The possible impact of the universal two-child policy on pregnancy outcomes.

PURPOSE: The implementation of the universal two-child policy contributes to adverse pregnancy outcomes, but how the policy change leads to adverse pregnancy outcomes is not well elaborated. In this study, we aimed to compare maternal characteristics and complications, accessed the change in the proportion of maternal characteristics and maternal complications, and evaluated the mediation of maternal characteristics on maternal complications. METHODS: Demographic and clinical data of three-level sample facilities were extracted from China's National Maternity Near Miss Obstetrics Surveillance System from Jan 1, 2012 to May 31, 2021. The associations between the universal two-child policy and maternal risk factors, the universal two-child policy and maternal complications, and maternal risk factors and maternal complications were evaluated using multivariate logistic regression analyses, with odds ratios (ORs) and 95% confidence intervals (CIs). Mediation analysis was used to estimate the potential mediation effects on the associations between the policy and maternal complications. Population-attributable fractions (PAF) were conducted to quantify the maternal complications burden attributable to the implementation of the universal two-child policy. RESULTS: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facilities. After adjusting for covariables, there were significant associations between the universal two-child policy and maternal risk factors (P < 0.001), the universal two-child policy and an increased risk of maternal complications (P < 0.001), and maternal risk factors and maternal complications(P < 0.001). The effects of the universal two-child policy on maternal near miss and medical disease were significantly mediated by maternal risk factors with mediation proportions of 19.77% and 4.07% at the municipal-level sample facility, and mediation proportions for 2.72% at the county-level sample facility on medical disease. The universal two-child policy contributed 19.34%, 5.82%, 8.29%, and 46.19% in the incidence of the maternal near miss, antepartum or intrapartum complication, post-partum complication, and medical disease at municipal-level sample facility, respectively. The corresponding PAF% at county-level sample facility was 40.49% for maternal near miss, 32.39% for the antepartum or intrapartum complication, 61.44% for post-partum complication, and 77.72% for medical disease. For provincial-level sample facility, the incidence of maternal near miss, antepartum or intrapartum complications, and medical diseases decreased (P < 0.05) and no statistically significant difference occurred in the incidence of post-partum complications. CONCLUSIONS: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facility. Maternal risk factors may play a mediating role in the effect of policy change and maternal complications. Provincial hospitals have been able to improve the quality of perinatal health care and reduce adverse pregnancy outcomes by adjusting their obstetric service strategies in the context of the new birth policy.

[ZEB2 Regulates the Migration and Invasion of PANC-1 Pancreatic Cancer Cells: An Experimental Study].

Objective: To investigate the effects and mechanisms of zinc finger E-box binding homeobox transcription factor-2 ( ZEB2) on the proliferation, colony formation, migration, and invasion abilities and the epithelial-mesenchymal transition (EMT) of PANC-1 cells, a human pancreatic cancer cell line. Methods: Data on the expression of ZEB2 in pancreatic cancer tissues and paracancerous tissues from The Cancer Genome Atlas (TCGA) database were analyzed. PANC-1 pancreatic cancer cells were divided into si-NC group, si- ZEB2 group, pcDNA3.1 group, and pcDNA3.1- ZEB2 group. qRT-PCR and Western blot were conducted to confirm the effectiveness of ZEB2 knockdown or overexpression. CCK-8, colony formation, wound healing, and Transwell assays were conducted to examine the effects of ZEB2 on the proliferation, colony formation, migration, and invasion of PANC-1 cells. qRT-PCR and immunofluorescence assays were performed to examine the expression of E-cadherin and vimentin, the EMT markers, in the cells. Prediction of proteins interacting with ZEB2 was made through the STRING database. Results: TCGA database analysis showed that the expression level of ZEB2 in pancreatic cancer tissues was significantly higher than that in adjacent tissues ( P<0.05). Compared with those of cells in the control group, the proliferation, colony formation, migration, and invasion of cells in the si- ZEB2 group were decreased ( P<0.05). Compared with those of cells in the pcDNA3.1 group, the proliferation, colony formation, migration and invasion of cells in the pcDNA3.1- ZEB2 group were increased (all P<0.05). According to the results of qRT-PCR and immunofluorescence assays, compared with those of the si-NC group, the expression of E-cadherin mRNA, an epithelial marker, in the si- ZEB2 group increased, while the expression of vimentin mRNA, an mesenchymal marker, and the protein decreased. Compared with those of the pcDNA3.1 group, the expression of E-cadherin mRNA in the PANC-1 cells of the pcDNA3.1- ZEB2 group decreased, while the expression of vimentin mRNA and the protein increased (all P<0.05). Analysis with the STRING database predicted that 10 proteins had close interaction with ZEB2. Conclusion: Overexpression of ZEB2 promotes the migration, invasion, and the EMT process of PANC-1 pancreatic cancer cells.

The Current Status of Insufficient Sleep Duration and Its Influencing Factors Among Children and Adolescents: A Household Based Cross-Sectional Study in Zhejiang Province, China.

PURPOSE: Insufficient sleep duration is common among children and adolescents worldwide, and the decline of sleep duration during the recent years is troubling. This study aimed to learn the status of insufficient sleep duration and to explore its influencing factors among children and adolescents in Zhejiang Province, China. DESIGN AND METHODS: A stratified sampling technique was employed in the present cross-sectional study. Demographic characteristics, sports time as well as sedentary behavior were investigated. RESULTS: A greater proportion of children than adolescents reported insufficient sleep duration (36.4% versus 19.2%, p = 0.001). For children, insufficient sleep duration was associated with age (OR = 1.290, 95%CI: 1.069-1.557), watching movies or TV shows with smartphones after school (OR = 3.098, 95%CI: 1.293-7.420), surf the internet after school (OR = 0.113, 95%CI: 0.013-0.969), walk to school (OR = 0.289, 95%CI: 0.105-0.793). For adolescents, insufficient sleep duration was associated with watch TV after school (OR = 0.379, 95%CI: 0.148-0.970), watching movies or TV shows with smartphones after school (OR = 4.744, 95%CI: 1.799-12.507), do homework after school (OR = 0.265, 95%CI: 0.086-0.813). CONCLUSIONS: An unhealthy sedentary screen lifestyle profile may have influence on insufficient sleep duration. Urgent actions are needed to improve sleep duration among children and adolescents.

[Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer].

Objective To investigate the expression of Cripto-1 in pancreatic cancer and to analyze its clinical significance. Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ 2=4.787,P=0.029).However,multivariate analysis failed to demonstrate overexpression of Cripto-1 an independent prognostic indicator in patients with pancreatic cancer(HR=1.341,95% CI=0.800-2.248,P=0.266).Conclusions Cripto-1 may play an important role in the development and progression of pancreatic cancer.It can be a potential prognostic biomarker for patients with pancreatic cancer.

Adult breakfast habits and nutritional status: A household based cross-sectional study in Zhejiang Province, China.

BACKGROUND AND OBJECTIVES: Although Dietary Guidelines for Chinese Residents offers advice for breakfast in China, current breakfast consumption habits are unclear. The aim of this study was to describe the frequency of breakfast consumption among adults and explore its associations with daily food consumption and daily nutrient intake. METHODS AND STUDY DESIGN: A stratified cluster sampling technique was employed in this cross-sectional study. Demographic characteristics, breakfast consumption, and daily food and nutrient intake were investigated. RESULTS: Dietary data were collected for 3251 adult residents through interviews. We determined that residents with an annual income of

Reduced CENPU expression inhibits lung adenocarcinoma cell proliferation and migration through PI3K/AKT signaling.

CENPU (centromere protein U), a centromere component essential for mitosis, relates with some cancers progression. However, it is not well illustrated in lung adenocarcinoma (LAC). Here, we aimed to investigate the potential effect of CENPU on LAC progression and prognosis. In this experiment, expression level of CENPU and association between its expression and LAC patients' clinicopathological characteristics and prognosis were analyzed. The proliferation, migration and invasive abilities of LAC cells were determined by CCK-8, colony formation, transwell assays. Western blot was used to detect PI3K/AKT signaling key proteins. We found CENPU level was overexpressed in LAC tissues on comparing normal tissues. Moreover, CENPU overexpression correlated with clinicopathological variables and predicted an independent prognostic indicator in LAC patients. Functionally, CENPU downregulation significantly inhibited LAC cell proliferation, migration and invasion in, which was possibly mediated by PI3K/AKT pathway inactivation. Our findings insinuate targeting CENPU may be a potential therapeutic strategy for LAC.

A rare intrahepatic subcapsular hematoma (ISH) after laparoscopic cholecystectomy: a case report and literature review.

BACKGROUND: Intrahepatic subcapsular hematoma (ISH) is an extremely rare, life-threatening complication after laparoscopic cholecystectomy (LC). Only few cases have been reported. Herein, we reported a rare giant ISH after LC and summarized all of the reported cases. CASE PRESENTATION: A 32-year old woman with recurrent acute cholecystitis for one year, underwent elective LC without intra-operative complications and was discharged 2 days after operation. On the next day after discharge, she developed severe right upper abdominal pain and was sent to our emergency department. The computed tomography scan showed a 10.9 × 12.5 × 6.6 cm ISH in the right liver without free fluid and the hemoglobin dropped to 86 g/l from 127 g/l. Postoperative hemorrhagic shock and a giant ISH after LC were diagnosed. After fluid resuscitation, the hemodynamic was still unstable and the hemoglobin kept dropping. An emergency laparoscopic exploration was performed and the ISH was confirmed, however no active bleeding point was found. A drainage tube was placed under liver for early warning of rupture. Patient was discharged home 10 days after readmission. CONCLUSIONS: Giant ISH is an extremely rare, life-threatening complication after LC. This case showed that the need to consider this rare complication in patients suffering abdominal pain after LC and timely and correct diagnosis and treatment were crucial to saving the lives of the patients.

Dietary Patterns Associated Metabolic Syndrome in Chinese Adults.

Dietary pattern has been revealed to be associated with metabolic syndrome. However, the association was not well documented in Chinese due to the complexity of Chinese foods. We mainly assessed the dietary patterns and examined their effects on metabolic syndrome among Chinese adults. Four dietary patterns including 'Refined Grains & Vegetables' Pattern, 'Dairy & Eggs' Pattern, 'Organ Meat & Poultry' Pattern, and 'Coarse Grains & Beans' Pattern were extracted. 'Dairy & Eggs' Pattern was associated with a decreased odds of metabolic syndrome in women, and 'Coarse Grains & Beans' Pattern was associated with a decreased odds of hypertension in men. These results provided a scientific basis for future research and dietary guideline perfection.

[Icariin Promoted Osteogenic Differentiation of SD Rat Bone Marrow Mesenchymal Stem Cells: an Experimental Study].

OBJECTIVE: To observe features of Icariin in promoting osteogenic differentiation of SD rat bone marrow mesenchymal stem cells (BMSCs) in vitro. METHODS: (1) SD rats' BMSCs were isolated and purified by mechanically isolated and cultured by whole bone marrow adherent method. Effects of various concentrations Icariin on serum activities of alkaline phosphatase (ALP) were detected using amino antipyrine phenol determination method at day 3, 6, 9, 12, 15, 18, and 21. Calcium nodes of each groups were detected using alizarin red staining. Roles of various concentrations Icariin in promoting osteogenic differentiation of BMSCs were observed. (2) BMSCs were divided into the blank control group, the osteogenic induced group, and the Icariin group (0.5 microg/mL). ALP activities were detected at day 7, 14, and 21 of culture. Meanwhile, ALP positive staining rate and calcium nodes were detected at day 14 and 21 respectively. Additionally, mRNA expressions of Runt-related transcription factor-2 (Runx2) and Osteocalcin were detected at day 7, 14, and 21 by real-time fluorescent quantitative PCR. RESULTS: (1) 0.05-5.0 microg/mL Icariin could significantly elevate serum ALP activities. Of them, 0.2-2.0 microg/mL Icariin significantly increased calcium nodes numbers (P < 0.01). (2) When Icariin promoted osteogenic differentiation of BMSCs, Runx2 mRNA expression levels and ALP activities increased earlier and then decreased, while osteocalcin mRNA expression levels continued to increase (P < 0.01). Compared with the osteogenic induced group, ALP activities and ALP positive staining rate were both elevated after 14 days of Icariin treatment in the Icariin group (P < 0.05, P < 0.01). CONCLUSIONS: Icariin could promote the differentiation of BMSCs to osteoblasts by up-regulating Runx2 mRNA expression levels. It also could promote the mineralization by increasing ALP secretion and Osteocalcin mRNA expression levels, thereby promoting mature of newly generated osteoblasts.

Burden of self-reported acute gastrointestinal illness in China: a population-based survey.

BACKGROUND: Acute gastrointestinal illness (AGI) is an important public-health problem worldwide. Previous national studies of the incidence of AGI in China were performed decades ago, and detailed information was not available. This study therefore sought to determine the magnitude, distribution, and burden of self-reported AGI in China. METHODS: Twelve-month, retrospective face-to-face surveys were conducted in 20 sentinel sites from six provinces between July 2010 and July 2011. RESULTS: In total, 39686 interviews were completed. The overall adjusted monthly prevalence of AGI was 4.2% (95% confidence interval, 4.0-4.4), corresponding to 0.56 episodes of AGI per person-year. Rates of AGI were highest in children aged < 5 years. Healthcare was sought by 56.1% of those reporting illness. Of the cases who visited a doctor, 32.7% submitted a stool sample. The use of antibiotics was reported by 49.7% of the cases who sought medical care and 54.0% took antidiarrhoeals. In the multivariable model, gender, age, education, household type, residence, season, province and travel were significant risk factors of being a case of AGI. CONCLUSIONS: This first population-based study in China indicated that AGI represents a substantial burden of health. Further research into the specific pathogens is needed to better estimate the burden of AGI and foodborne disease in China.

[Study on level of dietary iodine intake and its contribution rate of residents in Zhejiang].

OBJECTIVE: To assess the level of dietary iodine intake and its contribution in Zhejiang. METHODS: A total of 9798 subjects were recruited in this survey with multi-stage stratified cluster random sampling method in April, 2010, the 24-hours dietary recall method and the "food composition table" were used to obtain the dietary iodine intake, and edible salt and drinking water samples were collected to detect the content of iodine. RESULTS: A total of 9798 subjects were included in this survey. The mean intake of dietary iodine in Zhejiang residents per standard man-days was (395.13 ± 78.16) µg/d, which in between of Recommended Nutrient Intake (RNI) 150 µg/d and Tolerable Upper Intake Level (UL) 1000 µg/d; the iodine intake of 18.40% (1803/9798) subjects was lower than estimated average requirement of iodine (EAR), 4.68% (459/9798) subjects was higher than the UL. The means of dietary iodine intake in various areas were (498.85 ± 96.77) µg/d, (384.50 ± 88.76) µg/d and (326.33 ± 78.32)µg/d in inland areas, sub-coastal areas and coastal areas, successively (F = 27.17, P < 0.05); the proportions of dietary iodine intake lower than EAR were 34.89% (1239/3551), 10.48% (370/3530) and 7.14% (197/2717) in coastal areas, sub-coastal area and inland areas, successively (χ(2) = 62.87, P < 0.01) , while those higher than UL were 5.10% (180/3530), 4.86% (132/2717) and 4.14% (147/3551) in sub-coastal area, inland areas and coastal areas.In the condition of ignoring cooking loss, the mean contribution of dietary iodine intake in edible salt, all kinds of food and drinking water were 74.92% (296.03/395.13), 23.85% (94.24/395.13) and 1.23% (4.86/395.13), successively; the contributions of edible salt in inland areas, sub-coastal areas and coastal areas were 83.72% (417.64/498.85), 73.05% (280.88/384.50) and 66.83% (280.09/326.33), successively; the contributions of drinking water in sub-coastal areas, coastal areas and inland areas were 1.61% (6.19/384.50) , 1.44% (4.70/326.33) and 0.65% (3.24/498.85) , successively (χ(2) = 7.24, P = 0.032) ; the contribution of laver in coastal areas, sub-coastal areas and inland areas were 22.57% (73.65/326.33), 17.11% (65.79/384.50) and 8.09% (40.36/498.85), successively (χ(2) = 82.17, P < 0.01) ; the contribution of sea fish in coastal areas, sub-coastal areas and inland areas were 2.38% (7.77/326.33), 0.72% (2.77/384.50) and 0.68% (3.39/498.85) (χ(2) = 19.47, P = 0.012). CONCLUSIONS: The dietary iodine intake of Zhejiang residents was at recommended intake levels; the iodized salt turns out to be the main source, the iodine nutrition level was relatively low in coastal areas of Zhejiang, which the coverage of iodized salt should be improved.

[Effects of drynariae rhizoma water-extraction on the ability of osteogenic differentiation and it's mechanism].

OBJECTIVE: To investigate the effects of Drynariae Rhizoma water-extraction on the ability of osteogenic differentiation and the expression of TGF-beta1 and BMP-2 in inducing mesenchymal stem cells (MSCs) differentiation into osteoblast and its mechanism. METHODS: MSCs were isolated and purified by differential time adherent method; The most effective concentration of the Drynariae Rhizoma water-extraction on the proliferation and ostogenic differentiation of MSCs was confirmed by MTT method and the activity and positive staining of alkaline phosphatase (ALP) respectively; According to different induced condition, MSCs were divided into 4 groups: control group, classic group (induced by the classic osteoblast-induced system), Drynariae Rhizoma water-extraction group (induced by the most effective concentration of Drynariae Rhizoma water-extraction on differentiation into osteoblast) and Drynariae Rhizoma water-extraction + classic group (induced by the combination of classic osteoblast-induced system and the most effective concentration of Drynariae Rhizoma water-extraction on differentiation into osteoblast). ALP,type I collagen (Col I), bone gla protein (BGP) and calcium nodes in each group were detected and compared to indicate the osteogenic differentiation of each group. TGF-beta1 and BMP-2 were detected by ELISA. RESULTS: The most effective concentration of the Drynariae Rhizoma water-extraction on the proliferation and osteogenic differentiation of MSCs was 5 microg/mL and 50 microg/mL, respectively. The classic group, Drynariae Rhizoma water-extraction group and Drynariae Rhizoma water-extraction + classic group could promote the osteogenic differentiation of MSCs and increase the expression of TGF-beta1 and BMP-2. CONCLUSION: The Drynariae Rhizoma water-extraction can promote the proliferation and osteogenic differentiation of MSCs. Epimedium water-extraction can improve the differentiation of MSC into osteoblast and its mechanism may be related to increasing the expression of TGF-beta1 and BMP-2.

A self-attention-based neural network for three-dimensional multivariate modeling and its skillful ENSO predictions.

Large biases and uncertainties remain in real-time predictions of El Niño-Southern Oscillation (ENSO) using process-based dynamical models; recent advances in data-driven deep learning algorithms provide a promising mean to achieve superior skill in the tropical Pacific sea surface temperature (SST) modeling. Here, a specific self-attention-based neural network model is developed for ENSO predictions based on the much sought-after Transformer model, named 3D-Geoformer, which is used to predict three-dimensional (3D) upper-ocean temperature anomalies and wind stress anomalies. This purely data-driven and time-space attention-enhanced model achieves surprisingly high correlation skills for Niño 3.4 SST anomaly predictions made 18 months in advance and initiated beginning in boreal spring. Further, sensitivity experiments demonstrate that the 3D-Geoformer model can depict the evolution of upper-ocean temperature and the coupled ocean-atmosphere dynamics following the Bjerknes feedback mechanism during ENSO cycles. Such successful realizations of the self-attention-based model in ENSO predictions indicate its great potential for multidimensional spatiotemporal modeling in geoscience.

Synthesis of MnOOH and its application in a supporting hexagonal Pd/C catalyst for the oxygen reduction reaction.

With the expansion of global energy problems and the deepening of research on oxygen reduction reaction (ORR) in alkaline media, the development of low cost and high electrocatalytic performance catalysts has become a research hotspot. In this study, a hexagonal Pd-C-MnOOH composite catalyst was prepared by using the triblock copolymer P123 as the reducing agent and protective agent, sucrose as the carbon source and self-made MnOOH as the carrier under hydrothermal conditions. When the Pd load is 20% and the C/MnOOH ratio is 1 : 1, the 20% Pd-C-MnOOH-1 : 1 catalyst obtained by the one-step method has the highest ORR activity and stability in the alkaline system. At 1600 rpm, the limiting diffusion current density and half-wave potential of the 20% Pd-C-MnOOH-1 : 1 electrocatalyst are -4.78 mA cm-2 and 0.84 V, respectively, which are better than those of the commercial 20%Pd/C catalyst. According to the Koutecky-Levich (K-L) equation and the linear fitting results, the electron transfer number of the 20%Pd-C-MnOOH-1 : 1 electrocatalyst for the oxygen reduction reaction is 3.8, which is similar to that of a 4-electron process. After 1000 cycles, the limiting diffusion current density of the 20%Pd-C-MnOOH-1 : 1 catalyst is -4.61 mA cm-2, which only decreases by 3.7%, indicating that the 20%Pd-C-MnOOH-1 : 1 catalyst has good stability. The reason for the improvement of the ORR performance of the Pd-C-MnOOH composite catalyst is the improvement of the conductivity of the carbon layer formed by original carbonization, the regular hexagonal highly active Pd particles and the synergistic catalytic effect between Pd and MnOOH. The method of introducing triblock copolymers in the synthesis of oxides and metal-oxide composite catalysts is expected to be extended to other electrocatalysis fields.

Efficacy and safety of combined Chinese and Western medicine in the treatment of knee osteoarthritis: a prospective, multicenter cohort study.

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p < 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p < 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. Clinical Trial Registration: (https://www.chictr.org.cn/), identifier (ChiCTR1900027175).

Trim21 depletion alleviates bone loss in osteoporosis via activation of YAP1/ß-catenin signaling.

Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21-/-) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21-/- and Ctsk-cre; Trim21f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/ß-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

Puerarin stimulates osteoblasts differentiation and bone formation through estrogen receptor, p38 MAPK, and Wnt/ß-catenin pathways.

Puerarin is an isoflavone extracted from Radix Puerariae, a traditional Chinese herb used to treat many diseases such as osteoporosis. In this study, puerarin was shown to stimulate alkaline phosphatase (ALP) activity, type I collagen (Col I) secretion, and mineralized nodules formation of primary osteoblasts. Whereas the estrogen receptor (ER) antagonist ICI 182780 was able to reduce the increase in ALP activity and Col I secretion induced by puerarin. Furthermore, puerarin was shown to elevate levels of phospho-p38 mitogen-activated protein kinase (MAPK) and ß-catenin proteins in a time-dependent manner. Pretreatment of osteoblasts with ICI 182780 can reduce this elevation, whereas pretreatment with p38 MAPK inhibitor SB 203580 did not affect the increase of ß-catenin protein. Meanwhile, intragastric administration of puerarin protected against reduction in bone mineral density and bone mineral content in ovariectomized rats, and improved femur trabecular bone structure. Taken together, ER, p38 MAPK, and Wnt/ß-catenin pathways were involved in puerarin-stimulated osteoblasts differentiation and bone formation.

[Exposure assessment on dietary lead and cadmium of residents in three areas of Zhejiang province from 2009 to 2010].

OBJECTIVE: To assess the safety of dietary lead and cadmium intake in 3 areas of Zhejiang province. METHODS: Using the total dietary study method, the study was conducted in 3 regions which represented coastal, city and rural areas in Zhejiang province from 2009 to 2010. The dietary survey was conducted on the residents (512 subjects) and the categories and volume of food consumption were obtained. The analytical food samples were obtained by food consumption survey, food aggregation, food sampling and preparation. The food samples were detected by inductively coupled plasma mass spectrometry (ICP-MS). The safety of dietary lead and cadmium intake was evaluated. RESULTS: The median dietary lead intake (P50) in Zhejiang province was 37.8 µg/d. The 97.5% dietary lead intake (P97.5) was 72.3 µg/d. The P50 dietary lead intakes of different age and gender groups ranged from 23.2 to 44.2 µg/d. The P97.5 dietary lead intakes of different age and gender groups ranged from 34.2 to 88.1 µg/d. The P50 dietary cadmium intake in Zhejiang province was 9.6 µg/d. The P97.5 dietary cadmium intake was 15.7 µg/d. The P50 dietary cadmium intakes of different age and gender groups ranged from 6.4 to 11.4 µg/d, accounting 15.6% - 42.6% of PTMI (provisional tolerable monthly intake, 25 µg/kg). The P97.5 dietary cadmium intakes of different age and gender groups ranged from 10.5 to 21.4 µg/d, accounting 27.5% - 77.6% of PTMI. Vegetable (11.3 µg), cereal (11.0 µg) and meat (9.8 µg) were the first three food sources which accounted for 84.9% of dietary lead (P50: 37.8 µg/d). Cereal (3.6 µg), vegetable (2.1 µg) and legume (0.9 µg) were the first three food sources which accounted for 68.8% of dietary cadmium (P50: 9.6 µg/d). CONCLUSION: Dietary lead and cadmium intakes of most residents in 3 areas of Zhejiang province as well as the average level are safe.

[Effects of yigu capsule containing serum on the osteoblast differentiation and the expressions of osteoprotegerin and bone morphogenetic protein 2 after treatment by advanced glycation end products in vitro].

OBJECTIVE: To observe the effects of Yigu Capsule (YGC) containing serum on the differentiation and the expressions of osteoprotegerin (OPG) and bone morphogenetic protein 2 (BMP-2) in osteoblasts after treatment by advanced glycation end products (AGEs), and to explore the mechanisms of YGC for treating osteoporosis (OP). METHODS: Forty 10-month-old female Sprague Dawley (SD) rats were randomly divided into four groups equally, i.e., the low dose YGC group, the moderate dose YGC group, the high dose YGC group, and the blank control group. The YGC containing serum and the control serum were prepared with the method of gastric perfusion. Primary osteoblasts of newborn SD rats was extracted and cultured, then they were passaged and divided into five groups, i. e., the vehicle control group, the model group, the low dose YGC group, the moderate dose YGC group, and the high dose YGC group. The model group was treated by AGEs (400 mg/L), the three YGC groups were treated by AGEs (400 mg/L) and YGC containing serum at different concentrations. Alkaline phosphatase (ALP) activity, type I collagen (ColI), bone gla protein (BGP), and mineralization of osteoblasts were tested using pNPP, ELISA, and Alizarin dyeing. The mRNA and protein levels of BMP-2 and OPG were respectively determined using RT-PCR and ELISA. RESULTS: Primary osteoblasts from newborn SD rats could be used well in this experiment. Compared with the vehicle control group, the ALP, ColI, BGP, the mRNA and protein levels of BMP-2 and OPG of osteoblasts decreased in the model group, and the mineralized nodes were reduced, showing statistical difference (P<0.01). Compared with the model group, the ALP, ColI, BGP, the mRNA and protein levels of BMP-2 and OPG of osteoblasts increased in the three YGC groups, and the mineralized nodes increased in a dose-dependent manner, showing statistical difference (P<0.05, P<0.01). CONCLUSIONS: YGC containing serum could promote the differentiation and mineralization of osteoblasts, and improve the expressions of OPG and BMP-2 after treatment by AGEs. These might be one of YGC's mechanisms for treating OP.

[Time-effect and dose-effect relationships study on the effect of tonifying kidney and activating blood formulas contained serum on MSCs proliferation and osteogenic differentiation].

OBJECTIVE: To screen the optimal cell proliferation and osteogenic differentiation concentration of SD rats' Mesenchymal stem cells (MSCs) affected by compound Bushenhuoxue (CB) contained serum. METHODS: 30 SD female rats, aged 10 months, were randomly divided into low-dose (11.6 g/kg), medium dose (34.8 g/kg) and high dose CB group (104.4 g/kg), 10 rats in each group (qd, 12 d). Rats blood of three groups were taken respectively in 0.5, 1.0, 1.5, 2.0, 3.0 h after the last intragastric infusion, blood serum was separated, and different concentrations of CB contained serum were given to MSCs form SD female rats aged 3 months. MTT method was used to determine the effect of CB on MSCs proliferation. Alkaline phosphatase (ALP) was detected to determine the osteogenic differentiation of MSCs from each group. RESULTS: The 25% concentration of CB contained serum collected from SD rats one hour after intragastric infusion with low dose CB was proved to be the most effective concentration on the proliferation of MSCs; The 25%-30% concentration of CB contained serum collected from SD rats one hour after intragastric infusion with high dose CB was proved to be the most effective concentration on the differentiations of MSCs into osteoblast. CONCLUSION: CB contained serum could promote the proliferation and osteogenic differentiation of MSCs.