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Four new tirucallane-type triterpenoids, polystanins H–K (1–4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans. [ABSTRACT FROM AUTHOR]

Introduction: Although the prevalence of Asian chronic lymphocytic leukemia (CLL) patients is not as high as that of Caucasians, there are more atypical CLLs in Asia whose genetic characteristics and their clinical significance are distinct and remain unclear. Methods: A retrospective analysis of 85 CLL samples in our center was conducted from 2019 to 2022. We used next‐generation sequencing with a 172 gene panel to explore the multi‐gene mutational data and the mutational status of immunoglobulin heavy variable (IGHV) gene. Results: MYD88 (20.0%) was the most frequently mutated gene, much higher than in Europe, followed in order by TP53 (18.8%), NOTCH1 (14.1%), IGLL5 (11.8%), and DNMT3A (8.2%). In addition, the incidence of ATM and SF3B1 mutations was relatively lower in our centre compared to Europe. Mutated (M)‐IGHV patients were more likely to have a cooccurrence of MYD88 mutation, while complex karyotype and DNMT3A mutation were more common in the unmutated (U)‐IGHV group. MYD88 mutated CLL was characterized by prevalence in young males in high‐risk staging, with isolated 13q deletion and concomitant mutation of IGLL5. CLL patients with MYD88 and TP53 mutation showed an unfavorable prognosis. Conclusion: These results would be valuable in helping to understand the characteristics and significance of cytogenetic genetics in Chinese patients with CLL. [ABSTRACT FROM AUTHOR]

It is commonly accepted that host genes show high methylation in cervical intraepithelial neoplasia 3 (CIN3) or worse (CIN3+). However, study quality varies, as does the clinical performance of markers in different populations. We aimed to validate candidate gene DNA methylation with standardized testing methods in the same batch of samples. We first compared the performance of 16 DNA methylation markers for detecting CIN3+ in the 82-sample training set, including 24 subjects with ≤ CIN1, 10 subjects with CIN2, 23 subjects with CIN3, and 25 subjects with cervical cancer (CC). Then five methylation markers were selected and subsequently validated among an independent set of 74 subjects, including 47 subjects with ≤ CIN1, 13 subjects with CIN2, 6 subjects with CIN3, and 8 subjects with CC. The results in the validation set revealed that methylation analysis of the SOX1 (SOX1m) showed a superior level of clinical performance (AUC = 0.879; sensitivity = 85.7%; specificity = 90.0%). SOX1m had better accuracy than cytology, with a reduced referral rate (23.0% vs. 31.4%) and a lower number of overtreatment (5 vs. 13) cases among high-risk human papillomavirus (hrHPV)-positive women. Importantly, among hrHPV-positive and SOX1m-negative women, only 1 CIN3 patient was at risk for follow-up after 1 year, whereas 1 CIN3 patient and 1 CC patient were at risk among hrHPV-positive and cytology-negative women. In this investigation, we screened 16 reported methylation markers to provide a basis for future studies related to potential precancerous lesion/cancer methylation markers in the Chinese population. The study also revealed that SOX1m has optimal CIN3+ detection performance, suggesting that it may be a promising biomarker for detecting CIN3+ in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. Methods: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. Results: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45–0.84; p < 0.01), deltoid (0.77, 95% CI 0.60–0.94; p = 0.04), thenar (0.72, 95% CI 0.55–0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73–0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. Conclusions: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock. [ABSTRACT FROM AUTHOR]

Background: Caudal epidural block (CEB) may be beneficial in anorectal surgery because its use may extend postoperative analgesia. This dose-finding study aimed to estimate the minimum effective anesthetic concentrations for 95% patients(MEC95) of 20 ml or 25 ml of ropivacaine in with CEB. Patients and methods: In this double-blind, prospective study, the concentration of ropivacaine administered in 20 ml and 25 ml for ultrasound-guided CEB were determined using the sample up-and-down sequential allocation study design of binary response variables. The first participant was given 0.5% ropivacaine. Depending on whether a block was successful or unsuccessful, the concentration of local anesthesia was decreased or increased by 0.025% in the next patient. Every five minutes for 30 min, the sensory blockade using a pin-prick sensation at S3 dermatome compared to at T6 dermatome were evaluated every 5 min within 30 min. An effective CEB was defined as a a reduction of sensation at S3 dermatome and the existence of flaccid anal sphincter. Anesthesia was considered successful if the surgeon could perform the surgery without additional anesthesia. We determined the MEC50 using the Dixon and Massey up-and-down method and estimated the MEC95 using probit regression. Results: The concentration of ropivacaine administered in 20 ml for CEB ranged from 0.2% to 0.5%. Probit regression with a bias-corrected Morris 95% CI derived by bootstrapping showed an MEC50 and MEC 50 of ropivacaine for anorectal surgical anesthesia were 0.27% (95% CI, 0.24 to 0.31) and 0.36%(95% CI, 0.32 to 0.61). The concentration of ropivacaine administered in 25 ml for CEB ranged from 0.175 to 0.5. Probit regression with a bias-corrected Morris 95% CI derived by bootstrapping showed an MEC50 and MEC95 for CEB were 0.24% (95% CI, 0.19 to 0.27) and 0.32% (95% CI, 0.28 to 0.54). Conclusion: With ultrasound-guided CEB, the MEC95 of 0.36% ropivacaine at 20 ml and 0.32% ropivacaine at 25 ml provide adequate surgical anesthesia/analgesia 95% of patients undergoing anorectoal surgery. Trial registration: Clinicaltrails.gov: Retrospectively registered (ChiCTR2100042954; Registration date:1/2, 2021). [ABSTRACT FROM AUTHOR]

The sympathoadrenal system has been shown to stimulate the secretory activity of enteroendocrine cells, although the response is transient. Our aim was to investigate the effects of long-term catecholamine excess on circulating glucagon-likepeptide-1 (GLP-1) levels in patients with pheochromocytoma/paraganglioma (PPGL). Thirty patients diagnosed with PPGL were analyzed. A significant negative association was observed between fasting plasma GLP-1 levels and elevated plasma-free metanephrine (r = − 0.407 , p = 0.026). After adjustment for age, sex, body mass index (BMI), serum creatinine, and the presence of hyperglycemia, the negative association between plasma GLP-1 and metanephrine persisted by multiple linear regression analysis (β = − 0.493 , p = 0.013). Positive correlations between fasting glucose and plasma metanephrine (r = 0.380 , p = 0.038) and normetanephrine levels (r = 0.450 , p = 0.013) were also found. Mean fasting levels of total GLP-1 increased significantly from 25.81 to 39.01 pmol/L (p = 0.017) after PPGL resection. In conclusion, long-term overproduction of catecholamines appears to induce suppression of GLP-1 production compared to an acute response to a stress stimulus. Further studies are required to elucidate the mechanism of GLP-1 secretion with chronic exposure to catecholamine. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose–response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment. Methods: The proposed methodology of integrated dose–response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose–response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM. Results: This developed strategy was successfully applied to rhubarb. The dose–response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case. Conclusion: An integrated dose–response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics. [ABSTRACT FROM AUTHOR]

Background: Engineering programs have increasingly incorporated design challenges into courses. These design challenges vary in the degree to which they present complex, ill‐structured, and relevant problems, and therefore may vary in the degree to which they support students to learn to frame design problems. Purpose/Hypothesis: We characterized how first‐year engineering students with little formal design training approach problem framing. We developed design challenges informed by funds of knowledge. We compared the development of problem framing skills in first‐year students who completed these challenges to students who completed more traditional challenges and to students in capstone design. Design/Method: Students completed a pre/post performance‐based assessment of problem framing skills. We analyzed student responses in terms of design requirements, design practices, and design styles. We used descriptive statistics and correlations to characterize how students initially approached problem framing and repeated‐measures ANOVA to compare groups of students. Results: First‐year students approached framing a design problem in one of four primary ways. Compared to students in the original course, they showed growth in attending to an underlying need, considering contexts of use, and depicting design function. Compared to capstone students, they also showed growth in considering stakeholder roles and planning the next steps. Conclusions: Funds of knowledge can provide a means to evaluate possible design challenges as authentic yet accessible for first‐year students, in turn, providing opportunities to support the development of the design problem framing ability. [ABSTRACT FROM AUTHOR]

Objectives: Typically, prognostic capability of gene expression profiling (GEP) is studied in the context of clinical trials, for which 50%‐80% of patients are not eligible, possibly limiting the generalizability of findings to routine practice. Here, we evaluate GEP analysis outside clinical trials, aiming to improve clinical risk assessment of multiple myeloma (MM) patients. Methods: A total of 155 bone marrow samples from MM patients were collected from which RNA was analyzed by microarray. Sixteen previously developed GEP‐based markers were evaluated, combined with survival data, and studied using Cox proportional hazard regression. Results: Gene expression profiling‐based markers SKY92 and the PR‐cluster were shown to be independent prognostic factors for survival, with hazard ratios and 95% confidence interval of 3.6 [2.0‐6.8] (P <.001) and 5.8 [2.7‐12.7] (P <.01) for overall survival (OS). A multivariate model proved only SKY92 and the PR‐cluster to be independent prognostic factors compared to cytogenetic high‐risk patients, the International Staging System (ISS), and revised ISS. A substantial number of high‐risk individuals could be further identified when SKY92 was added to the cytogenetic, ISS, or R‐ISS. In the cytogenetic standard‐risk group, ISS I/II, and R‐ISS I/II, 13%, 23%, and 23% of patients with adverse survivals were identified. Conclusions: For the first time, this study confirmed the prognostic value of GEP markers outside clinical trials. Conventional prognostic models to define high‐risk MM are improved by the incorporation of GEP markers. [ABSTRACT FROM AUTHOR]

ICU readmissions and post-discharge mortality pose significant challenges. Previous studies used EHRs and machine learning models, but mostly focused on structured data. Nursing records contain crucial unstructured information, but their utilization is challenging. Natural language processing (NLP) can extract structured features from clinical text. This study proposes the Crucial Nursing Description Extractor (CNDE) to predict post-ICU discharge mortality rates and identify high-risk patients for unplanned readmission by analyzing electronic nursing records. Developed a deep neural network (NurnaNet) with the ability to perceive nursing records, combined with a bio-clinical medicine pre-trained language model (BioClinicalBERT) to analyze the electronic health records (EHRs) in the MIMIC III dataset to predict the death of patients within six month and two year risk. A cohort and system development design was used. Based on data extracted from MIMIC-III, a database of critically ill in the US between 2001 and 2012, the results were analyzed. We calculated patients' age using admission time and date of birth information from the MIMIC dataset. Patients under 18 or over 89 years old, or who died in the hospital, were excluded. We analyzed 16,973 nursing records from patients' ICU stays. We have developed a technology called the Crucial Nursing Description Extractor (CNDE), which extracts key content from text. We use the logarithmic likelihood ratio to extract keywords and combine BioClinicalBERT. We predict the survival of discharged patients after six months and two years and evaluate the performance of the model using precision, recall, the F 1 -score, the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), and the precision–recall curve (PR curve). The research findings indicate that NurnaNet achieved good F 1 -scores (0.67030, 0.70874) within six months and two years. Compared to using BioClinicalBERT alone, there was an improvement in performance of 2.05 % and 1.08 % for predictions within six months and two years, respectively. CNDE can effectively reduce long-form records and extract key content. NurnaNet has a good F 1 -score in analyzing the data of nursing records, which helps to identify the risk of death of patients after leaving the hospital and adjust the regular follow-up and treatment plan of relevant medical care as soon as possible. [ABSTRACT FROM AUTHOR]

Objective. This study tends to assess the dose-dependent effects of spironolactone on TGF-β1 expression, atrial fibrosis, and the vulnerability to atrial fibrillation in spontaneously hypertensive rats (SHRs) and tries to clarify the association of atrial fibrosis with the vulnerability to atrial fibrillation. Methods. Forty 20-week-old male SHRs were randomly divided into 4 groups (10 rats per group): 3 spironolactone groups were lower-dose group (10 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SL), medium-dose group (40 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SM), higher-dose group (80 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SH) and one hypertension group (2 ml saline solution for stomach gavage, group H). Ten matched homologous WKY rats were set as the control group (group C). After 7 weeks of gavage, a multiple electroconductive physiological recorder was used to detect atrial electrical parameters, including P-wave duration, PR interval, and atrial effective refractory period (AERP), the inducibility, and duration of atrial fibrillation. HE staining was used to determine myocardial cell size. Masson staining was used to detect the deposition of the interstitial collagen fibers in atrial muscle. The expression of TGF-β1 was detected by immunohistochemistry and western blot. Results. Compared with group C, the myocardial cell size, atrial fibrosis, TGF-β1 expression, P-wave duration, PR interval, AERP, inducibility, and duration of atrial fibrillation in group H were conspicuously increased (p < 0.05); compared with group H, there was no significant difference in the myocardial cell size, atrial fibrosis, TGF-β1 expression, and electrophysiological indexes in group SH upon spironolactone intervention (p > 0.05); compared with group H, the myocardial cell size, atrial fibrosis, the expression of TGF-β1, P-wave duration, PR interval, the inducibility, and duration of atrial fibrillation in the group SL and group SM were all decreased (p < 0.05); compared with group SM, the effect in the group SL was more prominent (p < 0.01). Conclusion. Hypertension can lead to cardiomyocyte hypertrophy, deposition of interstitial fibrosis in myocardial tissue, and an increase in the vulnerability to atrial fibrillation. Spironolactone showed a certain dose-dependent effect in SHRs. Lower-dose spironolactone was superior to higher-dose spironolactone in the aspect of reducing hypertensive atrial fibrosis and TGF-β1 expression, as well as preventing the occurrence of atrial fibrillation. [ABSTRACT FROM AUTHOR]

Using two waves of data, this study aimed to identify the peer relationship profiles of 1295 rural Chinese adolescents based on a person-centered approach and to examine the interactions among these profiles, left-behind status, and gender in predicting subsequent subjective well-being. Latent profile analyses identified four profiles: a socially competent profile, a socially accepted profile, an isolated profile, and a rejected profile. These profiles were linked to left-behind status (i.e. both-parent migration, father-only migration, mother-only migration, and non-parent migration) and gender. Moreover, left-behind status moderated the longitudinal relations between the peer relationship profiles and subjective well-being for boys and girls. [ABSTRACT FROM AUTHOR]

Objective. Inflammation is one of the key mechanisms involved in functional impairment after stroke. Intercellular adhesion molecule-1 (ICAM-1) is an important inflammatory molecule in the body. The purpose of our study was to determine the correlation between ICAM-1 and the prognosis of acute ischemic stroke (AIS). Methods. 286 AIS patients treated at Beijing Tiantan Hospital were continuously included in the study. The demographic data of the patients were collected, and the fasting blood within 24 hours of admission was collected to detect the clinical indicators. The functional prognosis was measured using the modified Rankin Scale (mRS) 3 months after stroke. The poor prognosis is defined as mRS ≥ 3. The enzyme-linked immunosorbent assay (ELISA) was used to determine the serum ICAM-1 levels. Results. The serum ICAM-1 levels of patients with poor prognosis were significantly higher than that of patients with good prognosis (144.2 ± 14.8 vs 117.5 ± 12.1 pg/ml). Receiver operating characteristic curve (ROC) analysis showed that the sensitivity and specificity of serum ICAM-1 for predicting the prognosis of AIS were 74% and 76%, respectively. In logistic regression analysis, the serum ICAM-1 level is still an independent predictor of poor prognosis (odds ratio [OR]: 0.52; 95% confidence interval [CI]: 0.318-0.839). Conclusions. Higher serum ICAM-1 levels on admission in AIS patients might increase the risk of poor prognosis. [ABSTRACT FROM AUTHOR]

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group (p < 0.05). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues (p < 0.05). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC (p < 0.05). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1. [ABSTRACT FROM AUTHOR]

With the aging of the population and the extension of life expectancy, osteoporosis is becoming a global epidemic. Although there are several drugs used to treat osteoporosis in clinical practice, such as parathyroid hormone or bisphosphonates, they all have some serious side effects. Therefore, a safer drug is called for osteoporosis, especially for the prevention in the early stage of the disease, not only the treatment in the later stage. Panax notoginseng saponin (PNS), a traditional Chinese herb, has been used as anti-ischemic drug due to its function on improving vascular circulation. In order to verify whether Panax notoginseng saponins (PNS) could be used to prevent osteoporosis, ovariectomy (OVX) was induced in female C57BL/C6J mice, followed by orally administration with 40 mg/kg/d, 80 mg/kg/d, and 160 mg/kg/d of three different dosages of PNS for 9 weeks. Serum biochemical analysis, micro-CT, histological evaluation, and immunostaining of markers of osteogenesis and angiogenesis were performed in the sham, osteoporotic (OVX), and treatment (OVX+PNS) groups. Micro-CT and histological evaluation showed that compared to sham group, the bone mass of OVX group reduced significantly, while it was significantly restored in the moderate-dose PNS (40 mg/kg and 80 mg/kg) treatment groups. The expression of CD31 and osteocalcin (OCN) in the bone tissue of treatment group also increased, suggesting that PNS activated osteogenesis and angiogenesis, which subsequently increased the bone mass. These results confirmed the potential function of PNS on the prevention of osteoporosis. However, in the high dose of PNS (160 mg/kg) group, the antiosteoportic effect had been eliminated, which also suggested the importance of proper dose of PNS for the prevention and treatment of osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: The relationship between an increasing elderly population and wide-ranging neurological conditions has led to heightened rates of cognitive function impairment. Some researchers have found that health literacy risk may be associated with cognitive impairment in older adults. Objectives: The purpose of this study was to delineate the difference in health literacy risk between older adults with mild cognitive impairment and those with normal cognitive function. Methods: We conducted a survey study to explore the health literacy risk in older adults with and without mild cognitive impairment. Data were collected from 412 subjects between 60 and 91 years of age (260 without and 152 with mild cognitive impairment) between June and December 2016 in China. Cognitive function was measured using the Mini-Mental Status Examination, Montreal Cognitive Assessment, Global Deterioration Scale, Activities of Daily Living, and Hamilton Depression Rating Scale. Health literacy was measured using the Chinese Citizen Health Literacy Questionnaire. Results: The scores of total health literacy and its three dimensions (basic health knowledge and mind, basic skills, and health lifestyle and behavior) were lower in those with mild cognitive impairment. Older adults with normal cognitive function had adequate or marginal health literacy levels, whereas those with mild cognitive impairment had marginal or inadequate health literacy levels. Using multiple logistic regression analysis, we found that health literacy risk, education level, age, marital status, and body mass index were independent risk factors for mild cognitive impairment. Discussion: These results suggest that low health literacy may be a predictor of mild cognitive impairment. Screening for lower health literacy risk should be included in multidimensional geriatric evaluation. [ABSTRACT FROM AUTHOR]

Understanding the factors affecting activities of daily living (ADL) is important in Alzheimer's disease (AD), because decline in ADL contributes to many poor health outcomes. Existing studies often investigate the factors in isolation without a theoretical framework. The purpose of the present study was to provide preliminary results on how cognition, physical performance, and behavioral and psychological symptoms of dementia mediate the relationship of aerobic fitness and ADL in AD. A cross‐sectional analysis was used (n = 28: average age 78 [8] years, education 16 (3) years, Mini‐Mental State Examination scores 20 [4]). The results showed that aerobic fitness is not linked to ADL directly, and its association with ADL was mediated by physical performance and global cognition. Our findings provide preliminary support for aerobic fitness as a potential therapeutic target, as enhanced aerobic fitness could simultaneously modify other factors affecting ADL. Nurses are in a unique position for coordinating exercise safety assessment and prescription and educating older adults with AD about exercise participation. [ABSTRACT FROM AUTHOR]

Two new dihydro-β-agarofuran sesquiterpenes chiapen T (1) and chiapen U (2), along with chiapen A (3), 1β-hydroxy-2β,6α,12-triacetoxy-8β-(β-nicotinoyloxy)-9β-(benzoyloxy)-β-dihydroagarofuran (4), wilforlide B (5), 3-hydroxy-2-oxo-3-friedelen-29-oic acid (6), epikatonic acid (7), 22-epi-maytenfolic acid (8), maytenoic acid (9), wilforic acid F (10), wilforic acid B (11), were reported for the first time from the Celastrus angulatus. The structures of all the compounds were elucidated by HR-ESI-MS, 1 D and 2 D NMR spectra, as well as single-crystal X-ray diffraction analyses. Compounds 1 and 2 were examined for anti-inflammatory activity, respectively. None of them showed potent activity. [ABSTRACT FROM AUTHOR]

Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. [ABSTRACT FROM AUTHOR]

Objectives: Depressive symptoms are common in older people; most previous research on elderly depression focused on individual-level characteristics or neighborhood socioeconomic status. Modifiable neighborhood characteristics of older people dwelling in low-income communities are under-studied. This study aims to identify potentially modifiable social and physical neighborhood characteristics that influence depressive symptoms independent of individual-level characteristics among older Chinese. Method: Data came from a cross-sectional survey conducted in four low-income public rental housing estates in Hong Kong in 2012. We interviewed a total of 400 elderly residents. The structured questionnaire covered demographics, activities of daily living, recent fall history, neighborhood support networks, and perceived proximity by walk to community facilities. Multiple regression was used to test whether inclusion of neighborhood factors in addition to individual characteristics increases model fit in explaining depressive symptoms in elders with low socioeconomic status. Results: At individual level, activities of daily living and income significantly predicted depressive symptoms. Receiving support from friends or neighbors is associated with fewer depressive symptoms. However, participants who received organizational support had a 1.17 points of increase on the 15-item Geriatric Depression Scale (GDS-15). At-ease walkable proximity to medical facilities was positively associated with a better GDS score. Conclusion: Neighborhood support networks and perceived proximity by walk to community facilities contribute significantly to depressive symptoms among low-income elders. Programs and policies that facilitate neighborhood support and commuting or promote facility accessibility may help ameliorate depressive symptoms common among low-income elders. [ABSTRACT FROM AUTHOR]

Gambogic acid (GA) is the major active ingredient of gamboges, a brownish to orange resin product from Garcinia hanburyi tree in Southeast Asia. This compound exhibits anti-cancer effect on solid tumors. In this study, we investigated the effects of GA on the growth and differentiation of acute myeloid leukemia cells by growth-inhibition detection, morphological changes observation, nitroblue tetrazolium reduction, and the expression of the relative cell-surface differentiation markers. The results showed that GA could inhibit cell growth and promote differentiation in U937 and HL-60 cells. In addition, GA upregulated the expression of p21waf1/cip1 in the two cell lines. Finally, downregulating the p21waf1/cip1 expression with small interfering RNA partially blocked GA-induced cell growth inhibition and differentiation. These results of this study revealed that GA may be used as one of the investigational drugs for acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

Disclosing the mechanism of primary angle closure glaucoma with pupillary block is important to the diagnosis as well as treatments, such as the laser peripheral iridotomy. Comparing with abundant clinical researches, there have been fewer quantitative studies of the aqueous humor flows with synechia iris configurations, and the efficacy of laser peripheral iridotomy in treating glaucoma. Based on the mathematical models of aqueous humor flow and iris deformation, the flow fields were simulated by computational fluid dynamics with normal and synechia iris configurations (iris-lens gap of 30, 5 and 2 μm, respectively), and through one-way fluid-structure coupling technique the deformations of the iris under the flow field pressure were calculated by finite element analysis. The efficacy of glaucoma treatment with different orifice sizes was also investigated. Results show that the pressure difference between anterior and posterior chambers and iris deformation increase dramatically with the iris-lens gap distance less than 5 μm, and when further decreasing this gap may lead the iris touch the cornea causing angle closure glaucoma with noticeable iris bombé. Laser peripheral iridotomy simulation results show that iridotomy size of 0.2 mm can effectively decrease the pressure difference across the iris and relieve iris bombé. This is a biomechanical numerical study, and the results are reasonable compare to those of published works. It may shed additional light on the diagnosis and treatment of angle closure glaucoma with pupillary block. • Detailed simulations of aqueous humor flow inside the eye with pupillary block. • Numerical analysis of iris deformation due to an excess of pressure in posterior chamber. • Prediction of the orifice size of laser peripheral iridotomy necessary to avoid glaucoma. [ABSTRACT FROM AUTHOR]

Electroacupuncture (EA) at ST36 is effective for improving gastric motility. However, the underlying mechanism remains poorly understood. The aim of this study was to investigate the effects of EA on gastric contraction and to determine whether interstitial cells of Cajal (ICCs) are involved. Rats were randomized into control, diabetic (DM), diabetic with sham EA (DM + SEA), diabetic with low frequency EA (DM + LEA) and diabetic with high frequency EA (DM + HEA) groups. EA was performed everyday for four and eight weeks. Contractions in antrum strips were explored using the organ bath technique. Western blotting was employed to determine c-kit and transmembrane stem cell factor (M-SCF) expression in the gastric antrum, and levels of soluble stem cell factor (S-SCF) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The distribution of ICCs was further assessed by immunohistochemistry. The results were as follows: (1) Contractions in the DM group were attenuated at four and eight weeks, but LEA and HEA restored the attenuated contraction. (2) ICCs were significantly decreased at eight weeks without alteration at four weeks in DM group, but were rescued in the LEA and HEA groups. (3) Whereas M-SCF and S-SCF in the DM group were slightly decreased at four weeks and were dramatically reduced at eight weeks, LEA and HEA markedly enhanced SCF at eight weeks. Collectively, the data suggest that in diabetic rats, LEA and HEA at ST36 could facilitate contraction of the gastric antrum, possibly by involving the SCF/c-kit pathway. [ABSTRACT FROM AUTHOR]

Aim: Periodontitis (PD) is the sixth most prevalent disease around the world and is involved in the development and progression of multiple systemic diseases. Previous studies have reported that PD may aggravate liver injuries. The objective of this study was to investigate whether and how PD affects liver fibrosis. Materials and Methods: Ligature‐induced PD (LIP) was induced in male C57/B6J mice, and sub‐gingival plaques (PL) from patients with PD were applied to mouse teeth. Liver fibrosis was induced by carbon tetrachloride (CCl4) injection. The mice were randomly divided into six groups: Oil, Oil+LIP, Oil+LIP+PL, CCl4, CCl4+LIP, and CCl4+LIP+PL. Alveolar bone resorption was evaluated by methylene blue staining. Hepatic function was analysed by serum alanine aminotransferase and hepatic hydroxyproline. Picrosirius red and α‐smooth muscle actin (SMA) staining were used to evaluate the fibrotic area. RNA sequencing and quantitative RT‐PCR were used to measure gene expression. Western blotting was used to measure protein levels. Flow cytometry was used to analyse the accumulation of immune cells. Mouse microbiota were analysed using 16S rRNA gene sequencing. Results: Mice in the CCl4+LIP+PL group displayed higher serum alanine aminotransferase and hepatic hydroxyproline as well as more Picrosirius red‐positive and α‐SMA‐positive areas in liver samples than those of the CCl4 group, suggesting that PD (LIP+PL) aggravated CCl4‐induced hepatic dysfunction and liver fibrosis. Consistently, the expression of fibro‐genic genes and the protein levels of transforming growth factor β were much higher in the CCl4+LIP+PL group than in the CCl4 group. Flow cytometry revealed that PD increased the accumulation of immune cells, including Kupffer cells, B cells, and Th17 cells, in the liver of mice with CCl4 treatment. PD also increased the expression of inflammatory genes and activated pro‐inflammatory nuclear factor‐kappa B pathway in the livers of CCl4‐injected mice. Moreover, PD altered both oral and liver microbiota in CCl4‐injected mice. Conclusions: PD aggravates CCl4‐induced hepatic dysfunction and fibrosis in mice, likely through the increase of inflammation and alteration of microbiota in the liver. [ABSTRACT FROM AUTHOR]

This study investigated the fire needle and phototherapy combination for treating vitiligo through a meta-analysis of the published literature. Indeed, vitiligo is a common chronic skin condition characterized by the appearance of white patches. It is the most prevalent disorder, affecting approximately 1% of the global population. There is no known cure or clinical recommendation for treating vitiligo. The majority of medical guidelines suggest vitiligo treatment with the use of fire needles. Here, vitiligo was treated with a novel mechanism combining a fire needle with phototherapy. The handheld phototherapy devices include a fire needle option for disease treatment. Miniature lesions that could be used to detect and treat vitiligo at an early stage could be managed by hybrid-capable devices. The real-time study included more than 3,435 patients. The dosages were altered to control the adverse effects. Following treatment, granulation tissues developed on the injured skin, diminishing the shallow area and wound surface. The case studies demonstrate that combining phototherapy and fire needle therapy is more practical than the other methods. [ABSTRACT FROM AUTHOR]

Background: Taking ischemic and bleeding risks into consideration, insufficient data exist on dual antiplatelet therapy after percutaneous coronary intervention in elderly Chinese patients with coronary artery disease. Objective: We aimed to investigate the effectiveness and safety of ticagrelor in comparison with clopidogrel on a background of aspirin for elderly Chinese patients with coronary artery disease 12 months after percutaneous coronary intervention. Methods: A single-center retrospective cohort study was conducted. Selected from patients with coronary artery disease aged ≥ 75 years from January 2010 to July 2019, 908 eligible subjects receiving dual antiplatelet therapy after percutaneous coronary intervention for up to 12 months were consecutively enrolled in the study. The included patients received ticagrelor in combination with aspirin (n = 264) or clopidogrel in combination with aspirin (n = 644). Effectiveness endpoints were evaluated by the major adverse cardiovascular events, encompassing all-cause death, non-fatal myocardial infarction, and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium bleeding. Results: The patients who were treated with ticagrelor were slightly younger than those who were treated with clopidogrel (79.1 ± 3.7 vs 80.7 ± 4.5 years, p < 0.01). The ticagrelor cohort contained a higher percentage of patients undergoing a prior percutaneous coronary intervention (37.9% vs 24.5%, p < 0.01), and a lower percentage of smokers (19.3% vs 27.2%, p < 0.05), compared with the clopidogrel cohort. The levels of glucose, total cholesterol, and low-density lipoprotein-cholesterol in the ticagrelor group were higher while the level of triglycerides and high-density lipoprotein-cholesterol were lower (p < 0.05) than those in the clopidogrel group. Left main percutaneous coronary intervention was performed more frequently among the ticagrelor-treated patients (23.5% vs 9.3%, p < 0.01), while patients in the clopidogrel group underwent more left circumflex percutaneous coronary intervention (34.3% vs 23.1%, p < 0.01). We found that ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel using the inverse probability of treatment weighting model (odds ratio, 0.493; 95% confidence interval 0.356–0.684). There was no difference in terms of the risk of Bleeding Academic Research Consortium bleeding between the two groups (p > 0.05). Conclusions: Ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel at 12 months in elderly Chinese patients with coronary artery disease, without a significant increase of Bleeding Academic Research Consortium bleeding events. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study is to investigate the influence of grading rehabilitation nursing mode on limb function, speech function, and QOL of stroke patients. Methods. From January 2018 to April 2019, the stroke patients who received treatment in our hospital were selected as the study participants. Based on the random number table, they were assigned to CG (n = 60) and OG (n = 60). The routine rehabilitation nursing mode was used in the CG, and the grading rehabilitation nursing mode was used in the OG. The limb function, speech function, QOL, and nursing satisfaction were evaluated in both the groups, and the survival curve was analyzed after 12 months of follow-up. Results. The motor function of upper and lower limbs in OG was significantly higher than that in CG, and the total effective rate of speech function recovery in OG was 95.00%, which was obviously higher than 81.67% in CG (P < 0.05); the total QOL score in OG was (80.72 ± 7.15), which was significantly higher than (69.53 ± 6.42) in CG. The nursing satisfaction of the OG was higher (P < 0.05). The Kaplan–Meier curve analysis revealed that the difference of 12-month survival rate between CG and OG was statistically significant (χ2 = 4.710, P = 0.030). Conclusion. The application of grading rehabilitation nursing mode in stroke patients can effectively facilitate the recovery of extremity function and speech function, ameliorate the QOL and nursing satisfaction of patients, reduce the death and disability of patients, and prolong the survival time of patients. [ABSTRACT FROM AUTHOR]

There is increasing evidence that starvation induces autophagy, which may be protective during starvation, in an AMPK-dependent manner. Polysaccharides from Fuzi (FPS) reportedly have protective effects on nutrition-limited livers. The present study was designed to determine whether FPS protected H9c2 cells against starvation-induced cytotoxicity using an AMPK/mTOR-dependent mechanism. H9c2 cells were incubated in serum and glucose starvation media for 12 hours to establish a cell injury model. 3-Methyladenine (3MA, an autophagy inhibitor) was used to identify the exact role of autophagy in starvation. Cells were incubated with different FPS concentrations, and the cell injury levels, autophagy activity and AMPK/mTOR phosphorylation were measured. Adenine 9-β-D-arabinofuranoside (Ara-A, an AMPK inhibitor) and 5-amino-4-imidazole-carboxamide riboside (AICAR, an AMPK activator) were used to identify whether the AMPK/mTOR pathway was involved in FPS-mediated cardioprotection. We demonstrated that starvation decreased cell viability in a time-dependent manner, and 3MA-induced autophagy inhibition aggravated the reduced cell viability. FPS treatment attenuated the cell viability decrement and the starvation-induced decline in the mitochondrial membrane potential (MMP), and autophagy; also, the AMPK/mTOR pathways were activated during treatment. Ara-A treatment abolished the protective effect of FPS, while AICAR treatment had a similar effect to FPS. We conclude that autophagy attenuates starvation-induced cardiomyocyte death, and FPS increases autophagy activity to protect against starvation-induced cytotoxicity in H9c2 cells, likely through AMPK/mTOR pathway activation. [ABSTRACT FROM AUTHOR]

Background: Plasmapheresis is widely used for severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) to remove excessive triglycerides from plasma. This study aimed to evaluate whether plasmapheresis could improve the duration of organ failure in HTG-AP patients. Methods: We analyzed a cohort of patients from a multicenter, prospective, long-running registry (the PERFORM) collecting HTG-AP patients admitted to the study sites within 72 h from the onset of symptoms. This study was based on data collected from November 2020 to March 2023. Patients who had organ failure at enrollment were involved in the analyses. The primary outcome was time to organ failure resolution within 14 days. Multivariable Cox regression model was used to evaluate the association between plasmapheresis and time to organ failure resolution. Directed acyclic graph (DAG) was used to identify potential confounders. Results: A total of 122 HTG-AP patients were included (median [IQR] sequential organ failure assessment (SOFA) score at enrollment, 3.00 [2.00–4.00]). Among the study patients, 46 underwent plasmapheresis, and 76 received medical treatment. The DAG revealed that baseline serum triglyceride, APACHE II score, respiratory failure, cardiovascular failure, and renal failure were potential confounders. After adjusting for the selected confounders, there was no significant difference in time to organ failure resolution between patients undergoing plasmapheresis and those receiving exclusive medical treatment (HR = 1.07; 95%CI 0.68–1.68; P = 0.777). Moreover, the use of plasmapheresis was associated with higher ICU requirements (97.8% [45/46] vs. 65.8% [50/76]; OR, 19.33; 95%CI 2.20 to 169.81; P = 0.008). Conclusions: In HTG-AP patients with early organ failure, plasmapheresis was not associated with accelerated organ failure resolution compared to medical treatment but may be associated with more ICU admissions. Trial registration: The PERFORM study was registered in the Chinese Clinical Trial Registry (ChiCTR2000039541). Registered 30 October 2020. [ABSTRACT FROM AUTHOR]

Background: Bone implant infections pose a critical challenge in orthopedic surgery, often leading to implant failure. The potential of implant coatings to deter infections by hindering biofilm formation is promising. However, a shortage of cost-effective, efficient, and clinically suitable coatings persists. Polyvinyl alcohol (PVA), a prevalent biomaterial, possesses inherent hydrophilicity, offering potential antibacterial properties. Methods: This study investigates the PVA solution's capacity to shield implants from bacterial adhesion, suppress bacterial proliferation, and thwart biofilm development. PVA solutions at concentrations of 5%, 10%, 15%, and 20% were prepared. In vitro assessments evaluated PVA's ability to impede bacterial growth and biofilm formation. The interaction between PVA and mCherry-labeled Escherichia coli (E. coli) was scrutinized, along with PVA's therapeutic effects in a rat osteomyelitis model. Results: The PVA solution effectively restrained bacterial proliferation and biofilm formation on titanium implants. PVA solution had no substantial impact on the activity or osteogenic potential of MC3T3-E1 cells. Post-operatively, the PVA solution markedly reduced the number of Staphylococcus aureus and E. coli colonies surrounding the implant. Imaging and histological scores exhibited significant improvements 2 weeks post-operation. Additionally, no abnormalities were detected in the internal organs of PVA-treated rats. Conclusions: PVA solution emerges as an economical, uncomplicated, and effective coating material for inhibiting bacterial replication and biofilm formation on implant surfaces, even in high-contamination surgical environments. [ABSTRACT FROM AUTHOR]

Background: Post-procedural quality control of endoscopic submucosal dissection (ESD) is emphasized in guidelines. However, this process can be tedious and time-consuming. Recently, a pre-training model called generative pre-trained transformer (GPT) on a public natural language processing platform has emerged and garnered significant attention, whose capabilities align well with the post-procedural quality control process and have the potential to streamline it. Therefore, we developed a simple program utilizing this platform and evaluated its performance. Methods: Esophageal ESDs were retrospectively included. The manual quality control process was performed and act as reference standard. GPT's prompt was optimized through multiple iterations. A Python program was developed to automatically submit prompt with pathological report of each ESD procedure and collect quality control information provided by GPT. Its performance on quality control was evaluated with accuracy, precision, recall, and F-1 score. Results: 165 cases were involved into the dataset, of which 5 were utilized as the prompt optimization dataset and 160 as the validation dataset. Definitive prompt was achieved through seven iterations. Time spent on the validation dataset by GPT was 13.47 ± 2.43 min. Accuracies of pathological diagnosis, invasion depth, horizontal margin, vertical margin, vascular invasion, and lymphatic invasion of the quality control program were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), 0.931, 1.0, and 1.0, respectively. Precisions were (0.965, 0.969) (95% CI), (0.934, 0.954) (95% CI), and 0.957 for pathological diagnosis, invasion depth, and horizontal margin, respectively. Recalls were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), and 0.931 for factors as mentioned, respectively. F1-score were (0.945, 0.957) (95% CI), (0.928, 0.948) (95% CI), and 0.941 for factors as mentioned, respectively. Conclusions: This quality control program was qualified of post-procedural quality control of esophageal ESDs. GPT can be easily applied to this quality control process and reduce workload of the endoscopists. [ABSTRACT FROM AUTHOR]

The 5′-HOXD genes are important for chondrogenesis in vertebrates, but their roles in osteoarthritis (OA) are still ambiguous. In our study, 5′-HOXD genes involvement contributing to cartilage degradation and OA was investigated. In bioinformatics analysis of 5′-HOXD genes, we obtained the GSE169077 data set related to OA in the GEO and analyzed DEGs using the GEO2R tool attached to the GEO. Then, we screened the mRNA levels of 5′-HOXD genes by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR). We discovered that OA chondrocyte proliferation was inhibited, and apoptosis was increased. Moreover, it was discovered that SOX9 and COL2A1 were downregulated at mRNA and protein levels, while matrix metalloproteinases (MMPs) and a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTSs) were upregulated. According to the results of differentially expressed genes (DEGs) and qRT-PCR, we evaluated the protein level of HOXD11 and found that the expression of HOXD11 was downregulated, reversed to MMPs and ADAMTSs but consistent with the cartilage-specific factors, SOX9 and COL2A1. In the lentivirus transfection experiments, HOXD11 overexpression reversed the effects in OA chondrocytes. In human OA articular cartilage, aberrant subchondral bone was formed in hematoxylin–eosin (H&E) and Safranin O and fast green (SOFG) staining results. Furthermore, according to immunohistochemistry findings, SOX9 and HOXD11 expression was inhibited. The results of this study established that HOXD11 was downregulated in OA cartilage and that overexpression of HOXD11 could prevent cartilage degradation in OA. [ABSTRACT FROM AUTHOR]

Background: Maternal and child health (MCH) hospitals play an essential role in providing MCH services in China, while the supply has become increasingly challenging in the past decade, especially among secondary MCH hospitals. In this study we aimed to evaluate the technical efficiency (TE) of secondary MCH hospitals in Hubei province (China) to generate evidence-based decision-making for efficiency improvement. Methods: The data were collected from the Department of Maternal and Child Health of Health Commission of Hubei Province in 2019. A total of 59 out of 74 secondary MCH hospitals were included as our study sample. Four input indicators (number of health professionals, number of beds, number of equipment with value greater than 10,000 RMB Yuan, building area for hospital operations) and three output indicators (number of total diagnostic patients, number of discharged patients, and number of birth deliveries) were selected based on previous literature. TE scores of the sample hospitals were estimated by using Bootstrap-Data Envelopment Analysis (Bootstrap-DEA). Results: After bias-correction with Bootstrap-DEA model, the average TE score of the MCH hospitals was 0.673. 20 (33.89%) MCH hospitals had TE scores below the average. No MCH hospitals achieved excellent efficiency; 16 (27.11%) MCH hospitals reached good efficiency; and 26 (44.06%) MCH hospitals fell into poor and failing efficiency. Besides, 17 MCH hospitals had TE scores of 1 before bias-corrections, while none of them reached 1 after bias correction. Conclusions: Significant capacity variations existed among the secondary MCH hospitals in terms of input and output indicators and their overall TE was low in Hubei of China. For better improvement, the secondary MCH hospitals in Hubei need to improve their internal management and strengthen the construction of their information systems. A series of policy supports are needed from the health and insurance administrations to optimize health resources. Third-party performance evaluation can be piloted to improve efficiency and overall performance of the MCH hospitals. The policy recommendations we raise for MCH hospitals in Hubei can be worth learning for some low- and middle- income countries. [ABSTRACT FROM AUTHOR]

Purpose: Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopaedic hip joint disease that occurs in young- and middle-aged people. Previous experimental studies have shown that autophagy might be involved in the pathological process of SONFH, but the pathogenesis of autophagy in SONFH remains unclear. We aimed to identify and validate the key potential autophagy-related genes involved in SONFH to further illustrate the mechanism of autophagy in SONFH through bioinformatics analysis. Methods: The GSE123568 mRNA expression profile dataset, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). The autophagy-related genes involved in SONFH were screened by intersecting the GSE123568 dataset with the set of autophagy genes. The differentially expressed autophagy-related genes involved in SONFH were identified with R software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially expressed autophagy-related genes involved in SONFH were conducted by using R software. Then, the correlations between the expression levels of the differentially expressed autophagy-related genes involved in SONFH were confirmed with R software. Moreover, the protein–protein interaction (PPI) network was analysed by using the Search Tool for the Retrieval of Interacting Genes (STRING), significant gene cluster modules were identified with the MCODE Cytoscape plugin, and hub genes among the differentially expressed autophagy-related genes involved in SONFH were screened by using the CytoHubba Cytoscape plugin. Finally, the expression levels of the hub genes of the differentially expressed autophagy-related genes involved in SONFH were validated in hip articular cartilage specimens from necrotic femur heads (NFHs) by using the GSE74089 dataset and further verification by qRT-PCR. Results: A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 34 differentially expressed autophagy-related genes involved in SONFH were particularly enriched in death domain receptors, the FOXO signalling pathway and apoptosis. Correlation analysis revealed significant correlations among the 34 differentially expressed autophagy-related genes involved in SONFH. The PPI results demonstrated that the 34 differentially expressed autophagy-related genes interacted with each other. Ten hub genes were identified by using the MCC algorithms of CytoHubba. The GSE74089 dataset showed that TNFSF10, PTEN and CFLAR were significantly upregulated while BCL2L1 was significantly downregulated in the hip cartilage specimens, which was consistent with the GSE123568 dataset. TNFSF10, PTEN and BCL2L1 were detected with consistent expression by qRT-PCR. Conclusions: Thirty-four potential autophagy-related genes involved in SONFH were identified via bioinformatics analysis. TNFSF10, PTEN and BCL2L1 might serve as potential drug targets and biomarkers because they regulate autophagy. These results expand the autophagy-related understanding of SONFH and might be useful in the diagnosis and prognosis of SONFH. [ABSTRACT FROM AUTHOR]

Existing studies cannot evaluate the time-varying properties of frailty and polypharmacy despite raising concerns about their combined effects in older individuals. This study investigated the longitudinal association between different combined statuses of frailty and polypharmacy on risks of adverse outcomes. Retrospective cohort study. Subjects aged between 65 and 100 years (n = 100,000) were identified from Taiwan's National Health Insurance Research Database. Frailty was categorized into fit, mild, moderate, and severe frailty based on the multimorbidity frailty index. Concomitant use of 5 to 9 and ≥10 chronic medications was considered polypharmacy and excessive polypharmacy. We used generalized estimating equation models to examine the association among 12 groups of combined effects of frailty and polypharmacy and risks of all-cause mortality, all-cause hospitalization, and unplanned hospitalization. Age-stratified analyses were conducted for those aged 65 to 74, 75 to 84, and 85+ years. Compared with fit without polypharmacy, severe frailty with excess polypharmacy was associated with increased risks of adverse outcomes, particularly unplanned hospitalization (adjusted relative risk (aRR): 20.01 [95% confidence interval (CI)] 19.30–20.75). However, the combined effects varied in distinct groups. Within each polypharmacy category, there were dose-response associations between frailty category and adverse outcomes. For instance, within the polypharmacy group, the aRRs of mortality were 1.58 (1.52–1.64), 2.70 (2.60–2.80), 4.62 (4.44–4.82), and 6.81 (6.50–7.13) for the fit and mild, moderate, and severe frailty groups, respectively. By contrast, within each frailty category, the dose-response association between polypharmacy and adverse outcomes was limited to fit and mildly frail people. Age-stratified analyses yielded similar results. Both frailty and polypharmacy modified the risks of mortality and hospital admissions in older people, but the combined effects varied in distinct groups. This study thus highlights the potential to optimize care of older people by capturing the dynamic and combined changes related to frailty and polypharmacy. [ABSTRACT FROM AUTHOR]

Background: Rural residents with chronic conditions have a stronger need for health services, which should make using family doctor contract services a priority. This study aimed to evaluate the rate of willingness among rural residents with chronic conditions to contract with family doctors and examine its determinants. Methods: A cross-sectional study was conducted from May, 2018 to June, 2018 in Shandong Province in China. A total of 769 rural unsigned residents with chronic conditions were included in the analysis. Using the Andersen model as the theoretical framework, logistic regression models were chosen to analyse the factors associated with willingness to contract with family doctors. Results: This study found that the rate of willingness to contract with family doctors among chronic patients in rural Shandong was 46.7%. A higher willingness was observed in those living a further distance from the village clinic (more than 600 m: OR = 1.85, 95%CI =1.17–2.93), having received publicity for family doctor contract services (OR = 1.71, 95% CI = 1.06–2.76), reporting need for utilizing a chronic disease management program (OR = 3.36, 95% CI = 2.20–5.23), and reporting need for higher medical insurance reimbursement (OR = 1.91, 95% CI = 1.28–2.83). Conclusions: The prevalence of contract willingness was relatively low among unsigned rural residents with chronic conditions in rural Shandong, China. The need factors were powerful factors affecting their willingness to contract with family doctors. The government should therefore strengthen targeted publicity and education to rural residents with chronic conditions and provide targeted healthcare services, such as chronic disease management programs and medical services with higher reimbursement rates, to promote their willingness to contract with family doctors. [ABSTRACT FROM AUTHOR]

To compare the efficacy of tramadol with pethidine on the treatment of post spinal anaesthesia shivering. Electronic databases including PubMed, Google Scholar, Embase and Cochrane were searched to find the randomized controlled trials (RCTs) comparing the efficacy of tramadol with pethidine on the treatment of post spinal anaesthesia shivering. Review Manager 5.3 was used. The meta-analysis was conducted with fixed-effect model or random-effect model according to the heterogeneity. Seven randomized controlled trials involving 463 patients were included. Compared with pethidine, tramadol had a significantly higher incidence of effective rate of shivering treatment (OR: 3.02, 95% CI 1.25 to 7.28, P = 0.01; I2 = 0%), shorter time to cease shivering (mean difference − 1.72, 95% CI − 2.59 to − 0.84, P = 0.0001; I2 = 89%) and lower recurrent rate of shivering (OR 0.18, 95% CI 0.05 to 0.57, P = 0.004; I2 = 0%), with a lower incidence of nausea and vomiting (OR 0.20, 95% CI 0.09 to 0.41, P < 0.0001; I2 = 23%). There was no significant difference in the incidence of pruritus between tramadol and pethidine. Tramadol is superior to pethidine when used for shivering treatment after spinal anaesthesia. [ABSTRACT FROM AUTHOR]

To investigate the impact of baseline painful physical symptoms (PPS) on subsequent first-episode major depressive disorder (MDD) in adults with subthreshold depressive symptoms, including subgroup analyses to assess whether the associations differ in individuals with and without physical diseases. A total of 2343 adults with subthreshold depressive symptoms were recruited at 34 primary health care centers. PPS were measured at baseline. First-episode MDD during follow-up was diagnosed by professional psychiatrists using the Mini-International Neuropsychiatric Interview. Baseline PPS showed independent impacts on first-episode MDD in adults with subthreshold depressive symptoms without physical diseases, but not in those with physical diseases. A non-linear association (P < 0.001) was observed between PPS burden and the risk of first-episode MDD. The HR s for first-episode MDD exhibited a rapidly increasing trend between PPS burden scores of 10–16, and maintained consistently high when scores exceeded 16. The analyses for specific PPS revealed that headache, neck pain, and heart or chest pain were independently associated with first-episode MDD in participants without physical diseases, the HR s were 1.57 (1.15–2.36), 1.53 (1.02–2.30), and 1.69 (1.14–2.50), respectively. Further network analysis demonstrated that heart or chest pain serves as a bridge symptom among the seven specific PPS and first-episode MDD in those without physical diseases. PPS burden and heart or chest pain may be significant indicators for first-episode MDD in adults with subthreshold depressive symptoms without physical diseases. Future studies should investigate whether interventions targeting PPS can prevent episode MDD in this subthreshold population. [ABSTRACT FROM AUTHOR]

Introduction: Chronic obstructive pulmonary disease (COPD) is highly prevalent and underdiagnosed worldwide. The validity and reliability of COPD Population Screening (COPD-PS) questionnaire are not properly known in a large-sample Chinese population. Methods: This is a national multicenter prospective study that enrolled 1,824 outpatients from 12 hospital sites in China. Scores of the Chinese version of COPD-PS questionnaire, demographic data, and clinical information were collected. The validity and the test-retest reliability were evaluated. Results: 1,824 participants were involved in this study, and 404 (22.1%) were diagnosed with COPD. The overall area under the curve (AUC) of the receiver operating characteristic (ROC) for COPD-PS questionnaire was 0.761 (95% CI: 0.734–0.787). A cut-off point of 4 was recommended, corresponding to a sensitivity of 74.50% and a specificity of 64.37%. The COPD-PS questionnaire showed an overall Pearson's correlation of 0.88. Conclusions: The COPD-PS questionnaire can be used in screening COPD patients from the general Chinese population with respiratory symptoms. [ABSTRACT FROM AUTHOR]

Simple Summary: A considerable number of patients with colorectal cancer (CRC) do not have elevated serum carcinoembryonic antigen (CEA) levels before undergoing radical surgery for colorectal cancer, but they may still have a poor prognosis. It is imperative to find sensitive and dependable prognostic markers to quickly identify high-risk populations who are susceptible to adverse outcomes in order to offer timely interventions to improve prognosis. In this real-world study of more than 1000 samples, a nomogram based on serum tumor markers and other clinicopathological features was used to accurately forecast the 3-year and 5-year overall survival rates of stage I–III CRC patients after radical resection with normal preoperative CEA, and its predictive power and clinical applicability markedly exceed those of the AJCC 8th TNM stage. In addition, we found the potential prognostic values of carbohydrate antigen 125 (CA125) and carbohydrate antigen 242 (CA242) as supplementary tumor markers in CRC patients who have normal preoperative CEA. We aimed to develop a clinical predictive model for predicting the overall survival (OS) in stage I–III CRC patients after radical resection with normal preoperative CEA. This study included 1082 consecutive patients. They were further divided into a training set (70%) and a validation set (30%). The selection of variables for the model was informed by the Akaike information criterion. After that, the clinical predictive model was constructed, evaluated, and validated. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were employed to compare the models. Age, histologic type, pT stage, pN stage, carbohydrate antigen 242 (CA242), and carbohydrate antigen 125 (CA125) were selected to establish a clinical prediction model for OS. The concordance index (C-index) (0.748 for the training set and 0.702 for the validation set) indicated that the nomogram had good discrimination ability. The decision curve analysis highlighted that the model has superior efficiency in clinical decision-making. NRI and IDI showed that the established nomogram markedly outperformed the TNM stage. The new clinical prediction model was notably superior to the AJCC 8th TNM stage, and it can be used to accurately assess the OS of stage I–III CRC patients undergoing radical resection with normal preoperative CEA. [ABSTRACT FROM AUTHOR]

This study explored the health effect of perceived built environment on depression of the Chinese elderly people in rural areas. A multifaceted approach in examining perceived built environment was used. A sample of 670 older residents in rural area of China were interviewed, and data were collected mainly for exploratory factor analysis, confirmatory factor analysis and moderation analysis. Results showed a reliable construct of perceived built environment which was developed by this study. A significant moderating role of personal income per month in the significantly negative relationship between perceived built environment and depression was confirmed. That is, the health effect of perceived built environment on depression became weakened among people of higher income levels. This study added evidence for the health effect of perceived built environment on depression among Chinese elderly people. Additionally, individual income was identified as an important influencing factor in such effect. Discussion on the negative relationship between perceived built environment and depression, as well as the moderating effect of personal income in such relationship were presented. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies of the kidney and urinary tract (CAKUTs) are some of the most common birth defects affecting newborns. CAKUTs often have poor birth outcomes owing to the limited experience of physicians in developing countries regarding antenatal and postnatal diagnosis. We aimed to estimate the epidemiology of CAKUTs using data from a hospital-based registry in Zhejiang Province, China. Methods: We included a total of 2790 newborns with CAKUTs, identified among 1,748,038 births during 2010–2016. The prevalence and type of CAKUTs, maternal and neonatal characteristics, and associated malformations were analyzed. Results: The average prevalence of CAKUTs born to mothers overall and mothers aged ≥35 years were both around 1.60 per 1000 births (95% confidence interval (CI), 1.54–1.66; 95% CI, 1.44–1.83, respectively) during the study period. The prevalence of CAKUTs changed over time among all women and women of advanced maternal age, although no significant trends were observed. CAKUTs were more likely to occur in male than female newborns (odds ratio (OR) 1.28, 95% CI 1.18–1.38), in multiple births than singletons (OR 1.53, 95% CI 1.21–1.92) and in urban areas than rural areas (OR 1.27, 95% CI 1.18–1.37). The overall prenatal detection rate of CAKUTs was 73.87%. The average gestational age at antenatal diagnosis was 26.57 ± 8.70 weeks. A total 22.69% CAKUTs had associated malformations. Congenital heart defects were the most common anomalies, accounting for 8.89% of the whole population. The main proportion in subgroups was hydronephrosis, representing 31.79% of registered CAKUTs. Conclusions: There was a nearly twofold increase in the prevalence of CAKUTs from 2010 to 2016 in Zhejiang Province. CAKUTs are strongly associated with male sex, multiple births, urban areas, and other nonurinary congenital malformations. [ABSTRACT FROM AUTHOR]

Background: Pressure ulcers (PUs) are encountered in all types of care settings. The incidence of PUs in the intensive care unit (ICU) is higher for a variety of reasons. The Braden Scale is a widely used tool to assess the risk of PU, but its predictive power is controversial in ICU settings. In this systematic review and meta‐analysis, we aimed to evaluate the predictive accuracy of the Braden Scale for measurement of risk of PU in adult ICU patients. Methods: A comprehensive literature search in English databases (PubMed, Cochrane Library, OVID, and Web of Science), Chinese databases (SinoMed, CNKI, and Wanfang), and gray literature was performed. Studies assessing the predictive value of the Braden Scale for risk of PU in adult ICU patients were searched. Quality of the studies was scored with Quality Assessment of Diagnostic Accuracy Studies‐2. Country, study design, setting, blinding, and characteristics of included studies were extracted. Results: Eleven full‐text articles containing 10 044 patients, comprising 1058 patients with PUs were included. The pooled sensitivity and specificity of the Braden Scale for predicting PU risk in ICU adults were 0.89 (95% CI, 0.87‐0.91; I2 = 94.9%, P =.0000) and 0.28 (95% CI, 0.27‐0.29; I2 = 99.2%, P =.0000), respectively. The pooled DOR was 6.29 (95% CI: 4.09‐9.68). The overall weighted AUC was 0.7812 ± 0.0331 (95% CI: 0.7163‐0.8461) and the Q* value was 0.7196 ± 0.0283 (95% CI: 0.6641‐0.7751). Significant heterogeneity was noted among the included studies. Meta‐regression analysis showed that there was no heterogeneity in blinding (P =.074), study design (P =.679), or cut‐off value (P =.821). Conclusions: This meta‐analysis demonstrated that the Braden Scale had a moderate predictive validity with good sensitivity and low specificity in adult critically ill patients. Further development and modification of this tool or generation of a new tool with higher predictive power is warranted for use in ICU populations. Relevance to clinical practice: The first step in prevention of PU is risk assessment. In this meta‐analysis, we aimed to evaluate the predictive power of the Braden Scale for assessing risk of PU in ICU adult patients, which could potentially guide clinical practice. [ABSTRACT FROM AUTHOR]

Background: Elderly rheumatoid arthritis (ERA) population faces multiple treatment dilemma. Here we aim to investigate if Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) exhibit better effects in an ERA mice model. Methods: ERA mice model was established by adding D-galactose (Dgal) to collagen-induced arthritis (CIA) mice. The model was then assigned into control group (CIA + Dgal), MTX treatment group (MTX), GCNY treatment group (GCNY), and integrative treatment group (MTX + GCNY). Pathological scoring was performed to evaluate the severity between the groups. Proteomic analysis was applied to investigate the secretory phenotype of the ERA mouse model and the underlying mechanism of GCNY, MTX and their combination. Representative cytokines related to proteomic results were further validated by ELISAs. Results: CIA + Dgal mice showed more aggressive joints damage than the CIA mice. Besides changes in the inflammatory pathway such as Pi3k-Akt signaling pathway in both model, differential expressed proteins (DEPs) indicated metabolism-related pathways were more obvious in CIA + Dgal mice. Low-dose MTX failed to show pathological improvement in CIA + Dgal mice, while GCNY improved joints damage significantly. Besides down-regulated inflammation-related targets, GCNY-regulated DEPs (such as Apoc1 ~ 3, Grk2 and Creb3l3) were broadly enriched in metabolism-related pathways. MTX + GCNY showed the best therapeutic effect, and the DEPs enriched in a variety of inflammatory,metabolism and osteoclast differentiation signaling pathway. Notably, MTX + GCNY treatment up-regulated Dhfr, Cbr1, Shmt1 involved in folic acid biosynthesis and anti-folate resistance pathways indicated a coincidence synergic action. ELISAs confirmed CPR and Akt that elevated in CIA + Dgal mice were significantly ameliorated by treatments, and adding on GCNY elevated folic acid levels and its regulator Dhfr. Conclusion: Aging aggravated joints damage in CIA, which probably due to metabolic changes rather than more severe inflammation. GCNY showed significant effects in the ERA mice model especially when integrated with MTX to obtain a synergic action. [ABSTRACT FROM AUTHOR]

As a common malignant tumor, the morbidity and mortality of lung cancer have been rising in recent years. The concept of "premetastatic niche" may lead to a revolutionary change in antitumor metastasis therapeutic strategies. Traditional Chinese medicine with multitargets and lower poisonous agents may be a potentially effective means to intervene in the "premetastatic niche (PMN)" to prevent and treat tumor metastasis. Astragalus polysaccharide (APS) is a substance with strong immune activity in Astragalus membranaceus that has excellent biological activities such as immunomodulation, anti-inflammatory, and antitumor. In this study, we constructed a tumor lung metastasis animal model to explore the intervention mechanism of APS on the premetastatic niche. We found that APS inhibited the formation of the lung premetastatic niche and inhibited the recruitment of myeloid-derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and gene expression of S1PR1, STAT3, and p-STAT3 in the S1PR1/STAT3 signaling pathway were suppressed by APS. In line with the above findings, our results confirmed that APS may inhibit the accumulation of MDSCs in the premetastatic niche through the intervention of the S1PR1-STAT3 signaling pathway to achieve the antitumor effect. [ABSTRACT FROM AUTHOR]

Aims To investigate whether 'low sugar' and related claims influence consumers' perceptions of the healthiness or other attributes of alcoholic drinks, promote greater consumption or impact diet and activity behaviour intentions. Method N  = 501 Australian women aged 18–35 viewed and rated six images of alcoholic drinks in a randomized online experiment with a 2 (claim: low sugar claim, no claim control) × 2 (drink type: cider, ready-to-drink spirits) between-subjects design. Results Participants who viewed drinks with low sugar claims rated them as healthier, less harmful to health, lower in sugar and kilojoules, and more suitable for weight management and a healthy diet than participants who viewed identical drinks with no claim (P  < 0.001- P  = 0.002). Drinks with low sugar claims were also perceived as being lower in alcohol (P  < 0.001) despite being of equivalent alcohol content. There were no significant differences in anticipated social approval associated with consumption or in hypothetical intended consumption of the drinks, but participants who viewed drinks with low sugar claims were less likely to indicate they would compensate for consumption of the drink by modifying food intake or physical activity (P  = 0.01). Conclusions Low sugar and related claims on alcoholic drinks can generate a health halo: consumers generalise from a specific favourable attribute (low sugar) to misperceive other favourable health- and nutrition-related attributes, including lower alcohol content. Findings support calls to reconsider the permissibility of low sugar claims on alcoholic drinks as they may mislead consumers. [ABSTRACT FROM AUTHOR]

Background: While single-method studies have reported on the effectiveness of simulated interprofessional teaching, our understanding of its full effects remains incomplete. Teaching design also provides no relevant theoretical guidance, which reduces the scientific quality and rigor of research. The purpose of this work was to study the effects of the simulated interprofessional education (SIPE) teaching model based on the 3P theory on the course of "Clinical Critical Thinking Training" through a convergent mixed method, and to provide the basis for future teaching design. Methods: A convergent mixed-method design was used, which consisted of a survey and a semi-structured interview. Data collection took place from September 2021 to July 2022. A cluster sampling method was used to select 60 full-time nursing students from a school in China, and randomly divide them into a control group of 36 and an experimental group of 24. According to the principle of voluntary participation, 6 students majoring in clinical medicine and 6 students majoring in pharmacy were recruited to join the experimental group to form an interprofessional team. The students studied "Clinical Critical Thinking Training" together, in which the control group used traditional simulation teaching and the experimental group used SIPE. The CCTDI (California Critical Thinking Disposition Inventory) and AITCS-II Student (Assessment of Interprofessional Team Collaboration in Student Learning Scale) were used for quantitative evaluation before and after the course, and descriptive statistics and Mann–Whitney U test were used to compare the critical thinking and interprofessional collaboration skills of the two groups of students. Semi-structured interviews were used for qualitative evaluation. Thematic analysis was used to understand student development on the basis of inter-professional core competencies and learning experience. Results: The students' interprofessional cooperation abilities and critical thinking scores improved compared with the beginning of the course, but the scores of the experimental group were significantly higher than the control group (p < 0.05). Three themes emerged regarding simulated interprofessional teaching: clarifying team positioning, improving team efficiency, and optimizing the learning experience. Conclusion: SIPE can build students' critical thinking, teamwork, and interprofessional core competencies, which makes it a useful teaching design. [ABSTRACT FROM AUTHOR]

Mass media campaigns can change attitudes and behaviours to improve population health. However, a key challenge is achieving share of voice in a complex and cluttered media environment. The aim of this study was to compare advertising expenditure on public health campaigns for obesity prevention (and related healthy eating and physical activity campaigns) with competing commercial categories of (a) sugary drinks, (b) artificially sweetened drinks and (c) diet/weight loss products and programmes. These commercial products may either undermine or dilute public health messages by directly contributing to poor health or confusing the public about the best ways to sustain a healthy lifestyle. Monthly estimates of advertising expenditure in Australian media (television, outdoor, cinema, radio, newspapers, magazines and digital) were obtained from Nielsen Media for 2016–18. Eligible public health advertising expenditure for the entire period (total AUD$27M) was vastly outweighed by the commercial categories of sugary drinks (AUD$129M) and diet/weight loss products and services (AUD$122M). Artificially sweetened drinks accounted for an additional AUD$23M of expenditure. These results highlight the need to rebalance the ratio of advertising to support public health in Australia through increased funding for obesity prevention and related campaigns, and critically, through government regulation to limit competing commercial advertising. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals. Methods: Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix. Results: We identified 38 genetic loci (p < 5 × 10−6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10−07), nd300 (p = 1.89 × 10−06), erythrocyte rigidity (p = 1.29 × 10−06), assigned viscosity (p = 6.20 × 10−08) and whole blood high cut relative (p = 7.30 × 10−08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10−06) and nd300 (p = 2.94 × 10−06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10−09) and whole blood high cut relative (p = 2.09 × 10−07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10−06) and erythrocyte deformation (p = 1.14 × 10−06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10−06 and p = 4.29 × 10−07) and plasma viscosity (p = 1.01 × 10−06 and p = 4.59 × 10−07) was found. Conclusion: These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study. [ABSTRACT FROM AUTHOR]

Objective  Cystatin C (CysC) references are useful for the monitoring of renal function in neonates. However, the standard CysC references in newborn infants have not been determined. The aim of this study was to establish a useful reference range for CysC in newborns. Study Design  Serum CysC levels were measured in 1,919 blood samples from 1,044 newborns during their first 28 days of life. CysC levels were analyzed for associations between subgroups dichotomized by postnatal age (PA) and gestational age (GA). The serum CysC reference intervals were determined according to the PA and GA. The associations between the serum CysC level and other biochemical parameters as well as perinatal factors were also analyzed. Results  In this study, the mean GA was 35.8 ± 2.9 weeks and the birth weight (BW) was 2,614 ± 697 g. Reference ranges of serum CysC were determined, and a general decreasing trend of CysC levels was observed as the GA increased. CysC levels differed significantly among the PA and GA categories (p  < 0.001). Serum CysC levels were relatively stable throughout the GA range but were impacted by the white blood cell count within the first postnatal 24 hours. Moreover, CysC levels always correlated positively with serum creatinine concentrations (p  < 0.001). Serum Cr levels were influenced by multiple factors, including BW, GA, total bilirubin, direct bilirubin, white blood cell count, C-reactive protein, and blood urea nitrogen. Conclusion  Reference levels of serum CysC should be determined according to the PA and GA. In contrast to Cr, serum CysC is a reliable index for assessing renal function in neonates as it is influenced by very few factors. The CysC reference levels will allow neonatologists to accurately evaluate renal function in the neonatal population. Key Points Cystatin C is a useful marker of the glomerular filtration rate in neonates. A reference range for cystatin C using 1,919 blood samples of 1,044 newborns was determined. In contrast to creatinine, only a few nonrenal factors influence serum cystatin C. [ABSTRACT FROM AUTHOR]