Stage-specific and location-specific cartilage calcification in osteoarthritis development.

OBJECTIVES: This study investigated the stage-specific and location-specific deposition and characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies. METHODS: Normal and OA cartilages were serially sectioned for micro-CT, scanning electron microscopy with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, focused ion beam scanning electron microscopy, high-resolution electron energy loss spectrometry with transmission electron microscopy, nanoindentation and atomic force microscopy to analyse the structural, compositional and mechanical properties of cartilage in OA progression. RESULTS: We found that OA progressed by both top-down calcification at the joint surface and bottom-up calcification at the osteochondral interface. The top-down calcification process started with spherical mineral particle formation in the joint surface during early-stage OA (OA-E), followed by fibre formation and densely packed material transformation deep into the cartilage during advanced-stage OA (OA-A). The bottom-up calcification in OA-E started when an excessive layer of calcified tissue formed above the original calcified cartilage, exhibiting a calcified sandwich structure. Over time, the original and upper layers of calcified cartilage fused, which thickened the calcified cartilage region and disrupted the cartilage structure. During OA-E, the calcified cartilage was hypermineralised, containing stiffer carbonated hydroxyapatite (HAp). During OA-A, it was hypomineralised and contained softer HAp. This discrepancy may be attributed to matrix vesicle nucleation during OA-E and carbonate cores during OA-A. CONCLUSIONS: This work refines our current understanding of the mechanism underlying OA progression and provides the foothold for potential therapeutic targeting strategies once the location-specific cartilage calcification features in OA are established.

Identification of an Ultrathin Osteochondral Interface Tissue with Specific Nanostructure at the Human Knee Joint.

Cartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without conferring fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of the osteochondral interface tissue remain unclear. Here, we identified an ultrathin ∼20-30 µm graded calcified region with two-layered micronano structures of osteochondral interface tissue in the human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Results from finite element simulations revealed that within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to force transmission. Nanoscale heterogeneity in the hydroxyapatite, coupled with enrichment of elastic-responsive protein-titin, which is usually present in muscle, endowed the osteochondral tissue with excellent mechanical properties. Collectively, these results provide novel insights into the potential design for high-performance interface materials for osteochondral interface regeneration.

Associations between the supply and utilization of primary care and newborn, children and maternal health in rural counties of Guangdong Province, China.

BACKGROUND: The Chinese government is ambitious regarding strengthening the primary care system for women and children. Primary care contributes to better health outcomes among neonates, infants, children and pregnant women, especially for vulnerable groups. However, few published studies have examined this issue in China. OBJECTIVE: This study examined whether greater supply and utilization of primary care was associated with improved health outcomes among targeted populations in the total and interprovincial migrant populations in the rural counties of Guangdong Province, China. METHODS: This ecological study analysed annual panel data from all 63 rural counties in Guangdong Province from 2014 to 2016 (n = 189). A linear random-effects panel data model was applied. RESULTS: Higher proportions of primary care visits were significantly associated with reduced incidences of low birth weight (P < 0.05) and preterm birth rates (P < 0.05) for the total population, and were significantly associated with reduced infant (P < 0.1) and under-five (P < 0.01) mortality rates for migrants. Greater primary care physician supply was significantly associated with reduced maternal mortality (P < 0.1) rates among migrants. However, primary care indicators were insignificant for both the total and migrant populations regarding neonatal mortality rates, as well as the infant and under-five mortality rates in the total population (P > 0.1). CONCLUSIONS: These findings support existing evidence regarding associations between primary care and improved health outcomes among newborns, children and pregnant women, especially for disadvantaged populations. However, associations were not significant for all studied health outcomes, implying the need for further study.

The association between the supply and utilization of community-based primary care and child health in a context of hospital-oriented healthcare system in urban districts of Guangdong, China: a panel dataset, 2014-2016.

BACKGROUND: Since 2009, the Chinese government has been reforming the healthcare system and has committed to reinforcing increased use of primary care. To date, however, the Chinese healthcare system is still heavily reliant on hospital-based specialty care. Studies consistently show an association between primary care and improved health outcomes, and the same association is also found among the disadvantaged population. Due to the "hukou" system, interprovincial migrants in the urban districts are put in a weak position and become the disadvantaged. Therefore, the aim of this study is to investigate whether greater supply and utilization of primary care was associated with reduced child mortality among the entire population and the interprovincial migrants in urban districts of Guangdong province, China. METHODS: An ecological study was conducted using a 3-year panel data with repeated measurements within urban districts in Guangdong province from 2014 to 2016, with 178 observations in total. Multilevel linear mixed effects models were applied to explore the associations. RESULTS: Higher visit proportion to primary care was associated with reductions in the infant mortality rate and the under-five mortality rate in both the entire population and the interprovincial migrants (p < 0.05) in the full models. The association between visit proportion to primary care and reduced neonatal mortality rate was significant among the entire population (p < 0.05) while it was insignificant among the interprovincial migrants (p > 0.05). CONCLUSIONS: Our ecological study based in urban districts of Guangdong province found consistent associations between higher visit proportion to primary care and improvements in child health among the entire population and the interprovincial migrants, suggesting that China should continue to strengthen and develop the primary care system. The findings from China adds to the previously reported evidence on the association between primary care and improved health, especially that of the disadvantaged.

Growth of HIV-uninfected children born to HIV-infected mothers in Guangdong, China: an 18-month longitudinal follow-up study.

BACKGROUND: To evaluate the early growth (weight and length) of HIV-exposed uninfected (HEU) children from the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) program in Guangdong Province, China. METHODS: A total of 731 HEU children were longitudinally followed up at 7 time points, with anthropometric measurement conducted of weight and length (supine) in the first 18 months. Z scores were calculated, with and without adjustment for gestational age. RESULTS: A total of 708 HEU children were included in the final follow-up cohort, and 105 (14.83%) children completed all 7 follow-up visits. The mean of adjusted weight-for-age Z scores in these children was above zero and showed a decreasing trend in 18 months. The mean of adjusted length-for-age Z scores showed a decreasing trend and was above zero in the first 12 months; this declined to under zero at age 18 months. The proportion of underweight was 0.28-2.19% and that of stunting was 0.71-4.63% at each follow-up month-age. Slower growth in HEU children was associated with no sustained food subside after 6 month, mothers' hemoglobin content less than 100 g/L during pregnancy, preterm birth, and low birth weight (p < 0.05). CONCLUSIONS: HEU children could catch up to WHO growth standards in first 18 months in Guangdong; however, growth declined after 12 months, and these children need sustained nutritional support.

The association between ambient temperature and preterm birth in Shenzhen, China: a distributed lag non-linear time series analysis.

BACKGROUND: A few studies have examined the association between ambient temperature and preterm birth (PTB), and the results have been inconsistent. This study explored the association between ambient temperature and PTB in Shenzhen, China. METHODS: Data of daily singleton PTB, air pollution and meteorological variables from 2005 to 2011 were collected in Shenzhen. A distributed lag non-linear model (DLNM) was used to investigate the association of the low and high temperatures (1st, 5th, 95th, and 99th percentiles) with PTB. RESULTS: The median temperature was 24.5 °C and the 1st, 5th, 95th, and 99th percentiles of daily mean temperatures were 9, 12.5, 29.9 and 30.7 °C, respectively. The prevalence of singleton PTB was 5.61 % in Shenzhen. The association between temperature and PTB was not linear. There was an immediate positive association of low temperature (1st and 5th percentiles) and a negative association of high temperature (95th and 99th percentiles) with PTB. The effect of low temperature 9 °C (1st) on PTB on the current day was stronger than that of 12.5 °C (5th), with a relative risk (RR) of 1.54 (95 % CI: 1.36-1.75) and 1.49 (95 % CI: 1.35-1.63), respectively. The cumulative RR (up to 30 days) of 9 and 12.5 °C was 1.72 (95 % CI: 1.28-2.33) and 1.96 (95 % CI: 1.60-2.39), respectively. The cumulative effects (up to 30 days) of high temperature (95th and 99th percentiles) on PTB were 0.69 (95 % CI: 0.60-0.80) and 0.62 (95 % CI: 0.52-0.74), respectively. The cumulative effect (up to 30 days) of low temperatures on vaginal delivery PTB was lower than that of the cesarean section PTB with an RR of 1.58 (95 % CI: 1.12-2.22) and 1.93 (95 % CI: 1.21-3.08), respectively. CONCLUSIONS: This study suggests that low temperature might be a risk factor, while high temperature might be a protective factor of PTB in Shenzhen.

Obstacles to the coordination of delivering integrated prenatal HIV, syphilis and hepatitis B testing services in Guangdong: using a needs assessment approach.

BACKGROUND: Integration of services for Prevention of Mother-To-Child Transmission of HIV (PMTCT) into routine maternal and child health care is promoted as a priority strategy by the WHO to facilitate the implementation of PMTCT. Integration of services emphasizes inter-sectoral coordination in the health systems to provide convenient services for clients. China has been integrating prenatal HIV, syphilis and hepatitis B testing services since 2009. However, as the individual health systems are complex, effective coordination among different health agencies is challenging. Few studies have examined the factors that affect the coordination of such complex systems. The aim of this study is to assess the effectiveness of and examine challenges for integrated service delivery. Findings will provide the basis for strategy development to enhance the effective delivery of integrated services. METHODS: The research was conducted in Guangdong province in 2013 using a needs assessment approach that includes qualitative and quantitative methods. Quantitative data was collected through a survey and from routine monitoring for PMTCT and qualitative data was collected through stakeholder interviews. RESULTS: Routine monitoring data used to assess key indicators of coordination suggested numerous coordination problems. The rates of prenatal HIV (95%), syphilis (47%) and hepatitis B (47%) test were inconsistent. An average of only 20% of the HIV positive mothers was referred in the health systems. There were no regular meetings among different health agencies and the clients indicated complicated service processes. The major obstacles to the coordination of delivering these integrated services are lack of service resource integration; and lack of a mechanism for coordination of the health systems, with no uniform guidelines, clear roles or consistent evaluation. CONCLUSIONS: The key obstacles that have been identified in this study hinder the coordination of the delivery of integrated services. Our recommendations include: 1) Facilitate integration of the funding and information systems by fully combining the service resources of different health agencies into one unit; 2) Establish regular meetings to facilitate exchange of information and address problems; 3) Establish a client referral network between different health agencies with agreed guidelines, clear roles and consistent evaluation.

[Comparison of the effect of three ß-thalassemia prenatal screening strategies using in Guangdong province].

OBJECTIVE: To compare the effect of three ß-thalassemia prenatal screening strategies in Guangdong province. METHODS: A total of 13 284 hospital-delivered couples and 13 369 newborns were recruited from 91 hospitals in 21 counties or districts of Guangdong province from June to December 2012. Mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were tested for all the couples, and all the couples and newborns were detected by 17 types of ß-globin gene mutations. The effect of three ß-thalassemia prenatal screening strategies were compared as following: (1) MCV/MCH with Hb A2 serial screening (SS): Hb A2 was tested if the woman's MCV < 82 fl and (or) MCH < 27 pg. If the woman's Hb A2 > 3.5, it meant positive. And if the woman was ß-thalassemia carrier and her husband's Hb A2 > 3.5, it meant couple positive. (2) MCV/MCH with Hb A2 parallel screening (PS): if the woman's MCV < 82 fl and (or) MCH < 27 pg and (or) Hb A2 > 3.5 pg, it meant couple positive. And the husband would be tested for ß-globin gene mutations if the woman was ß-thalassemia carrier. (3) MCV/MCH with Hb A2 serial screening for couples (SSC): if one of the couple or both of them had MCV < 82 fl and (or) MCH < 27 pg, the couple would be tested for Hb A2, and if one of the couple got Hb A2 > 3.5, it meant couple positive. RESULTS: (1) For the SS strategy, the sensitivity was 92.69% (583/629); the specificity was 99.87% (12 638/12 655); the positive predictive value was 97.17% (583/600); and the negative predictive value was 99.64% (12 638/12 684). The results of ß-globin gene mutations tested showed that the rate of ß-thalassemia carriers was 4.74% (629/13 284) in the 13 284 pregnant women, and it was 4.29% (570/13 284) in their husbands. (2) The SS strategy detected 27 (0.20%, 27/13 284) ß-thalassemia carrier couples. For the SS strategy detecting ß-thalassemia carrier couples, the missed diagnosis rate was 11.11% (3/27); the sensitivity was 88.89% (24/27); the specificity was 100.00% (27/27); the positive predictive value was 100.00% (24/24); and the negative predictive value was 99.98% (13 257/13 260). (3) When using the SS strategy for 13 369 offsprings, there were 582 ß-thalassemia carriers (4.35%, 582/13369), including 578 (99.31%, 578/582) minor ß-thalassemia, 3 (0.52%, 3/582) intermedia ß-thalassemia and 1 (0.17%, 1/582) major ß-thalassemia. The SS strategy detected 25 fetuses who needed ß-thalassemia prenatal diagnosis. (4) For the PS strategy, the sensitivity was 98.09% (617/629); the specificity was 88.73% (11 229/12 655); the positive predictive value was 30.20% (617/2 043); and the negative predictive value was 99.89% (11 229/11 241). (5) When using the PS strategy for the ß-thalassemia carrier couples, the sensitivity was 100.00% (27/27); the specificity was 95.55% (12 667/13 257); the positive predictive value was 4.38% (27/617); and the negative predictive value was 100.0% (12 667/12 667). (6) The PS strategy detected 28 fetuses who needed ß-thalassemia prenatal diagnosis in 13 369 offsprings. (7) For the SSC strategy, the sensitivity was 93.80% (590/629); the specificity was 95.75% (12 117/12 655); the positive predictive value was 52.30% (590/1 128); and the negative predictive value was 99.68% (12 117/12 156). When the SSC strategy was used for the husbands, the sensitivity was 92.28% (526/570); the specificity was 95.27% (12 112/12 714);the positive predictive value was 46.63% (526/1 128); and the negative predictive value was 99.64% (12 112/12 156). (8) When the SSC strategy was used in ß-thalassemia carrier couples, the sensitivity was 100.00% (27/27); the specificity was 91.69% (12 156/13 257); the positive predictive value was 2.39% (27/1 128); and the negative predictive value was 100.00% (12 156/12 156). (9) The SSC strategy detected 28 fetuses who needed ß-thalassemia prenatal diagnosis. CONCLUSIONS: All the three ß-thalassemia prenatal screening strategies had good effect in clinical practice and public health. While in the high-prone area of ß-thalassemia, MCV/MCH with Hb A2 parallel screening and MCV/MCH with Hb A2 serial screening for couples stratigies were better.

Prevalence of congenital heart defect in Guangdong province, 2008-2012.

BACKGROUND: Congenital heart defect (CHD) is the most common major malformations in infants. Little is known about the main epidemiologic characteristics of CHD prevalence in Guangdong province, China. Our study was undertaken to investigate the time trends in the prevalence of CHD in Guangdong province from 2008 to 2012. METHODS: Data were retrieved from the Guangdong Hospital-Based Birth Defects Monitoring System during 2008-2012. All infants more than 28 weeks of gestation and infants up to 7 days of age in monitoring hospitals were monitored. We used prevalence rate to describe the difference in prevalence of CHD between rural and urban areas. Odds ratio (OR) and 95% confidence interval (CI) for CHD were calculated for the rural and urban areas. The CHD rate was calculated on the basis of birth defects per 10,000 births. RESULTS: A total of 1,005,052 births were reported to the Birth Defects Monitoring Network of Guangdong Province, of which 5268 cases were diagnosed as CHD. The overall prevalence of CHD was 52.41 per 10,000 births (95% CI: 51.00 ~ 53.83) in provincial-wide, 66.08 per 10,000 births (95% CI: 63.77 ~ 68.39) in urban areas, and 40.23 per 10,000 births (95% CI: 38.52 ~ 41.93) in rural areas. The prevalence of CHD increased with maternal age both in urban areas (P < 0.01) and in rural areas (P < 0.01). CONCLUSION: The increasing trends of CHD prevalence suggest that maternal age and the improvement of diagnosis ability might play a critical role.

High prevalence of thalassemia in migrant populations in Guangdong Province, China.

BACKGROUND: The objectives of this study were to estimate the prevalence of thalassemia and to analyze the need for public health services for migrant populations in different cities in Guangdong Province, China. METHODS: A cross-sectional survey was conducted in 21 cities of Guangdong Province. Twenty-three types of a- and ß-globin gene mutations were detected in a total of 14,230 pregnant women and 14,249 husbands. RESULTS: There was a 16.45% prevalence of thalassemia among the 28,479 individuals, and the prevalences of α-, ß-, and combined α-/ß- thalassemia were 12.03%, 3.80%, and 0.63%, respectively. Compared with the native city residents in the province, the migrants from within the province and the immigrants from outside the province had lower prevalences of thalassemia, but the prevalence values were >11%. CONCLUSIONS: The prevalence values for thalassemia gene mutations were high in all three population groups studied in Guangdong Province. The results indicate that all segments of the Guangdong population should be screened for thalassemia.

Injectable conductive hydrogel remodeling microenvironment and mimicking neuroelectric signal transmission after spinal cord injury.

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.

Advanced 3D-Printing Bioinks for Articular Cartilage Repair.

Chondral lesions caused by stressors, such as injury or inflammation, lead to osteoarthritis (OA). OA is a degenerative joint disease that has become a challenge worldwide. As the articular cartilage is incapable of self-regeneration due to the absence of vessels and nerves, novel cartilage repair techniques are urgently needed. Three-dimensional (3D) bioprinting, which allows the precise control of internal architecture and geometry of printed scaffolds, has stepped up to be a promising strategy in cartilage restoration. With regards to 3D bioprinting, bioinks with proper chemical and mechanical properties play one of the most critical roles in designing successful cartilage tissue constructs. In particular, hydrogels as 3D hydrophilic cross-linked polymer networks are highly recommended as bioinks because of their fine biocompatibility, easy fabrication, and tunable mechanical strength. Herein, we highlight the widely used polymers for hydrogel preparation and further provide a non-exhaustive overview of various functional modified additives (such as cells, drugs, bioactive factors and ceramic) to exploit the unique properties suitable for bioprinted cartilage. Finally, a prospective on future development for 3D-bioprinting in cartilage repair is elucidated in this review.

Equity in maternal and child health care utilization in Guangdong province of China 2009-2019: A retrospective analysis.

Background: Equity is the principal challenge of maternal and child health care (MCH) across the world, especially in China. Existing researches focused on equity in MCH resources and outcomes. There is an evidence gap regarding equity of MCH services utilization, revealing the black box between equity in MCH resources and MCH outcomes. In the study, we evaluate the changes of equity in integrated MCH service utilization in Guangdong province of China during 2009-2019. Methods: Data used in this study are from the Guangdong Maternal and Child Health Routine Reporting System and the Guangdong Health Statistical Yearbook (2009-2019). The Gini coefficient (G) and Theil index (T) were employed to assess equity and source of inequity in four geographic regions of Guangdong province. Results: Generally, among the integrated MCH care, coverage of pre-pregnancy care (<50%) is lower than in other stages. In the past decade, inequity of MCH care in the Equalization of Essential Public Health Service (EEPHS) program has gradually reduced to G < 0.1. Screening of genetic metabolic disease and of hearing showed largest reductions of inequity (G reducing from 0.3-0.4 to 0.03-0.04). Inequity in reproductive health tests for brides-to-be, psychological assessment and consultation, education classes for mother-to-be and health management of children under 3 were mainly contributed by intra-region disparities in 2019. Conclusion: Equity has gradually improved in the last decade in Guangdong. The national EEPHS program and the Integrated Prevention of Mother-to-Child Transmission of HIV, Syphilis and HBV of Guangdong have played important roles in reducing inequity in MCH service utilization. Further strategies, targeting pre-pregnancy reproductive healthcare, psychological assessments and consultations for the pregnant and education classes for mothers-to-be, should be taken to promote coverage and equity.

Discovery of Muscle-Tendon Progenitor Subpopulation in Human Myotendinous Junction at Single-Cell Resolution.

The myotendinous junction (MTJ) is a complex and special anatomical area that connects muscles and tendons, and it is also the key to repairing tendons. Nevertheless, the anatomical structure and connection structure of MTJ, the cluster and distribution of cells, and which cells are involved in repairing the tissue are still unclear. Here, we analyzed the cell subtype distribution and function of human MTJ at single-cell level. We identified four main subtypes, including stem cell, muscle, tendon, and muscle-tendon progenitor cells (MTP). The MTP subpopulation, which remains the characteristics of stem cells and also expresses muscle and tendon marker genes simultaneously, may have the potential for bidirectional differentiation. We also found the muscle-tendon progenitor cells were distributed in the shape of a transparent goblet; muscle cells first connect to the MTP and then to the tendon. And after being transplanted in the MTJ injury model, MTP exhibited strong regenerative capability. Finally, we also demonstrated the importance of mTOR signaling for MTP maintenance by in vitro addition of rapamycin and in vivo validation using mTOR-ko mice. Our research conducted a comprehensive analysis of the heterogeneity of myotendinous junction, discovered a special cluster called MTP, provided new insights into the biological significance of myotendinous junction, and laid the foundation for future research on myotendinous junction regeneration and restoration.

In-cytoplasm mitochondrial transplantation for mesenchymal stem cells engineering and tissue regeneration.

Stem cell therapies are unsatisfactory due to poor cell survival and engraftment. Stem cell used for therapy must be properly "tuned" for a harsh in vivo environment. Herein, we report that transfer of exogenous mitochondria (mito) to adipose-derived mesenchymal stem cells (ADSCs) can effectively boost their energy levels, enabling efficient cell engraftment. Importantly, the entire process of exogeneous mitochondrial endocytosis is captured by high-content live-cell imaging. Mitochondrial transfer leads to acutely enhanced bioenergetics, with nearly 17% of higher adenosine 5'-triphosphate (ATP) levels in ADSCs treated with high mitochondrial dosage and further results in altered secretome profiles of ADSCs. Mitochondrial transfer also induced the expression of 334 mRNAs in ADSCs, which are mainly linked to signaling pathways associated with DNA replication and cell division. We hypothesize that increase in ATP and cyclin-dependent kinase 1 and 2 expression might be responsible for promoting enhanced proliferation, migration, and differentiation of ADSCs in vitro. More importantly, mito-transferred ADSCs display prolonged cell survival, engraftment and horizontal transfer of exogenous mitochondria to surrounding cells in a full-thickness skin defect rat model with improved skin repair compared with nontreated ADSCs. These results demonstrate that intracellular mitochondrial transplantation is a promising strategy to engineer stem cells for tissue regeneration.

Advanced hydrogels for the repair of cartilage defects and regeneration.

Cartilage defects are one of the most common symptoms of osteoarthritis (OA), a degenerative disease that affects millions of people world-wide and places a significant socio-economic burden on society. Hydrogels, which are a class of biomaterials that are elastic, and display smooth surfaces while exhibiting high water content, are promising candidates for cartilage regeneration. In recent years, various kinds of hydrogels have been developed and applied for the repair of cartilage defects in vitro or in vivo, some of which are hopeful to enter clinical trials. In this review, recent research findings and developments of hydrogels for cartilage defects repair are summarized. We discuss the principle of cartilage regeneration, and outline the requirements that have to be fulfilled for the deployment of hydrogels for medical applications. We also highlight the development of advanced hydrogels with tailored properties for different kinds of cartilage defects to meet the requirements of cartilage tissue engineering and precision medicine.

Biomimetic Joint Paint for Efficient Cartilage Repair by Simultaneously Regulating Cartilage Degeneration and Regeneration in Pigs.

Irregular partial-thickness cartilage defect is a common pathogenesis of osteoarthritis (OA) with no available treatment in clinical practice. Currently, cartilage tissue engineering is only suitable for a limited area of full-thickness cartilage defect. Here, we design a biomimetic joint paint for the intractable partial-thickness cartilage defect repair. The joint paint, composed of a bridging layer of chondroitin sulfate and a surface layer of gelatin methacrylate with hyaluronic acid, can quickly and tightly adhere to the cartilage defect by light activation. Being treated by the joint paint, the group of rabbit and pig models with partial-thickness cartilage defects showed a restoration of a smooth cartilage surface and the preservation of normal glycosaminoglycan content, whereas the untreated control group exhibited serious progressive OA development. This paint treatment functions by prohibiting chondrocyte apoptosis, maintaining chondrocyte phenotype, and preserving the content of glycosaminoglycan in the partial-thickness cartilage defects. These findings illustrated that the biomimetic joint paint is an effective and revolutionary therapeutics for the patients with noncurable partial-thickness cartilage defects.

Effect of the 2008 cold spell on preterm births in two subtropical cities of Guangdong Province, Southern China.

BACKGROUND: A few studies have reported that low temperatures were associated with an increased risk of preterm birth. However, the effect of extreme weather events, such as cold spell, on preterm birth has not been studied in China. OBJECTIVE: This study was conducted to evaluate the impact of the 2008 cold spell on preterm birth in two subtropical cities of Guangdong Province. METHODS: Data of daily preterm birth, air pollution and meteorological variables from 2006 to 2010 were collected in Dongguan and Shenzhen. A Poisson regression with a distributed lag nonlinear model was used to investigate the association between the 2008 cold spell and daily rate of preterm birth for each city. RESULTS: During the 2008 cold spell, total vaginal preterm births were increased by 22.44% and 21.25% in Dongguan and Shenzhen, respectively. The effect of the cold spell on preterm births lasted for more than 1 week, the lag0-6 days cumulative relative risk (RR) is 1.32 (95% CI: 1.10-1.58) and 1.40 (95% CI: 1.18-1.68) in Dongguan and Shenzhen, respectively. The effects were found to be more pronounced for the pregnant women with 34-36 gestation weeks, maternal age < 35 years group. CONCLUSION: This study demonstrates that cold spell could increase the risk of preterm births in Dongguan and Shenzhen, and the effect lasts for more than 1 week. Specific measures should be considered to protect the pregnant women, especially the vulnerable subgroups.

The prevalence and molecular spectrum of α- and ß-globin gene mutations in 14,332 families of Guangdong Province, China.

OBJECTIVE: To reveal the familial prevalence and molecular variation of α- and ß-globin gene mutations in Guangdong Province. METHODS: A total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters. RESULTS: A high prevalence of α- and ß-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or ß-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or ß-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and ß-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers. CONCLUSIONS: There was a high prevalence of α- and ß-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.