Y-labeled NE3TA-PY. Our findings suggest that the new chelator (NE3TA-PY) produced excellent Lu-177 radiolabeling and in vitro complex stability profiles.