Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Meta-analysis of the accuracy of the serum procalcitonin diagnostic test for osteomyelitis in children.

OBJECTIVE: This study sought to assess the sensitivity, specificity, and predictive utility of serum procalcitonin (PCT) in the diagnosis of pediatric osteomyelitis. METHODS: A systematic computer-based search was conducted for eligible literature focusing on PCT for the diagnosis of osteomyelitis in children. Records were manually screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Statistical analysis was performed using Review Manager software 5.3, Meta-disc software1.4, STATA 12.0, and R 3.4 software. RESULT: A total of 5 investigations were included. Of these, 148 children with osteomyelitis were tested for bacterial cultures in PCT. For PCT in the diagnosis of pediatric osteomyelitis, diagnostic meta-analysis revealed a pooled sensitivity and specificity of 0.58 (95% confidence interval (CI): 0.49 to 0.68) and 0.92 (95% CI: 0.90 to 0.93) respectively. The PCT had the greatest area under the curve (AUC) at 0.80 for the diagnosis of osteomyelitis in children. The Deeks' regression test for asymmetry results indicated that there was no publication bias when evaluating publication bias (P = 0.90). CONCUSION: This study provided a comprehensive review of the literature on the use of PCT in pediatric osteomyelitis diagnosis. PCT may be used as a biomarker for osteomyelitis diagnosis; however, its sensitivity was low. It still needs to be validated by a large sample study.

Caregiving risk perception characteristics and associated factors among informal caregivers of functionally dependent elderly individuals at home: a qualitative study.

BACKGROUND: This study explored risk perception characteristics and influencing factors among informal caregivers of functionally dependent elderly individuals at home, aiming to improve caregivers' caregiving risk perception and coping abilities and ultimately enhance the quality of life for these individuals. METHODS: We used purposive sampling to select 22 informal caregivers from a community in Zhengzhou City, Henan Province, China, between March and September 2023 and conducted face-to-face semi-structured in-depth interviews. The data were analyzed using Colaizzi's seven-step analysis method. RESULTS: We extracted two themes, caregiving risk perception characteristics and caregiving risk perception associated factors, and eight sub-themes, perceived risk possibility, perceived risk anticipation, perceived severity of consequences, past caregiving experiences, health literacy, psychological status, caregiving burden, and family social support. CONCLUSION: There were differences in how informal caregivers perceived the risks associated with caring for functionally dependent elderly individuals at home, which various factors could influence. It was essential to provide training that covered the knowledge and skills needed for caregiving, improve caregivers' awareness of safety risks, and establish a correct perception of caregiving risks. The government must construct and refine a comprehensive framework for caregiver respite services. Simultaneously, healthcare professionals should proactively undertake health education endeavors to augment the recognition of care safety risks among informal caregivers, thereby cultivating an accurate awareness of care risk perception.

Measuring the quality of transitional care based on elderly patients' experiences with the partners at care transitions measure: a cross-sectional survey.

BACKGROUND: The quality of transitional care is closely related to the health outcomes of patients, and understanding the status of transitional care for patients is crucial to improving the health outcomes of patients. Therefore, this study aims to investigate the quality of transitional care in elderly patients with chronic diseases and analyze its influencing factors, to provide a basis for improving transitional care services. METHODS: This is a cross-sectional study. We used the Chinese version of the Partners at Care Transitions Measure (PACT-M) to survey patients with chronic diseases aged 60 years and older who were about to be discharged from five tertiary hospitals in Henan and Shanxi provinces. We used the mean ± standard deviation to describe the quality of transitional care, t-test or one-way ANOVA, and regression analysis to explore the factors affecting the quality of transitional care for patients. RESULTS: 182 elderly patients with chronic diseases aged ≥ 60 years completed the PACT-M survey. The scores of PACT-M1 and PACT-M2 were (30.69 ± 7.87) and (25.59 ± 7.14) points, respectively. The results of the t-test or one-way ANOVA showed that the patient's marital status, ethnicity, religion, educational level, preretirement occupation, residence, household income per month, and living situation had an impact on the quality of transitional care for elderly patients with chronic diseases (P < 0.05). The results of regression analyses showed that patients' preretirement occupation, social support, and health status were the main influences on the quality of transitional care for elderly patients with chronic diseases (P < 0.05), and they explained 63.1% of the total variance. CONCLUSIONS: The quality of transitional care for older patients with chronic illnesses during the transition from hospital to home needs further improvement. Factors affecting the quality of transitional care included patients' pre-retirement occupation, social support, and health status. We can improve the hospital-community-family tertiary linkage service to provide coordinated and continuous transitional care for patients based on their occupation, health status, and social support to enhance the quality of transitional care and the patient's health.

Investigating sleep quality and sleep hygiene awareness among Chinese adults: an association and network analysis study.

PURPOSE: The relationships between sleep quality and sleep hygiene awareness in the Chinese population were unclear. We aimed to investigate the associations and related factors between sleep quality and sleep hygiene awareness in adults and to identify the most central domain for sleep quality using network analysis. METHODS: A cross-sectional survey was conducted from April 22 to May 5, 2020. Adults (18 years old or above) who had access to smartphones were invited to participate in this survey. The Pittsburg Sleep Quality Index (PSQI) and the Sleep Hygiene Awareness and Practice Scale (SHAPS) were used to evaluate the sleep quality and sleep hygiene awareness of the participants. Propensity score matching (PSM) was used as sensitivity analysis to reduce the confounding effects. Multiple logistic regression was performed to evaluate the associations. The R packages "bootnet" and "qgraph" were used to estimate the connection and calculate the network centrality indices between good and poor sleepers. RESULTS: In total, 939 respondents were included in the analysis. Of them, 48.8% (95% CI: 45.6-52.0%) were identified as poor sleepers. Participants with nervous system diseases, psychiatric diseases, and psychological problems were more likely to have poor sleep quality. The notion that using sleep medication regularly was beneficial to sleep was associated with poor sleep quality. Similarly, the notion that waking up at the same time each day disrupted sleep was also associated with poor sleep quality. The findings were consistent before and after PSM. Subjective sleep quality was the most central domain for sleep quality in good and poor sleepers. CONCLUSION: Poor sleep quality was positively associated with certain sleep hygiene notions in Chinese adults. Effective measures such as self-relief, sleep hygiene education, and cognitive behavioral treatment may have been needed to improve sleep quality, especially during the COVID-19 outbreak.

The prevalence of disability and associated factors among community adults in the baseline of CHCN-BTH Cohort Study.

BACKGROUND: Disability was a major public health problem in China. However, the prevalence of disabilities in community-dwelling adults and their relationships to chronic physical conditions were unclear. We aimed to estimate the prevalence of disabilities and associated factors among a large community-based cohort in China. METHODS: Participants who were local permanent residents aged 18 years or above and completed the disability assessments were selected from the Cohort study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Disability was assessed using five questions about impairments and activity limitations based on the International Classification of Functioning (ICF), Disability and Health. Univariate, multivariate and multilevel logistic regressions were conducted to estimate the associations between disabilities and associated factors. RESULTS: Totally, 12,871 community-dwelling adults completed the survey. Among of them, 12.9% (95% CI: 12.3%-13.5%) reported having any disability. The prevalence of any disability was significantly higher in participants who were older age, widowed, retired and smokers, had higher BMI, average monthly income < 5000 RMB, lower education level, lower physical exercise frequency and heavy physical labor. Multilevel logistic regressions showed that there were significant associations between disabilities with chronic physical conditions, especially in the vision impairment with lower back pain, and hearing impairment as well as difficulty walking without special equipment with injuries. CONCLUSIONS: Many Chinese adults suffered from disabilities. Sustained efforts should be made to develop specific population-based health promotion and prevention programs for disabilities in China. TRAIL REGISTRATION: ChiCTR1900024725 (25/07/2019).

Combined effects of ambient air pollution and PM2.5 components on renal function and the potential mediation effects of metabolic risk factors in China.

Growing evidence links long-term air pollution exposure with renal function. However, little research has been conducted on the combined effects of air pollutant mixture on renal function and multiple mediation effects of metabolic risk factors. This study enrolled 8996 adults without chronic kidney disease (CKD) at baseline from the CHCN-BTH cohort study. Three-year exposure to air pollutants [particulate matter ≤ 2.5 µm (PM2.5), PM10, PM1, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)] and PM2.5 components [black carbon (BC), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-) and organic matter (OM)] were assessed using well-validated machine learning methods. Linear mixed models were applied to investigate the associations between air pollutants and estimated glomerular filtration rate (eGFR). Quantile G-computation was used to assess the combined effects of pollutant mixtures. Causal mediation analysis and Bayesian mediation analysis were employed to estimate the mediation effects of metabolic risk factors. An interquartile range increases in BC (-0.256, 95 %CI: -0.331, -0.180) and OM (-0.603, 95 %CI: -0.810, -0.397) were significantly associated with eGFR decline; while O3 (1.151, 95 %CI: 0.813, 1.489), PM10 (0.721, 95 %CI: 0.309, 1.133), NH4+ (0.990, 95 %CI: 0.638, 1.342), and NO3- (0.610, 95 %CI: 0.405, 0.815) were associated with higher eGFR. The combined effect of the PM2.5 component mixture was found to be associated with lower eGFR (-1.147, 95 % CI: -1.456, -0.839), with OM contributing 72.4 % of the negative effect. Univariate mediation analyses showed that high-density lipoprotein (HDL) mediated 7.1 %, 6.9 %, and 6.1 % effects of O3, BC, and OM, respectively. However, these mediation effects were not significant in Bayesian mediation analysis. These findings suggest the effect of the PM2.5 component mixture on eGFR decline and the strong contribution of OM. Metabolic risk factors may not mediate the effects of air pollutants. Further study is warranted to clarify the potential mechanisms involved.

Depression among schoolchildren and adolescents aged 9-17 years during the outbreak of COVID­19 in Beijing: a cross-sectional online survey.

The COVID-19 outbreak and related confinement have highly impacted psychological health among children and adolescents. This study aimed to explore the potential risk factors for depression among primary and middle school students and provide advices for psychological interventions during the outbreaks. An online cross-sectional survey was conducted among 18 primary and middle school students via quota sampling in Beijing during March 2020. The Center for Epidemiological Studies Depression Scale (CES-D) was used to assess depression. Differences between characteristics and depression were examined by chi-square tests. Multivariate logistic regression was used to reveal the potential risk factors for depression. A total of 7377 participants were included. The proportion of depression was 29.7%. Students in rural areas, with higher school categories, in graduating grades, with poor or excessive sleep duration, and without daily exercise were associated with a higher proportion of depression. Furthermore, students with a higher knowledge performance of COVID-19 showed a lower proportion of depression (odds ratio [OR] = 0.900, 95% confidence intervals [95% CI]: 0.888-0.913). Students who worried about academic performance (OR = 1.919, 95% CI: 1.718-2.144) or COVID-19 infection (OR = 1.450, 95% CI: 1.268-1.658) exhibited a high proportion of depression. The proportion of depression among primary and middle school students was negatively associated with the knowledge score and positively associated with their worry. Our findings suggest that psychological intervention might be more necessary for students with specific characteristics.

Pyrometallurgy treatment of electroplating sludge, emulsion mud and coal ash: ZnAlFeO4 spinel separation and stabilization in calcium metasilicate glass.

Electroplating sludge was a hazardous waste comprised of heavy metals and other Fe/Al/Ca/Si impurities, and produced massively in surface treatment industry. In the past, it was commonly purified via hydrometallurgy, chlorination and reduction calcination routes, but also blended as additive in rotary kiln, to stabilize the heavy metals in geopolymer. Herein, an alternative strategy was developed to treat a real electroplating sludge for recycling magnetic Zn-rich spinel and stabilizing Zn in calcium metasilicate glass via a facile pyrometallurgy route with the blending of emulsion mud and coal ash. The sludge contained 35.6% Zn and 0.54% Cr and then was blended with 50% emulsion mud. After calcination at 1200 °C, the product was highly dispersed, whilst octahedral ZnAlFeO4 spinel with Zn content of 40.0% were formed and separated by using magnet, in accordance with the recycling efficiency of 51.2% Zn from the electroplating sludge. But after calcination at 1400 °C, the gypsum in emulsion mud was decomposed as CaO and accelerated the dissolution of Si-bearing substance as calcium metasilicate glass for covering ZnAlFeO4 spinel, resulting in the Zn leaching of 1568 mg/L. By adding 50% Si-rich coal ash in the calcination system, more calcium metasilicate glass were generated, and then the Zn concentration in the toxic leaching test was only 12.09 mg/L. During the calcination, Cr showed similar performance to Al/Fe and involved in the spinel formation. This provided a new route to recycle Zn from Zn-rich electroplating sludge and to solidify heavy metals via calcium metasilicate glass route.

Chromosome-scale genome assembly of Rhododendron molle provides insights into its evolution and terpenoid biosynthesis.

BACKGROUND: Rhododendron molle (Ericaceae) is a traditional Chinese medicine, which has been used to treat rheumatism and relieve pain since ancient times. The characteristic grayanoids of this plant have been demonstrated to be the chemical basis for the analgesic activity. Moreover, unlike morphine, these diterpenoids are non-addictive. Grayanoids mainly distribute in the leaves, flowers, roots, and fruits of R. molle, with low content. Currently the research on the biosynthesis of grayanoids is hindered, partially due to lack of the genomic information. RESULTS: In the present study, a total of 744 Mb sequences were generated and assembled into 13 chromosomes. An ancient whole-genome duplication event (Ad-ß) was discovered that occurred around 70 million years ago. Tandem and segmental gene duplications led to specific gene expansions in the terpene synthase and cytochrome P450 (CYP450) gene families. Two diterpene synthases were demonstrated to be responsible for the biosynthesis of 16α-hydroxy-ent-kaurane, the key precursor for grayanoids. Phylogenetic analysis revealed a species-specific bloom of the CYP71AU subfamily, which may involve the candidate CYP450s responsible for the biosynthesis of grayanoids. Additionally, three putative terpene biosynthetic gene clusters were found. CONCLUSIONS: We reported the first genome assembly of R. molle and investigated the molecular basis underpinning terpenoids biosynthesis. Our work provides a foundation for elucidating the complete biosynthetic pathway of grayanoids and studying the terpenoids diversity in R. molle.

TIPS plus sequential systemic therapy of advanced HCC patients with tumour thrombus-related symptomatic portal hypertension.

OBJECTIVES: Portal vein tumour thrombus (PVTT)-related symptomatic portal hypertension (SPH) leads to a poor prognosis in hepatocellular carcinoma (HCC) patients. A transjugular intrahepatic portosystemic shunt (TIPS) can effectively relieve SPH but its effect remains unclear in PVTT-related SPH. This study aimed to evaluate the clinical value of the TIPS procedure combined with sequential systemic therapy in advanced HCC patients with PVTT-related SPH. METHODS: After 1:1 propensity score matching (PSM), this retrospective study analysed 42 patients who underwent TIPS placement plus sequential systemic therapy (group A) and 42 patients who received only symptomatic and supportive treatment (group B). The evaluated outcomes were overall survival (OS) and SPH control rate. Cox proportional hazards regression analysis was used to compare OS in the two groups. RESULTS: In group A, the technical success rate of the TIPS procedure was 95.2%, and no severe complications occurred. The rebleeding rates in group A and group B were 5.0% and 73.7%, respectively (p < 0.001), and the ascites control rates were 92.0% and 28.0%, respectively (p < 0.001). The median OS of group A was significantly better than that of group B (9.6 [95% CI: 7.1, 12.0] vs. 4.9 [95% CI: 3.9, 5.8], months, p < 0.001). Multivariable analysis showed that TIPS plus sequential systemic therapy (hazard ratio [HR] = 5.799; 95% CI: 3.177, 10.585; p < 0.001) was an independent prognostic factor related to OS. Additionally, PVTT degree (I+II) (p = 0.008), AFP ≤ 400 ng/ml (p = 0.003), and Child-Pugh class A (p = 0.046) were significant predictors of OS. CONCLUSION: TIPS plus sequential systemic therapy is safe and feasible for treating advanced HCC with tumour thrombus-related SPH. KEY POINTS: • Portal vein tumour thrombus (PVTT) is common in advanced hepatocellular carcinoma (HCC) and transforms compensated portal hypertension into symptomatic portal hypertension (SPH). • HCC patients with PVTT-related SPH have a very poor prognosis, and there are no effective treatments recommended by the guidelines. • Therefore, a treatment strategy that utilises a transjugular intrahepatic portosystemic shunt (TIPS) to manage SPH combined with sequential systemic therapy in advanced HCC patients is explored in this study for its feasibility and clinical value. This research can fill the gap in current research data to provide clinically meaningful treatment options.

Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness.

OBJECTIVES: To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. METHODS: This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA (n = 52) or continued TACE (n = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. RESULTS: Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. CONCLUSION: Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key PointThe debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation.The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment.During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.

A Systematic Implementation of Telemedicine in Singapore's COVID-19 Community Recovery Facilities.

Introduction: This article describes the experience of the Singapore Armed Forces (SAF) implementing telemedicine consultations for COVID-19-positive patients recovering within community recovery facilities (CRFs) in a semi-inpatient setting. Materials and Methods: The SAF adopted a systematic approach to telemedicine implementation and scaling up, with Phase 1 being the deployment of medical teams operating on-site clinics daily at six CRFs and telemedicine only provided for after-hours medical consultations on an ad hoc basis. Subsequently in Phase 2, most clinical consultations in the CRFs were conducted virtually. Results: Phases 1 and 2 recorded 1,902 and 449 clinical consultations, respectively. The mean number of clinical encounters was 33 per 1,000 occupants per day in Phase 1, and 12 per 1,000 occupants per day in Phase 2 (p < 0.001). Acute respiratory illness (52.3% in Phase 1 and 46.7% in Phase 2) was the most common reason for consultations. With full telemedicine in Phase 2, there was reduction in the mean number of clinical encounters per 1,000 occupants per day (p = 0.001), lower man-hours in personal protective equipment (PPE) (p < 0.001), and rise in escalation of care (p < 0.001) but without adverse events reported. Conclusions: Telemedicine for patients was safe, improved medical manpower efficiency, and reduced man-hours in PPE. The increased escalation of care in Phase 2 due to the lack of physical examination capabilities was to be expected to ensure patients' safety. Overall, it is recommended that for stable and mild medical conditions, telemedicine is a viable, safe, and efficient health care delivery tool in crisis situations similar to COVID-19.

Comparison between surgery and thermal ablation for adrenal metastases: a retrospective study.

PURPOSE: To retrospectively compare the efficacy and safety of surgical resection (SR) and thermal ablation for the treatment of adrenal metastases. METHODS: From January 2008 to December 2018, 133 patients with adrenal metastases who underwent SR (n = 76) or thermal ablation (n = 57) were enrolled. The mean tumor size was 58.00 ± 10.65 mm (22-80 mm) in the SR group and 58.03 ± 12.76 mm (34-89 mm) in the thermal ablation group. Local progression-free survival (LPFS) and safety were compared between the two groups using the Kaplan-Meier method and log-rank tests. Cox proportional hazard regression models were used to evaluate the prognostic factors of LPFS. Complications, hospitalization days, and blood loss were also assessed. RESULTS: The median follow-up was 29.0 months (range, 20.4-37.6 months). No treatment-related mortality was observed. The 1-, 3- and 5-year LPFS rates were 74.0%, 62.8%, and 31.4% in the SR group and 72.8%, 68.7%, and 51.5% in the ablation group, with the median LPFS of 41.5 months (95% CI: 9.3-23.4 months) vs. 47.9 months (95% CI 20.6-75.8 months), respectively (p = 0.784). Tumor size ≥3 cm was the only significant risk factor for LPFS (p = 0.031). The ablation group was superior to the SR group with a lower major complication rate (4.1% vs. 14.5%, p = 0.03), less blood loss (1 ml vs. 100 ml, p < 0.001), and a shorter hospital stay (2 d vs. 6 d, p < 0.001). CONCLUSION: Thermal ablation provided a similar LPFS and less comorbidities than SR, indicating that it is an effective and safe treatment for adrenal metastases.

Single-nodule hepatitis B virus-associated hepatocellular carcinoma smaller than 3 cm: two phenotypes defined by cluster analysis and their association with the outcome of ablation as the first-line therapy.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a heterogeneous disease. This study aimed to identify the heterogeneity related to the prognosis of ablation in patients with single-nodule hepatitis B virus (HBV)-associated HCC ≤3 cm. METHODS: A total of 359 patients with single-nodule HBV-associated HCC ≤3 cm treated with curative thermal ablation were retrospectively investigated. Hierarchical cluster analysis was applied to obtain more homogeneous patient clusters concerning demographic and physiological characteristics. Discriminant analysis was performed to identify the relatively important variables for cluster analysis. Multiple correspondence analysis (MCA) was used to clarify the relationship between clusters and categorical variables. Overall survival (OS) was compared among clusters using the Kaplan-Meier model. RESULTS: A two-cluster model was identified. Cluster 1 (n = 85) showed a higher percentage of female and older patients, higher inflammation response (higher prognostic nutritional index [PNI] and Glasgow prognostic score [GPS]), worse liver function (higher albumin-bilirubin grade and Child-Pugh grade), and relatively poorer immune status (higher neutrophil-to-lymphocyte ratio [NLR]) than cluster 2 (n = 274). NLR and GPS were the two most influential variables for cluster analysis (p < .0001). Cluster 2 had a significantly better prognosis than cluster 1. MCA revealed a clear negative correlation between inflammation status and liver function. Compared with cluster 1, the hazard ratios for OS of cluster 2 were 0.47 and 0.52 before and after adjusting for age, respectively (p < .05). CONCLUSIONS: This study identified two sub-phenotypes of patients with single-nodule HBV-associated HCC ≤3 cm and their association with the outcome of thermal ablation alone as the first-line therapy. Key points Thermal ablation alone as the first-line therapy is not suitable for all patients with single-nodule hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) ≤3 cm. Patients with single-nodule HBV-associated HCC ≤3 cm can be identified as two sub-phenotypes associated with the outcome of thermal ablation alone as the first-line therapy, based on key preoperative clinical characteristics, especially inflammatory response and immune status. Patients with single-nodule HBV-associated HCC ≤3 cm characterized by late-onset disease, worse liver function, poorer immune status, and higher inflammatory response (with higher inflammatory response being the most important factor) are not suitable for thermal ablation alone as the first-line therapy. In contrast, patients with single-nodule HBV-associated HCC ≤3 cm characterized by early-onset disease, better liver function, lower inflammatory response, and good immune status (with lower inflammatory response being the most important factor) are particularly suitable for thermal ablation alone. Implications for patient care In the treatment of patients with single-nodule HBV-associated HCC ≤3 cm, thermal ablation alone as the first-line therapy should be carefully considered after recognizing the key clinical characteristics, among which inflammatory response and immune status are the two most important factors involved in clinical heterogeneity, and inflammatory response is closely related to the prognosis of thermal ablation alone as the first-line therapy for these patients.

Association study of fasting blood glucose and salt sensitivity of blood pressure in community population: The EpiSS study.

BACKGROUND AND AIMS: To evaluate the association between fasting blood glucose (FBG) and salt sensitivity of blood pressure (SSBP). METHODS AND RESULTS: This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. Subjects were classified into salt sensitive (SS) and salt resistant groups according to blood pressure (BP) changes during the modified Sullivan's acute oral saline load and diuresis shrinkage test. Multivariate logistic and linear regression were used to evaluate associations between FBG with SS or BP changes. A total of 2051 participants were included in the analyses with 581 (28.33%) for SS. Multiple analysis showed that for every interquartile range increase in FBG, the OR (95%CI) for SS was 1.140 (1.069, 1.215), ß (95%CI) for mean arterial pressure change (ΔMAP1), systolic and diastolic BP changes during saline load were 0.421 (0.221, 0.622), 0.589 (0.263, 0.914) and 0.340 (0.149, 0.531), respectively. Compared to the lowest FBG quartile (Q1), the OR (95%CI) for SS in Q3 and Q4 were 1.342 (1.014, 1.776) and 1.577 (1.194, 2.084), respectively. Compared to subjects with normal FBG, the ß (95%CI) for ΔMAP1 was 0.973 (0.055, 1.891) in subjects with impaired FBG, and was 1.449 (0.602, 2.296) in patients with diabetes mellitus. Stratified analyses showed significant and stronger associations between FBG with SSBP in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers. CONCLUSION: Our findings suggest FBG is an independent, dose-dependent associated factor for SSBP, and prevention of SS focusing on controlling FBG elevation in the early stage is important.

Construction of a ceRNA coregulatory network and screening of hub biomarkers for salt-sensitive hypertension.

Salt-sensitive hypertension (SSH) is an independent risk factor for cardiovascular disease. The regulation of long non-coding RNAs, mRNAs and competing endogenous RNAs (ceRNAs) in the pathogenesis of SSH is uncertain. An RNA microarray was performed to discover SSH-associated differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs), and 296 DElncRNAs and 44 DEmRNAs were identified, and 247 DElncRNAs and 44 DEmRNAs among these RNAs were included in the coexpression network. The coregulatory network included 23 ceRNA loops, and six hub RNAs (lnc-ILK-8:1, lnc-OTX1-7:1, lnc-RCAN1-6:1, GIMAP8, SUV420H1 and PIGV) were identified for further population validation. The ceRNA correlations among lnc-OTX1-7:1, hsa-miR-361-5p and GIMAP8 were confirmed in SSH and SRH patients. A larger-sample validation confirmed that GIMAP8, SUV420H1 and PIGV were differentially expressed between the SSH and SRH groups. In addition, SUV420H1 was included in the SSH screening model, and the area under the curve of the model was 0.720 (95% CI: 0.624-0.816). Our study explored the transcriptome profiles of SSH and constructed a ceRNA network to help elucidate the mechanism of SSH. In addition, SUV420H1 was identified as a hub element that participates in SSH transcriptional regulation and as a potential biomarker for the early diagnosis of SSH.

Cryoablation combined with transarterial infusion of pembrolizumab (CATAP) for liver metastases of melanoma: an ambispective, proof-of-concept cohort study.

BACKGROUND: The presence of liver metastasis correlates with poor therapeutic response of PD-1 blockade therapy in melanoma. A novel treatment protocol by combining cryoablation with transarterial infusion of pembrolizumab (CATAP) was proposed, and its feasibility and safety was assessed among this group of patients. METHODS: This registered ambispective cohort study enrolled fifteen melanoma patients with multiple hepatic metastases who received planned two-stage CATAP therapy: in the combined stage, subtotal cryoablation on day 1, in which one to two intrahepatic lesions were ablated completely with other lesions left untreated, sequentially combined transarterial infusion of pembrolizumab on day 3, every three weeks, for at least one cycle; in the infusion stage, arterial infusion of pembrolizumab was recommended at three-week interval until disease progression. The primary endpoint was objective response rate by RECIST (version 1.1); secondary end points included progression-free survival (PFS) and safety; exploratory endpoints were changes of cytokines and immune cell compositions in peripheral blood samples. RESULTS: Of the 15 patients enrolled, no grade 3-4 adverse events or major complications were observed. One patient (6.7%) achieved complete response, and 3 (20.0%) achieved partial response. The overall response rates of CATAP for the entire cohort and patients with cutaneous melanoma were 26.7% (95% confidence interval (CI) 4.3-49.0%) and 33.3% (95% CI 2.5-64.1%), respectively. Clinical response was observed in a proportion of patients (2/6; 33.3%) who failed first-line intravenous pembrolizumab treatment. The median overall PFS time and hepatic PFS time were 4.0 (95% CI 2.5-5.5) and 5.73 (95% CI 1.1-10.4) months, respectively. A significant increase in CD3-CD16 + CD56 + cells (natural killer cells; P = 0.0124) and a marginally significant decrease in CD4 + CD25 + cells (regulatory T cells; P = 0.0546) were observed three weeks after the first cycle of treatment in the combined stage. CONCLUSIONS: The CATAP therapy demonstrated positive clinical activity and a favorable safety profile for melanoma patients with liver metastasis.

The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.

OBJECTIVES: FOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required. METHODS: Patients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups. RESULTS: The ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%). CONCLUSIONS: These data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.