Spatiotemporal heterogeneity of the association between socioeconomic development and health policy attention: a geographically and temporally weighted regression modeling study in China.

Objectives: Health policy attention (HPA) refers to the extent of attention given by governments to health issues in public policy and is generally influenced by socioeconomic development. This study aimed to examine the spatiotemporal heterogeneity and clustering of the associations between socioeconomic factors and HPA. Study design: Longitudinal study. Methods: This study examined the spatiotemporal heterogeneity of the association between public and provincial government attention, economic development, and demographic transition and HPA by using geographically and temporally weighted regression (GTWR). Word2Vec machine learning technology was utilized to calculate HPA data in 323 cities and independent variable data was collected in each city in China over the period of 2018-2021. Results: The results showed that there is a substantial overall rise in HPA levels throughout China following the COVID-19 pandemic. Furthermore, the GTWR results revealed significant spatiotemporal heterogeneity in the associations between HPA and public and provincial government attention, economic development, and demographic transition, particularly in the context of COVID-19. The impact of provincial government attention on HPA decreased from the capital of the political center outward, while the impact of public financial investment decreased in less developed cities during the pandemic. It was only cities with high levels of aging are more likely to receive greater HPA. Conclusion: The finding highlighted the remarkable spatial and temporal variations in the associations between the variables and HPA across different regions in China, emphasizing the need for region-specific policies to strengthen the focus on health by municipal governments.

Geographic Disparities in Access to Assisted Reproductive Technology Centers in China: Spatial-Statistical Study.

A study on infertility in China found that while 543 health care institutions are approved for assisted reproductive technology (ART), only 10.1% offer all ART services, with a significant skew toward the eastern regions, highlighting the accessibility challenges faced by rural and remote populations; this study recommends government measures including travel subsidies and education initiatives to improve ART access for economically disadvantaged individuals.

Therapeutic potential of mesenchymal stem cell-derived exosomes in skeletal diseases.

Skeletal diseases impose a considerable burden on society. The clinical and tissue-engineering therapies applied to alleviate such diseases frequently result in complications and are inadequately effective. Research has shifted from conventional therapies based on mesenchymal stem cells (MSCs) to exosomes derived from MSCs. Exosomes are natural nanocarriers of endogenous DNA, RNA, proteins, and lipids and have a low immune clearance rate and good barrier penetration and allow targeted delivery of therapeutics. MSC-derived exosomes (MSC-exosomes) have the characteristics of both MSCs and exosomes, and so they can have both immunosuppressive and tissue-regenerative effects. Despite advances in our knowledge of MSC-exosomes, their regulatory mechanisms and functionalities are unclear. Here we review the therapeutic potential of MSC-exosomes for skeletal diseases.

Cirsilineol inhibits RANKL-induced osteoclast activity and ovariectomy-induced bone loss via NF-κb/ERK/p38 signaling pathways.

BACKGROUND: Postmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast formation and function. Targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Cirsilineol, an active constituent of Vestita Wall, has shown numerous biological activities and has been used to treat many metabolic diseases. However, whether cirsilineol inhibits osteoclast activity and prevents postmenopausal osteoporosis still remain unknown. MATERIALS AND METHODS: Primary bone marrow macrophages (BMMs) and RAW264.7 cells were used. Osteoclast activity was measured by TRAP staining, F-actin staining, and bone resorption assay after BMMs were treated with cirsilineol at concentrations of 0, 1, 2.5 and 5 µM. RT-PCR and western blotting were performed to evaluate the expression of osteoclast-related genes. In addition, female C57BL/6 mice underwent OVX surgery and were treated with cirsilineol (20 mg/kg) to demonstrate the effect of cirsilineol on osteoporosis. RESULTS: Cirsilineol significantly inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation in a concentration- and time-dependent manner, respectively. Additionally, cirsilineol inhibited F-actin ring formation, thus reducing the activation of bone resorption ability. Cirsilineol suppressed the expression of osteoclast-related genes and proteins via blocking nuclear factor (NF)-κb, ERK, and p38 signaling cascades. More importantly, cirsilineol treatment in mice with osteoporosis alleviated osteoclasts hyperactivation and bone mass loss caused by estrogen depletion. CONCLUSION: In this study, the protective effect of cirsilineol on osteoporosis has been investigated for the first time. In conclusion, our findings prove the inhibitory effect of cirsilineol on osteoclast activity via NF-κb/ERK/p38 signaling pathways and strongapplication of cirsilineol can be proposed as a potential therapeutic strategy.

Association between maternal health service utilization and under-five mortality rate in China and its provinces, 1990-2017.

BACKGROUND: The United Nations (UN) Sustainable Development Goal - 3.2 aims to eliminate all preventable under-five mortality rate (U5MR). In China, government have made efforts to provide maternal health services and reduce U5MR. Hence, we aimed to explore maternal health service utilization in relation to U5MR in China and its provinces in 1990-2017. METHODS: We obtained data from Global Burden of Disease 2017, China Health Statistics Yearbook, China Statistical Yearbook, and Human Development Report China Special Edition. The trend of U5MR in each province of China from 1990 to 2017 was analyzed using Joinpoint Regression model. We measured the inequities in maternal health services using HEAT Plus, a health inequity measurement tool developed by the UN. The generalized estimating equation model was used to explore the association between maternal health service utilization (including prenatal screening, hospital delivery and postpartum visits) and U5MR. RESULTS: First, in China, the U5MR per 1000 live births decreased from 50 in 1990 to 12 in 2017 and the average annual percentage change (AAPC) was - 5.2 (p < 0.05). Secondly, China had a high maternal health service utilization in 2017, with 96.5% for prenatal visits, 99.9% for hospital delivery, and 94% for postnatal visits. Inequity in maternal health services between provinces is declining, with hospital delivery rate showing the greatest decrease (SII, 14.01 to 1.87, 2010 to 2017). Third, an increase in the rate of hospital delivery rate can significantly reduce U5MR (OR 0.991, 95%CI 0.987 to 0.995). Postpartum visits rate with a one-year lag can reduce U5MR (OR 0.993, 95%CI 0.987 to 0.999). However, prenatal screening rate did not have a significant effect on U5MR. CONCLUSION: The decline in U5MR in China was associated with hospital delivery and postpartum visits. The design and implementation of maternal health services may provide references to other low-income and middle-income countries.

The role of military service in preventing depression in China: evidence from a nationally representative longitudinal survey.

BACKGROUND: Despite recognition in the West that military veterans experience more mental health issues than the general population, little research has focused on this subject in China. This study examined the associations between male veterans' military experience and depression in China. METHODS: A sample of 12,914 men including 669 veterans was included in the final analysis and propensity score matching, multivariable regressions and fixed effect model were used. RESULTS: The military experience was associated with a lower likelihood of depression in male veterans. In the subgroup analysis, military experience was associated with a lower likelihood of depression among married and urban male veterans. Military experience was also associated with a lower likelihood of depression in both "junior college and above" and "below junior college" groups. In contrast, evidence was lacking regarding the associations between military experience and depression for unmarried and rural veterans. CONCLUSIONS: Individual characteristics could influence the relationship between military experience and depression in male veterans, and the mental health of veterans should be paid more attention and guaranteed.

Temporal Trends in Cardiovascular Health Status Among Chinese School-Aged Children From 1989 to 2018: Multiwave Cross-Sectional Analysis.

BACKGROUND: Despite the release of updated metrics for Life's Essential 8 (LE8), key indicators for assessing cardiovascular health (CVH) status, there is currently no report on their distribution among Chinese children. OBJECTIVE: This study aimed to assess the nationwide distribution of CVH in Chinese school-aged children using LE8 scores and analyze temporal changes in these scores over time. METHODS: Participants aged 7 to 19 years from 11 waves (between 1989 and 2018) of the China Health and Nutrition Survey were included in this study. LE8 components were grouped into 2 domains of health behaviors (diet, physical activity, nicotine exposure, sleep) and health factors (BMI, blood lipids, blood glucose, blood pressure). Scores of overall CVH and each LE8 metric were calculated individually. Temporal changes were assessed with joint point regression models by rural and urban living residence. The causal relationships between health behaviors and health factors that changed the most over time were built with cross-lagged panel models. RESULTS: A total of 21,921 participants, 52.6% (n=11,537) of whom were male, who had data for at least 4 CVH components were included in the analysis. The mean age was 13 (SD 3.6) years. The overall CVH score remained stable in most regions, with the lowest found in Shandong from East China, which had a mean between 67 (SD 10.9) and 67.2 (SD 12.4). In contrast, the highest score was found in Guizhou from Southwest China, with a mean between 71.4 (SD 10.8) and 74.3 (SD 10.3). In rural areas, the diet score decreased significantly from 1997 onward with a speed of 0.18 (95% CI: 0.15-0.21; P<.001) per year, and the BMI score decreased significantly from 2005 onward with a speed of 0.56 (95% CI 0.44-0.68; P<.001) per year. In urban areas, the diet score decreased from 1994 onward with a speed of 0.03 (95% CI: 0.001-0.07; P=.04) per year, and the BMI score decreased from 2002 onward with a speed of 0.63 (95% CI 0.47-0.79; P<.001) per year. The sleep score dropped constantly in both urban and rural areas, with a speed of 0.69 (95% CI 0.58-0.80; P<.001) and 0.69 (95% CI: 0.52-0.86; P<.001) per year, respectively. A decline in the diet score led to a decline in the BMI score with a coefficient of 0.190 (95% CI 0.030-0.351; P=.02), while a decline in the BMI score led to a decline in sleep health with a coefficient of 0.089 (95% CI 0.010-0.168; P=.03). CONCLUSIONS: Chinese school-aged children and adolescents were generally of moderate CVH status, but mutual influences existed between CVH metrics. Dietary interventions should be prioritized for promoting overall CVH in the future.

Impact of some antiviral drugs on health care utilization for patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: We aimed to assess the impact of antiviral drugs (fluvoxamine,remdesivir, lopinavir/ritonavir (LPV/r), molnupiravir, andnirmatrelvir/ritonavir (NRV/r)) on health care utilization (HCU) inCOVID-19 patients. We summarized findings from randomized controlledtrials (RCTs) and observational studies. METHODS: We systematically searched four medical databases (PubMed, Web of Science, Embase, Cochrane Library) for COVID-19 studies up to February 15, 2023. A comprehensive review, meta-analysis, sensitivity analysis, and subgroup analysis were conducted. Pooled effects with 95% confidence intervals (CIs) were calculated for antiviral drugs' impact on hospitalization, mechanical ventilation (MV), and intensive care unit (ICU) outcomes. RESULTS: Our analysis included 34 studies (584,978 patients). Meta-analysisindicated potential benefits: remdesivir and molnupiravir potentiallyreduced MV risk, and NRV/r correlated with lower hospitalizationrates. However, LPV/r did not notably curb HCU. Remdesivir waspreferable for high-risk COVID-19 patients, while molnupiravir andNRV/r were recommended for those aged 60 and above. CONCLUSION: Remdesivir, molnupiravir, and NRV/r may reduce HCU during the COVID-19 pandemic. However, due to limited study details and significant heterogeneity in effect estimates, further precise evidence is crucial, especially concerning emerging variants.

Exploring cognitive trajectories and their association with physical performance: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS: Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.

Identification of hub genes and therapeutic drugs in osteonecrosis of the femoral head through integrated bioinformatics analysis and literature mining.

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease leading to severely limited function. By far, the etiology and pathogenesis of ONFH are not fully understood, and surgery is the only effective way to treat ONFH. This study aims to identify hub genes and therapeutic drugs in ONFH. Two gene expression profiles were downloaded from the gene expression omnibus database, and the hub genes and candidate drugs for ONFH were identified through integrated bioinformatics analysis and cross-validated by literature mining. A total of 159 DEGs were identified. PTGS2, LRRK2, ANXA5, IGF1R, MCL1, TIMP2, LYN, CD68, CBL, and RUNX2 were validated as 10 hub genes, which has considerable implications for future genetic research and related research fields of ONFH. Our findings indicate that 85 drugs interact with ONFH, with most drugs exhibiting a positive impact on ONFH by promoting osteogenesis and angiogenesis or inhibiting microcirculation embolism, rather than being anti-inflammatory. Our study provides novel insights into the pathogenesis, prevention, and treatment of ONFH.

Spatial Accessibility Evaluation and Location Optimization of Primary Healthcare in China: A Case Study of Shenzhen.

The unbalanced allocation of healthcare resources is a major challenge that hinders access to healthcare. Taking Shenzhen as an example, this study aimed to enhance equity in obtaining healthcare services, through measuring and visualizing the spatial accessibility of community healthcare centers (CHC), and optimizing CHC geospatial allocation. We used the number of health technicians per 10,000 to represent the CHC's service capacity, combined with resident points and census data to calculate the population the CHC needs to carry, and then analyzed the accessibility based on the Gaussian two-step floating catchment area method. In 2020, five regions in Shenzhen had better spatial accessibility scores: Nanshan (0.250), Luohu (0.246), Futian (0.244), Dapeng (0.226), and Yantian (0.196). The spatial accessibility of CHCs shows a gradual decrease from the city center to the edge, which is affected by economic and topographic factors. With the support of the maximal covering location problem model, we selected up to 567 candidate locations for the new CHC, which could improve Shenzhen's accessibility score from 0.189 to 0.361 and increase the coverage population by 63.46% within a 15-min impedance. By introducing spatial techniques and maps, this study provides (a) new evidence for promoting equitable access to primary healthcare services in Shenzhen and (b) a foundation for improving the accessibility of public service facilities in other areas.

Does music intervention relieve depression or anxiety in people living with dementia? A systematic review and meta-analysis.

BACKGROUND: This study aimed to summarize the available evidence on music intervention alleviating depression or anxiety in dementia. METHODS: A comprehensive literature search was performed to analyze the effects of music intervention on depression or anxiety. Subgroups were created to explore the effect of intervention period, duration, and frequency on efficacy. The effect size was reported as a mean standardized difference (SMD) with 95% confidence interval (CI). RESULTS: The analysis included 19 articles involving 614 samples. Thirteen studies for relieving depression revealed that, with an increase in intervention period, the efficacy decreased and then increased, whereas with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Seven studies verifying the impact on anxiety relief revealed that the effect of intervention within 12 wk is significant; with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Collaborative analysis showed that long low-frequency interventions are more efficient than short high-frequency interventions. CONCLUSIONS: Music intervention can relieve depression or anxiety in people living with dementia. Weekly short interventions of more than 45 min are effective for emotional regulation. Future research should concentrate on severe dementia and follow-up impact.

Spatiotemporal and Seasonal Trends of Class A and B Notifiable Infectious Diseases in China: Retrospective Analysis.

BACKGROUND: China is the most populous country globally and has made significant achievements in the control of infectious diseases over the last decades. The 2003 SARS epidemic triggered the initiation of the China Information System for Disease Control and Prevention (CISDCP). Since then, numerous studies have investigated the epidemiological features and trends of individual infectious diseases in China; however, few considered the changing spatiotemporal trends and seasonality of these infectious diseases over time. OBJECTIVE: This study aims to systematically review the spatiotemporal trends and seasonal characteristics of class A and class B notifiable infectious diseases in China during 2005-2020. METHODS: We extracted the incidence and mortality data of 8 types (27 diseases) of notifiable infectious diseases from the CISDCP. We used the Mann-Kendall and Sen's methods to investigate the diseases' temporal trends, Moran I statistic for their geographical distribution, and circular distribution analysis for their seasonality. RESULTS: Between January 2005 and December 2020, 51,028,733 incident cases and 261,851 attributable deaths were recorded. Pertussis (P=.03), dengue fever (P=.01), brucellosis (P=.001), scarlet fever (P=.02), AIDS (P<.001), syphilis (P<.001), hepatitis C (P<.001) and hepatitis E (P=.04) exhibited significant upward trends. Furthermore, measles (P<.001), bacillary and amebic dysentery (P<.001), malaria (P=.04), dengue fever (P=.006), brucellosis (P=.03), and tuberculosis (P=.003) exhibited significant seasonal patterns. We observed marked disease burden-related geographic disparities and heterogeneities. Notably, high-risk areas for various infectious diseases have remained relatively unchanged since 2005. In particular, hemorrhagic fever and brucellosis were largely concentrated in Northeast China; neonatal tetanus, typhoid and paratyphoid, Japanese encephalitis, leptospirosis, and AIDS in Southwest China; BAD in North China; schistosomiasis in Central China; anthrax, tuberculosis, and hepatitis A in Northwest China; rabies in South China; and gonorrhea in East China. However, the geographical distribution of syphilis, scarlet fever, and hepatitis E drifted from coastal to inland provinces during 2005-2020. CONCLUSIONS: The overall infectious disease burden in China is declining; however, hepatitis C and E, bacterial infections, and sexually transmitted infections continue to multiply, many of which have spread from coastal to inland provinces.

Global burden of female breast cancer and its association with socioeconomic development status, 1990-2044.

BACKGROUND: Breast cancer is a widespread disease in women worldwide. AIM: We aimed to explore the global epidemiological trends of female breast cancer (FBC) between 1990 and 2044. METHODS AND RESULTS: Disease burden, population, and socio-demographic index (SDI) data were obtained from the Global Health Data Exchange (GHDx) database. We analyzed temporal trends, age differences, risk factors, and geographic patterns of FBC disease burden globally and explored the association between age-standardized incidence rate (ASIR) of FBC and SDI. Bayesian age-period-cohort model was also performed to predict the changes in FBC incidence worldwide from 2020 to 2044. First, the global ASIR of FBC increased by 14.31% from 1990 to 2019 (95% Uncertainty Interval 4.75% to 23.98%). The death rate presented a falling trend. Second, alcohol use is the most-highlighted risk factor for FBC in some high-income regions such as Europe. A high fasting plasma glucose levels is the most prominent risk factor for FBC in Latin America and Africa. Third, the ASIR of the FBC increases with the SDI. Fourth, the incidence is expected to increase faster among women aged 35-60 years and fastest for those aged 50-54 years from 2020 to 2044. Countries with a high incidence of FBC that is expected to increase significantly include Barbados, Burkina Faso, Senegal, Monaco, Lebanon, Togo, and Uganda. CONCLUSION: The disease burden of FBC varies worldwide; the findings suggest attaching importance to the control of middle and low-middle SDI regions. Public health as well as cancer prevention experts should pay more attention to regions and populations at an increased risk of developing FBC, focusing on their prevention and rehabilitation while conducting further epidemiological studies to investigate the risk factors of their increase.

[Early clinical application of Mako robot-assisted total knee arthroplasty in knee osteoarthritis].

OBJECTIVE: To investigate the early efficacy of Mako robot-assisted total knee arthroplasty (TKA) in the treatment of knee osteoarthritis (KOA) and summarize the initial application experience. METHODS: Retrospective analysis of 73 patients with KOA treated with Mako robot-assisted TKA from June 2021 to December 2021. There were 16 males and 57 females, aged from 54 to 81 years old with an average of (67.8±6.6) years old. The hip knee and ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), lateral femoral component angle (LFCA) and lateral tibial component angle (LTCA) were recorded and analyzed. WOMAC score and KSS were used to compare the functional recovery of patients preoperatively, 3 and 6 months postoperatively. RESULTS: All the 73 patients were successfully treated without serious complications such as vascular and nerve injury, and all the incisions healed well at stageⅠwithout infection. The patients were followed up from 4 to 11 months with an average of (7.0±2.7) months, and the satisfaction rate of the last follow-up was 90.41% (66/73). WOMAC scores were (23.1±5.4) at 3 months and (14.8±4.1) at 6 months postoperatively. KSS clinical scores were ( 76.1±4.0) at 3 months and (82.1±3.7) at 6 months postoperatively;KSS functional scores were (74.3±3.1) at 3 months and (78.6±2.1) at 6 months after operation. Postoperative imaging showed good position of the prosthesis, HKA angle was (178.5±2.1)°, LDFA was (91.2±1.8)°, MPTA was(89.9±1.5) °, LFCA was (7.6±3.1)°, LTCA was (88.2±1.1)°. The mechanical axis within ±3° in sixty cases(82.2%), and the mechanical axis within ±6° in all the patients. CONCLUSION: Mako robot-assisted TKA is a safe and effective surgery in the treatment of knee osteoarthritis, which exhibited good efficacy in the correction of lower limb alignment, soft tissue balance and improvement of knee function. The long-term efficacy needs further follow-up observation.

Nasopharyngeal Carcinoma Burden and Its Attributable Risk Factors in China: Estimates and Forecasts from 1990 to 2050.

Nasopharyngeal carcinoma (NPC) is an uncommon and aggressive malignant head and neck cancer, which is highly prevalent in southern and southwestern provinces in China. The aim of this study was to examine the disease burden and risk factors of nasopharyngeal carcinoma in China from 1990 to 2019 and to predict the incidence trends from 2020 to 2049. All data were extracted from the 2019 Global Burden of Disease (GBD) study. Joinpoint regression and age-period-cohort (APC) models were chosen to analyze prevalence trends. The temporal trends and age distribution of risk factors were also analyzed descriptively. Bayesian APC models were used to predict the prevalence from 2020 to 2049. The results indicate a higher disease burden in men and older adults. Their attributable risk factors are smoking, occupational exposure to formaldehyde, and alcohol use. We predict that the incidence will be on the rise in all age groups between 2020 and 2049, with the highest incidence in people aged 70 to 89 years. In 2049, the incidence rate is expected to reach 13.39 per 100,000 (50-54 years), 16.43 (55-59 years), 17.26 (60-64 years), 18.02 (65-69 years), 18.55 (70-74 years), 18.39 (75-79 years), 19.95 (80-84 years), 23.07 (85-89 years), 13.70 (90-94 years), and 6.68 (95+ years). The findings of this study might deserve consideration in China's NPC prevention and control policy design.

Second-Child Fertility Intentions among Urban Women in China: A Systematic Review and Meta-Analysis.

With the adjustment of China's fertility policy, the topic of women's fertility has attracted much attention. In particular, urban women face a difficult choice between family and work. This study analyzed the prevalence and determinants of second-child fertility intention among urban women in China and aimed to provide evidence for improving fertility rate measures. A systematic review and meta-analysis were conducted using quantitative primary studies. We identified 16 cross-sectional studies that investigated a total of 24,979 urban women. The prevalence of second-child fertility intentions was 37%. A subgroup analysis revealed that the highest prevalence was observed between 2016 and 2017, and the lowest was observed in first-tier cities. Meta-analyses indicated that 18 factors were significantly associated with second-child fertility intentions, including demographic factors, fertility attitude, husbands, children, parents, or others. The findings of this study highlight the low second-child fertility intentions among urban women in China. Therefore, policymakers should consider various aspects, gradually optimizing fertility-supporting facilities, while encouraging fertility.

Rejuvenation of tendon stem/progenitor cells for functional tendon regeneration through platelet-derived exosomes loaded with recombinant Yap1.

The regenerative capabilities including self-renewal, migration and differentiation potentials shift from the embryonic phase to the mature period of endogenous tendon stem/progenitor cells (TSPCs) characterize restricted functions and disabilities following tendon injuries. Recent studies have shown that tendon regeneration and repair rely on multiple specific transcription factors to maintain TSPCs characteristics and functions. Here, we demonstrate Yap, a Hippo pathway downstream effector, is associated with TSPCs phenotype and regenerative potentials through gene expression analysis of tendon development and repair process. Exosomes have been proven an efficient transport platform for drug delivery. In this study, purified exosomes derived from donor platelets are loaded with recombinant Yap1 protein (PLT-Exo-Yap1) via electroporation to promote the stemness and differentiation potentials of TSPCs in vitro. Programmed TSPCs with Yap1 import maintain stemness and functions after long-term passage in vitro. The increased oxidative stress levels of TSPCs are related to the phenotype changes in duplicative senescent processes. The results show that treatment with PLT-Exo-Yap1 significantly protects TSPCs against oxidative stressor-induced stemness loss and senescence-associated secretory phenotype (SASP) through the NF-κB signaling pathway. In addition, we fabricate an Exos-Yap1-functioned GelMA hydrogel with a parallel-aligned substrate structure to enhance TSPCs adhesion, promote cell stemness and force regenerative cells toward the tendon lineage for in vitro and in vivo tendon regeneration. The application of Exos-Yap1 functioned implant assists new tendon-like tissue formation with good mechanical properties and locomotor functions in a full-cut Achilles tendon defect model. Thus, PLT-Exo-Yap1-functionalized GelMA promotes the rejuvenation of TSPCs to facilitate functional tendon regeneration. STATEMENT OF SIGNIFICANCE: This is the first study to explore that the hippo pathway downstream effector Yap is involved in tendon aging and repair processes, and is associated with the regenerative capabilities of TSPCs. In this syudy, Platelet-derived exosomes (PLT-Exos) act as an appropriate carrier platform for the delivery of recombinant Yap1 into TSPCs to regulate Yap activity. Effective Yap1 delivery inhibit oxidative stress-induced senescence associated phenotype of TSPCs by blocking ROS-mediated NF-κb signaling pathway activation. This study emphasizes that combined application of biomimetic scaffolds and Yap1 loaded PLT-Exos can provide structural support and promote rejuvenation of resident cells to assist functional regeneration for Achilles tendon defect, and has the prospect of clinical setting.

Musculoskeletal Disorder Burden and Its Attributable Risk Factors in China: Estimates and Predicts from 1990 to 2044.

Musculoskeletal disorders are one of the three major disabling diseases in the world. However, the current disease burden in China is not well-known. This study aimed to explore the burden and risk factors of musculoskeletal disorders in China from 1990 to 2019, predicting the incidence trend from 2020 to 2044. All data were extracted from the Global Burden of Disease Study 2019 (GBD 2019). Joinpoint regression and age-period-cohort (APC) models were selected to analyze the epidemic trend, and descriptive analyses of the time trends and age distributions of risk factors were performed. The Bayesian APC model was used to foresee the incidence trend from 2020 to 2044. The results indicated that the burden of musculoskeletal disorders is higher in women and older adults. Its attributable risk factors were found to be tobacco, a high body mass index, kidney dysfunction and occupational risks. In 2044, musculoskeletal disorders in China showed a downward trend for 35-59-year-olds and a slight upward trend for 30-34- and 65-84-year-olds. The 70-74 year age group saw the largest increase in incidence at 4.66%. Overall, the incidence increased with age. Therefore, prevention and control policies should focus on women and the elderly, and health interventions should be carried out based on risk factors.

Lip and Oral Cavity Cancer Burden and Related Risk Factors in China: Estimates and Forecasts from 1990 to 2049.

Lip and oral cavity cancer is a common malignancy faced by many developing countries, and the disease burden is high in China. This study explored this cancer burden and its risk factors using data from China in the GBD 2019, along with predicting the incidence trends in 2020-2049. Data on age-standardized rates (ASR), incidence, death and disability-adjusted life years (DALY), by sex, age and risk factors were collected from the Institute for Health Metrics and Evaluation (IHME). Joinpoint regression and Age-Period-Cohort (APC) models were selected to analyze the epidemic trend of this cancer in China, and descriptive analysis was used for the time trend and age distribution of risk factors. The Bayesian APC model was selected to foresee the incidence trend in 2020-2049. This cancer burden was found to be in an upward trend in China in 1990-2019. The upward trend was more pronounced among men than among women. These cancer deaths and DALYs are overwhelmingly attributable to smoking and drinking. On APC analysis, the younger generation in China demonstrated a lower cancer risk. In 2049, the incidence of this cancer is projected to be 3.99/100,000, 6.07/100,000, 7.37/100,000, 10.49/100,000, 14.82/100,000, 19.19/100,000, 20.71/100,000, 23.64/100,000, 16.42/100,000 and 9.91/100,000 among those aged 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80-84, 85-89, 85-89 and over 95 years, respectively. Disease control policies and early screening should focus on men and the elderly and target different risk factors.