The effect of health quotient and time management skills on self-management behavior and glycemic control among individuals with type 2 diabetes mellitus.

Objective: The aim of this study was to evaluate the present status of self-management behavior and glycemic control in individuals diagnosed with Type 2 Diabetes Mellitus (T2D), as well as to examine the impact of health quotient (HQ) and time management skills on both self-management behavior and glycemic control. Methods: Between October 2022 and March 2023, a purposive sampling method had been utilized to select 215 participants with type T2D. The survey concluded a general information questionnaire, an HQ scale, a diabetes time management questionnaire and a self-management behavior questionnaire. The health quotient(HQ)encompasses the individuals' knowledge, attitude toward health, and the ability to maintain their own well-being. The diabetes time management questionnaire was reverse-scored, with higher scores indicating an enhanced competence in time management. The path among variables was analyzed using structural equation modeling(SEM). Results: SEM showed that the direct effect of HQ on time management was -0.566 (p < 0.05), the direct effect of time management on the effect of self-management was -0.617 (p < 0.05), the direct effect of HQ on self-management was 0.156, and the indirect effect was 0.349 (p < 0.05); the relationship between health quotient and self-management was partially mediated by time management, with a mediating effect size of 68.8%. In addition, self-management had a direct effect on HbAlc, with a size of -0.394 (p < 0.05); The impacts of both HQ and time management on HbAlc were found to be mediated by self-management, with HQ demonstrating an indirect effect of -0.199 (p < 0.05) and time management showing an indirect effect of 0.244 (p < 0.05). Conclusion: Health quotient and time management in patients with T2D serve as catalysts for self-management behavior. They affect HbAlc level indirectly through self-management practices. The suggestion is to prioritize the cultivation of rational time organization and management skills in T2D patients, as well as enhance their health quotient level. This can facilitate a more effective improvement in patients' self-management behaviors, ultimately achieving the objective of maintaining optimal glycemic control.

Effects of light therapy on sleep and circadian rhythm in older type 2 diabetics living in long-term care facilities: a randomized controlled trial.

Background: Light influences the secretion of melatonin in the body and regulates circadian rhythms, which play an important role in sleep and mood. The light level of rooms in long-term care facilities is usually far below the threshold required to regulate the body's circadian rhythm, and insufficient light can easily lead to sleep and mood disturbances among older residents in nursing homes. Therefore, the objective of this study was to investigate the effects of light therapy on sleep and circadian rhythm in older adults with type 2 diabetes residing in long-term care facilities. Methods: This study was a prospective, single-blind, randomized controlled trial. Participants were randomly assigned to either the light therapy (LT) group or the control group and received the intervention for four weeks. Primary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and objective sleep parameters recorded by a sleep monitoring bracelet, Morningness-Eveningness Questionnaire (MEQ). The secondary outcome included glycated serum protein (GSP). Data was collected at three time points: at baseline (T0), immediate post-treatment (T1), and 4-week follow-up (T2). A linear mixed model analysis was used to analyzed the data. Results: We enrolled 45 long-term care residents. Compared with the control group, significant reductions in PSQI scores were observed at T1 and T2. At T2, the sleep score of objective sleep parameters was significantly higher in the LT group compared to the control group. Additionally, compared to the baseline T0, MEQ scores were significantly lower in the LT group at T1 and T2, with no significant difference in the control group. There was no significant difference between groups in glycated serum protein values at T1 and T2. However, compared to T0, glycated serum protein values decreased in the LT group while increased in the control group at T2. Conclusion: Light therapy had a positive effect on subjective sleep quality and circadian rhythm time type in long-term care residents with type 2 diabetes, and had a possible delayed effect on objective sleep. However, no discernible alterations in blood glucose levels were detected in this study.

Anti-Toxoplasma gondii antibodies as a risk factor for the prevalence and severity of systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. METHODS: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. RESULTS: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70-3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14-2.70, P = 0.011) compared to ATxA-IgG- patients. Relative to ATxA-IgG- patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. CONCLUSIONS: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations.

PIM1 attenuates cisplatin-induced AKI by inhibiting Drp1 activation.

Cisplatin, an effective anti-cancer drug, always causes acute kidney injury (AKI) by inducing mitochondrial damage. PIM1 is a serine/threonine kinase, which has been shown to regulate mitochondrial function. However, the role and mechanisms of PIM1 in cisplatin-induced AKI remain unexplored. This study aimed to investigate the effects of PIM1 in cisplatin-induced AKI and its underlying mechanisms. To established Cisplatin-induced AKI model, mice were given a single intraperitoneal injection(20 mg/kg) and BUMPT cells were treated with cisplatin(20 µM). PIM1 inhibitor AZD1208 was used to inhibit PIM1 and PIM1-experssing adenovirus was used to overexpress PIM1. Drp1 inhibitor P110 and pcDNA3-Drp1K38A were used to inhibit the activation of Drp1 and mitochondrial fission. The indicators of renal function, renal morphology, apoptosis and mitochondrial dysfunction were assessed to evaluate cisplatin-induced nephrotoxicity. We observed that PIM1 was activated in cisplatin-induced AKI in vivo and cisplatin-induced tubular cells injury in vitro. PIM1 inhibition aggravated cisplatin-induced AKI in vivo, while PIM1 overexpression attenuated cisplatin-induced kidney injury in vivo and in vitro. Moreover, inhibiting PIM1 exacerbated mitochondrial damage in mice, but overexpressing PIM1 relieved mitochondrial damage in mice and BUMPT cells. In mice and BUMPT cells, inhibiting PIM1 deregulated the expression of p-Drp1S637, overexpressing PIM1 upregulated the ex-pression of p-Drp1S637. And inhibiting Drp1 activity alleviated cell damage in BUMPT cells with PIM1 knockdown or inhibition. This study demonstrated the protective effect of PIM1 in cisplatin-induced AKI, and regulation of Drp1 activation might be the underlying mechanism. Altogether, PIM1 may be a potential therapeutic target for cisplatin-induced AKI.

TRIM26 restricts Epstein-Barr virus infection in nasopharyngeal epithelial cells through K48-linked ubiquitination of HSP-90ß.

The tripartite interaction motif (TRIM) family of proteins is known for their antiviral activity through different mechanisms, such as interfering with viral components, regulating immune responses, and participating in autophagy-mediated defense pathways. In this study, we investigated the role of tripartite interaction motif 26 (TRIM26), which is encoded by a major histocompatibility complex (MHC) gene, in regulating Epstein-Barr virus (EBV) infection of nasopharyngeal epithelial cells. We found that TRIM26 expression was induced upon EBV infection and that it indirectly targeted EphA2, a crucial epithelial receptor for EBV entry. Our results showed that TRIM26 interacted with heat shock protein 90-beta (HSP-90ß) and promoted its polyubiquitination, which led to its degradation via the proteasome pathway. This, in turn, affected EphA2 integrity and suppressed EBV infection. These findings suggest that TRIM26 could be a valuable target for developing therapeutic interventions against EBV infection and its associated pathogenesis.

Factors affecting the willingness of patients with type 2 diabetes to use digital disease management applications: a cross-sectional study.

Background: The global burden of type 2 diabetes has significantly increased, leading to a considerable impact on healthcare systems worldwide. While the advent of mobile healthcare has provided some relief by addressing the shortage of certain medical resources, its adoption among the Chinese population remains relatively low. To extend the benefits of mHealth to a greater number of Chinese diabetic patients, it is essential to investigate the factors that influence their willingness to utilize it and implement targeted interventions based on these influencing factors. The Technology Acceptance Model (TAM) is widely employed to examine users' ultimate usage behaviors, and previous studies have indicated the potential relevance of the Perceived Risk (PR) theory and the eHealth Literacy Theory to users' usage behaviors. Objective: Our objective was to investigate the determinants that affect the willingness of Chinese patients diagnosed with type 2 diabetes patients to utilize digital disease management applications (DDMAs). Methods: We conducted a cross-sectional study of patients with type 2 diabetes in three tertiary general hospitals in Chengdu using questionnaires designed by the investigators. Participants were sampled using a convenience sampling method. The questionnaire comprised three sections: socio-demographic profile and medical history; current awareness and willingness to use digital disease management applications; and the current level of e-health literacy. Structural equation modeling was employed to assess the impact of patient awareness of DDMAs and e-health literacy on the willingness to use such DDMAs. Results: (1) Patients' attitudes toward using DDMAs were significantly influenced by perceived ease of use (ß = 0.380, P < 0.001) and perceived usefulness (ß = 0.546, P < 0.001); (2) Electronic health literacy exerted a significant impact on patients' perceived usefulness (ß = 0.115, P = 0.018) and perceived ease of use (ß = 0.659, P < 0.001); (3) Patients' willingness to use was significantly influenced by perceived usefulness (ß = 0.137, P < 0.001) and use attitude (ß = 0.825, P < 0.001). Conclusions: The present research findings hold both theoretical and practical significance, and can serve as a guide for healthcare practitioners and researchers to gain a deeper comprehension of the acceptance of digital disease management applications (DDMAs) among type 2 diabetes patients.

A systematic bibliometric analysis on the clinical practice of CGM in diabetes mellitus from 2012 to 2022.

Background: Continuous glucose monitoring (CGM) has revolutionized diabetes management, but a comprehensive analysis of its clinical implementation is lacking. This study aims to explore CGM in diabetes practice over the past decade using bibliometric analysis. It will identify trends, research focal points, and provide a framework for future investigations. Materials and methods: The Web of Science Core Collection (WOSCC) was utilized to acquire literature pertaining to the employment of continuous glucose monitoring (CGM) in diabetes that was published between the years 2012 and 2022, and to conduct a comprehensive analysis of the associated citation data. To achieve bibliometric visualization and analysis of the collated data, the bibliography package in the Rstudio(v.4.2.2), Citespace 6.2.R4, and VOS viewer were employed. Results: A total of 3024 eligible publications were extracted from 91 countries, with the United States being the leading country in terms of the number of issued articles. Furthermore, the annual publication rate has shown a gradual increase during the past decade. Among the various journals in this field, DIABETES TECHNOLOGY & THERAPEUTICS was identified as the most highly cited one. Keyword clustering analysis of the extracted publications indicates that the research hotspots in the past decade have primarily focused on "continuous glucose monitoring", "glycemic variability", "type 1 diabetes", "hypoglycemia", and "glycemic control". Moreover, the analysis of keyword emergence reveals that "Time In Range" and "Young Adult" represent the current research frontiers for the years 2012-2022. Conclusion: The concept of Time in Range (TIR) has garnered considerable attention as a significant area of inquiry and an emerging research trend in the clinical practice of Continuous Glucose Monitoring (CGM) for Diabetes Mellitus. Moreover, recent investigations have demonstrated a growing focus on young adults with type 1 diabetes as the research population of interest. In the foreseeable future, research endeavors will persist in the pursuit of improving glycemic management among young adults through the utilization of continuous glucose monitoring (CGM) technology, while also delving into the examination of the Time in Range metric via supplementary clinical investigations.

Efficacy of a smartphone application for helping individuals with type 2 diabetes mellitus manage their blood glucose: a protocol for factorial design trial.

BACKGROUND: China has the largest number of individuals with type 2 diabetes mellitus (T2DM) in the world, and most lack knowledge about glycemic control and health management. This trial will examine whether a smartphone application can improve blood glucose management among individuals with T2DM. METHODS: This will be a 2-center, factorial design, equal proportional distribution, superiority trial conducted in outpatient endocrinology clinics at two tertiary hospitals in Chengdu, China. The trial will enroll smartphone-literature individuals at least 18 years old who have been diagnosed with T2DM based on glycosylated hemoglobin (HbA1c) of at least 7.0%. Individuals will be randomly assigned to receive routine care with standard education about T2DM and glycemic control (Control), routine care as well as weekly telephone reminders to self-monitor blood glucose (Reminder), routine care and a smartphone application providing information about glycemic control and health management with T2DM (App), or the combination of routine care, the smartphone application, and weekly telephone reminders (App + Reminder). After 6 months of these interventions, participants will be analyzed for the primary outcome of HbA1c as well as the secondary outcomes of blood glucose monitoring frequency, body mass index, blood pressure, knowledge about diabetes, health beliefs related to diabetes, diabetes self-management behavior, and satisfaction with the smartphone application. DISCUSSION: This trial will determine whether a smartphone application can improve glycemic management among Chinese with T2DM. The findings may help guide the development of effective applications in China and elsewhere. TRIAL REGISTRATION: Registration in the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2100042297: https://www.chictr.org.cn/bin/userProject . 17 January 2021.

Regulation of adipose tissue development and energy metabolism by VEGFB isoforms.

Obesity is caused by imbalanced energy intake and expenditure. Excessive energy intake and storage in adipose tissues are associated with many diseases. Several studies have demonstrated that vascular growth endothelial factor B (VEGFB) deficiency induces obese phenotypes. However, the roles of VEGFB isoforms VEGFB167 and VEGFB186 in adipose tissue development and function are still not clear. In this study, genetic mouse models of adipose-specific VEGFB167 and VEGFB186 overexpression (aP2-Vegfb167 tg/+and aP2-Vegfb186tg/+) were generated and their biologic roles were investigated. On regular chow, adipose-specific VEGFB186 is negatively associated with white adipose tissues (WATs) and positively regulates brown adipose tissues (BATs). VEGFB186 upregulates energy metabolism and metabolism-associated genes. In contrast, VEGFB167 has a nominal role in adipose development and function. On high-fat diet, VEGFB186 expression can reverse the phenotypes of VEGFB deletion. VEGFB186 overexpression upregulates BAT-associated genes and downregulates WAT-associated genes. VEGFB186 and VEGFB167 have very distinct roles in the regulation of adipose development and energy metabolism. As a key regulator of adipose tissue development and energy metabolism, VEGFB186 may be a target for obesity prevention and treatment.

De Novo Evolution of an Antibody-Mimicking Multivalent Aptamer via a DNA Framework.

Multivalent interactions can often endow ligands with more efficient binding performance toward target molecules. Generally speaking, a multivalent aptamer can be constructed via post-assembly based on chemical structural information of target molecules and pre-identified monovalent aptamers derived from traditional systematic evolution of ligands by exponential enrichment (SELEX) technology. However, many target molecules may not have known matched aptamer partners, thus a de novo evolution will be highly desired as an alternative strategy for directed selection of a high-avidity, multivalent aptamer. Here, inspired by the superiority of multivalent interactions between antibodies and antigens, a direct SELEX strategy with a preorganized DNA framework library for an "Antibody-mimicking multivalent aptamer" (Amap) selection to epithelial cell adhesion molecule (EpCAM), a model target protein is reported. The Amap presents a relatively good binding affinity through both aptamer moieties concurrently binding to EpCAM, which has been confirmed by affinity analysis and molecular modeling. Furthermore, dynamic interactions between Amap and EpCAM are directly visualized by magnetic tweezers at the single-molecule level. A nice binding affinity of Amap to EpCAM-positive cancer cells has also been verified, which hints that their Amap-SELEX strategy has the potential to be a new route for de novo evolution of multivalent aptamers.

OGG1 aggravates renal ischemia-reperfusion injury by repressing PINK1-mediated mitophagy.

Renal ischemia-reperfusion injury (IRI) is mainly responsible for acute kidney injury for which there is no effective therapy. Accumulating evidence has indicated the important role of mitophagy in mitochondrial homeostasis under stress. OGG1 (8-oxoguanine DNA glycosylase) is known for functions in excision repair of nuclear and mitochondrial DNA. However, the role of OGG1 in renal IRI remains unclear. Herein, we identified OGG1, induced during IRI, as a key factor mediating hypoxia-reoxygenation-induced apoptosis in vitro and renal tissue damage in a renal IRI model. We demonstrated that OGG1 expression during IRI negatively regulates mitophagy by suppressing the PINK1/Parkin pathway, thereby aggravating renal ischemic injury. OGG1 knockout and pharmacological inhibition attenuated renal IRI, in part by activating mitophagy. Our results elucidated the damaging role of OGG1 activation in renal IRI, which is associated with the regulatory role of the PINK1/Parkin pathway in mitophagy.

MiR-20a-5p alleviates kidney ischemia/reperfusion injury by targeting ACSL4-dependent ferroptosis.

Ischemia/reperfusion injury (IRI) is prone to occur after kidney transplantation, leading to delayed graft function (DGF). MicroRNAs play a crucial role in the pathogenesis of ischemia/reperfusion-induced acute kidney injury, and miR-20a-5p was found to be the most significantly upregulated gene in a DGF patient cohort. However, the roles of microRNAs in transplanted kidneys remain largely unknown. In this study, we found that miR-20a-5p was upregulated in the kidneys of acute kidney injury mice and in patients with DGF. We identified early growth response-1 as a critical upstream target and verified the binding of early growth response-1 to a predicted sequence in the promoter region of the miR-20a-5p gene. Functionally, the miR-20a-5p mimic attenuated IRI and postischemic renal fibrosis, whereas the miR-20a-5p inhibitor delivery aggravated IRI and fibrosis. Importantly, delivery of the miR-20a-5p mimic or inhibitor in the donor kidneys attenuated or aggravated renal loss and structural damage in cold storage transplantation injury. Furthermore, our study identified miR-20a-5p as a negative regulator of acyl-CoA synthetase long-chain family member 4 (ACSL4) by targeting the 3' untranslated region of ACSL4 mRNA, thereby inhibiting ACSL4-dependent ferroptosis. Our results suggest a potential therapeutic application of miR-20a-5p in kidney transplantation through the inhibition of ACSL4-dependent ferroptosis.

Light Therapy to Improve Sleep Quality in Older Adults Living in Residential Long-Term Care: A Systematic Review.

OBJECTIVES: Because light can regulate sleep rhythms, numerous studies have investigated whether light therapy can improve sleep disorders in older people, but its efficacy remains controversial. Therefore, this systematic review aimed to examine and summarize current evidence about the efficacy of light therapy to improve sleep for older people in residential long-term care. DESIGN: Systematic review. SETTING AND PARTICIPANTS: Older people living in long-term care settings. METHODS: Systematic searches were conducted in the databases PubMed, Web of Science, Cochrane, EMBASE, CINAHL, China National Knowledge Infrastructure, China Science and Technology Journal Database, WanFang, Chinese Biomedical Literature Database, and in reference lists within relevant articles. Studies were eligible for inclusion if they evaluated light therapy for older people with sleep disorders in long-term care settings. RESULTS: This systematic review includes 21 articles, summarizing light therapy with different durations and intensities. The light intervention was typically administered between 7:00 and 12:00 am for 30-120 minutes. The interventions lasted from 1 week to several months, and the intensity of the light intervention usually ranged from 2500 to 10,000 lux. Short-term exposure (30-60 minutes) with high light levels (≥10,000 lux), relatively long-term exposure (1-2 hours) with moderate light levels (2500-10,000 lux), or long-term exposure (1-4 hours or full day) with low light levels (≤2500 lux) were associated with improved sleep indicators for older people in long-term care settings. CONCLUSIONS AND IMPLICATIONS: The efficacy of light therapy in long-term care settings may be affected by the duration of exposure, time and length of intervention, intensity of light, and equipment used to administer the therapy. Further research must be conducted to optimize light therapy parameters. Large, high-quality randomized controlled trials are needed to deepen our understanding of the effects of light therapy on sleep in older people living in long-term care settings.

Higher pharyngeal epithelial gene expression of angiotensin-converting Enzyme-2 in patients with upper respiratory infection.

We analyzed the expression of ACE2 in the pharyngeal epithelium and examined its relationship with clinical features and serological parameters in patients with upper respiratory infection (URI). The expression level of the ACE2 gene was significantly higher in patients with URI (n = 125) than in healthy control (HC) individuals (n = 52) (p < 0.0001). The ACE2 gene expression level was significantly and positively correlated with age (r=0.1799, p = 0.0447) and body temperature (r=0.1927, p = 0.0427), which may help explain increasing coinfections with SARS-CoV-2 and other respiratory pathogens.

Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity.

BACKGROUND: Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis; however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. METHODS: Real-time transcription-polymerase chain reaction (RT-PCR) analysis was used to determine the expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA), and 30 age- and sex-matched healthy controls (HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. RESULTS: Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for antinuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289), and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779-0.9775, p < 0.001) to discriminate SLE from controls. CONCLUSIONS: These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.

Adipose vascular endothelial growth factor B is a major regulator of energy metabolism.

Excessive fat accumulation causes obesity and many diseases. Previous study demonstrates VEGFB universal knockout induces obese phenotypes including expansion of white adipose tissue, whitening of brown adipose tissue, increase of fat accumulation and reduction in energy consumption. However, roles of VEGFB in adipose tissues are not clear. In this study, we have generated a mouse model with adipose-specific VEGFB repression using CRISPR/dCas9 system (Vegfb AdipoDown ) and investigated the roles of VEGFB in adipose development and energy metabolism. VEGFB repression induced significant changes in adipose tissue structure and function. Vegfb AdipoDown mice have larger body sizes, larger volume of white adipose tissues than its wild type littermates. Adipose-specific VEGFB repression induced morphological and functional transformation of adipose tissues toward white adipose for energy storage. Metabolic processes are broadly changed in Vegfb AdipoDown adipose tissues including carbohydrate metabolism, lipid metabolism, nucleotide metabolism and amino acid metabolism. We have demonstrated that adipose VEGFB repression can recapitulate most of the phenotypes of the whole body VEGFB knockout mouse. Intriguingly, approximately 50% VEGFB repression in adipose tissues can almost completely mimic the effects of universal Vegfb deletion, suggesting adipose VEGFB is a major regulator of energy metabolism and may be important in prevention and treatment of obesity.

OXTR overexpression leads to abnormal mammary gland development in mice.

Oxytocin receptor (OXTR) is a G-protein coupled receptor and known for regulation of maternal and social behaviors. Null mutation (Oxtr-/-) leads to defects in lactation due to impaired milk ejection and maternal nurturing. Overexpression of OXTR has never been studied. To define the functions of OXTR overexpression, a transgenic mouse model that overexpresses mouse Oxtr under ß-actin promoter was developed (++Oxtr). ++Oxtr mice displayed advanced development and maturation of mammary gland, including ductal distention, enhanced secretory differentiation and early milk production at non-pregnancy and early pregnancy. However, ++Oxtr dams failed to produce adequate amount of milk and led to lethality of newborns due to early involution of mammary gland in lactation. Mammary gland transplantation results indicated the abnormal mammary gland development was mainly from hormonal changes in ++Oxtr mice but not from OXTR overexpression in mammary gland. Elevated OXTR expression increased prolactin-induced phosphorylation and nuclear localization of STAT5 (p-STAT5), decreased progesterone level, leading to early milk production in non-pregnant and early pregnant females, whereas low prolactin and STAT5 activation in lactation led to insufficient milk production. Progesterone treatment reversed the OXTR-induced accelerated mammary gland development by inhibition of prolactin/p-STAT5 pathway. Prolactin administration rescued lactation deficiency through STAT5 activation. Progesterone plays a negative role in OXTR regulated prolactin/p-STAT5 pathways. The study provides evidence that OXTR overexpression induces abnormal mammary gland development through progesterone and prolactin-regulated p-STAT5 pathway.

Clinical Study of 3D Imaging and 3D Printing Technique for Patient-Specific Instrumentation in Total Knee Arthroplasty.

Patient-specific instrumentation (PSI) was designed to improve the accuracy of preoperative planning and postoperative prosthesis positioning in total knee arthroplasty (TKA). However, better understanding needs to be achieved due to the subtle nature of the PSI systems. In this study, 3D printing technique based on the image data of computed tomography (CT) has been utilized for optimal controlling of the surgical parameters. Two groups of TKA cases have been randomly selected as PSI group and control group with no significant difference of age and sex (p > 0.05). The PSI group is treated with 3D printed cutting guides whereas the control group is treated with conventional instrumentation (CI). By evaluating the proximal osteotomy amount, distal osteotomy amount, valgus angle, external rotation angle, and tibial posterior slope angle of patients, it can be found that the preoperative quantitative assessment and intraoperative changes can be controlled with PSI whereas CI is relied on experience. In terms of postoperative parameters, such as hip-knee-ankle (HKA), frontal femoral component (FFC), frontal tibial component (FTC), and lateral tibial component (LTC) angles, there is a significant improvement in achieving the desired implant position (p < 0.05). Assigned from the morphology of patients' knees, the PSI represents the convergence of congruent designs with current personalized treatment tools. The PSI can achieve less extremity alignment and greater accuracy of prosthesis implantation compared against control method, which indicates potential for optimal HKA, FFC, and FTC angles.

[Euphorbia fischeriana extract reactivates latent HIV through nuclear factor-κB pathway].

OBJECTIVE: To investigate the effect of Euphorbia fischeriana extract on latent HIV reactivation and the pathway involved in this process and discuss the value of Euphorbia fischeriana extract in eliminating HIV. METHODS: Fresh tissues of Euphorbia fischeriana root were crushed into powder after quick freezing with liquid nitrogen and extracted with acetone followed by a three-day vacuum freeze-drying for dehydration of the extract. The extract (EFE) was separated using RP-C18 column with high-performance liquid chromatography (HPLC) and identified with mass spectrometry (MS). The activity of reactivated latent HIV was analyzed by fluorescence-activated cell sorting in a J-Lat 10.6 cell model treated with EFE (50 µg/mL) for 24 h, using TNF-α (10 ng/mL) as the positive control. The effect of a NF-κB pathway inhibitor (Bay 11-7082) on EFE activity was tested. The changes in P65 expression in the cell nuclei within 2 h and HIV protein p24 expression within 24 h were analyzed by Western blotting in cells treated with EFE. RESULTS: EFE was obtained by one-step acetone extraction, and the concentration of prostratin in the extract was around 0.53 mmol/L. About 50% of the cells showed HIV reactivation after treatment with 50 µg/mL EFE for 24 h accompanied by a significantly increased p24 expression. The activity of EFE in reactivating latent HIV was inhibited by Bay 11-7082 in a concentration-dependent manner, and p65 accumulation was detected in the cell nuclei within 2 h. CONCLUSION: EFE we obtained contains the active compounds of prostratin and its analogues and shows a strong capacity to reactivate latent HIV through classical NF-κB pathway.