A Circular Network of Coregulated L-Threonine and L-Tryptophan Metabolism Dictates Acute Lower Limb Ischemic Injury.

Lower limb ischemia is characterized by reduced arterial perfusion in the lower limbs, leading to tissue ischemia and cell death. It is primarily caused by thrombosis and the rupture of arterial plaques, resulting in damage to ischemic muscle tissues. Metabolic processes are crucial in its development. Herein we combined single-cell data with metabolomics data to explore the pathways and mechanisms influencing lower limb ischemia. We analyzed single-cell and metabolomics data. In single-cell analysis, we identified different cell subpopulations and key regulatory genes, and biological enrichment analysis was performed to understand their functions and relationships. For metabolomics, mass spectrometry and chromatography techniques were employed to analyze metabolites in clinical samples. We performed differential analysis, correlation analysis, and Mendelian randomization to determine the relationships between key metabolites and genes. Nebl, Dapl1, Igfbp4, Lef1, Klrd1, Ciita, Il17f, Cd8b1, Il17a, Cd180, Il17re, Trim7, and Slc6a19 were identified to play a crucial role in lower limb ischemia. Important metabolites included L-threonine and L-tryptophan. The metabolism of L-threonine and L-tryptophan is linked to lower limb ischemia and thrombosis. B0AT1, encoded by SLC6A19, is closely related to these metabolites and appears to play a key role in lower limb ischemia development. Our analysis revealed the roles of key genes and metabolites in lower limb ischemia. These findings enhance our understanding of the pathogenesis of lower limb ischemia and provide new insights into its prevention and treatment.

Identification of three novel P450 enzymes involved in the oxidative modification of a newly discovered fusicoccane diterpene.

Fusicoccane (FC)-type diterpenoids are a class of diterpenoids characterized by a unique 5-8-5 ring system and exhibit diverse biological activities. Recently, we identified a novel FC-type diterpene synthase MgMS, which produces a myrothec-15(17)-en-7-ol (1) hydrocarbon skeleton, however, its tailoring congeners have not been elucidated. Here, we discovered two additional gene clusters Bn and Np, each encoding a highly homologous terpene synthase to MgMS but distinct tailoring enzymes. Heterologous expression of the terpene synthases BnMS and NpMS yielded the same product as MgMS. Subsequent introduction of three P450 enzymes MgP450, BnP450 and NpP450 from individual gene clusters resulted in four new FC-type diterpenoids 2-5. Notably, MgP450 serves as the first enzyme responsible for hydroxylation of the C19 methyl group, whereas NpP450 functions as a multifunctional P450 enzyme involved in the oxidations at C5, C6, and C19 positions of the 5-8-5 tricyclic skeleton. C5 oxidation of the hydrocarbon skeleton 1 led to broadening of the NMR signals and incomplete spectra, which was resolved by high-temperature NMR spectral analysis.

Enhanced cerebral blood flow similarity of the somatomotor network in chronic insomnia: Transcriptomic decoding, gut microbial signatures and phenotypic roles.

Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.

Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization.

BACKGROUND: The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine. Stem cells can self-organise into microsized organ units, partially modelling tissue function and regeneration. Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases. However, the lack of vasculature limits the utility of dental pulp organoids. AIM: To improve survival and aid in recovery after stem cell transplantation, we demonstrated the three-dimensional (3D) self-assembly of adult stem cell-human dental pulp stem cells (hDPSCs) and endothelial cells (ECs) into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium (CM). METHODS: During culture, primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM. The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids. The biological characteristics of the organoids were analysed, and the regulatory pathways associated with angiogenesis were studied. RESULTS: The combination of these two agents resulted in prevascularized human dental pulp organoids (Vorganoids) that more closely resembled dental pulp tissue in terms of morphology and function. Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis. The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids. CONCLUSION: In this innovative study, we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration, facilitating the development of clinical treatment strategies.

Analysis of gait characteristics and related factors in patients with Parkinson's disease based on wearable devices.

BACKGROUND: Postural instability and gait disorder dominant (PIGD) is one of the most common disabling symptoms of Parkinson's disease (PD), which seriously affects patients' quality of life. Therefore, it is essential to identify PIGD and develop targeted interventions to reduce the risk of PIGD in PD patients. AIM: This study aimed to investigate the gait characteristics of PD patients based on wearable devices and to establish a predictive model for their related influencing factors. METHODS: The retrospective medical records of patients from January 2020 to September 2023 were collected, including 159 patients with PD (divided into PIGD [n = 73] and non-PIGD [n = 86] groups) and 200 healthy patients (as the healthy control group). Information from social demographic data, a blood test, scale scores, gait analysis based on wearable devices, white matter lesions, and the Fazekas scale was extracted and analyzed. RESULTS: Compared with the healthy control group, the mean step length, mean rate, mean angular velocity, and step length were lower in the PD group, while the mean steps were higher in the turning test. The incidence of PIGD was 46% in PD patients, and PD patients with the non-tremor onset mode were more likely to develop PIGD than those with the tremor onset mode. Compared to the non-PIGD group, the PIGD group showed more serious gait problems in different experimental tasks and had a higher Hoehn and Yahr (H-Y) stage, Hamilton Anxiety Scale (HAMA) score, Hamilton Depression Scale score, periventricular white matter (PVWM) score, deep white matter score, and Fazekas scale score, but they had lower hemoglobin levels, D-dimer levels, Tinetti Balance scores, Tinetti Gait scores, Berg Balance Scale scores, and Mini-Mental State Examination (MMSE) scores. Logistic regression analysis showed that the MMSE score was negatively correlated with the occurrence of PIGD, while the HAMA score, H-Y stage, PVWM score, and non-tremor form of onset were positively correlated with the occurrence of PIGD CONCLUSION: The incidence of gait disorder in PD patients is higher than that in the normal population. Moreover, cognitive dysfunction, anxiety state, H-Y stage, PVWM score, and the non-tremor mode of onset can be considered independent risk factors for PIGD.

Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis.

The hippocampus plays an important role in the pathophysiological mechanism of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Nevertheless, the connection between the resting-state activity of the hippocampal subregions and neuropsychiatric disorders in patients remains unclear. This study aimed to explore the changes in functional connectivity (FC) in the hippocampal subregions of patients with anti-NMDAR encephalitis and its association with clinical symptoms and cognitive performance. Twenty-three patients with anti-NMDAR encephalitis and 23 healthy controls (HC) were recruited. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and completed clinical cognitive scales. Based on the Brainnetome Atlas, the rostral (anterior) and caudal (posterior) hippocampi of both the left and right hemispheres were selected as regions of interest (ROIs) for FC analysis. First, a one-sample t-test was used to observe the whole-brain connectivity distribution of hippocampal subregions within the patient and HC groups at a threshold of p < 0.05. The two-sample t-test was used to compare the differences in hippocampal ROIs connectivity between groups, followed by a partial correlation analysis between the FC values of brain regions with statistical differences and clinical variables. This study observed that the distribution of whole-brain functional connectivity in the rostral and caudal hippocampi aligned with the connectivity differences between the anterior and posterior hippocampi. Compared to the HC group, the patients showed significantly decreased FC between the bilateral rostral hippocampus and the left inferior orbitofrontal gyrus and between the right rostral hippocampus and the right cerebellum. However, a significant increase in FC was observed between the right rostral hippocampus and left superior temporal gyrus, the left caudal hippocampus and right superior frontal gyrus, and the right caudal hippocampus and left gyrus rectus. Partial correlation analysis showed that FC between the left inferior orbitofrontal gyrus and the right rostral hippocampus was significantly negatively correlated with the California Verbal Learning Test (CVLT) and Brief Visuospatial Memory Test (BVMT) scores. The FC between the right rostral hippocampus and the left superior temporal gyrus was negatively correlated with BVMT scores. FC abnormalities in the hippocampal subregions of patients with anti-NMDAR encephalitis were associated with cognitive impairment, emotional changes, and seizures. These results may help explain the pathophysiological mechanisms and clinical manifestations of anti-NMDAR encephalitis and NMDAR dysfunction-related diseases such as schizophrenia.

White matter microstructural alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis: A tract-based spatial statistics study.

BACKGROUND: Cognitive impairment is common in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis; however, neural mechanisms underlying this impairment remain unclear. Diffusion tensor imaging (DTI) is a potential method for studying the condition of white matter fibers in patients with anti-NMDAR encephalitis, allowing for an analysis of the neuroimaging mechanisms of cognitive impairment in conjunction with cognitive scales. This study aimed to explore white matter microstructural alterations and their correlation with cognitive function in patients with anti-NMDAR encephalitis. METHODS: DTI data were collected from 22 patients with anti-NMDAR encephalitis (aged 29.00(19.75, 39.50) years; 12 males, 10 females) and 20 healthy controls (HCs) (aged 24.50(21.25, 32.00); 12 males, 8 females) matched for age, sex, and educational level. Changes in the white matter microstructure were analyzed using tract-based spatial statistics. Pearson correlation analysis was used to explore the correlation between white matter integrity and neuropsychological scores. RESULTS: Compared with HCs, patients with anti-NMDAR encephalitis showed decreased fractional anisotropy and increased mean diffusivity values in extensive white matter regions, which were associated with disease severity, memory, and executive and visuospatial functions. CONCLUSION: Widespread impairment of the structural integrity of the white matter in the brain is significantly associated with cognitive dysfunction in patients with anti-NMDAR encephalitis, providing neuroimaging evidence for studying the underlying mechanisms.

The quality of telemedicine consultations for sexually transmitted infections in China.

The burden of sexually transmitted infections (STIs) continues to increase in developing countries like China, but the access to STI care is often limited. The emergence of direct-to-consumer (DTC) telemedicine offers unique opportunities for patients to directly access health services when needed. However, the quality of STI care provided by telemedicine platforms remains unknown. After systemically identifying the universe of DTC telemedicine platforms providing on-demand consultations in China in 2019, we evaluated their quality using the method of unannounced standardized patients (SPs). SPs presented routine cases of syphilis and herpes. Of the 110 SP visits conducted, physicians made a correct diagnosis in 44.5% (95% CI: 35.1% to 54.0%) of SP visits, and correctly managed 10.9% (95% CI: 5.0% to 16.8%). Low rates of correct management were primarily attributable to the failure of physicians to refer patients for STI testing. Controlling for other factors, videoconference (vs SMS-based) consultation mode and the availability of public physician ratings were associated with higher-quality care. Our findings suggest a need for further research on the causal determinants of care quality on DTC telemedicine platforms and effective policy approaches to promote their potential to expand access to STI care in developing countries while limiting potential unintended consequences for patients.

The construction and operational models of internet hospitals in China: a hospital-based survey study.

BACKGROUND: China has empowered and continues to empower internet hospitals, which saw an increase in their development due to the pandemic, to fight against COVID-19. The construction and operational models of internet hospitals can be categorized as self-constructed and self-managed models, self-constructed and enterprise-run models, hospital and enterprise joint-owned models, and hosted by a third-party platform. Despite the growing importance of internet hospitals, there have been few systematic summaries of their construction and operational models. The primary purpose of the study was to understand the construction and operational models of internet hospitals in China. METHODS: Data was collected from 39 internet hospitals and 356 medical staff between September 2020 and April 2021, via internet hospital and hospital staff surveys. T-tests were used to compare the continuous variables, while Chi-square tests were employed to compare the proportions of categorical variables. The self-perception of the internet hospitals' services was assessed using a 5-point Likert scale on 16 aspects and a root cause analysis was conducted to identify the root causes and influencing factors of current deficiencies experienced by internet hospitals. RESULTS: Among the 39 internet hospitals, 22 (56.4%) were self-constructed and self-managed. Compared to other models of Internet hospitals, self-constructed and self-managed hospitals had lower percentages of professionals providing online services (P = 0.006), numbers of doctors outside of the entity (P = 0.006), numbers of online nurses (P = 0.004), and the ratio of online nurses to offline doctors (P < 0.001). Of the 16 aspects evaluated with regards to the medical staff's self-perception of the internet hospital services, the highest scores were given for fee transparency, fee rationality, travel cost capital, patience and responsibility, and consultation behaviors. The root causes included five aspects: human, channels, prices, services, and time. CONCLUSIONS: While the self-constructed and self-managed model was found to be the most prevalent form of internet hospital in China, the different models of internet hospitals can have an impact on both the quantity and quality of online healthcare services. This study contributes to the existing literature on internet hospitals' construction and operational models, offering additional policy implications for telemedicine management.

IEPAPI: a method for immune epitope prediction by incorporating antigen presentation and immunogenicity.

CD8+ T cells can recognize peptides presented by class I human leukocyte antigen (HLA-I) of nucleated cells. Exploring this immune mechanism is essential for identifying T-cell vaccine targets in cancer immunotherapy. Over the past decade, the wealth of data generated by experiments has spawned many computational approaches for predicting HLA-I binding, antigen presentation and T-cell immune responses. Nevertheless, existing HLA-I binding and antigen presentation prediction approaches suffer from low precision due to the absence of T-cell receptor (TCR) recognition. Direct modeling of T-cell immune responses is less effective as TCR recognition's mechanism still remains underexplored. Therefore, directly applying these existing methods to screen cancer neoantigens is still challenging. Here, we propose a novel immune epitope prediction method termed IEPAPI by effectively incorporating antigen presentation and immunogenicity. First, IEPAPI employs a transformer-based feature extraction block to acquire representations of peptides and HLA-I proteins. Second, IEPAPI integrates the prediction of antigen presentation prediction into the input of immunogenicity prediction branch to simulate the connection between the biological processes in the T-cell immune response. Quantitative comparison results on an independent antigen presentation test dataset exhibit that IEPAPI outperformed the current state-of-the-art approaches NetMHCpan4.1 and mhcflurry2.0 on 100 (25/25) and 76% (19/25) of the HLA subtypes, respectively. Furthermore, IEPAPI demonstrates the best precision on two independent neoantigen datasets when compared with existing approaches, suggesting that IEPAPI provides a vital tool for T-cell vaccine design.

Prognostic CT features in patients with untreated thymic epithelial tumors.

To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with pathologically confirmed TETs were retrospectively reviewed. The subjects included 113 male and 81 female patients between 15 and 78 years of age, with a mean age of 53.8 years. Clinical outcomes were categorized according to whether relapse, metastasis or death occurred within 3 years after the first diagnosis. Associations between clinical outcomes and CT imaging features were determined using univariate and multivariate logistic regression analyses, while the survival status was analyzed by Cox regression. In this study, we analyzed 110 thymic carcinomas, 52 high-risk thymomas and 32 low-risk thymomas. Percentages of poor outcome and patient death in thymic carcinomas were much higher than those in patients with high-risk and low-risk thymomas. In the thymic carcinomas groups, 46 patients (41.8%) experienced tumor progression, local relapse or metastasis and were categorized as having poor outcomes; vessel invasion and pericardial mass were confirmed to be independent predictors by logistic regression analysis (p < 0.01). In the high-risk thymoma group, 11 patients (21.2%) were categorized as having poor outcomes, and the CT feature pericardial mass was confirmed to be an independent predictor (p < 0.01). In survival analysis, Cox regression showed that CT features of lung invasion, great vessel invasion, lung metastasis and distant organ metastasis were independent predictors for worse survival in the thymic carcinoma group (p < 0.01), while lung invasion and pericardial mass were independent predictors for worse survival in high-risk thymoma group. No CT features were related to poor outcome and worse survival in the low-risk thymoma group. Patients with thymic carcinoma had poorer prognosis and worse survival than those with high-risk or low-risk thymoma. CT can serve as an important tool for predicting the prognosis and survival of patients with TETs. In this cohort, CT features of vessel invasion and pericardial mass were related to poorer outcomes in those with thymic carcinoma and pericardial mass in those with high-risk thymoma. Features including lung invasion, great vessel invasion, lung metastasis and distant organ metastasis indicate worse survival in thymic carcinoma, whereas lung invasion and pericardial mass indicate worse survival in high-risk thymoma.

Predicting insomnia severity using structure-function coupling in female chronic insomnia patients.

Functional connectivity between brain regions is constrained by the underlying structural pathways. However, how this structure-function coupling is disrupted in female patients with insomnia disorder is unclear. This study examines if the whole-brain pattern of structure-function coupling could be used to predict unseen female patients' insomnia severity index. Resting-state functional MRI and diffusion-weighted imaging were performed in 82 female participants with chronic insomnia. Structure-function coupling was computed using the Spearman rank correlations between structural and functional connectivity profiles. Using relevance vector regression approach and 10-fold cross-validation, we predicted the individuals' insomnia severity index using the pattern of whole-brain structure-function coupling. Finally, we extracted the contribution of each regional coupling to the prediction model. The pattern of structure-function coupling could be used to significantly predict unseen individuals' insomnia severity index scores (r = 0.29, permutation P < 0.001; mean absolute error (MAE) = 4.59, permutation P < 0.001). Moreover, the brain regions with high functional hierarchy, including regions in the default mode network, mainly displayed negative contribution weights, while the regions with lower functional hierarchy, including occipital regions and the precentral gyrus, mainly displayed positive contribution weights. This is the first study to demonstrate an association between structure-function coupling and the insomnia severity index in females with insomnia disorder. Importantly, our data suggest that insomnia severity is associated with a reduction in structure-function coupling in higher-order brain regions and an increase in structure-function coupling in lower-order brain regions.

Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis.

Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions deciphered from circulating cfDNA methylation signatures. We show that the estimated fractions of tumor-derived cfDNA from cancer patients increase significantly as cancer progresses in two independent datasets. Employing the predicted tumor fractions, we establish a Bayesian diagnostic model in which training samples are only derived from late-stage patients and healthy individuals. When validated on early-stage patients and healthy individuals, this model exhibits a sensitivity of 86.1% for cancer early detection and an average accuracy of 76.9% for tumor localization at a specificity of 94.7%. By highlighting the potential of tumor fractions on cancer early diagnosis, our approach can be further applied to cancer screening and tumor progression monitoring.

Factors Influencing Adoption and Use of Telemedicine Services in Rural Areas of China: Mixed Methods Study.

BACKGROUND: The shortage of medical resources in rural China reflects the health inequity in resource-limited settings, whereas telemedicine could provide opportunities to fill this gap. However, evidence of patient acceptance of telemedicine services from low- and middle-income countries is still lacking. OBJECTIVE: We aimed to understand the profile of patient end-user telemedicine use and identify factors influencing telemedicine service use in rural China. METHODS: Our study followed a mixed methods approach, with a quantitative cross-sectional survey followed by in-depth semistructured interviews to describe telemedicine use and its associated factors among rural residents in Guangdong Province, China. In the quantitative analysis, explanatory variables included environmental and context factors, household-level factors, individual sociodemographic factors, access to digital health care, and health needs and demand factors. We conducted univariate and multivariate analyses using Firth logistic regression to examine the correlations of telemedicine uptake. A thematic approach was used, guided by the Social Cognitive Theory for the qualitative analysis. RESULTS: A total of 2101 households were recruited for the quantitative survey. With a mean age of 61.4 (SD 14.41) years, >70% (1364/2101, 72.94%) of the household respondents were male. Less than 1% (14/2101, 0.67%) of the respondents reported experience of using telemedicine. The quantitative results supported that villagers living with family members who had a fever in the past 2 weeks (adjusted odds ratio 6.96, 95% CI 2.20-21.98; P=.001) or having smartphones or computers (adjusted odds ratio 3.71, 95% CI 0.64-21.32; P=.14) had marginally higher telemedicine uptake, whereas the qualitative results endorse these findings. The results of qualitative interviews (n=27) also supplemented the potential barriers to telemedicine use from the lack of knowledge, trust, demand, low self-efficacy, and sufficient physical and social support. CONCLUSIONS: This study found extremely low use of telemedicine in rural China and identified potential factors affecting telemedicine uptake. The main barriers to telemedicine adoption among rural residents were found, including lack of knowledge, trust, demand as well as low self-efficacy, and insufficient physical and social support. Our study also suggests strategies to facilitate telemedicine engagement in low-resource settings: improving digital literacy and self-efficacy, building trust, and strengthening telemedicine infrastructure support.

A cell adhesion-promoting multi-network 3D printing bio-ink based on natural polysaccharide hydrogel.

Due to its high biosafety, gellan gum (GG) hydrogel, a naturally occurring polysaccharide released by microorganisms, is frequently utilized in food and pharmaceuticals. In recent years, like GG, natural polysaccharide-based hydrogels have become increasingly popular in 3D-printed biomedical engineering because of their simplicity of processing, considerable shear thinning characteristic, and minimal pH dependence. To mitigate the negative effects of the GG's high biological inertia, poor cell adhesion, single cross-linked network, and high brittleness. Mesoporous silica nanospheres (MMSN) and Aldehyde-based methacrylated hyaluronic acid (AHAMA) were combined to sulfhydrated GG (TGG) to create a multi-network AHAMA/TGG/MMSN hydrogel in this study. For this composite hydrogel system, the multi-component offers several crosslinking networks: the double bond in AHAMA can be photocrosslinked by activating the photoinitiator, aldehyde groups on its side chain can create Schiff base bonds with MMSN, while TGG can self-curing at room temperature. The AHAMA/TGG/MMSN hydrogel, with a mass ratio of 2:6:1, exhibits good cell adhesion, high strength and elasticity, and great printability. We believe that this innovative multi-network hydrogel has potential uses in tissue regeneration and biomedical engineering.

Age-related changes in the risk of high blood pressure.

Background and aims: Understanding the age-related trend of risk in high blood pressure (BP) is important for preventing heart failure and cardiovascular diseases. But such a trend is still underexplored. This study aims to (a) depict the relationship of BP patterns with age, and (b) understand the trend of high BP prevalence over time in different age groups. Materials and methods: Health check-up data with an observational period of 8 years (January 1, 2011, to December 31, 2018) was used as the data source. A total of 71,468 participants aged over 18 years old with complete information on weight, height, age, gender, glucose, triglyceride, total cholesterol, systolic (SBP), and diastolic blood pressure (DBP) were included for analysis. Generalized additive models were adopted to explore the relationship between the risk of high BP and age. Variance analysis was conducted by testing the trend of high BP prevalence in age groups over time. Results: Risk of high SBP showed a continuous rise from age 35 to 79 years and a concurrent early increase in the risk of high DBP; after age 50-65 years, high DBP risk declined. The risk of SBP rises linearly with age for men, whereas increases non-linearly for women. In addition, a significant increasing trend of high SBP risk among middle-aged people was found during the past decade, men experienced a later but longer period of increase in high SBP than women. Conclusion: The high SBP risk progresses more rapidly in the early lifetime in women, compared to the lifetime thereafter. Thresholds of increasing trend of SBP suggest a possible need for hypertension screening in China after the age of 40.

Evaluation of a village-based digital health kiosks program: A protocol for a cluster randomized clinical trial.

Background: To address disparities in healthcare quality and access between rural and urban areas in China, reforms emphasize strengthening primary care and digital health utilization. Yet, evidence on digital health approaches in rural areas is lacking. Objective: This study will evaluate the effectiveness of Guangdong Second Provincial General Hospital's Digital Health Kiosk program, which uses the Dingbei telemedicine platform to connect rural clinicians to physicians in upper-level health facilities and provide access to artificial intelligence-enabled diagnostic support. We hypothesize that our interventions will increase healthcare utilization and patient satisfaction, decrease out-of-pocket costs, and improve health outcomes. Methods: This cluster randomized control trial will enroll clinics according to a partial factorial design. Clinics will be randomized to either a control arm with clinician medical training, a second arm additionally receiving Dingbei telemedicine training, or a third arm with monetary incentives for patient visits conducted through Dingbei plus all prior interventions. Clinics in the second and third arm will then be orthogonally randomized to a social marketing arm that targets villager awareness of the kiosk program. We will use surveys and Dingbei administrative data to evaluate clinic utilization, revenue, and clinician competency, as well as patient satisfaction and expenses. Results: We have received ethical approval from Guangdong Second Provincial General Hospital (IRB approval number: GD2H-KY IRB-AF-SC.07-01.1), Peking University (IRB00001052-21007), and the University of North Carolina at Chapel Hill (323385). Study enrollment began April 2022. Conclusions: This study has the potential to inform future telemedicine approaches and assess telemedicine as a method to address disparities in healthcare access.Trial registration number: ChiCTR2100053872.

Changes in blood pressure and related risk factors among nurses working in a negative pressure isolation ward.

Objective: To observe changes in blood pressure (ΔBP) and explore potential risk factors for high ΔBP among nurses working in a negative pressure isolation ward (NPIW). Methods: Data from the single-center prospective observational study were used. Based on a routine practice plan, female nurses working in NPIW were scheduled to work for 4 days/week in different shifts, with each day working continuously for either 5 or 6 h. BP was measured when they entered and left NPIW. Multivariable logistic regression was used to assess potential risk factors in relation to ΔBP ≥ 5 mm Hg. Results: A total of 84 nurses were included in the analysis. The ΔBP was found to fluctuate on different working days; no significant difference in ΔBP was observed between the schedules of 5 and 6 h/day. The standardized score from the self-rating anxiety scale (SAS) was significantly associated with an increased risk of ΔBP ≥ 5 mm Hg (odds ratio [OR] = 1.12, 95% CI: 1.00-1.24). Working 6 h/day (vs. 5 h/day) in NPIW was non-significantly related to decreased risk of ΔBP (OR = 0.70), while ≥ 2 consecutive working days (vs. 1 working day) was non-significantly associated with increased risk of ΔBP (OR = 1.50). Conclusion: This study revealed no significant trend for ΔBP by working days or working time. Anxiety was found to be significantly associated with increased ΔBP, while no <2 consecutive working days were non-significantly related to ΔBP. These findings may provide some preliminary evidence for BP control in nurses who are working in NPIW for Coronavirus Disease 2019 (COVID-19).