UBL3 overexpression enhances EV-mediated Achilles protein secretion in conditioned media of MDA-MB-231 cells.

Cancer cells communicate within the tumor microenvironment (TME) through extracellular vesicles (EVs), which act as crucial messengers in intercellular communication, transporting biomolecules to facilitate cancer progression. Ubiquitin-like 3 (UBL3) facilitates protein sorting into small EVs as a post-translational modifier. However, the effect of UBL3 overexpression in EV-mediated protein secretion has not been investigated yet. This study aimed to investigate the effect of UBL3 overexpression in enhancing EV-mediated Achilles protein secretion in MDA-MB-231 (MM) cells by a dual-reporter system integrating Akaluc and Achilles tagged with Ubiquitin where self-cleaving P2A linker connects Akaluc and Achilles. MM cells stably expressing Ubiquitin-Akaluc-P2A-Achilles (Ubi-Aka/Achi) were generated. In our study, both the bioluminescence of Ubiquitin-Akaluc (Ubi-Aka) and the fluorescence of Achilles secretion were observed. The intensity of Ubi-Aka was thirty times lower, while the Achilles was four times lower than the intensity of corresponding cells. The ratio of Ubi-Aka and Achilles in conditioned media (CM) was 7.5. They were also detected within EVs using an EV uptake luciferase assay and fluorescence imaging. To investigate the effect of the UBL3 overexpression in CM, Ubi-Aka/Achi was transiently transfected into MM-UBL3-KO, MM, and MM-Flag-UBL3 cells. We found that the relative fluorescence expression of Achilles in CM of MM-UBL3-KO, MM, and MM-Flag-UBL3 cells was 30 %, 28 %, and 45 %, respectively. These findings demonstrated that UBL3 overexpression enhances EV-mediated Achilles protein secretion in CM of MM cells. Targeting UBL3 could lead to novel therapies for cancer metastasis by reducing the secretion of pro-metastatic proteins, thereby inhibiting disease progression.

Heptanol-mediated phase separation determines phase preference of molecules in live cell membranes.

The localization of many membrane proteins within cholesterol- and sphingolipid-containing microdomains is essential for proper cell signaling and function. These membrane domains, however, are too small and dynamic to be recorded, even with modern super-resolution techniques. Therefore, the association of membrane proteins with these domains can only be detected with biochemical assays that destroy the integrity of cells require pooling of many cells and take a long time to perform. Here, we present a simple membrane fluidizer-induced clustering approach to identify the phase-preference of membrane-associated molecules in individual live cells within 10-15 min. Experiments in phase-separated bilayers and live cells on molecules with known phase preference show that heptanol hyperfluidizes the membrane and stabilizes phase separation. This results in a transition from nanosized to micronsized clusters of associated molecules allowing their identification using routine microscopy techniques. Membrane fluidizer-induced clustering is an inexpensive and easy to implement method that can be conducted at large-scale and allows easy identification of protein partitioning in live cell membranes.

The efficacy and safety of mirabegron for adult and child patients with neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

AIMS: We aimed to investigate the effectiveness and safety of mirabegron for adult and child patients with neurogenic lower urinary tract dysfunction (NLUTD). METHODS: A comprehensive search for articles about mirabegron treatment of NLUTD patients was conducted in PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov databases. Retrospective studies and randomized-controlled studies were included if they met the inclusion criteria and were evaluated by different quality evaluation methods according to study types. Mean difference (MD) and 95% confidence intervals (CIs) were calculated using fixed-effects models or random models depending on heterogeneity. Clinical and urodynamic parameters were pooled to evaluate the efficacy, and safety was measured by adverse events rate. RESULTS: A total of 10 studies with 314 participants were finally included. Four retrospective and six prospective studies containing two randomized-control trials met the inclusion criteria with moderate and high evidence levels. Compared to the baseline date, the pooled results suggested that patients who underwent mirabegron treatment presented less urinary frequency (MD = -0.70; 95% CI: -1.08 to -0.32; p < 0.01) and less incontinence (MD = -1.62; 95% CI: -2.20 to -1.03; p < 0.01), showed conspicuous improvements in adult and child patients' urodynamic parameters, while the incidence of adverse events (10.0% on average, 0%-31.25%) also demonstrated the safety of mirabegron. CONCLUSION: Mirabegron can significantly improve urodynamic parameters and quality of life in adult and child patients with NLUTD, and increase patient compliance with a smaller complication rate.

Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

Deep Learning in Automated Region Proposal and Diagnosis of Chronic Otitis Media Based on Computed Tomography.

OBJECTIVES: The purpose of this study was to develop a deep-learning framework for the diagnosis of chronic otitis media (COM) based on temporal bone computed tomography (CT) scans. DESIGN: A total of 562 COM patients with 672 temporal bone CT scans of both ears were included. The final dataset consisted of 1147 ears, and each of them was assigned with a ground truth label from one of the 3 conditions: normal, chronic suppurative otitis media, and cholesteatoma. A random selection of 85% dataset (n = 975) was used for training and validation. The framework contained two deep-learning networks with distinct functions: a region proposal network for extracting regions of interest from 2-dimensional CT slices; and a classification network for diagnosis of COM based on the extracted regions. The performance of this framework was evaluated on the remaining 15% dataset (n = 172) and compared with that of 6 clinical experts who read the same CT images only. The panel included 2 otologists, 3 otolaryngologists, and 1 radiologist. RESULTS: The area under the receiver operating characteristic curve of the artificial intelligence model in classifying COM versus normal was 0.92, with sensitivity (83.3%) and specificity (91.4%) exceeding the averages of clinical experts (81.1% and 88.8%, respectively). In a 3-class classification task, this network had higher overall accuracy (76.7% versus 73.8%), higher recall rates in identifying chronic suppurative otitis media (75% versus 70%) and cholesteatoma (76% versus 53%) cases, and superior consistency in duplicated cases (100% versus 81%) compared with clinical experts. CONCLUSIONS: This article presented a deep-learning framework that automatically extracted the region of interest from two-dimensional temporal bone CT slices and made diagnosis of COM. The performance of this model was comparable and, in some cases, superior to that of clinical experts. These results implied a promising prospect for clinical application of artificial intelligence in the diagnosis of COM based on CT images.

[Analysis of potential pharmacodynamic material basis of Euonymus alatus in treatment of nephritis based on integrated chemomics and network biology].

This paper was aimed to explore the potential pharmacodynamics effect of Euonymus alatus in the treatment of nephritis based on integrated chemomics and network biology. The chemical constituent database of E. alatus was constructed by consulting litera-ture and using online database. The chemical constituents were identified by UPLC-Q-TOF/HRMS~E and UNIFI software. On this basis, a series of comparisons, molecular docking studies and in-depth analysis of the chemical constituents and nephritis disease targets were carried out with use of network biology method, and the potential pharmacodynamic effect of E. alatus for the treatment of nephritis was investigated by reviewing the existing. In this study, 62 chemical constituents were collected in the database of chemical consti-tuents of E. alatus, and 24 chemical constituents were identified by mass spectrum. Subsequently, based on the network biology me-thod, 22 important chemical constituents and 5 key targets were obtained by reverse screening. Molecular docking study showed that a total of 11 chemical constituents such as quercetin, kaempferol, and catechinmay be the potential material basis for E. alatus in the treatment of nephritis. Starting with chemomics and using the technology of network biology, we established a network interaction model between drug components and disease targets in this study. Through the interaction between targets in complex networks, we can find the key targets easily and quickly. By docking the key targets with small drug molecules, we can screen out the potential pharmacodynamic components, providing a reference for the follow-up study of active ingredients.

[Thermodynamic characteristics of moxa floss and its biological effects and therapeutic mechanism on osteoarthritis rats].

Moxa floss is the main material of moxibustion, which plays a therapeutic role through the thermal effect of combustion. In this paper, TG/DSC thermal analysis method was used to study the characteristic parameters of combustion heat of moxa floss produced in Qichun, and the thermal therapeutic effect and mechanism of moxibustion were studied through moxibustion OA animal model. The results show that the combustion process of moxa floss can be divided into three stages: drying, combustion oxidation and carbonization, and ash burnout. The combustion properties of moxa floss are between herbaceous and woody, and tend to be woody, with flammable, slow and lasting combustion characteristics. Moxibustion can relieve the pathological state of knee joint synovium to a certain extent, reduce knee joint swelling and blood stasis in OA rats, reduce interstitial edema, and improve local inflammation. The mechanism and target point of moxibustion treatment for OA may be up-regulating TRPM3 gene to activate ion channels, affecting calcium metabolism and reducing OA swelling degree; down-regulation of GAPDH affects glucose metabolism of knee synovial cells and mediates anti-inflammatory effect. Down-regulation of pain-related gene MMP24 is helpful to relieve OA pain. Up-regulation of CTNNB1 activates Wnt/ß-catenin signaling pathway and affects differentiation and regeneration of OA chondrocytes. This study reveals the pyrolysis characteristics of moxa floss for the first time and discusses the biological effect and possible mechanism of moxibustion heat, providing new ideas for the quality evaluation of moxa floss and the mechanism of moxibustion therapy.

Income inequality and healthcare utilization of the older adults-based on a study in three provinces and six cities in China.

Purpose: The objective of this study is to gain a more nuanced understanding of the specific impact of income inequality on the utilization of healthcare services for older adults. Additionally, the study aims to elucidate the moderating and mediating roles of public transfer income and psychological health in this context. Methods: A systematic examination of the impact of income inequality on healthcare utilization among older adults was conducted through field questionnaire surveys in six cities across three major geographical regions (West, Central, and East). The analysis employed baseline regression, as well as mediating and moderating effect tests. Results: First, there is a negative relationship between income inequality and the use of therapeutic healthcare services (ß1 = -0.484, P < 0.01) and preventive healthcare services (ß2 = -0.576, P < 0.01) by older adults. This relationship is more pronounced in the low- and medium-income groups as well as in the western region. The mediating effect of psychological state is significant (ß3 = -0.331, P < 0.05, ß4 = -0.331, P < 0.05). Public transfer income plays a significant role in regulation. The moderating effect of public transfer income on therapeutic services was more significant in low-income groups (ß5 = 0.821, P < 0.01). The moderating effect of public transfer income on preventive services was more significant in middle-income groups (ß6 = 0.833, P < 0.01). Conclusion: The study clearly demonstrates a significant negative correlation between income inequality and the utilization of healthcare services by older adults. Furthermore, the study reveals that this relationship is particularly pronounced among older adults in low- and medium-income and Western regions. This detailed analysis of regional and income level heterogeneity is of particular value in this field of research. Secondly, this study attempts to integrate the two pivotal dimensions of public transfer income and psychological state for the first time, elucidating their moderating and mediating roles in this relationship. The findings indicate that public transfer income serves as a moderating factor, exerting a notable "reordering effect" on income inequality and resulting in a "deprivation effect." Such factors may impede the utilization of medical services, potentially influencing the psychological state of older adults.

Analysis of Anonymous Student Narratives About Experiences with Emergency Medicine Residency Programs.

Background: Academic emergency medicine (EM) communities have viewed anonymous online communities (AOC) such as Reddit or specialty-specific "applicant spreadsheets" as poor advising resources. Despite this, robust EM AOCs exist, with large user bases and heavy readership. Insights about applicants' authentic experiences can be critical for applicants and program leadership decision-making. To date, there are no EM studies to qualitatively assess EM AOC narratives during the application cycle. Our goal was to perform a qualitative analysis of students' EM program experiences through a publicly available AOC. Methods: This was a qualitative analysis of a publicly available, time-stamped, user-locked AOC dataset: "Official 2020-2021 Emergency Medicine Applicant Spreadsheet." We extracted and then de-identified all data from selected sub-sheets entitled "Virtual Interview Impressions" and "Rotation Impressions." Four investigators used constant comparative method to analyze the data inductively, and they subsequently met to generate common themes discussed by students. Preliminary thematic analysis was conducted on a random sample of 37/183 (20%) independent narratives to create the initial codebook. This was used and updated iteratively to analyze the entire narrative set consisting of 841 discrete statements. Finally, two unique codes were created to distinguish whether the identified sub-themes, or program attributes, were likely "modifiable" or "non-modifiable." Results: We identified six major themes: living and working conditions; interpersonal relationships; learning experiences, postgraduate readiness, and online/virtual supplements. Common sub-themes included patient population (13%); resident personality (7%); program leadership personality (7%); relationship with faculty/leadership (6%); geography (4%); practice setting (4%); program reputation (4%), and postgraduate year-3 experiences (4%). Modifiable sub-themes outnumbered non-modifiable sub-themes, 60.7% to 39.3%. Conclusion: In this analysis of selected medical students' narratives in an AOC, the majority of identified themes represented topics that may serve as external feedback for EM residency programs and their clerkships. Selective use of AOCs may set a precedent for future program assessments by applicants and inform program leadership of important programmatic elements in the eyes of applicants. It elucidates important themes in their interactions or learning experiences with programs and creates opportunities for learner-centric program improvement.

Laparoscopic total mesorectal excision versus transanal total mesorectal excision for mid and low rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic total mesorectal excision (LaTME) and transanal total mesorectal excision (TaTME) are popular mid and low rectal cancer trends. However, there is currently no systematic comparison between LaTME and TaTME of mid and low rectal cancer. Therefore, we systematically study the perioperative and pathological outcomes of LaTME and TaTME in mid and low rectal cancer. METHODS: Articles included searching through the Embase, Cochrane Library, PubMed, Medline, and Web of science for articles on LaTME and TaTME. We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42022380067). RESULTS: There are 8761 participants included in 33 articles. Compared with TaTME, patients who underwent LaTME had no statistical difference in operation time (OP), estimated blood loss (EBL), postoperative hospital stay, over complications, intraoperative complications, postoperative complications, anastomotic stenosis, wound infection, circumferential resection margin, distal resection margin, major low anterior resection syndrom, lymph node yield, loop ileostomy, and diverting ileostomy. There are similarities between LaTME and TaTME for 2-year DFS rate, 2-year OS rate, distant metastasis rat, and local recurrence rate. However, patients who underwent LaTME had less anastomotic leak rates (RR 0.82; 95% CI: 0.70-0.97; I2 = 10.6%, P = .019) but TaTME had less end colostomy (RR 1.96; 95% CI: 1.19-3.23; I2 = 0%, P = .008). CONCLUSION: This study comprehensively and systematically evaluated the differences in safety and effectiveness between LaTME and TaTME in the treatment of mid and low rectal cancer through meta-analysis. Patients who underwent LaTME had less anastomotic leak rate but TaTME had less end colostomy. There is no difference in other aspects. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research.

[Shock modeling of large area third-degree burn in miniature swine].

OBJECTIVE: To report a novel method of establishing a stable shock model of swine. METHODS: A total of 12 Guangxi BA-MA female miniature swines (aged 4-6 months) into A and B groups according to a random number table. Total body surface area (TBSA) was calculated according to the Meeb-Rubner formula. After intravenous anesthesia and other steps, solidified gasoline was used as burns material to establish TBSA 40% skin burn (Group A: 45 s, Group B: 50 s). Burn depth by was judged by visual and histopathological examination. Fluid resuscitation was instituted at 2 h post injury. At the same time, the hourly and pre-injury data of heart rate (HR), blood pressure (BP), urinary volume, central venous pressure (CVP) and pulmonary arterial wedge pressure (PAWP) were recorded. The actual input quantities of fluid resuscitation were assessed at the 1st and 2nd 24 h post injury. And shock condition was estimated by shock index at 2 h post injury. RESULTS: All miniature swines were successfully modeled without any mortality. The burn wound observed by visual examination and light microscope showed that Group A was of deep II burn and Group B III burn. Compared with the pre-injury data, HR (111 ± 6 vs 74 ± 9, 119 ± 13 vs 75 ± 13 beats/min) increased, urinary volume (0.99 ± 0.06 vs 1.45 ± 0.05, 0.82 ± 0.04 vs 1.47 ± 0.06 ml×kg(-1)×h(-1)), CVP and PAWP decreased at 2nd 24 h post-injury in two groups (P < 0.01, P < 0.05). But the changes of BP (120 ± 6/93 ± 9 vs 120 ± 6/94 ± 6, 121 ± 15/90 ± 11 vs 124 ± 10/91 ± 8 mm Hg) had no statistical significance (P > 0.05). The average value of HP in 48 h post-injury had no statistical significance in two groups (P > 0.05). The recovery liquid quantity in the first 24 h of Group B (1.66 ± 0.10 ml×kg(-1)×1%(-1) TBSA) was significantly more than Group A (1.53 ± 0.05 ml×kg(-1)×1%(-1) TBSA) (P < 0.05). The ratio between liquid input and output of Groups A and B showed that the comparison had no statistical significance (P > 0.05). In the second 24 h post-injury, the recovery liquid quantity (0.69 ± 0.17, 0.65 ± 0.16 ml×kg(-1)×1%(-1) TBSA) and the ratio between liquid in and out (1.48 ± 0.28, 1.52 ± 0.27)% between Groups A and B had no statistical significance (P > 0.05). The shock index at 2 h post-injury showed that Groups A and B were in shock compensatory period (0.92 ± 0.07) and mild shock state (1.00 ± 0.16) respectively (P > 0.05). CONCLUSION: Such a shock model is stable and dependable.

Floating clavicle with medial clavicular fracture causing diagnostic dilemma - A case report and literature review.

INTRODUCTION AND IMPORTANCE: A rare case of a fracture of the medial third of the clavicle on the basis of the "floating clavicle" was hereby reported. To the best of our knowledge, this complex clavicle fracture has not yet been published. This article aims to describe, for the first time, a case of the diagnosis and treatment of this special clavicle fracture. CASE PRESENTATION: The 26-year-old male patient suffered from a right sternoclavicular dislocation, a fracture of the right medial third of the clavicle, and a dislocation of the right acromioclavicular joint due to a car accident. In the course of treatment, he was missed diagnosis, and after active adjustment of treatment plan, good therapeutic effect was achieved. CLINICAL DISCUSSION: A special case of a floating clavicle was hereby reported. The missed diagnosis of sternoclavicular dislocation will cause great difficulties in the management of the disease. Based on the condition and clear diagnosis of the patient, surgical treatment was actively recommended for the patient. The selection of the implant for surgical treatment varied due to its specificity. A comprehensive literature review is also provided. CONCLUSION: Clavicular bone fracture is common in clinical practice. At the same time, the injury of sternoclavicular joint and acromioclavicular joint should be vigilant. For the complex clavicle fracture reported in this paper, the computed tomography scan with 3D reconstruction can assist in diagnosis. In the case of definite diagnosis, the use of a contralateral distal clavicular plate in combination with the conventional clavicular hook plate is an appropriate choice.

Efficacy and Safety of Robot-assisted AUS Implantation Surgery in Treating Severe Stress Urinary Incontinence: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the effectiveness and safety of robot-assisted artificial urinary sphincter (AUS) implantation surgery for female patients with severe stress urinary incontinences (SUI) by performing a systematic literature review. METHODS: A comprehensive search was carried out across multiple databases, including PubMed, EMBASE, Web of Science Clarivate, Cochrane library, Medicine and clinicaltrials.gov between inception to March 2022. Studies were included if they met the inclusion criteria and were evaluated by different quality evaluation methods according to study types. P value and 95% confidence intervals (CI) of outcome measures mainly including continence rates, intraoperative and postoperative complication rates were pooled to present the efficacy and safety. RESULTS: A total of 9 studies with 157 participants were finally included. Eight retrospective and 1 prospective study met the inclusion criteria with moderate and high evidence levels. The pooled results showed that patients with robot-assisted AUS implantation treatment, presented great continence rate (P = .83, 95%CI:0.76-0.89) but high complication rate (Intraoperation: 0.21 95%CI:0.11-0.34; Postoperation: 0.20 95%CI: 0.12-0.29). In addition, subgroup analysis of 2 approaches showed that compared with the posterior approach, the traditional surgical approach had better efficacy and safety. CONCLUSION: The results of this study indicated that robot-assisted AUS implantation surgery improved SUI patients' urinary continence, but the complication rates were high, which mainly included intraoperative vaginal and bladder injury and postoperative acute urinary retention. More evidence from prospective studies is needed to provide guidance for clinical practice.

[Morphological changes associated with low-tone hearing loss in guinea pig models of early endolymphatic hydrops].

The present study was to explore the functional and morphological changes in cochleas of guinea pig models of early endolymphatic hydrops. Thirty albino guinea pigs were randomly divided into three groups: control, 4-week model and 8-week model groups. For each group, n = 10. Model groups were operated on the right ears to result in endolymphatic hydrops with the method of slight destruction of endolymphatic sac and duct from extradural posterior cranial fossa approach, and the animals in control group were sham operated. Electrocochleogram recorded by trans-tympanic approach and auditory brainstem response (ABR) were tested in preoperative model groups, control group, 4-week model group and 8-week model group to assess the hearing changes. Histologic morphometry was used to quantify hydrops by testing scala media area (SMA) ratio. Scanning electron microscope was used to assess the changes of cochlea hair cells. The results showed that the summating potential/compound action potential (SP/AP) ratio of electrocochleogram in 4-week model group (0.33 ± 0.14) and 8-week model group (0.43 ± 0.14) increased significantly, compared with that in control group (0.07 ± 0.06). The maximum SMA ratio in 4-week model group (2.64 ± 0.10) and 8-week model group (3.54 ± 0.13) increased significantly, compared with that in control group (1.06 ± 0.08). The results of maximum SMA ratio correlated with SP/AP ratio of electrocochleogram (r = 0.86). The results of hearing threshold of ABR revealed that the operated ears of model groups were higher than the preoperative results at frequencies of 2 kHz and 4 kHz. And the damage of cochlea hair cells in operated ears occurred in apical and subapical turns. These results suggest the increased SP/AP ratio of electrocochleogram can indicate early endolymphatic hydrops. There is low-tone hearing loss in guinea pig models of early endolymphatic hydrops, and it may be associated with the abnormalities of the stereocilia among the outer hair cells in operated ears which occurs in apical and subapical turns.

Urban-Rural Differences: The Impact of Social Support on the Use of Multiple Healthcare Services for Older People.

Background: There are many kinds of chronic diseases, high incidence and high hospitalization rate in older people caused by population aging. The increasing demand for healthcare services has become an increasingly prominent problem in Chinese society. The purpose of this paper is to explore the influence of social support on multiple healthcare services for older people and the urban-rural differences among them. Methods: The data are from our field survey in Shaanxi province in 2019. Using the Anderson model as the basic explanatory framework, this paper uses the Tobit-model to analyses the impact of social support for older people on the utilization of therapeutic healthcare services, and the Logit-model to analyze the impact of living arrangements and social support on the utilization of preventive healthcare services for older people. Results: This paper examines the impact of formal and informal support on outpatient, inpatient, and preventive healthcare services for older people, provides an in-depth analysis of the differences in the impact of social support on healthcare service utilization between urban and rural older people and analyses the contribution of various factors to the impact. The coefficient effect is divided into two parts: the coefficient "premium" of urban older people relative to urban and rural older people as a whole, which accounts for 10.8% of the total difference; and the "premium" of urban and rural older people as a whole to rural older people, which accounts for 18.9% of the total difference. The coefficient effect accounts for 29.7 per cent of the total difference. Conclusions: Rural older people place greater importance on the quantity of formal social support, while urban older people place greater importance on the quality of formal social support. The phenomenon of raising children for old age was evident in the use of healthcare services by rural older people, while the phenomenon of distant relatives being better than close neighbors was evident in the use of healthcare services by urban older people. Free preventive healthcare services in rural China have largely compensated for the lack of health benefits for rural older people.

Effect of long term glucocorticoid treatment on human growth hormone secretion in children and adolescents and the safety and effectiveness of recombinant human growth hormone treatment.

OBJECTIVE: Long term glucocorticoid (prednisolone) treatment on human growth hormone (hGH) secretion in children and adolescents and to investigate the effectiveness and safety of the recombinant human growth hormone (rhGH) treatment. METHODS: Twelve patients (age: 10.4∓1.2 years) who were treated in Peking Union Medical College Hospital from September 1999 to November 2009 were enrolled in this study. All of them had taken prednisolone with a dose of 0.5∓2.0 mg/(kg.d) for 6~18 months. Two different hGH stimulating tests was done and their growth and development was evaluated at regular intervals. Seven patients were given rhGH with a dose of 0.1 U/(kg.d) for 6~12 months to improve their growth and development after half a year of prednisolone withdrawal when their disease conditions were improved. RESULTS: The growth speed of these 12 children decreased significantly during prednisolone treatment compared with before prednisolone treatment (1.2∓0.3cm/year vs.3.7∓1.2 cm/year,P12 months than those with a 6~12 months course (P0.05). The growth speed of seven children who received rhGH therapy for half a year were increased from 2.2∓0.1cm/year to 7.8∓0.5cm/year (P<0.05), and then to 6.9∓0.4cm/year one year later. CONCLUSIONS: The long-term glucocorticoid treatment can decrease the hGH secretion, and thus leads to short stature and agenesis. However, the rhGH replacement can safely and effectively improve growth and development in these children after their primary diseases are improved and glucocorticoids are withdrawn.

The Impact of Chinese College Students' Perceived Stress on Anxiety During the COVID-19 Epidemic: The Mediating Role of Irrational Beliefs.

Objective: To explore the underlying mechanism of the impact of perceived stress on anxiety of the Chinese college students during the COVID-19 epidemic. Methods: The Perceived Stress Scale, Irrational Belief Scale, and General Anxiety Scale were adopted in the current study. College students were randomly selected for online questionnaire survey. There were 1,598 valid questionnaires, and the proportion of women was 47.81%. Results: The perceived stress and anxiety, as well as the three dimensions of irrational beliefs (catastrophizing, low frustration tolerance, and depreciation) were significantly positively correlated; demandingness was not significantly correlated with anxiety. Further analysis found that the perceived stress had a significant positive predictive effect on the anxiety of college students. Catastrophizing, low frustration tolerance, and depreciation played part of the mediating role, and there was no significant difference in the strength of these mediating roles. Conclusion: The perceived stress of the COVID-19 epidemic had a positive effect on the anxiety of Chinese college students, this was partly mediated by irrational beliefs.

Combination of quantitative hepatitis B core antibody (qHBcAb) and aspartate aminotransferase (AST) can accurately diagnose immune tolerance of chronic hepatitis B virus infection based on liver biopsy.

BACKGROUND AND AIMS: Immune tolerance is defined as HBeAg positive, high hepatitis B virus load (HBV), persistent normal alanine aminotransferase (ALT), no or slight inflammation or fibrosis in liver histology. However, it is still unclear the threshold of high hepatitis B virus load and how to predict histology without liver biopsy. The aim of this study was to predict immune tolerance in HBeAg positive, alanine aminotransferase -normal populations with non-invasive indicators. METHODS: Two multi-center prospective cohort study recruited 907 treatment-naïve chronic hepatitis B (CHB) patients who had undergone liver biopsy in mainland China from August 2013 to September 2016 and April 2018 to June2019. Quantitative hepatitis B core antibody, AST and HBV DNA were investigated using commercial diagnostic assays and histological grading and staging was assessed by the Ishak scoring system. RESULTS: One hundred and thirteen untreated CHB patients with HBeAg-positive, normal alanine aminotransferase (ALT) and high level of HBV DNA (≥5log10 IU/mL) were enrolled in this study. The area under the receiver operating characteristic curves (AUROCs) of qHBcAb, AST, HBV DNA and qHBcAb-AST index were 79.6%, 80.5%, 76.4% and 87.7%. Our novel qHBcAb-AST index, which combined qHBcAb and AST showed better performance with higher sensitivity (88.6% [95% confidence interval (CI) 72.3% - 96.3%]) and negative predictive value (NPV) (93.8% [95% CI 84.2% - 98.0%]). CONCLUSIONS: The combination of qHBcAb and AST can more accurately predict the immune tolerance of people with HBeAg-positive, normal alanine aminotransferase (ALT).

3D printing hydrogel with graphene oxide is functional in cartilage protection by influencing the signal pathway of Rank/Rankl/OPG.

3Dprinting is defined as the use of printing technology to deposit living cells, and biomaterials on a given /a substrate. Graphene oxide nanoparticles (GO-np) have been used as a delivery vehicle for small molecule drugs in order to investigate the state of GO-np within 3D tissue constructs in terms of a composite 3D printing scaffold, which in turn is relevant to the protection of cartilage. We transplanted rats with hydrogel/GO-np and hydrogel, which in turn showed that hydrogel/GO-np protected the tissue of cartilage by the signal pathway of Rank/Rankl/OPG. Those findings indicated that GO-np may be potentially used to control the release of carrier materials and influence the signal pathway of Rank/Rankl/OPG.