1.Effects of resveratrol-derived carbonized polymer dots on macrophage polarization and osteogenic differentiation of human periodontal ligament stem cells under inflammatory conditions
LI Nuo ; WANG Yulong ; LIU Qing ; MIAO Leiying
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(10):827-840
Objective:
To investigate the effect and mechanism of resveratrol-derived carbonized polymer dots (RSV-CPDs) on macrophage polarization and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) under inflammatory conditions, and to provide an experimental basis for the treatment of periodontitis with RSV-CPDs.
Methods:
RSV-CPDs were prepared by high-temperature pyrolysis of resveratrol (RSV) in the presence of ammonia as a catalyst, and RSV-CPDs were characterized by transmission electron microscope (TEM), Fourier transform infrared spectrometer (FTIR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). CCK8 was used to detect the cytotoxicity of RSV-CPDs. The effects of RSV-CPDs on the apoptosis and cell polarization of macrophages stimulated by Porphyromonas gingivalis-lipopolysaccharide (P.g-LPS) were detected by flow cytometry: ① For the apoptosis detection experiment, the macrophages (RAW264.7) were divided into the control group (no treatment), P.g-LPS group [treated with P.g-LPS (2 μg/mL) for 24 h], RSV group [treated with P.g-LPS (2 μg/mL) + RSV (10 μg/mL) for 24 h], and RSV-CPDs group [treated with P.g-LPS (2 μg/mL) + RSV-CPDs (50 μg/mL) for 24 h]. ② For the cell polarization experiment, the macrophages (RAW264.7) were divided into four groups. They were the control group (no treatment), P.g-LPS + IFN-γ group [P.g-LPS (200 ng/mL) + IFN-γ (20 ng/mL) treated cells for 24 h], RSV group [P.g-LPS (200 ng/mL) + IFN-γ (20 ng/mL) + RSV (10 μg / mL) treated cells for 24 h], RSV-CPDs group [P.g-LPS (200 ng / mL) + IFN-γ (20 ng / mL) + RSV-CPD (50 μg / mL) treated cells for 24 h]. The supernatant of macrophages in the above four groups of cell polarization experiments was collected and mixed with osteogenic induction medium at a 1:1 ratio to culture hPDLSCs. The hPDLSCs were divided into the control group, P.g-LPS + IFN-γ group, RSV group, and RSV-CPDs group. The osteogenic trend of hPDLSCs was detected by alkaline phosphatase (ALP) staining and alizarin red staining (ARS). Real-time quantitative PCR (RT-qPCR) was used to detect the expression of osteogenesis-related genes. Western blot was used to detect the expression of osteogenesis-related proteins in hPDLSCs. Finally, transcriptome tests were used to explore the mechanism of the effect of RSV-CPDs on the phenotype of macrophages (THP-1) stimulated by inflammation.
Results:
TEM results showed that RSV-CPDs exhibited a uniform spherical structure. FTIR results showed the O-C=O peak of RSV-CPDs. XRD results confirmed that the newly synthesized RSV-CPDs exhibited an amorphous structure. XPS results showed that RSV-CPDs formed a hydrophilic carboxyl group. CCK-8 results showed that RSV had specific toxicity to RAW264.7 when the concentration exceeded 10 μg/mL (P = 0.011), while RSV-CPDs still had good biosafety to cells when the concentration reached 50 μg/mL (P > 0.05). Therefore, the concentration of RSV was 10 μg/mL and RSV-CPDs was 50 μg/mL. The results of flow cytometry showed that RSV-CPDs inhibited the apoptosis of macrophages under inflammatory stimulation (P = 0.008), and the inhibitory effect was better than that of its precursor RSV (P = 0.009). Compared with the P.g-LPS + IFN-γ group, CD86+ cells in the RSV group and RSV-CPDs group decreased by varying degrees (P < 0.001, P = 0.004), while CD206+ cells increased by varying degrees (P = 0.006, P = 0.008), and the proportion of CD206+ cells in the RSV-CPDs group was higher than that in the RSV group (P = 0.010). Compared with the P.g-LPS + IFN-γ group, the supernatant of macrophages treated with RSV-CPDs significantly increased the ALP expression (P = 0.005) and ARS level (P = 0.006) of hPDLSCs. The mRNA expression of osteogenic-related genes RUNX-2, OCN, and COL-1 significantly increased (P < 0.05), and the level of RUNX-2 protein also significantly increased (P = 0.001). Transcriptome results showed that compared with the P.g-LPS + IFN-γ group, the nuclear factor kappa-B (NF-κB) signaling pathway and tumor necrosis factor (TNF) signaling pathway in the RSV-CPDs group showed downward trends.
Conclusion
RSV-CPDs can inhibit the apoptosis of macrophages in the inflammatory state, promote M2 polarization, and bolster the osteogenic differentiation of hPDLSCs. The mechanism involved may be related to the inhibition of NF-κB and TNF signaling pathways.
2.Evaluation of asymptomatic ocular surface disorders in hospitalized patients with primary pterygium before surgery
Chengfang ZHU ; Zhirong LIN ; Xie FANG ; Xianwen XIAO ; Zhiwen XIE ; Shunrong LUO ; Bin LIU ; Xumin SHANG ; Nuo DONG ; Huping WU
International Eye Science 2024;24(1):131-135
AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.
3.MTHFD2 Is a Negative Regulatory Molecule for the Formation of Heterotypic Cell-in-Cell Structures
Peng-Fei FENG ; Chen-Yu LIU ; Yi-Nuo HUANG ; Zhuo-Ran SUN ; Yang-Yi ZHANG ; Hong-Yan HUANG ; Chen-Xi WANG ; Xiao-Ning WANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(6):819-826
Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P<0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P<0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.
4.The international pharmaceutical trade policies of the BRICS countries and its implications for China
Zuo-Kun LIU ; Wang-Yao MA ; Yi-Wu GU ; Yu-Yang ZHANG ; Ji-Yan MA ; Ming-Fan PANG ; Yi-Nuo SUN ; Yang-Mu HUANG
Chinese Journal of Health Policy 2024;17(4):65-71
This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.
5.Effects of Huoxue Bushen Anshen Prescription on Energy Metabolism of H9c2 Cardiomyocytes with Oxidative Stress Injury
Nuo CHENG ; Jie WANG ; Lanchun LIU ; Jiawen CHENG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):94-101
Objective To observe the effects of Huoxue Bushen Anshen Prescription on energy metabolism of H9c2 cardiomyocytes with oxidative stress injury.Methods H9c2 cardiomyocytes oxidative stress model was established with H2O2 to simulate myocardial injury.CCK-8 method was used to select the best conditions for modeling and the appropriate concentration of drugs.Cells were divided into normal group,model group,trimetazidine hydrochloride group and Huoxue Bushen Anshen Prescription group.Na+-K+-ATPase activity,real-time ATP generation rate,mitochondrial pressure,gycolysis rate,and long-chain fatty acid oxidationl pressure on H9c2 cardiomyocytes after treatment were performed,and the changes in energy metabolism of cardiomyocytes were observed.Results Compared with the normal group,the Na+-K+-ATPase activity,glycolytic ATP production rate,mitochondrial ATP production rate,basal oxygen consumption,non mitochondrial oxygen consumption,ATP production capacity,cellular reserve respiratory capacity and maximum respiratory capacity of H9c2 cells in the model group decreased,the glycolytic rate slowed down,long chain fatty acid basal respiration,acute response and maximum respiratory value decreased(P<0.05,P<0.01).Compared with the model group,the H9c2 cells in Huoxue Bushen Anshen Prescription group showed an increase in Na+-K+-ATPase activity,an increase in glycolytic ATP production rate and mitochondrial ATP production rate,an increase in basal oxygen consumption,non mitochondrial oxygen consumption,ATP production capacity,cellular reserve respiratory capacity and maximum respiratory capacity,an increase in basal glycolysis rate,and an increase in long-chain fatty acid basal respiration,acute response and maximum respiratory value(P<0.05,P<0.01).Conclusion Huoxue Bushen Anshen Prescription can significantly improve the activity of Na+-K+-ATPase in cH9c2 ardiomyocytes with oxidative stress injury,increase the rate of ATP production,improve mitochondrial pressure,glycolysis rate and oxidation pressure of long chain fatty acids,and improve the energy metabolism of cardiomyocytes.
6.Study on the Mechanism of Huoxue Bushen Anshen Prescription in Improving Oxidative Damage of H9c2 Cells by Regulating AhR-JDP2-Nrf2 Axis
Nuo CHENG ; Jie WANG ; Jiawen CHENG ; Lanchun LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):102-108
Objective To explore the mechanism of Huoxue Bushen Anshen Prescription in improving the oxidative damage of H9c2 cells based on AhR-JDP2-Nrf2 axis.Methods H9c2 cells were divided into normal group,model group,TCM group,trimetazidine group,empty plasmid group,overexpression group,TCM+overexpression group and trimetazidine+overexpression group.The oxidative stress model of H9c2 cells was induced with H2O2 to imitate myocardial injury,and the cells were transfected with JDP2 overexpressed gene,intervened with Huoxue Bushen Anshen Prescription and trimetazidine hydrochloride respectively.Apoptosis was detected by flow cytometry,the contents of MDA,SOD and NADPH in cell supernatant were detected by kits,the protein expression of AhR,JDP2,Nrf2 and HO-1 were detected by Western blot,the mRNA expression of AhR,JDP2,Nrf2 and HO-1 were detected by RT-qPCR.Results Compared with the normal group,the early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells in the model group increased(P<0.01),the contents of MDA,SOD and NADPH in cell supernatant increased(P<0.05),the expression of AhR,JDP2,Nrf2,HO-1 protein and mRNA increased(P<0.05).Compared with the model group,the early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells in the TCM group and the trimetazidine group significantly decreased(P<0.01),the contents of MDA,SOD and NADPH decreased(P<0.05),the expression of AhR,JDP2,Nrf2 and HO-1 protein and mRNA decreased in the TCM group(P<0.05).Compared with the empty plasmid group,the overexpression group showed an increase in early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells(P<0.01),an increase in MDA and NADPH content in cell supernatant(P<0.01),an decrease in SOD content(P<0.01),and an increase in the expressions of AhR,JDP2,Nrf2,HO-1 protein and mRNA in H9c2 cells(P<0.05).Compared with the overexpression group,the early apoptosis rate,late apoptosis rate and total apoptosis rate of H9c2 cells in the TCM+overexpression group and the trimetazidine+overexpression group were significantly decreased(P<0.05,P<0.01),the MDA and NADPH contents in cell supernatant were decreased(P<0.01),the SOD content increased(P<0.01),and the expressions of AhR,JDP2,Nrf2,HO-1 protein and mRNA in H9c2 cells decreased(P<0.05).Conclusion Huoxue Bushen Anshen Prescription can regulate the AhR-JDP2-Nrf2 axis by regulating the expression of JDP2,alleviate the oxidative damage of H9c2 cells,reduce the apoptosis of cardiomyocytes,and protect cardiomyocytes.
7.Situation,characteristics and challenges of traditional medicine cooperation under multilateral mechanisms
Yi-Nuo SUN ; Yu-Yang ZHANG ; Zong-Bin WANG ; Zuo-Kun LIU ; Yang-Mu HUANG
Chinese Journal of Health Policy 2023;16(12):56-63
Multilateral mechanisms are important platforms and vehicles for cooperation in traditional medicine.Relying on multilateral platforms,China is able to enhance the international influence of the domestic traditional Chinese medicine and form synergies with other member countries to enhance regional or cross-regional radiation effects in order to promote sustainable development of traditional medicine around the world.This paper focuses on China's participation in major multilateral health cooperation mechanisms,including global initiatives(WHO-led global cooperation framework,the Belt and Road Initiative),regional multilateral mechanisms(ASEAN countries,China-Japan-Korea Health Cooperation Mechanism,Shanghai Cooperation Organization(SCO),The Greater Mekong Subregion(GMS)),and cross-regional multilateral mechanisms(BRICS,Forum On China-Africa Cooperation(FOCAC),G20),and sorts out the cooperation policies and actions in traditional medicine under different mechanisms,to analyze the characteristics and challenges of the existing mechanisms in traditional medicine cooperation,and to provide evidence for China's promotion on multilateral cooperation in traditional medicine.
8.High-value utilization technology and approach of Chinese medicinal residues under background of "Dual Carbon".
Yue-Yue FANG ; Nuo CHEN ; Ping XIAO ; Sen ZHANG ; Hai-Feng LIU ; Shu-Lan SU ; Sheng GUO ; Jin-Ao DUAN
China Journal of Chinese Materia Medica 2023;48(19):5142-5151
In recent years, the traditional Chinese medicine(TCM)industry has experienced rapid development, resulting in a significant amount of Chinese medicinal residues generated during the industrial manufacturing process. Currently, the main methods of handling Chinese medicinal residues include stacking, landfilling, and incineration, which lead to substantial resource waste and potential environmental pollution. With "carbon peak" and "carbon neutrality"( "Dual Carbon")becoming national strategic goals, the TCM industry is ushering in a new wave of "low-carbon" trends, and the high-value utilization of Chinese medicinal residues has become a breakthrough for implementing a low-carbon economy in the TCM sector. From the perspective of a low-carbon economy, this article reviewed literature in China and abroad to summarize the microbial transformation technology, enzymatic conversion technology, biomass pyrolysis, gasification, hydrothermal liquefaction, and other high-value utilization technologies for Chinese medicinal residues. It also overviewed the applications of Chinese medicinal residue in feed additives, organic fertilizers, edible mushroom cultivation substrates, preparation of activated carbon for wastewater treatment, and new energy batteries. Considering the current status of resource utilization of Chinese medicinal residues, feasible strategies and suggestions for resource development and utilization were proposed to improve the quality and efficiency of the Chinese medicinal resource industry chain and promote green development, thereby providing research ideas and theoretical basis for achieving carbon peak and carbon neutrality goals.
Drugs, Chinese Herbal
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Medicine, Chinese Traditional
;
China
;
Technology
;
Industry
9.PHF5A Promotes Proliferation and Migration of Non-Small Cell Lung Cancer by Regulating of PI3K/AKT Pathway.
Houhui WANG ; Fanglei LIU ; Chunxue BAI ; Nuo XU
Chinese Journal of Lung Cancer 2023;26(1):10-16
BACKGROUND:
There have been many significant advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC). However, the mechanism underlying the progression of NSCLC is still not clear. Plant homodomain finger-like domain-containing protein 5A (PHF5A) plays an important role in processes of chromatin remodeling, morphological development of tissues and organs and maintenance of stem cell pluripotency. This study aims to investigate the role of PHF5A in the proliferation and migration of NSCLC.
METHODS:
A549 and PC-9 PHF5A overexpression cell lines were constructed. PHF5A expression was decreased in H292 and H1299 cells by using siRNA. Flow cytometry was used to detect the cell cycle. MTT assay and clone formation assay were used to examine the proliferative ability of NSCLC, while migration assay and wound healing assay were performed to evaluate the ability of migration. Western blot analysis was used to measure the expressions of PI3K, p-AKT and the associated downstream factors.
RESULTS:
Up-regulation of PHF5A in A549 and PC-9 cells increased the proliferation rate, while down-regulation of PHF5A in H292 and H1299 cells inhibited the proliferation rate at 24 h, 48 h and 72 h (P<0.05). The metastatic ability was elevated in the PHF5A-overexpresion groups, while reduced in the PHF5A-down-regulation group (P<0.05). In addition, reduced expression of PHF5A induced cell cycle arrest at G1/S phase (P<0.05). Furthermore, decreased expression of PHF5A reduced the expression levels of PI3K, phosphorylation of AKT, c-Myc (P<0.05) and elevated the expression of p21 (P<0.05).
CONCLUSIONS
These results demonstrated that PHF5A may play an important role in progression of NSCLC by regulating the PI3K/AKT signaling pathway.
Humans
;
Carcinoma, Non-Small-Cell Lung/pathology*
;
Lung Neoplasms/pathology*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Cell Line, Tumor
;
Cell Proliferation/genetics*
;
Cell Movement/genetics*
;
Gene Expression Regulation, Neoplastic
;
Trans-Activators/genetics*
;
RNA-Binding Proteins/metabolism*
10.Association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years.
Meng Jie CUI ; Qi MA ; Man Man CHEN ; Tao MA ; Xin Xin WANG ; Jie Yu LIU ; Yi ZHANG ; Li CHEN ; Jia Nuo JIANG ; Wen YUAN ; Tong Jun GUO ; Yan Hui DONG ; Jun MA ; Yi XING
Journal of Peking University(Health Sciences) 2023;55(3):415-420
OBJECTIVE:
To analyze the association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years, and to provide suggestions for the prevention and control of metabolic syndrome in Chinese children and adolescents.
METHODS:
Data were collected from the research project "Development and Application of Technology and Related Standards for Prevention and Control of Major Diseases among Students" of public health industry in 2012. This project is a cross-sectional study design. A total of 65 347 students from 93 primary and secondary schools in 7 provinces including Guangdong were selected by stratified cluster random sampling method. Given the budget, 25% of the students were randomly selected to collect blood samples. In this study, 10 176 primary and middle school students aged 7 to 17 years with complete physical measurements and blood biochemical indicators were selected as research objects. Chi-square test was used to compare the distribution differences of growth patterns under different demographic characteristics. Birth weight, waist circumference and blood biochemical indexes were expressed in the form of mean ± standard deviation, and the differences among different groups were compared by variance analysis. Binary Logistic regression model was used to analyze the relationship between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years.
RESULTS:
The prevalence of metabolic syndrome in children and adolescents was 6.56%, 7.18% in boys and 5.97% in girls. The risk of metabolic syndrome was higher in the catch-down growth group than in the normal growth group (OR=1.417, 95%CI: 1.19-1.69), and lower in the catch-up growth group(OR=0.66, 95%CI: 0.53-0.82). After adjusting for gender, age and so on, the risk of developing metabolic syndrome in the catch-down growth group was higher than that in the normal growth group (OR=1.25, 95%CI: 1.02-1.52), but there was no significant difference between the catch-up growth group and the normal growth group (OR=0.79, 95%CI: 0.62-1.01). Stratified analysis showed that the association between different growth patterns and metabolic syndrome was statistically significant in the 7-12 years group, urban population, and Han Chinese student population.
CONCLUSION
There is a correlation between different growth patterns and metabolic syndrome in children and adolescents. The risk of developing metabolic syndrome in children and adolescents with catch-down growth is higher than that in the normal growth group, which suggests that attention should be paid to the growth and development of children and adolescents, timely correction of delayed growth and prevention of adverse health outcomes.
Male
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Female
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Humans
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Child
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Adolescent
;
Metabolic Syndrome/epidemiology*
;
Cross-Sectional Studies
;
Students
;
Urban Population
;
Asian People
;
China/epidemiology*
;
Prevalence


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