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We attempted to determine the predictive ability of the first-day Sequential Organ Failure Assessment (SOFA) score in the cardiac intensive care unit, as well as a new score combining the anion gap (AG) with the SOFA score (SOFA-AG).Information was obtained from the Medical Information Mart for Intensive Care III (MIMIC III 1.4) database. We plotted the relationship between the maximum first-day AG and 90-day mortality after admission to the care unit. Patients were divided into five groups based on the hazard ratio (HR) and assigned scores of 0, 1, 2, 3, or 4 points. We compared the area under the curve (AUC) for the receiver-operating characteristic curve of the SOFA and that of the SOFA-AG.A total of 1316 patients were identified and divided into the following five groups: AG 8 to16 mmol/L; AG 16 to17 mmol/L; AG 17 to19 mmol/L; AG 19 to21 mmol/L; and AG ≥ 21 mmol/L. The SOFA-AG score had a greater AUC than the SOFA score at 7 days (0.770 vs. 0.711; P 0.001), 14 days (0.751 vs. 0.692; P 0.001), 28 days (0.741 vs. 0.684; P 0.001), and 90 days (0.727 vs. 0.667; P 0.001).The SOFA score showed moderate predictive value only for 7-day mortality after admission to the cardiac intensive care unit, but the SOFA-AG score had improved predictive ability for up to 90 days after admission.

In the course of malaria elimination in the Greater Mekong Subregion (GMS), malaria epidemiology has experienced drastic spatiotemporal changes with residual transmission concentrated along international borders and the rising predominance of Plasmodium vivax. The emergence of Plasmodium falciparum parasites resistant to artemisinin and partner drugs renders artemisinin-based combination therapies less effective while the potential spread of multidrug-resistant parasites elicits concern. Vector behavioral changes and insecticide resistance have reduced the effectiveness of core vector control measures. In recognition of these problems, the Southeast Asian International Center of Excellence for Malaria Research (ICEMR) has been conducting multidisciplinary research to determine how human migration, antimalarial drug resistance, vector behavior, and insecticide resistance sustain malaria transmission at international borders. These efforts allow us to comprehensively understand the ecology of border malaria transmission and develop population genomics tools to identify and track parasite introduction. In addition to employing in vivo, in vitro, and molecular approaches to monitor the emergence and spread of drug-resistant parasites, we also use genomic and genetic methods to reveal novel mechanisms of antimalarial drug resistance of parasites. We also use omics and population genetics approaches to study insecticide resistance in malaria vectors and identify changes in mosquito community structure, vectorial potential, and seasonal dynamics. Collectively, the scientific findings from the ICEMR research activities offer a systematic view of the factors sustaining residual malaria transmission and identify potential solutions to these problems to accelerate malaria elimination in the GMS.

There are several treatment options for patients with concomitant carotid and coronary artery disease, and it is difficult to identify an optimal treatment strategy that has consensus. Here, we performed a meta-analysis to compare the early and long-term outcomes of staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches.We performed a meta-analysis that compared staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches between July 1976 and September 2021. PubMed, EMBASE, and the Cochrane Library were systematically searched for related articles.Nineteen studies were identified with a total of 39,269 and 30,066 patients in the synchronous and staged groups, respectively. Early mortality was lower in the staged group than in the synchronous group (odds ratio OR 1.256, 95% confidence interval CI 1.006-1.569, P= P 0.05, IPatients treated with the synchronous approach had a significantly higher risk of early mortality, stroke, TIA, wound infection, and reoperation and a lower risk of myocardial ischemia than those treated with the staged approach. There was no significant difference in the long-term results between the 2 groups.

The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort.Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex.In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P 0.001), fever (male vs. female: 18.0% vs. 14.6%, P = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P 0.001), and treatment with cyclophosphamide (CYC) (P 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P = 0.026), high serum creatinine (P 0.001), higher end-stage renal failure rates (P = 0.002), musculoskeletal damage (P = 0.023), cardiovascular impairment (P = 0.009), and CYC use (P = 0.001); while leukopenia (P = 0.017), arthritis (P = 0.014), and mycophenolate usage (P = 0.013) rates were lower.Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.

Background: This study is part of a larger research effort to explore the molecular mechanism of hepatocellular carcinoma, reduce drug resistance and seek new targets. Objective: The objective of this study is to investigate the effect and mechanism of fibroblast growth factor receptor inhibitor AZD4547 on Sorafenib-resistant hepatoma cells. Methods: First, we constructed a Sorafenib-resistant hepatoma cell line Huh7R. Different groups of Huh7R cells were treated with Sorafenib, AZD4547, Sorafenib combined with AZD4547, and normal saline. The cell viability was detected by Cell Counting Kit-8. Then Fibroblast growth factor receptor and Toll-like receptor 4 were detected by Western blot, as well as the LC3 II/I, Beclin1, and P62. In addition, we used the autophagy inhibitor 3-methyladenine to identify the mechanism of AZD4547 combined with Sorafenib for inducing Sorafenib-resistant hepatoma cell death. Results: We find that AZD4547 combined with Sorafenib significantly inhibited the viability of Sorafenib-resistant hepatoma cell Huh7R. As for its mechanism, AZD4547 was able to inhibit fibroblast growth factor receptor activity, promote autophagy and regulate immunity. AZD4547 increased LC3 II/I, Beclin1, and Toll-like receptor 4 proteins, and decreased P62 protein level in Huh7R cells significantly when given in combination with sorafenib. Furthermore, 3-methyladenine inhibited autophagy and reversed the killing effect of the combination of AZD4547 and Sorafenib on Huh7R cells. Conclusion: The inhibition of fibroblast growth factor receptor activity by AZD4547 can significantly enhance autophagy and immune response, as well as promote the death of Sorafenib-resistant hepatoma cells.

This study aimed to compare the Kessler Psychological Distress Scale (K10) and Short-Form 12-Item Health Survey Mental Component Score (SF-12 MCS) for the effectiveness as screening tools for depression in Asian New Zealanders. A national, representative New Zealand Health Survey (NZHS) data set was used. In total, 1,277 participants were included in the analyses. The sensitivity and specificity values, as well as the areas under the receiver operating characteristics curves (AUROC), for the K10 and the SF-12 MCS scores were examined. The AUROCs for K10 and SF-12 MCS were 0.787 (95% CI [0.736, 0.837]) and 0.725 (95% CI [0.656, 0.793]), respectively. A less than optimal sensitivity and positive predictive value of K10 support the need to reexamine the optimal cut-off point according to the results of the Youden index. Strengthening the K10 predictive accuracy will increase the practical application among Asian populations.

Objective Warfarin anticoagulation management requires sequential decision-making to adjust dosages based on patients’ evolving states continuously. We aimed to leverage reinforcement learning (RL) to optimize the dynamic in-hospital warfarin dosing in patients after surgical valve replacement (SVR). Materials and Methods 10 408 SVR cases with warfarin dosage–response data were retrospectively collected to develop and test an RL algorithm that can continuously recommend daily warfarin doses based on patients’ evolving multidimensional states. The RL algorithm was compared with clinicians’ actual practice and other machine learning and clinical decision rule-based algorithms. The primary outcome was the ratio of patients without in-hospital INRs >3.0 and the INR at discharge within the target range (1.8–2.5) (excellent responders). The secondary outcomes were the safety responder ratio (no INRs >3.0) and the target responder ratio (the discharge INR within 1.8–2.5). Results In the test set (n = 1260), the excellent responder ratio under clinicians’ guidance was significantly lower than the RL algorithm: 41.6% versus 80.8% (relative risk [RR], 0.51; 95% confidence interval [CI], 0.48–0.55), also the safety responder ratio: 83.1% versus 99.5% (RR, 0.83; 95% CI, 0.81–0.86), and the target responder ratio: 49.7% versus 81.1% (RR, 0.61; 95% CI, 0.58–0.65). The RL algorithms performed significantly better than all the other algorithms. Compared with clinicians’ actual practice, the RL-optimized INR trajectory reached and maintained within the target range significantly faster and longer. Discussion RL could offer interactive, practical clinical decision support for sequential decision-making tasks and is potentially adaptable for varied clinical scenarios. Prospective validation is needed. Conclusion An RL algorithm significantly optimized the post-operation warfarin anticoagulation quality compared with clinicians’ actual practice, suggesting its potential for challenging sequential decision-making tasks.

Mitochondria as one of the key subcellular organelles have been well recognized as a promising druggable target and are closely associated with energy supply and various cellular functions. Realizing high accumulation and prolonged retention of radiosensitizers in the cellular mitochondria of tumors is an effective way to improve radiotherapeutic efficacy. Herein, we develop mitochondria-targeting and protein sulfenic acid (PSA)-reactive gold nanoparticles (dAuNP-TPP) that are fabricated by incorporating triphenylphosphine and 1,3-cyclohexanedione onto the surface of AuNPs (∼20 nm) to improve CT imaging and radiotherapeutic efficacy of tumors. Taking advantage of the specific mitochondrial targeting and PSA-mediated on-site covalent immobilization, this nanosystem shows significantly enhanced accumulation and retention in mitochondria with approximately 5.22-fold higher enrichment than nonimmobilizable AuNP-TPP. More notably, the covalent immobilization of dAuNP-TPP in cellular mitochondria could induce a dramatic reduction of ATP, leading to serious mitochondrial disruption, combined with the radiosensitization effect, in consequence achieving efficient radiotherapy of breast tumors in vivo. This subcellular organelle-targeted and immobilizable strategy may offer a valuable and universal tool for efficient tumor treatment.

In 2007, the World Health Organization published a guide on age-friendly cities. However, little is known about interventions that have been implemented to promote age-friendly communities in rural and remote areas. This paper presents the findings from a scoping review undertaken to locate available evidence of interventions, strategies, and programs that have been implemented in rural and remote areas to create age-friendly communities.This scoping review used the Joanna Briggs Institute (JBI) methodology.A total of 219 articles were included in this review. No intervention studies were referred to as 'age-friendly'. However, there were interventions (mostly healthcare-related) that have been implemented in rural and remote areas with older people as participants. There were also non-evaluated community programs that were published in the grey literature. This review identified the common health interventions in older people and the indirect relevance to the WHO age-friendly framework domains in rural and remote contexts.The eight age-friendly domains were not explicitly utilised as a guide in the development of interventions for older people in rural and remote settings. Implementation of age-friendly interventions in rural and remote areas requires a multisectoral approach that is tailored to address the specific needs of individual communities. Age-friendly interventions also need to consider socio-ecological factors to adequately and holistically address community needs and ensure long-term sustainability.

Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstitial fibrogenesis. However, the origin of these myofibroblasts remains poorly understood. Here, we create new mouse models of pulmonary fibrosis and identify a previously unknown population of endothelial cell (EC)-like myofibroblasts in normal lung tissue. We show that these EC-like myofibroblasts significantly contribute myofibroblasts to pulmonary fibrosis, which is confirmed by single-cell RNA sequencing of human pulmonary fibrosis. Using the transcriptional profiles, we identified a small molecule that redirects the differentiation of EC-like myofibroblasts and reduces pulmonary fibrosis in our mouse models. Our study reveals the mechanistic underpinnings of the differentiation of EC-like myofibroblasts in pulmonary fibrosis and may provide new strategies for therapeutic interventions.

Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, there are limited reports on the relationship between serum uric acid levels and biological treatment efficacy. The purposes of this study were to compare the differences in serum uric acid levels between patients with psoriasis and healthy controls and analyze the risk of hyperuricemia.A total of 196 patients with psoriasis and 191 age- and sex-matched healthy controls were enrolled in this retrospective cohort study. One hundred and twenty-seven patients with severe psoriasis were treated with biologics. Sixty-eight patients received adalimumab, and 59 patients received secukinumab. Serum uric acid levels were measured at baseline, week 24, and week 48 of treatment.Patients with psoriasis had higher serum uric acid levels than healthy controls (6.4 ± 1.7 mg/dL vs. 5.7 ± 1.5 mg/dL, P 0.001). Hyperuricemia was found in 33.7% (66/196) of patients with psoriasis, which was significantly higher than that in healthy controls (13.1% [25/191], P 0.001). Serum uric acid levels and hyperuricemia were not related to the severity of psoriasis ( P 0.05). No significant changes in serum uric acid levels and hyperuricemia were observed following adalimumab treatment ( P 0.05). The serum uric acid level in patients treated with secukinumab was 6.7 ± 1.6 mg/dL at week 24, which was not statistically different from that at baseline (6.6 ± 1.4 mg/dL, P = 0.885). Serum uric acid levels were significantly decreased at week 48 (6.3 ± 1.5 mg/dL vs. 6.6 ± 1.4 mg/dL, P = 0.007) in patients treated with secukinumab. Secukinumab had no significant effect on hyperuricemia either ( P 0.05).The serum uric acid levels and prevalence of hyperuricemia in patients with psoriasis were significantly higher than those in healthy controls. Secukinumab treatment for 48 weeks successfully decreased serum uric acid levels in patients with psoriasis, whereas adalimumab had no significant effect on serum uric acid levels.

This study aimed to monitor the prevalence of HIV-1 drug resistance and risk factors associated with drug resistance in antiretroviral therapy (ART)-failure individuals in Liaoning Province, China. Plasma samples were collected from HIV-1-positive individuals who experienced ART failure in Liaoning Province between April 2018 and September 2019. Genotype resistance test was performed using an in-house assay on these collected samples. Factors associated with drug resistance were identified by logistic regression analysis. We collected a total of 468 ART-failure individuals, of which 256 were successfully included in the final study. Of these, the most predominant genotype was CRF01_AE, accounting for 77.73%. The resistance rate to any of the three classes of antiretroviral drugs (non-nucleoside reverse transcriptase inhibitors [NNRTIs], nucleoside reverse transcriptase inhibitors [NRTIs], and protease inhibitors [PIs]) was 64.84%. Among 256 ART-failure patients, 62.89% showed drug resistance to NNRTIs, 50.39% to NRTIs, and 3.13% to PIs. G190S (31.25%) and Y181C (25.78%) mutations were the most common NNRTIs resistance mutations. K65R (29.69%), M184V (28.52%) were the most common NRTIs resistance mutations. Factors associated with drug resistance included current ART regimen and viral load. The high drug resistance rate among ART-failure individuals in Liaoning Province needs more attention. Corresponding strategies for the risk factors associated with HIV drug resistance can better control and prevent the prevalence of resistance.

The aim of this study was to identify crucial proteins and N-glycosylated sites in the pathological mechanism of Kashin-Beck disease (KBD) compared with osteoarthritis (OA). Nine KBD knee subjects and nine OA knee subjects were selected for the study. Quantitative proteomics and N-glycoproteomics data of KBD and OA were obtained by protein and N-glycoprotein enrichment and LC-MS/MS analysis. Differentially expressed proteins or N-glycosylation sites were examined with a comparative analysis between KBD and OA. Total 2205 proteins were identified in proteomic analysis, of which 375 were significantly different. Among these, 121 proteins were up-regulated and 254 were down-regulated. In N-glycoproteomic analysis, 278 different N-glycosylated sites that were related to 187 N-glycoproteins were identified. Proteins and their N-glycosylated sites are associated with KBD pathological process including ITGB1, LRP1, ANO6, COL1A1, MXRA5, DPP4, and CSPG4. CRLF1 and GLG1 are proposed to associate with both KBD and OA pathological processes. Key pathways in KBD vs. OA proteomic and N-glycoproteomic analysis contained extracellular matrix receptor interaction, focal adhesion, phagosome, protein digestion, and absorption. N-glycosylation may influence the pathological process by affecting the integrity of chondrocytes or cartilage. It regulated the intercellular signal transduction pathway, which contributes to cartilage destruction in KBD.

Atherosclerosis, a silent chronic vascular pathology, is the cause of the majority of cardiovascular ischaemic events. Atherosclerosis is characterized by a series of deleterious changes in cellularity, including endothelial dysfunction, transmigration of circulating inflammatory cells into the arterial wall, pro-inflammatory cytokines production, lipid accumulation in the intima, vascular local inflammatory response, atherosclerosis-related cells apoptosis and autophagy. Proteins of Annexin A (AnxA) family, the well-known Ca

This study aimed to retrospectively examine the contribution of nurses to population health outcomes with reference to nurse visits and blood pressure measurement in primary health settings.A retrospective study was conducted using New Zealand Health Survey (NZHS) from 2012 to 2017.Adult population who are 18 years old and over living in New Zealand.Age, gender, and ethnicity, the service utilization of primary health care nurse visit and blood pressure measurement were extracted from the NZHS (2012-2017) to compare with the service utilization of primary health care nurses by different demographic groups.Females who have treated hypertension shows higher utilization of nurse visit than males. From 2015 to 2017, the participants in this cohort have visited a primary health care nurse at least more than once within a year. With blood pressure control, the overall pooled results show the impact of visiting primary health nurses on systolic and diastolic blood pressure control.Our study at a national scale, demonstrated the impact of nurse's contribution to population health outcomes among people living with hypertension in New Zealand. Nurses are key to improving population health outcomes and to achieve universal health coverage.

The widely recommended fracture prediction tool FRAX was developed based on and for the general population. Although several adjusted FRAX methods were suggested for type 2 diabetes (T2DM), they still need to be evaluated in T2DM cohort.This study was undertaken to develop a prediction model for Chinese diabetes fracture risk (CDFR) and compare its performance with those of FRAX.In this retrospective cohort study, 1730 patients with T2DM were enrolled from 2009.08 to 2013.07. Major osteoporotic fractures (MOFs) during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Multivariate Cox regression with backward stepwise selection was used to fit the model. The performances of the CDFR model, FRAX, and adjusted FRAX were compared in the aspects of discrimination and calibration.6.3% of participants experienced MOF during a median follow-up of 10 years. The final model (CDFR) included 8 predictors: age, gender, previous fracture, insulin use, diabetic peripheral neuropathy (DPN), total cholesterol, triglycerides, and apolipoprotein A. This model had a C statistic of 0.803 (95%CI 0.761-0.844) and calibration χThe CDFR model has good performance in 10-year MOF risk prediction in T2DM, especially in patients with insulin use or DPN. Future work is needed to validate our model in external cohort(s).

To investigate the implementation of treat-to-target (T2T) and treatment satisfaction from Chinese rheumatologists' perspectives.This retrospective analysis of a cross-sectional database collected from rheumatologists and their adult patients with RA in China using Adelphi Real World Disease Specific Programme™ methodology. Multivariate logistic regression models were used to evaluate factors associated with T2T use, achievement of T2T goals, and physician treatment satisfaction.Sixty physicians provided data for 600 patients, of whom 39.0% (234/600) were being treated using T2T, and 64.9% (366/564) had achieved their T2T goal. Physicians were satisfied with treatment in 74.3% (445/599) of patients. Patients with a higher pain score were more likely to be managed using T2T (odds ratio (OR) 1.25; p = 0.017), but less likely to have achieved the T2T goal (OR 0.76; p = 0.004). T2T use was more likely if patients had a longer time since diagnosis ( 2 vs ≤ 2 years; OR 1.61; p = 0.031) or received targeted synthetic or biologic disease-modifying antirheumatic drugs (tsDMARDs or bDMARDs; OR 6.90; p 0.001). T2T goal achievement was more likely for patients with higher body mass index (≥ 24 vs 24 kg/mT2T implementation in China is suboptimal. Our findings provide insight into T2T implementation and physician treatment satisfaction, supporting T2T use in Chinese RA clinical practice. Key Points • T2T implementation in China is currently suboptimal. • Patients with greater pain were more likely to be managed using T2T but were less likely to have achieved their T2T goals. • Physician treatment satisfaction was associated with T2T goal achievement.

This study aims to investigate the dosage pattern, efficacy, and safety of sacubitril/valsartan (Sac/Val) in Chinese heart failure with reduced ejection fraction (HFrEF) patients regarding real-world settings. Patients from 27 centers with a confirmed diagnosis of HFrEF and initiated Sac/Val treatment were enrolled. The primary objective was to evaluate the dosage pattern and change of heart failure status. In a final cohort of 983 patients, outpatient Sac/Val treatment demonstrated a similar beneficial effect in NT-proBNP and cardiac function. After initiating the treatment, overall and sub-population showed similar safety and efficacy. Patients who received a higher dose of Sac/Val (> 200 mg/d) demonstrated better improvement in LV function and reduction of NT-proBNP regardless of adjustment. Among Chinese HFrEF patients, Sac/Val showed a comparable reduction in NT-proBNP and improvement in cardiac function. Data further support guideline recommendations of Sac/Val in Chinese population. Optimal up-titration might provide further benefits. Further long-term and prognostic studies are needed. Graphical abstract

Objective. To study the expression and prognostic value of CDK6 in stomach cancer and the function of CDK4/6 inhibitor PD-0332991 on the proliferation of stomach cancer cells. Methods. Immunohistochemistry was used to detect the expression of CDK6 in stomach cancer tissues and adjacent normal tissues and to analyze the effect of CDK6 on clinicopathological parameters of stomach cancer patients. Kaplan-Meier plotter was employed to study the relationship between CDK6 and overall survival in stomach cancer. Western blot and RT-PCR were used to detect protein and gene expression of CDK6 in different cells. The effects of CDK4/6 inhibitor PD-0332991 on apoptosis and aging of stomach cancer cells were detected by flow cytometry and β-galactosidase aging staining assay. The effects of CDK4/6 inhibitor PD-0332991 on the invasion and migration of stomach cancer cells were explored by the wound healing experiment and the Transwell experiment. The supernatant of stomach cancer cells was collected, and the effect of CDK4/6 inhibitor PD-0332991 on tumor markers of stomach cancer cells was detected by biochemical immunoassay. Results. (1) CDK6 was highly expressed in stomach cancer tissues and cells. (2) Abnormally elevated CDK6 expression results in shorter survival in stomach cancer patients. (3) CDK4/6 inhibitor PD-0332991 could block the proliferation of stomach cancer cells, but not stomach epithelial proliferation. PD-0332991 could inhibit the secretion of pro-GRP by MGC 823. (4) PD-0332991 could advance the development of the apoptosis and senescence of stomach cancer cells and suppressed the invasion and migration of stomach cancer cells. Conclusion. CDK6 expression is elevated in gastric cancer, and the CDK4/6 inhibitor PD-0332991 can remarkably promote apoptosis and senescence of stomach cancer cells and effectively inhibit the migration and invasion of stomach cancer cells.

In this prospective interventional case series that included 474 patients, there were no significant differences in visual field (VF) parameters between fields from patients tested one-at-a-time and simultaneously, except for fixation losses.To test for differences in reliability and performance parameters of patients taking VF tests while using a remote patient monitoring system to supervise 1 or 2 test sessions simultaneously.In a prospective interventional case series, 861 eyes of 474 consecutive patients undergoing automated perimetry during a 6-month period were monitored during the test using an audio/video-enabled remote monitoring system. Two patients were simultaneously tested (simultaneous test) by a single technician if they were ready for testing at the same time. Patients were otherwise tested individually (single test). Performance and reliability parameters including false negatives, false positives, fixation losses, mean deviation, pattern standard deviation, VF index, and test duration were compared between patients undergoing simultaneous tests and single tests. Patients undergoing remotely monitored testing, for whom a prior VF could be found, had performance and reliability parameters compared with those prior tests. VFs were analyzed separately for 2 test strategies: SITA Standard 24-2 and SITA Faster 24-2C.No significant parameter differences were observed among SITA Standard 24-2 VFs between single and simultaneous tests, except for fixation losses (single: 16.8±19.7%, simultaneous: 22.5±25.0%, P=0.01). Similarly, there were no significant differences observed among SITA Faster 24-2C tests. Paired analyses comparing remotely monitored VFs with prior traditionally monitored VFs showed no significant differences for any parameters, except for fewer fixation losses with remote monitoring (traditional: 23.6±27.5%, remote 17.7±20.8%, P=0.003).Remote patient monitoring of VF testing enabled technicians to supervise testing of 2 patients simultaneously with preserved performance and reliability.

To examine loneliness experienced by middle-aged and older Chinese immigrants and its association with accepting technology as a companion (apps, Internet and robots) versus owning pets, when social distancing measures were implemented in New Zealand during the first COVID-19 outbreak.This study conducted a community-based cross-sectional survey. Chinese immigrants who were 45-87 years old (n = 173) were invited to answer an online survey in the Chinese language, collecting demographic data, responses to the 6-item De Jong Gierveld Loneliness Scale and experiences in using technology and pet ownership. Descriptive analyses and inferential statistics tests were utilised in the data analysis.A moderate level of overall loneliness with a mean score of 3.68 (SD 1.84), ranging from 0 to 6, was reported by participants. Emotional and social loneliness ranged from 0 to 3 with mean scores of 1.69 (SD 0.98) and 1.99 (SD 1.24), respectively. Self-reported health, financial status, English language abilities, transportation and experiences of using the Internet and apps were significantly related to experiencing loneliness. Loneliness had a weak association with acceptance of robots and pets, but 67.8% and 58.3% of participants who felt lonely, accepted companionship of robots and pets, respectively.The level of loneliness among older and middle-aged immigrants increased during the COVID-19 pandemic. Further evidence of the specific dimensions of loneliness and the utility of technology to alleviate loneliness among immigrant groups is needed. Interventions tailored for older people with specific cultural requirements to address loneliness are needed.

Frequent relapse is a prominent challenge in managing immunoglobulin G4-related disease (IgG4-RD). According to the types of organs involved in relapse, relapse patterns were divided into recurrent organ involvement (ROI) and new organ involvement (NOI). We aimed to investigate the discrepancy in clinical relapse patterns and establish an effective prognostic nomogram for NOI.We retrospectively enrolled 125 IgG4-RD patients who experienced relapse during the follow-up period. Patients were classified into two groups: those with NOI (including NOI and NOI + ROI) and without NOI (ROI). Logistic regression analyses were used to assess the risk factors for NOI. The results were externally validated by a separate prospective cohort of 39 patients with relapse.There were 81 (64.8%) and 44 (35.2%) patients without NOI and with NOI, respectively. Patients without NOI showed higher baseline disease activity. The most common ROIs were the lacrimal gland and submandibular gland, while the lung and urinary system were the most involved in NOI. Re-elevation of serum IgG4 level to 74.31% of baseline was associated with NOI. Multiple relapses, organ involvement type at baseline, glucocorticoids combined with immunosuppressive drugs (IM) or IM alone during the maintenance period, and relapse IgG4/baseline IgG4 ratio were included in the nomogram. Both internal and external validations showed good agreement and discrimination.About one third of IgG4-RD patients with relapse suffer from NOI. We developed a risk stratification model that can effectively predict the future risk of NOI. Glucocorticoid and IM combined therapy during maintenance is also recommended.

Background. Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are mainly characterized by progressive motor, sensory, or cognitive dysfunction in patients. Such diseases mostly occur in middle-aged and elderly people, and there is no effective cure. Studies have shown that neurodegenerative diseases are accompanied by neuroinflammation. The proinflammatory mediators produced neuroinflammation further damage neurons and aggravate the process of neurodegenerative diseases. Therefore, inhibiting neuroinflammation might be an effective way to alleviate neurodegenerative diseases. Pomiferin extracted from the fruit of the orange mulberry has a wide range of antioxidation and anti-inflammatory effects in peripheral tissues. However, it is not clear whether it plays a role on neuroinflammation. Methods. In our experiment, we studied the effect of Pomiferin on BV2 cell inflammation and its mechanism with cck-8, LDH, quantitative PCR, and ELISA and methods. We then investigated the effect of Pomiferin on the classical inflammatory pathway by Western blot methods. Results. The results showed that Pomiferin inhibited the production of ROS, NO, and proinflammatory mediators (IL-6, TNF-α, iNOS, and COX2) in BV2 cells. Further mechanism studies showed that Pomiferin activated the Akt/Nrf2 pathway and inhibited the NF-κB pathway. Conclusion. Our study demonstrated that Pomiferin exerts antineuroinflammatory effects through activating Akt/Nrf2 pathway and inhibiting NF-κB pathway.

Aims The ESC/EACTS myocardial revascularization guidelines recently standardized the definition of patients at high ischemic risk (HIR). However, the ability of ESC/EACTS-HIR criteria to stratify ischemic and bleeding risk in a contemporary real-world East Asian cohort remains unexplored. Methods A total of 10,167 consecutive patients undergoing PCI from prospective Fuwai PCI Registry (January 2013 to December 2013) were reviewed. ESC/EACTS-HIR features was defined as having at least one of the eight clinical and angiographic characteristics. The primary ischemic endpoint was target vessel failure (cardiac death, target vessel myocardial infarction [MI], or target vessel revascularization [TVR]); bleeding outcome was assessed using the BARC type 2, 3, or 5 bleeding. Median follow-up was 29 months. Results Compared with non-HIR patients, HIR patients (n=5,149, 50.6%) were associated with increased risk for target vessel failure (adjusted hazard ratio [HRadjust]: 1.48 [1.25-1.74]) and patient-oriented composite outcome (HRadjust: 1.44 [1.28-1.63]), as well as cardiac death, MI, and TVR. By contrast, the risk of clinically relevant bleeding was not significantly different between the two groups. (HRadjust: 0.84 [0.66-1.06]). Greater than or equal to three implanted stents and diabetic patients with diffuse multivessel coronary disease emerged as independent predictors for long-term adverse outcomes. There was no significant interaction between high bleeding risk (HBR) status and clinical outcomes associated with ESC/EACTS-HIR criteria (all Pinteraction ＞0.05). Conclusion The ESC/EACTS-HIR features identified patients at increased risk of thrombotic events, including cardiac death, but not for clinically relevant bleeding. Importantly, HBR did not modify cardiovascular risk subsequent to patients with ESC/EACTS-HIR features, suggesting its potential clinical applicability in tailoring antithrombotic therapy.

Bo Xie,1,* Yi Chen,2,* Yebei Hu,2 Yan Zhao,2 Haixin Luo,2 Jinhui Xu,1 Xiuzu Song1 1Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 2Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiuzu Song, Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, West Lake Road 38, Hangzhou, 310009, People’s Republic of China, Tel +86-571-87823102, Email songxiuzu@sina.comObjective: The treatment of vitiligo is often challenging to dermatologists. There is ample evidence to suggest that hydroxychloroquine (HCQ) is effective for vitiligo treatment; nonetheless, the underlying mechanism remains unknown. In the present study, we sought to uncover the molecular targets of HCQ by an integrated network-based pharmacologic and transcriptomic approach.Methods: The potential targets of HCQ were retrieved from databases based on the crystal structure. Targets related to vitiligo were screened and intersected with potential targets of HCQ. A protein-protein interaction network of the intersected targets was generated. Interactions between the targets were verified by molecular docking. Moreover, human vitiligo immortalized melanocytes (PIG3V) were evaluated after treatment with HCQ (1μg/mL) for 24h. The total RNA of PIG3V was extracted and determined by RNA-seq transcriptomics for differential gene expression analysis. Network pharmacology was then used to identify the relationships between putative targets of HCQ and differentially expressed genes.Results: Molecular docking analysis revealed four putative key targets (ACHE, PNMT, MC1R, and VDR) of HCQ played important roles in vitiligo treatment. According to the transcriptomic results, the melanosomal biogenesis-related gene BLOC1S5 was upregulated 138005.020 fold after HCQ treatment. Genes related to protein repair (MSRB3) and anti-ultraviolet (UV) effect (UVSSA) were upregulated 4.253 and 2.603 fold, respectively, after HCQ treatment.Conclusion: The expression of the BLOC1S5 gene is significantly upregulated, indicating upregulated melanosomal biogenesis after HCQ treatment. In addition, HCQ yields a protective effect on melanocytes by upregulating genes associated with damaged protein repair (MSRB3) and anti-UV effect (UVSSA). The protective effects of HCQ are mediated by binding to putative targets ACHE, PNMT, MC1R, and VDR according to network pharmacology and docking verification.Keywords: vitiligo, hydroxychloroquine, treatment, pigmentation, melanocyte protection

AimsHeart failure (HF) remains a major public health problem with increasing prevalence in China. This study evaluated the clinical performance and quality measures for HF management to identify gaps in the standardization of care for patients hospitalized for HF in China.Methods and resultsFollowing the results of China-HF stage I (2012-2015), the second stage of the China-HF was launched in 2017. Among 113 hospitals with ≥100 cases, the China-HF Stage II assessed the quality of care measures for HF and compared results with previous data in China and the US-based Get with The Guidelines-Heart Failure (GWTG-HF) registries. In total, 34938 patients hospitalized with HF were enrolled from January 2017 to October 2020. Echocardiographic left ventricular function and natriuretic peptide test were performed in 93.7% and 93.0% of the cases, respectively. Adherence to standardized guidelines in China-HF stage II was higher than that in the China-HF stage I, but generally lower than GWTG-HF registry with 78.2% of eligible patients was prescribed oral diuretics, 78.7% renin-angiotensin-system inhibitors, and 82.2% beta-blockers. Implantable cardioverter-defibrillators and cardiac resynchronization devices were implanted in 3.9% and 14.6%, respectively. In contrast, the proportion of eligible patients discharged with spironolactone (87.8%) was higher than GWTG-HF. The median length of hospitalization was 9 (6, 12) days, and 938 (2.8%) patients died or withdrew from treatment during hospitalization.ConclusionsDespite significant improvements in the use of guideline-recommended testing and therapy, there remain major gaps in quality of care for patients hospitalized for HF in China that are generally larger than gaps observed in the United States.

The social-economic-natural system is a complex system for human survival and development, and the data-driven system research provides a new value-added orientation to enhance the cognition of the ecosystem. Under the new data context, the social-economic-natural complex system shows new features. The research object is gradually changing from a single element to a multi-factor coupling direction, which makes the data system more diversified, data sources more extensive, data expression more visualized. The research scale shows the characteristics of gradually expanding, and the research object would be more detailed. In the process of data identification, expression and visualization, it is therefore necessary to strengthen the coupling of time, space, structure, quantity and order, as well as to focus on the integration with decision making and local services. The future research of complex ecosystems in the new era should be carried out in terms of key scientific issues and supporting technologies, the role of scale and multi-factor coupling, as well as scientific and technological support for local and global governance. Under the continuous innovation of data, strengthening the cognition of multi-source data, long-term monitoring and time series still needs to be studied in depth. Carrying out data-driven analysis of complex ecosystems not only provides technical support for ecosystem services and sustainable development and enhances the long-term data sharing mechanism, but also provides more value support for realizing decision making and information dissemination.社会-经济-自然系统是人类赖以生存和发展的复合系统,而数据驱动下的系统研究为加强生态系统的认知提供了新的增值导向。在新的数据语境下,社会-经济-自然复合系统呈现出一些新的特征,研究对象逐渐从单一要素向多要素耦合的方向转变,使支撑量化研究的数据体系更多样化、数据来源更广泛化、数据表达更具可视化,并呈现出研究尺度逐渐扩大化、研究对象更精细化的特征。在对数据的识别、表达和可视化的过程中,既要加强对时间、空间、结构、数量和秩序的耦合,也要注重与决策制定和地方服务的结合。新时期复合生态系统的未来研究方向应该从关键科学问题及支撑技术、尺度作用和多要素耦合以及地方和全球治理的科技支撑等方面展开,在数据的不断革新下,加强对多源数据、长期监测和时间序列的认知仍是需要深入研究的课题。开展复合生态系统的数据驱动分析,不仅能为生态系统的服务及可持续发展提供技术支撑,增强数据的长效共享机制,同时可为实现决策制定和信息传播等方面提供更多的价值支持。.

Background The effect of core decompression on the treatment of pre-collapse non-traumatic osteonecrosis of the femoral head (ONFH) is still limited. This study aimed to explore the efficacy of core decompression combined with intra-articular decompression (debridement of the hip joint and incision of the hip capsule) under hip arthroscopic guidance in patients with pre-collapse ONFH. Methods The clinical data of 101 patients with pre-collapse ONFH were analysed retrospectively. Sixty patients (80 hips) received small-diameter multi-channel core decompression alone in first half review period (group B). Forty-one patients (59 hips) were treated with small-diameter multi-channel core decompression combined with intra-articular decompression under hip arthroscopy guidance in second half review period (group A). The surgical duration; intraoperative bleeding; intra-articular pressure(IAP) before and after surgery; length of hospital stay; hospitalisation expenses; visual analogue scale (VAS) score before, 1 week, 4 weeks, 3 months and 1 year after surgery; and Harris score of the hip joint before, 3 months and 1 year after surgery were recorded and compared between group A and group B. X-ray examination was performed every month to observe the collapse of the femoral head within 2 years after surgery, which was compared using the Kaplan–Meier survival curve analysis. Results When the two groups were compared, the surgical duration was longer and hospitalisation expenses were higher in group A than in group B (P P P P Conclusion Small-diameter multi-channel core decompression combined with intra-articular decompression (debridement of the hip joint and incision of the hip capsule) under hip arthroscopic guidance for treating early ONFH can more effectively alleviate joint pain, improve joint function and delay ONFH progression.

Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse1–7. In the brain, the trafficking, gating kinetics and pharmacology of kainate receptors are tightly regulated by neuropilin and tolloid-like (NETO) proteins8–11. Here we report cryo-electron microscopy structures of homotetrameric GluK2 in complex with NETO2 at inhibited and desensitized states, illustrating variable stoichiometry of GluK2–NETO2 complexes, with one or two NETO2 subunits associating with GluK2. We find that NETO2 accesses only two broad faces of kainate receptors, intermolecularly crosslinking the lower lobe of ATDA/C, the upper lobe of LBDB/D and the lower lobe of LBDA/C, illustrating how NETO2 regulates receptor-gating kinetics. The transmembrane helix of NETO2 is positioned proximal to the selectivity filter and competes with the amphiphilic H1 helix after M4 for interaction with an intracellular cap domain formed by the M1–M2 linkers of the receptor, revealing how rectification is regulated by NETO2. The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.

Circular RNAs (circRNAs) are reported to participate in the development of diverse human malignancies. This work investigated the mechanism of circSKA3 in modulating medulloblastoma progression. A total of 15 cases of medulloblastoma were collected in this work. Daoy cells were used to construct cell models. The expression level of circSKA3, microRNA-520 h (miR-520 h), and cyclin-dependent kinase 6 (CDK6) mRNA in tissues or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was employed to detect CDK6 protein expression. CCK-8 experiment, Transwell assay, and flow cytometry were applied to detect the regulatory effects of circSKA3 on cell proliferation, migration, invasion, and cell cycle. Dual-luciferase reporter gene experiment was executed to determine the relationship between circSKA3 and miR-520 h, and between miR-520 h and CDK6. circSKA3 was remarkably up-modulated in medulloblastoma tissues. CircSKA3 depletion markedly suppressed Daoy cell viability, migration, invasion, and cell cycle progression. CircSKA3 overexpression induced the opposite effects. circSKA3 could decoyed miR-520 h, which targeted the 3' UTR of CDK6. circSKA3 expression in medulloblastoma tissues was negatively correlated with miR-520 h expression and positively correlated with CDK6 expression. "Rescue" experiments revealed that miR-520 h down-modulation or CDK6 overexpression remarkably counteracted the inhibitory effect of circSKA3 knockdown on Daoy cells. circSKA3 facilitates medulloblastoma progression through miR-520 h/CDK6.

Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can better escape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by which transcriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouse lungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved in the disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishment increased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 induced TRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT by reducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.

Objective. To investigate the effects of the training of aerobic function on clinical symptoms and quality of life in patients with medium and advanced lung cancer. Methods. The study objects were 84 patients with medium and advanced lung cancer who were treated in our hospital (July 2019–July 2021) and their materials were retrospectively reviewed. Depending on the different intervention modes, they were equally divided into control group (routine nursing intervention measures) and experiment group (training of aerobic function), with 42 cases in each group. The clinical symptoms and living quality were compared between the two groups. Results. After intervention, affective meaning, behavior/severity, cognitive/mood, and sensory scores in both groups were decreased, and the various indexes in the experiment group were lower compared with the control group (P

The PDCA cycle, also known as Deming's cycle, mainly includes four stages: planning, implementation, inspection, and processing. As a kind of atypical pneumonia with fever and cough, mycoplasma pneumonia harms the health of many children. The purpose of this study is to investigate the anti-inflammatory and antimycoplasma effects and safety of artificial intelligence e-health PDCA nursing mode on pediatric MPP, to investigate its clinical efficacy, to observe the changes of serum cytokines (IL-10, IL-2, IL-4, IFN-γ), and to explore the mechanism of action and possible targets for the treatment of MPP, to provide a new basis for clinical treatment of MPP. The experimental results show that in the experimental group using PDCA nursing mode, the total satisfaction is 97.22%, higher than the control group of 94.44%; in the experimental group, the hospital stay and symptom disappearance time were significantly shortened by four hours. The satisfaction of nursing staff was significantly increased in statistical significance P < 0.05 . Therefore, in a statistical sense, the artificial intelligence e-health PDCA nursing mode can significantly improve the clinical symptoms of MPP children with wind-heat stagnation of lung syndrome and phlegm-heat closure of lung syndrome, improve the treatment effect of childhood mycoplasma pneumonia epidemic, shorten the time of hospitalization and symptom disappeared, and play a great auxiliary role in the treatment of childhood mycoplasma pneumonia.

The complete mesogastrium excision (CME) based on D2 radical gastrectomy is believed to significantly reduce the local-regional recurrence compared with D2 radical gastrectomy in advanced gastric cancer, and it is widely used in China. This study aimed to explore whether D2 + CME is superior to D2 on surgical outcomes during gastrectomy from Chinese data.Feasible studies comparing the D2 + CME (D2 + CME group) and D2 (D2 group) published up to March 2020 are searched from electronic databases. The data showing surgical and complication outcomes are extracted to be pooled and analyzed.Fourteen records including 1352 patients were included. The D2 + CME group had a shorter mean operative time (weighted mean difference [WMD] = -16.72 min, 95% confidence interval [CI]: -26.56 to -6.87 min, P 0.001), lower mean blood loss (WMD = -39.08 mL, 95% CI: -49.94 to -28.21 mL, P 0.001), higher mean number of retrieved lymph nodes (WMD = 2.13, 95% CI: 0.58-3.67, P = 0.007), shorter time to first flatus (WMD = -0.31 d, 95% CI: -0.53 to - 0.10 d, P = 0.005), and postoperative hospital days (WMD = -1.09, 95% CI: -1.92 to -0.25, P = 0.010) than the D2 group. Subgroup analysis suggested that the advantages from the D2 + CME group were obvious in traditional open radical gastrectomy, proximal gastrectomy, and distal gastrectomy compared with D2 group. The evaluations of post-operative complications showed that the patients who underwent D2 + CME had a lower incidence of post-operative complications than the patients who underwent D2 surgery alone (relative risk [RR] = 0.65, 95% CI: 0.45-0.87, P = 0.003). The D2 radical gastrectomy plus CME improved 3-year overall survival (OS) (RR = 1.16, 95% CI: 1.02-1.32, P = 0.020) and lowered the local recurrence rate (RR = 0.51, 95% CI: 0.28-0.94, P = 0.030). The patients undergoing laparoscopic surgery or total gastrectomy had more significant advantages compared between D2 + CME and D2 groups in 3-year OS.The data from China show that D2 radical gastrectomy plus CME are reliable procedures and safety compared to D2 radical gastrectomy with faster recovery, lower risk, and better prognosis.

Chinese patent medicine (CPM) has been widely used in China for patients with osteoporosis (OP) but a comprehensive literature review is still important. Therefore, we performed meta-analysis using six electronic databases prior to 30 April 2021 only randomized controlled trials (RCTs) using CPM as the first-line treatment in adults with OP were included. Thirty RCTs met the inclusion criteria with a total of 2723 patients, and seven types of CPM were included. Compared with the control group, 23 studies showed significantly improved bone mineral density (BMD) (lumbar spine) (mean difference [MD] = 0.08; confidence interval [CI], 0.03 to 0.13), 15 studies showed significantly improved BMD (femoral) (MD = 0.05; 95% CI, 0.02 to 0.07), 6 studies showed significantly improved BMD (radius) (MD = 0.06; 95% CI, 0.03 to 0.09), 2 trials showed significantly improvement of BMD (ulna) (MD = 0.02; 95% CI, 0.01 to 0.03), and 4 trials showed significantly improved BMD (MD = 0.09; 95% CI, 0.09 to 0.10). The meta-analysis also showed that CPM had superior pain improvement, a higher total effectiveness rate, and a lower risk of adverse events compared with standard western treatment. The findings of this study suggest that CPM therapy may be a safe and effective alternative treatment modality for OP, it has potential benefits in relieving symptoms and improving BMD compared to western medications or placebos.

The study aims to explore the scheduling plan for the emergency of blockchain technology in the medical industry. Network security architecture for medical supplies management based on the Hyperledger Fabric optimized consensus mechanism is established by studying the characteristics of blockchain technology and its data structure composition. The supply chain model for medical device scheduling based on intelligent contracts is selected for the particularity of the nature and shape of medical devices in medical supplies. Ant colony algorithm is used to solve it. Case analysis and verification results show that the improved Hyperledger Fabric consensus mechanism has better security performance. Under the condition of 10,000 transactions, the probability of an attacker with the optimized consensus mechanism successfully controlling the transaction is only 7.2%. The optimized solution is about 50% higher than the original solution in terms of transaction processing speed. Over 1000 transactions, the transaction latency optimization rate is more than doubled. The total order completion time of the medical device scheduling model adopted by the intelligent contract is 26.3% higher than the historical service time of 19 days. The performance of the medical emergency material scheduling program that is added to the supply chain technology is better.

This study aims to clarify the relationship between the changes of pancreatic size after glucocorticoid (GC) therapy and relapse in IgG4-related autoimmune pancreatitis (AIP).We prospectively enrolled 205 newly diagnosed IgG4-related AIP patients. 145 patients were followed up for more than 3 years. These patients were divided into three groups according to the changes of pancreatic size after treatment of 6 months: pancreatic swelling, normal size, and pancreatic atrophy. Baseline clinical and laboratory parameters were compared among three groups. Kaplan-Meier survival analysis was performed in the 134 patients based on GC therapy. Besides, Cox regression analysis and logistic regression analysis were performed to identify risk factors associated with relapse and the potential variables affecting changes of pancreatic size after treatment.Age at diagnosis, white blood cell count, and serum IgG1 level at baseline were significantly different among the three groups. After treatment of 6 months, the pancreas of most patients (n = 81, 55.9%) could return to normal size, while persistent pancreatic swelling was found in 24.1% patients (n = 35), and atrophy was observed in 20.0% of the patients (n = 29). Kaplan-Meier survival analysis presented patients with pancreatic swelling after 6 months of GC therapy were more likely to relapse in the follow-up of 3 years. Persistent pancreatic swelling after treatment and salivary gland involvement at baseline were independent risk variables associated with relapse in IgG4-related AIP patients, while GC-based therapy was a protective factor of relapse. Logistic regression analysis revealed that older age at diagnosis was associated with pancreatic atrophy and higher baseline serum IgG1 level was associated with pancreatic swelling after treatment of 6 months.Patients with persistent pancreatic swelling after GC-based therapy of 6 months were more likely to relapse in the follow-up of 3 years. Older age at diagnosis and higher baseline serum IgG1 level were potential variables associated with pancreatic atrophy or swelling after treatment of 6 months. Key Points • Patients with persistent pancreatic swelling after glucocorticoid-based therapy were more likely to relapse in IgG4-related autoimmune pancreatitis. • Older age at diagnosis was associated with pancreatic atrophy after glucocorticoid-based therapy. • Higher baseline serum IgG1 level was associated pancreatic swelling after glucocorticoid-based therapy.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.

Background The purpose of this study was to evaluate the outcomes of bifocal bone transport in the treatment of femoral bone defects caused by infections. Methods Clinical and radiographic data of patients with infected femoral nonunion treated by the bifocal bone transport at our hospital were analyzed retrospectively, from January 2008 to December 2019. Depending on the location of bone defects, the patients were divided into three groups (proximal, intermediate, and distal). The Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria was applied to assess the bone and functional outcomes. Postoperative complications of three groups were documented and compared. Results Seventy-six cases of infected femoral bone defects (31 cases of proximal, 19 cases of intermediate, and 26 cases of distal) were managed by bifocal bone transport successfully with a mean follow-up time of 30.8 months (range, 23 to 41 months). There were 58 men (76.3%) and 18 women (23.6%), with a mean age of 38.8 years (range, 23 to 60 years). The bone union was received in 76 cases with a mean of 6.9 months (range, 5 to 8 months). Pin tract infection was observed in twenty-nine cases (38.1%), 7 cases (9.2%) of muscle contractures, 3 cases (7.9%) of joint stiffness, 13 cases (17.1%) of axial deviation, 2 cases (2.6%) of delayed union, one case (1.3%) of nonunion, and none (0%) of transport gap re-fracture. One patient (1.3%) was scheduled for knee arthroplasty when bone transport treatment ended. Conclusions Bone transport using an external rail fixator was a practical method to treat the femoral bone defects, since the satisfactory rate of bone union and limb function recovery. Complications of distal femoral bone transport were more severe than the proximal and intermedia, but the rate of complication was the least of the three groups. Soft-tissue-related complications were more likely to occur in the intermediate bone transport.

Purpose The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. Experimental design The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. Results Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). Conclusions Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.

Inflammatory bowel disease is a chronic disease of the intestinal tract, which is related to increased levels of various inflammatory mediators. This study aims to explore the anti-inflammatory mechanism of small molecular peptide WLS and its alleviating effect on inflammatory bowel disease (IBD). In TNF-α-induced HT-29 cells, WLS inhibited IL-8 secretion, decreased gene expression of pro-inflammatory cytokines IL-8, IL-6, IL-1β, and TNF-α, and inhibited the activation of MAPK/NF-κB signaling pathways. In the dextran sulfate sodium salt (DSS) induced colitis mouse model, WLS inhibited weight loss and disease activity index scores, increased colon length, improved colon histopathology, inhibited secretion of IL-6 and TNF-α in the colon, and down-regulated gene expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β, IFN-γ, IL-17A). This study revealed that WLS was a novel small molecule peptide with anti-inflammatory activity and may be a potential candidate for the treatment of inflammatory bowel disease.

Objective This study aims to investigate the incidence, occurrence timing and locations of preoperative DVT and identify the associated factors in this group. Methods A retrospective analysis of collected data in young and middle-aged (18–59 years) patients who presented with hip fracture between October 2015 and December 2018 was conducted. Before operation, patients were routinely examined for DVT by Duplex ultrasonography (DUS). Electronic medical records were retrieved to collect the data, involving demographics, comorbidities, injury and laboratory biomarkers after admission. Multivariate logistic regression analysis was performed to identify factors that were independently associated with DVT. Results Eight hundred and fifty-seven patients were included, and 51 (6.0%) were diagnosed with preoperative DVT, with 2.5% for proximal DVT. The average age of patients with DVT is 48.7 ± 9.4 year, while that of patients without DVT is 45.0 ± 10.9 year. The mean time from injury to diagnosis of DVT was 6.8 ± 5.5 days, 43.1% cases occurring at day 2–4 after injury. Among 51 patients with DVT, 97 thrombi were found. Most patients had thrombi at injured extremity (72.5%), 19.6% at uninjured and 7.8% at bilateral extremities. There are significantly difference between patients with DVT and patients without DVT in term of prevalence of total protein (41.2% vs 24.4%, P = 0.008), albumin (54.9% vs 25.6%, P = 0.001), low lactate dehydrogenase (51.0% vs 30.3%, P = 0.002), lower serum sodium concentration (60.8% vs 29.9%, P = 0.001), lower RBC count (68.6% vs 37.0%, P = 0.001), lower HGB (51.0% vs 35.1%, P = 0.022), higher HCT (86.3% vs 35.1%, P = 0.022) and higher platelet count (37.3% vs 11.3%, P = 0.001). The multivariate analyses showed increasing age in year (OR 1.04, 95% CI; P = 0.020), delay to DUS (OR, 1.26; P = 0.001), abnormal LDH (OR, 1.45; P = 0.026), lower serum sodium concentration (OR, 2.56; P = 0.007), and higher HCT level (OR, 4.11; P = 0.003) were independently associated with DVT. Conclusion These findings could be beneficial in informed preventive of DVT and optimized management of hip fracture in specific group of young and mid-aged patients.

The microRNA (miRNA) miR-576-5p was reported to facilitate tumor progression, but its underlying regulatory impacts on colon adenocarcinoma remain unknown. This work therefore attempted to examine the biological effects of miR-576-5p in colon adenocarcinoma. The Cancer Genome Atlas (TCGA) database was introduced to analyze miR-576-5p and NEGR1 messenger RNA (mRNA) expression levels between normal and cancer tissues. miR-576-5p and NEGR1 expression levels in colon adenocarcinoma cells and colon cells were evaluated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). NEGR1 protein expression was examined by Western blot. Furthermore, colon adenocarcinoma cell behaviors were evaluated via CCK-8, wound-healing, Transwell, and hanging drop experiments. The interaction between miR-576-5p and NEGRI was verified by dual-luciferase assay. miR-576-5p was upregulated in colon adenocarcinoma, and miR-576-5p overexpression notably facilitated the proliferative, migratory, invasive abilities of colon adenocarcinoma cells. NEGR1 was newly identified as one target of miR-576-5p, and, miR-576-5p/NEGR1 axis was subsequently verified to modulate cell proliferative, migratory, invasive, and aggregate abilities. miR-576-5p facilitated aggressive progression of colon adenocarcinoma cells by targeting NEGR1, which could be an underlying therapeutic target for colon adenocarcinoma.

Although the DNA damage response (DDR) is associated with the radioresistance characteristics of lung cancer cells, the specific regulators and underlying mechanisms of the DDR are unclear. Here, we identified the serine proteinase inhibitor clade E member 2 (SERPINE2) as a modulator of radiosensitivity and the DDR in lung cancer. Cells exhibiting radioresistance after ionizing radiation show upregulation of SERPINE2, and SERPINE2 knockdown improves tumor radiosensitivity in vitro and in vivo. Functionally, SERPINE2 deficiency causes a reduction in homologous recombination repair, rapid recovery of cell cycle checkpoints, and suppression of migration and invasion. Mechanistically, SERPINE2 knockdown inhibits the accumulation of p-ATM and the downstream repair protein RAD51 during DNA repair, and RAD51 can restore DNA damage and radioresistance phenotypes in lung cancer cells. Furthermore, SERPINE2 can directly interact with MRE11 and ATM to facilitate its phosphorylation in HR-mediated DSB repair. In addition, high SERPINE2 expression correlates with dismal prognosis in lung adenocarcinoma patients, and a high serum SERPINE2 concentration predicts a poor response to radiotherapy in non-small cell lung cancer patients. In summary, these findings indicate a novel regulatory mechanism by which SERPINE2 modulates the DDR and radioresistance in lung cancer.

The purpose of this study was to explore the possible association between dairy and NCDs and identify possible dairy types that could lower the odds of NCDs. Data were from the 2003–2016 NHANES, a cross-sectional study with 20,297 adults. Multivariable logistic regression analyses and restricted cubic spline (RCS) models were conducted. In the highest intake group (>250 g/d, 1 daily serving), yogurt and milk were inversely associated with the odds of general obesity and central obesity [OR (95% CI), general obesity, 0.74 (0.60–0.91) and 0.75 (0.68–0.83); central obesity, 0.70 (0.56–0.87), and 0.77 (0.70–0.86), respectively, p

Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs

Aim. To explore the expression levels of miR-210, miR-137, and miR-153 in patients with acute cerebral infarction. Material and Methods. 76 patients with acute cerebral infarction treated in our hospital from April 2016 to October 2017 were enrolled as the observation group. Another 64 normal patients were selected as the control group. The patients were divided into the death and survival groups based on 1-year mortality of patients. qRT-PCR was used to detect the expression of miR-210, miR-137, and miR-153 in the serum of each group. Receiver operating characteristic (ROC) curve was employed to analyze the diagnostic value and predictive value of miR-210, miR-137 and miR-153 death in patients. The correlation between miR-210, miR-137, and miR-153 in the serum of the observation group was analyzed by Pearson’s test. Results. Levels of miR-210 and miR-137 in the observation group were significantly lower than those in the control group, while levels of miR-153 in the observation group were significantly higher than those in the control group (all P < 0.05 ). The ROC curve of diagnosis of acute cerebral infarction showed that the area under curve of miR-210 was 0.836, that of miR-137 was 0.843, and that of miR-153 was 0.842. The 1-year survival rate was 71.05%. The 1-year survival of the low-expression group of miR-210 and miR-137 was significantly lower than that of the high-expression group, while the 1-year survival of the low-expression group of miR-153 was significantly higher than that of the high-expression group (all P < 0.05 ). The ROC curve for predicting death showed that the area under curve of miR-210 was 0.786, that of miR-137 was 0.824, and that of miR-153 was 0.858. Pearson’s correlation analysis showed that the expression of miR-210 was positively correlated with that of miR-137, while miR-137 was negatively correlated with that of miR-153 and miR-210 was negatively correlated with that of miR-153. Conclusion. miR-210, miR-137, and miR-153 have a certain value in the diagnosis and prediction of 1-year death of acute cerebral infarction and may be potential diagnostic and predictive indicators.

Background The effect of the living environment on public health has received increasingly scholarly attention. This study aims to explore the relationship between adolescents’ body weight and their living environmental factors. Methods This cross-sectional study comprised 1362 middle-school students from Nanjing and 826 from Changzhou in China. We further collected information on living environmental factors based on their home address and ran multivariate logistic regressions to explore potential correlations after considering a range of potential confounding factors. Results Approximately 25% (n = 303) of students from Nanjing and 26% (n = 205) of students from Changzhou were excessive body weight. In Nanjing, students’ BMI (Body Mass Index) showed a strong negative correlation with the number of sports venues in their neighborhood (Adjusted Odds Ratio (AOR): 0.64, 95%CI: 0.40–0.94) after controlling for other covariates. In Changzhou, we observed a positive correlation between adolescents’ body weight and the number of bus stops in their neighbourhood (AOR:1.63, 95%CI:1.11–2.38). Conclusions The living environment factors were independently associated with teenagers’ excessive body weight. We hypothesis that the environmental risk factors might be associated with political management, which will consequently affect personal health outcomes. Further research and proactive measures are required to manage those potential risks and attenuate the problem.

BACKGROUND Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence. METHODS Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression-based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post-admission. RESULTS By distinguishing recurrence-associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non-recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy. CONCLUSIONS Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment.