The impact of telehealth education on self-management in patients with coexisting type 2 diabetes mellitus and hypertension: a 26-week randomized controlled trial.

BACKGROUND: The prevalence of coexisting type 2 diabetes mellitus and hypertension is increasing globally and posing significant health challenges. Effective self-management is crucial for controlling the disease and preventing complications. Telehealth education has emerged as a promising approach to enhancing self-management. OBJECTIVE: This study aimed to investigate the effects of telehealth education on glycolipid metabolism, blood pressure, and self-management in patients with coexisting type 2 diabetes mellitus and hypertension. METHODS: This study included 174 patients diagnosed with type 2 diabetes and hypertension from October 2022 to March 2023 at the 900th Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army. The patients were randomly assigned to the control group or the telehealth education group. The control group received conventional diabetes education including diet and exercise guidance, while the telehealth education group received additional online education through the WeChatapplication. Both groups were followed up for 26 weeks and the changes in glycolipid metabolism, blood pressure, and self-management were compared between the groups. RESULTS: After 26 weeks of intervention, the telehealth education group showed statistically significant reductions in weight, body mass index, fasting blood glucose, 2 h postprandial blood glucose, and hemoglobin A1c compared to the control group (P < 0.05). The telehealth education group also exhibited a significant decrease in systolic blood pressure and low-density lipoprotein-C level (P < 0.05). The Summary of Diabetes Self-Care Activities score, which reflects the level of diabetes self-management, demonstrated that the telehealth education group had a significantly better total score as well as superior scores in all five sub-categories (diet, blood glucose testing, medication use, and foot care) compared to the control group (P < 0.05). CONCLUSION: Our findings confirmed that telehealth education effectively enhanced the self-management capabilities of patients with coexisting type 2 diabetes and hypertension, leading to better glycolipid and blood pressure control. The use of telehealth education may potentially improve the interaction between medical staff and patients in the management of chronic diseases.

Cost-Effectiveness Analysis of Camrelizumab Plus Rivoceranib Versus Sorafenib as a First-Line Therapy for Unresectable Hepatocellular Carcinoma in the Chinese Health Care System.

BACKGROUND AND OBJECTIVES: Camrelizumab plus rivoceranib showed significant clinical benefits in progression-free survival and overall survival compared to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to assess its cost effectiveness from the perspective of Chinese health care system. METHODS: A Markov state-transition model was developed based on the Phase 3 randomized CARES-310 clinical trial data. Health state utility values were obtained from the CARES-310 clinical trial, and direct medical costs were derived from the relevant literature and local charges. The measured outcomes included quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses were performed to assess the uncertainty of the model. RESULTS: In the base-case analysis, the incremental effectiveness and cost of camrelizumab plus rivoceranib versus sorafenib were 0.41 QALYs and $13,684.84, respectively, resulting in an ICER of $33,619.98/QALY, lower than the willingness-to-pay threshold of China ($35,864.61/QALY). Subgroup analyses revealed that the ICERs of camrelizumab plus rivoceranib versus sorafenib were $35,920.01 and $29,717.98 in patients with ALBI grade 1 and grade 2, respectively. One-way sensitivity analyses indicated that the cost of camrelizumab, the proportion of patients receiving subsequent treatment in the camrelizumab plus rivoceranib group, and the cost of rivoceranib were the most significant factors in the base-case analysis. Probabilistic sensitivity analysis suggested that the probabilities of cost effectiveness of camrelizumab plus rivoceranib were 61.27%, 51.46%, and 82.78% for any grade, and ALBI grade 1 and grade 2, respectively. CONCLUSIONS: Camrelizumab plus rivoceranib was more cost effective than sorafenib as first-line therapy for unresectable HCC in the Chinese setting.

Quality in screening and measuring blood pressure in China's primary health care: a national cross-sectional study using unannounced standardized patients.

Background: This study aims to evaluate primary care providers' adherence to the standard of measuring blood pressure for people aged 35 or above during their initial visit, as per Chinese guidelines, and to identify factors affecting their practices. Methods: We developed 11 standardized patients (SP) cases as tracer conditions to evaluate primary care, and deployed trained SPs for unannounced visits to randomly selected providers in seven provinces of China. The SPs used a checklist based on guidelines to record whether and how blood pressure was measured. Data were analyzed descriptively and regression analysis was performed to examine the association between outcomes and factors such as provider, patient, facility, and clinical case characteristics. Findings: The SPs conducted 1201 visits and found that less than one-third of USPs ≥35 had their blood pressure measured. Only 26.9% of migraine and 15.4% of diabetes cases received blood pressure measurements. Additionally, these measurements did not follow the proper guidelines and recommended steps. On average, 55.6% of the steps were followed with few providers considering influencing factors before measurement and only 6.0% of patients received both-arm measurements. The use of wrist sphygmomanometers was associated with poor blood pressure measurement. Interpretation: In China, primary care hypertension screening practices fall short of guidelines, with infrequent initiation of blood pressure measurements and inadequate adherence to proper measurement steps. To address this, priority should be placed on adopting, implementing, and upholding guidelines for hypertension screening and measurement. Funding: National Natural Science Foundation of China, Swiss Agency for Development and Cooperation, Doctoral Fund Project of Inner Mongolia Medical University, China Postdoctoral Science Foundation.

Improving early detection, diagnosis and intervention for children with autism spectrum disorder: A cross-sectional survey in China.

BACKGROUND: Detection and diagnosis of autism spectrum disorder (ASD) are prerequisites for early interventions. However, few studies focused on this topic. AIM: This study aims to characterize the timing from symptom detection to intervention in children with ASD and identify predictors of age at ASD diagnosis, presence of intervention, and the time lag between detection and diagnosis. METHODS AND PROCEDURES: A cross-sectional survey was conducted with 303 parents (111 fathers and 192 mothers, 21-54 years) of children with ASD in Guangzhou, China. OUTCOMES AND RESULTS: The median time from symptom observation to the first doctor visit was 3 months, while the time to ASD diagnosis averaged 6 months. Most children (76.24 %) were diagnosed within one year after detection, and 25.58 % had no intervention after diagnosis. Predictors of earlier ASD diagnosis included ASD-related symptoms identified at an older age, less serious symptoms, and initial symptoms with atypical motor development and sensory anomalies. ASD-related symptoms observed at an older age, initial symptoms with social deficits, sensory anomalies, and without language impairment, primary caregivers other than parents, families with lower income, and less social support utilization increased the odds of a time lag between detection and diagnosis. Children with fathers having lower education were less likely to receive interventions. CONCLUSIONS AND IMPLICATIONS: Earlier ASD identification and intervention might be facilitated by health education on typical symptoms of ASD for parents with young children and incorporating ASD screening during routine health examinations for children. For children whose primary caregivers are not their parents and from lower-income families, additional support may be required for timely diagnosis after reporting ASD-related symptoms. Moreover, more intervention supports are expected for children whose fathers have lower education levels. Helping families take full advantage of support is also important for early diagnosis and intervention.

Epigenetically modified AP-2α by DNA methyltransferase facilitates glioma immune evasion by upregulating PD-L1 expression.

Programmed death-ligand 1 (PD-L1) ensures that tumor cells escape T-cell-mediated tumor immune surveillance. However, gliomas are characteristic of the low immune response and high-resistance therapy, it is necessary to understand molecular regulatory mechanisms in glioblastoma, especially the limited regulation of PD-L1 expression. Herein, we show that low expression of AP-2α is correlated with high expression of PD-L1 in high-grade glioma tissues. AP-2α binds directly to the promoter of the CD274 gene, not only inhibits the transcriptional activity of PD-L1 but enhances endocytosis and degradation of PD-L1 proteins. Overexpression of AP-2α in gliomas enhances CD8+ T cell-mediated proliferation, effector cytokine secretion, and cytotoxicity in vitro. Tfap2a could increase the cytotoxic effect of Cd8+ T cells in CT26, B16F10, and GL261 tumor-immune models, improve anti-tumor immunity, and promote the efficacy of anti-PD-1 therapy. Finally, the EZH2/H3K27Me3/DNMT1 complex mediates the methylation modification of AP-2α gene and maintains low expression of AP-2α in gliomas. 5-Aza-dC (Decitabine) treatment combines with anti-PD-1 immunotherapy to efficiently suppress the progression of GL261 gliomas. Overall, these data support a mechanism of epigenetic modification of AP-2α that contributes to tumor immune evasion, and reactivation of AP-2α synergizes with anti-PD-1 antibodies to increase antitumor efficacy, which may be a broadly applicable strategy in solid tumors.

G protein-coupled receptor GPR68 inhibits lymphocyte infiltration and contributes to gender-dependent melanoma growth.

Introduction: Melanoma is a common and aggressive type of skin cancer with rising incidence rate globally. Gender is one of the determining factors, and overall males have a higher risk of developing melanoma as well as worse prognosis. Emerging evidence show that GPR68, a G protein-coupled receptor that is sensitive to acid and mechanical stimulations for cellular microenvironment, plays an important role in tumor biology. However, whether GPR68 is involved in gender-dependent regulation of tumor growth is unclear. Methods: We established a syngeneic melanoma model in Gpr68-deficient mice and investigated tumor growth in males and females. The GPR68 activation-induced cellular responses of melanocytes, including intracellular calcium dynamics, proliferation and migration were measured. The landscape of tumor-infiltrating immune cells were analyzed by flow cytometry and the expression various cytokines were checked by qRT-PCR. Results: GPR68 is required for melanoma growth in males but dispensable in females. GPR68 is expressed and functional in B16-F10 melanocytes, but the activity of the receptor does not directly contribute to proliferation and migration of the cells. GPR68 inhibits infiltration of CD45+ lymphocytes, CD8+ T cells and NK cells in melanoma in male mice, but has no apparent effect in females. Furthermore, GPR68 functionally inhibits the expression of IFNγ in the tumor infiltrating CD8+ T cells and NK cells as well as the inflammatory cytokine expression in the spleen in male mice but not in females. Our results show the gender-dependent modulatory effect of GPR68 on tumor-infiltrating immune cells and their tumor-killing capacity. Discussion: GPR68 is sensor for acid and mechanical stimulations, which are two important factors in the microenvironment associated with tumor growth and metastasis. Our results suggest a prominent role of the receptor molecules in tumor biology in a gender-dependent manner. Since GPCRs are more feasible to develop small molecule drugs compared to transcription factors, our study demonstrates the potential of GPR68 as a novel druggable therapeutic target for melanoma in male patients.

Validity of patients' online reviews at direct-to-consumer teleconsultation platforms: a protocol for a cross-sectional study using unannounced standardised patients.

INTRODUCTION: As direct-to-consumer teleconsultation (hereafter referred to as 'teleconsultation') has gained popularity, an increasing number of patients have been leaving online reviews of their teleconsultation experiences. These reviews can help guide patients in identifying doctors for teleconsultation. However, few studies have examined the validity of online reviews in assessing the quality of teleconsultation against a gold standard. Therefore, we aim to use unannounced standardised patients (USPs) to validate online reviews in assessing both the technical and patient-centred quality of teleconsultations. We hypothesise that online review results will be more consistent with the patient-centred quality, rather than the technical quality, as assessed by the USPs. METHODS AND ANALYSIS: In this cross-sectional study, USPs representing 11 common primary care conditions will randomly visit 253 physicians via the three largest teleconsultation platforms in China. Each physician will receive a text-based and a voice/video-based USP visit, resulting in a total of 506 USP visits. The USP will complete a quality checklist to assess the proportion of clinical practice guideline-recommended items during teleconsultation. After each visit, the USP will also complete the Patient Perception of Patient-Centeredness Rating. The USP-assessed results will be compared with online review results using the intraclass correlation coefficient (ICC). If ICC >0.4 (p<0.05), we will assume reasonable concordance between the USP-assessed quality and online reviews. Furthermore, we will use correlation analysis, Lin's Coordinated Correlation Coefficient and Kappa as supplementary analyses. ETHICS AND DISSEMINATION: This study has received approval from the Institutional Review Board of Southern Medical University (#Southern Medical Audit (2022) No. 013). Results will be actively disseminated through print and social media, and USP tools will be made available for other researchers. TRIAL REGISTRATION: The study has been registered at the China Clinical Trials Registry (ChiCTR2200062975).

The protective role of social support on prenatal depression among pregnant women of advanced maternal age: a Three-Trimester follow-up study in China.

The aim of this study was to compare the depressive symptoms during pregnancy between pregnant women aged over 35 years and those aged less than 35 years and to evaluate the protective effect of social support in early pregnancy against prenatal depressive symptoms. One hundred and seventy one women aged over 35 years and 342 trimester-matched women aged less than 35 years were included from a level III hospital in Shenzhen, China. The self-report Edinburgh Postnatal Depression Scale (EPDS) and Social Support Rating Scale (SSRS) were used to evaluate prenatal depression and social support in early pregnancy. The proportions of women aged over 35 years who screened positive for prenatal depression were 22.8%, 23.4%, and 24.0% in the first, second and third trimesters, respectively. Advanced maternal age (≥35 years) was a positive predictor of prenatal depressive symptoms (ß = 0.747, P = 0,008). Social support, especially objective support (ß = -0.030, P = 0.002) and subjective support (ß = -0.028, P = 0.006) in early pregnancy, had stronger protective effects against prenatal depressive symptoms for women aged over 35 years than younger women. Our findings support that older pregnant women experience more depressive symptoms than younger pregnant women, and social support could serve as a targeted intervention to decrease prenatal depressive symptoms.Impact statementWhat is already known on this subject? Depressive symptoms, which are strongly associated with adverse psychosocial and birth outcomes, appear to be prevalent and change in nature. Social support is an important protective factor against prenatal depression.What the results of this study add? Pregnant women of advanced maternal age experienced more depressive symptoms than younger women during the prenatal period. Social support, especially objective support and subjective support, had stronger protective effects against prenatal depression for women aged over 35 years than women aged less than 35 years.What the implications of these findings are for clinical practice? Screening of prenatal depression should be strengthened, especially for women aged over 35 years, and improving subjective support could improve their emotional experience.

Posttraumatic growth and rumination among parents of children with autism spectrum disorder: The mediating role of social support.

Although rumination and social support are regarded as essential predictors of posttraumatic growth (PTG), few studies have explored the associations among PTG, rumination, and social support in parents of children with autism spectrum disorder (ASD). This study examined whether social support mediates the relationship between rumination and PTG. Cross-sectional questionnaire data were collected from 385 parents of children with ASD from September 2019 to November 2020 by convenience sampling. Participants completed the Posttraumatic Growth Inventory, Event Related Rumination Inventory, and Social Support Rating Scale. Path analyses showed that subjective support partially mediates the relationship between deliberate rumination and PTG (ß = 0.073, P < 0.001), and indirect effects account for 15.30% of the total effects. In addition, a negative direct path was found between intrusive and PTG because of the suppression effect of subjective support (ß = -0.110, P < 0.01), and indirect effects accounted for 80% of the direct effects. For future studies, it underscores the essential role of subjective support and rumination in promoting PTG in parents of children with ASD.

Self-amplifying loop of NF-κB and periostin initiated by PIEZO1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration.

Abnormal mechanical load is a main risk factor of intervertebral disc degeneration (IDD), and cellular senescence is a pathological change in IDD. In addition, extracellular matrix (ECM) stiffness promotes human nucleus pulposus cells (hNPCs) senescence. However, the molecular mechanism underlying mechano-induced cellular senescence and IDD progression is not yet fully elucidated. First, we demonstrated that mechano-stress promoted hNPCs senescence via NF-κB signaling. Subsequently, we identified periostin as the main mechano-responsive molecule in hNPCs through unbiased sequencing, which was transcriptionally upregulated by NF-κB p65; moreover, secreted periostin by senescent hNPCs further promoted senescence and upregulated the catabolic process in hNPCs through activating NF-κB, forming a positive loop. Both Postn (encoding periostin) knockdown via siRNA and periostin inactivation via neutralizing antibodies alleviated IDD and NPCs senescence. Furthermore, we found that mechano-stress initiated the positive feedback of NF-κB and periostin via PIEZO1. PIEZO1 activation by Yoda1 induced severe IDD in rat tails without compression, and Postn knockdown alleviated the Yoda1-induced IDD in vivo. Here, we reported for the first time that self-amplifying loop of NF-κB and periostin initiated via PIEZO1 under mechano-stress accelerated NPCs senescence, leading to IDD. Furthermore, periostin neutralizing antibodies, which may serve as potential therapeutic agents for IDD, interrupted this loop.

The Prevalence and Factors Associated With Anxiety-Like and Depression-Like Behaviors in Women With Polycystic Ovary Syndrome.

Increasing evidence shows that polycystic ovary syndrome (PCOS) patients are particularly vulnerable to anxiety/depression-like behaviors. This study sought to determine the prevalence of anxiety/depression-like behaviors among women with PCOS and to identify factors associated with these behaviors. This study was a secondary analysis of three studies performed on Chinese women who were aged 18 to 40 and diagnosed with PCOS according to the modified Rotterdam criteria. We obtained 802 useable responses for the self-rating anxiety scale and 798 responses for the self-rating depression scale. The prevalence of anxiety-like and depression-like behaviors among women with PCOS was 26.1% (209/802) and 52.0% (415/798), respectively. Anxiety-like behaviors were associated with age, body image-related factors (including body mass index and waist-to-hip ratio), and hyperandrogenism-related factors (including free androgen index and hirsutism). Depression-like behaviors were associated with age, body image-related factors, hyperandrogenism-related factors, and metabolic factors (including fasting insulin, fasting plasma glucose, and homeostatic model assessment of insulin resistance). Body image-related factors and hyperandrogenism-related factors were related to both anxiety-like behaviors and depression-like behaviors in both infertile and fertile PCOS patients.

Effects of virtual reality cognitive training in individuals with mild cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Virtual reality (VR) is used to improve specific health needs by combining multiple technologies; it is increasingly being used in the medical field, showing satisfactory effects, especially in the management of chronic disease. The aim of this study was to assess the effects of VR cognitive training for individuals with mild cognitive impairment (MCI). METHODS: Peer-reviewed articles were searched from the PubMed, Embase, Web of Science, the Cochrane Library, Science Direct, and EBSCOhost databases, as well as CNKI, Sinomed, Vip. and Wan Fang, through 23 May 2021. We only included randomized controlled trials (RCTs) enrolling participants with MCI. RESULTS: Seventeen RCTs were included, with a total of 744 participants. Evidence of moderate quality showed that VR cognitive training significantly enhanced MCI patients' global cognitive function, as measured by the Montreal Cognitive Assessment (standardized mean difference [SMD] = 0.42; 95% confidence interval [CI], 0.04-0.79; p = 0.03) and executive function, as measured by trail making test A (SMD = -0.58; 95% CI, -0.80 to -0.35; p < 0.001). The meta-analysis indicated that the effects of VR cognitive training on delayed memory, immediate memory, attention and instrumental activities of daily living were not statistically significant (p > 0.05). CONCLUSION: The available data showed that VR cognitive training might be beneficial for improving global cognitive function and executive function in individuals with MCI, although the effects were short term.

A Cross-Sectional Survey of Family Care Behaviors for Children with Upper Respiratory Tract Infections in China: Are There Opportunities for Improvement?

OBJECTIVE: To describe family care behaviors for children with upper respiratory tract infections (URTIs) and explore related factors. DESIGN AND METHODS: Parents of children with URTIs were included in this cross-sectional study. Family care behaviors, disease-related knowledge, and parental self-efficacy were evaluated with validated measures. RESULTS: Among the 419 participants, 73.80% recognized diseases based on their children's abnormal presentation. Self-medication was the main home care measure (36.28% used only self-medication; 27.92% used both self-medication and physical cooling methods), and 36.5% received suggestions from medical professionals. All the participants took their children to the hospital, and 28.20% did so two or three times. The proportions of visits to level II or III hospitals were 49.64% and 83.87% for first and third hospital visits, respectively. Parents who had less disease knowledge and assessed children' diseases as more serious took their children to the hospital more often (p < 0.05); those whose nearest medical institution was a community health center were more likely to visit such centers (p < 0.001). CONCLUSIONS: Most of the parents recognized symptoms of URTIs and provided home care but lacked enough knowledge and professional support to take reasonable measures. Hospital visits were their primary choice. PRACTICAL IMPLICATIONS: Family care behaviors for children with URTIs could be improved through health education, and an internet nursing service or family doctor system is suggested. A hierarchical medical system is necessary to reduce hospital visits, as are more community health centers with pediatric services.

Conditional ablation of MAPK7 expression in chondrocytes impairs endochondral bone formation in limbs and adaptation of chondrocytes to hypoxia.

BACKGROUND: Long bones of limbs are formed through endochondral bone formation, which depends on the coordinated development of growth plates. Our previous studies have demonstrated that dysfunction of mitogen-activated protein kinase 7 (MAPK7) can cause skeletal dysplasia. However, little is known about the role of MAPK7 in the regulation of proliferation and differentiation of chondrocytes during growth plate development. RESULTS: Ablation of MAPK7 expression in chondrocytes led to growth restriction, short limbs and bone mass loss in postnatal mice. Histological studies revealed that MAPK7 deficiency increased the apoptosis and decreased the proliferation of chondrocytes in the center of the proliferative layer, where the most highly hypoxic chondrocytes are located. Accordingly, hypertrophic differentiation markers were downregulated in the central hypertrophic layer, beneath the site where abnormal apoptosis was observed. Simultaneously, we demonstrated that hypoxic adaptation and hypoxia-induced activation of hypoxia-inducible factor 1 subunit α (HIF1α) were impaired when MAPK7 could not be activated normally in primary chondrocytes. Concomitantly, vascular invasion into epiphyseal cartilage was inhibited when Mapk7 was deleted. CONCLUSIONS: We demonstrated that MAPK7 is necessary for maintaining proliferation, survival, and differentiation of chondrocytes during postnatal growth plate development, possibly through modulating HIF1α signaling for adaptation to hypoxia. These results indicate that MAPK7 signaling might be a target for treatment of chondrodysplasia.

MET promotes the proliferation and differentiation of myoblasts.

The receptor tyrosine kinase MET plays a vital role in skeletal muscle development and in postnatal muscle regeneration. However, the effect of MET on myogenesis of myoblasts has not yet been fully understood. This study aimed to investigate the effects of MET on myogenesis in vivo and in vitro. Decreased myonuclei and down-regulated expression of myogenesis-related markers were observed in Met p.Y1232C mutant heterozygous mice. To explore the effects of MET on myoblast proliferation and differentiation, Met was overexpressed or interfered in C2C12 myoblast cells through the lentiviral transfection. The Met overexpression cells exhibited promotion in myoblast proliferation, while the Met deficiency cells showed impediment in proliferation. Moreover, myoblast differentiation was enhanced by the stable Met overexpression, but was impaired by Met deficiency. Furthermore, this study demonstrated that SU11274, an inhibitor of MET kinase activity, suppressed myoblast differentiation, suggesting that MET regulated the expression of myogenic regulatory factors (MRFs) and of desmin through the classical tyrosine kinase pathway. On the basis of the above findings, our work confirmed that MET promoted the proliferation and differentiation of myoblasts, deepening our understanding of the molecular mechanisms underlying muscle development.

A novel ZRS variant causes preaxial polydactyly type I by increased sonic hedgehog expression in the developing limb bud.

PURPOSE: Preaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown. METHODS: A rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model. RESULTS: A novel g.101779T>A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression. CONCLUSION: Our results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms.