Recent Advances in Decellularized Matrix-Derived Materials for Bioink and 3D Bioprinting.

As an emerging 3D printing technology, 3D bioprinting has shown great potential in tissue engineering and regenerative medicine. Decellularized extracellular matrices (dECM) have recently made significant research strides and have been used to create unique tissue-specific bioink that can mimic biomimetic microenvironments. Combining dECMs with 3D bioprinting may provide a new strategy to prepare biomimetic hydrogels for bioinks and hold the potential to construct tissue analogs in vitro, similar to native tissues. Currently, the dECM has been proven to be one of the fastest growing bioactive printing materials and plays an essential role in cell-based 3D bioprinting. This review introduces the methods of preparing and identifying dECMs and the characteristic requirements of bioink for use in 3D bioprinting. The most recent advances in dECM-derived bioactive printing materials are then thoroughly reviewed by examining their application in the bioprinting of different tissues, such as bone, cartilage, muscle, the heart, the nervous system, and other tissues. Finally, the potential of bioactive printing materials generated from dECM is discussed.

Fu-Huang ointment ameliorates impaired wound healing associated with diabetes through PI3K-AKT signalling pathway activation.

A diabetic ulcer (DU) is a dreaded and resistant complication of diabetes mellitus with high morbidity. Fu-Huang ointment (FH ointment) is a proven recipe for treating chronic refractory wounds; however, its molecular mechanisms of action are unclear. In this study, we identified 154 bioactive ingredients and their 1127 target genes in FH ointment through the public database. The intersection of these target genes with 151 disease-related targets in DUs resulted in 64 overlapping genes. Overlapping genes were identified in the PPI network and enrichment analyses. The PPI network identified 12 core target genes, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulation of the PI3K/Akt signalling pathway was involved in the role of FH ointment in treating diabetic wounds. Molecular docking showed that 22 active compounds in FH ointment could enter the active pocket of PIK3CA. Molecular dynamics was used to prove the binding stability of the active ingredients and protein targets. We found that PIK3CA/Isobutyryl shikonin and PIK3CA/Isovaleryl shikonin combinations had strong binding energies. An in vivo experiment was conducted on PIK3CA, which was the most significant gene.This study comprehensively elucidated the active compounds, potential targets, and molecular mechanism of FH ointment application in treating DUs, and believed that PIK3CA is a promising target for accelerated healing.

Study on the protective effect of salidroside on memory impairment in mice under high altitude hypoxia / 中国药理学通报

Aim To explore the effect of salidroside on the learning and memory ability of mice under high altitude hypoxia. Methods Forty-eight C57BL/6J male mice were randomly divided into plain control group, plateau model group and salidroside group according to their body weight, with 16 mice in each group. The animals in each group were given prophylactic doses for three days and then rushed to a plateau with an altitude of 4 010 m. After one day of hypoxia exposure, Morris water maze was performed to test the learning and memory ability of mice; malondialdehyde(MDA), hydrogen peroxide(H

Latest advances in biomimetic nanomaterials for diagnosis and treatment of cardiovascular disease.

Cardiovascular disease remains one of the leading causes of death in China, with increasingly serious negative effects on people and society. Despite significant advances in preventing and treating cardiovascular diseases, such as atrial fibrillation/flutter and heart failure over the last few years, much more remains to be done. Therefore, developing innovative methods for identifying and managing cardiovascular disorders is critical. Nanomaterials provide multiple benefits in biomedicine, primarily better catalytic activity, drug loading, targeting, and imaging. Biomimetic materials and nanoparticles are specially combined to synthesize biomimetic nanoparticles that successfully reduce the nanoparticles' toxicity and immunogenicity while enhancing histocompatibility. Additionally, the biological targeting capability of nanoparticles facilitates the diagnosis and therapy of cardiovascular disease. Nowadays, nanomedicine still faces numerous challenges, which necessitates creating nanoparticles that are highly selective, toxic-free, and better clinically applicable. This study reviews the scientific accomplishments in this field over the past few years covering the classification, applications, and prospects of noble metal biomimetic nanozymes and biomimetic nanocarriers.

Research progress on effects of high altitude hypoxia environment on antiepileptic drugs / 中国药理学通报

Hie high altitude hypoxic environment affects the pharmacokinetic process of rlnjgs by changing the body's gastrointestinal emptying rate, organ blood flow, drug plasma protein binding rate, dnjg metabolizing enzymes and transporter expression.Epilepsy is a brain disease that requires long-term medication.Most anti-epileptic drugs have a low therapeutic index and a narrow range of effective blood drug concentrations.'Ilierapeu- tic dnjg monitoring (TDM) is commonly used clinically to find the best individualized medication method for antiepileptic dnjgs.rI1iis article summarizes the commonly used anti-epileptic dnjgs and their treatment windows in clinical practice, and analyzes the influence of the pharmacokinetics of anti-epileptic dnjgs in the high altitude hypoxic environment, so as to provide reference for the clinical use of anti-epileptic drugs at high altitude.

Effects of altitude hypoxia on cerebral blood distribution of sodium valproate in mice / 中国药理学通报

Aim To investigate the effects of altitude hypoxia on serum sodium valproate eoncentration and eerebral blood distribution.Methods Male mice were divided into control group and plateau group.Each group was given sodium valproate orally and intrave¬nously, respectively.UFLC-MS/MS was used to deter¬mine the concentration of sodium valproate in plasma and brain, and Western blot was used to detect the ex¬pression of P-gp in BBB.Results Compared with the control group, the ratio of brain/blood drug concentra¬tion in plateau group was up-regulated by 44.0% , 57.9% , 176.8% and 184.5% at 10, 30, 60 and 120 min, respectively.The ratio of brain/blood drug con-centration increased by 33.9% , 50.6% and 125.6% at 60 min, 120 min and 240 min in plateau group, re¬spectively.Compared with the control group, the ex¬pression of P-gp protein in BBB of mice in altitude group was significantly down-regulated by 58.46% (P < 0.05 ).Conclusions Compared with the control group, the brain/blood drug concentration ratio of val¬proic acid increases in high altitude hypoxia environ¬ment.Meanwhile, it is found that P-gp expression lev-el decreased in the brain mierovessels of mice under high altitude hypoxia environment, and the cerebral and blood distribution of valproic acid in mic increases in high altitude hypoxia environment.

GAO Hong's clinical experience in treatment of tic disorder with acupuncture technique of cultivating the primary and regulating the mind / 中国针灸

The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24+) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.

Using conditional inference to quantify interaction effects of socio-demographic covariates of US COVID-19 vaccine hesitancy

COVID-19 vaccine hesitancy has become a major issue in the U.S. as vaccine supply has outstripped demand and vaccination rates slow down. At least one recent global survey has sought to study the covariates of vaccine acceptance, but an inferential model that makes simultaneous use of several socio-demographic variables has been lacking. In this article, we present such a model using US-based survey data collected by Gallup. Our study agrees with the global survey results in some respects, but is also found to exhibit significant differences. For example, women and people aged between 25-54 were found to be more vaccine hesitant. Our conditional inference tree model suggests that trust in government, age and ethnicity are the most important covariates for predicting vaccine hesitancy, and can interact in ways that make them useful for communication-based outreach, especially if conjoined with census data. In particular, we found that the most vaccine hesitant individuals were those who identified as Black Republicans with a high school (or lower) education and lower income levels, who were involuntarily unemployed and trusted in the Trump administration.

Qinzhuliangxue mixture alleviates psoriasis-like skin lesions via inhibiting the IL6/STAT3 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease mediated by immunity. Our pre-clinical studies have proved that QZLX mixture can improve patients' clinical symptoms with psoriasis without noticeable adverse reactions. In a psoriasis-like mouse model induced by imiquimod, QZLX mixture has been shown to alleviate epidermal inflammation and inhibit the hyperproliferation of keratinocytes. However, its related molecular mechanism remains to be elucidated. AIM OF THE STUDY: To assess the mechanism of QZLX mixture against psoriasis. MATERIALS AND METHODS: This study combines network pharmacology and experiments to study the mechanism of QZLX against psoriasis. First, construct the active compound-target network and PPI network. Secondly, determine possible drug targets through Molecular docking and KEGG. Thirdly, high-performance liquid chromatography (HPLC) was used for the quality control of QZLX. Finally, use a mouse model of psoriasis to further confirm the role of QZLX. RESULTS: (1) Network pharmacology analysis shows that QZLX alleviates psoriasis's epidermal inflammation, and neovascularization may be achieved by inhibiting the IL6/STAT3 signaling pathway. (2) QZLX improves the pathological characteristics of IMQ-induced skin damage in psoriasis-like mice. (3) QZLX inhibits the IL6/STAT3 signaling pathway and reduces the expression of IL-17, IL-23, and TNF-α related to inflammation in peripheral blood, as well as the expression of S100A7 in the lesion area. QZLX is better than MTX in inhibiting neovascularization by down-regulating the expression of HIF-1 and CD31 in the lesion area. Finally, inhibition of Ki67 alleviates the excessive proliferation of keratinocytes. CONCLUSION: In sum, this study clarifies the mechanism of QZLX against psoriasis and provides evidence to support its clinical use.

Chemical Composition Analysis of Antibacterial and Anti-inflammatory Functions of Volatile Oils from Pelargonium graveolens L'Herit / 中国生物化学与分子生物学报

The components of volatile oils are generally complex, and they often have the functions of divergent dissolving surface, insecticidal and antibacterial. However, there are few reports on bacteriostasis, anti-inflammation and antioxidation roles of volatile oils of Pelargonium graveolens L'Herit. The volatile oil of Pelargonium graveolens L’Herit. was extracted by steam distillation, and GC-MS and peak area normalization analysis showed that it mainly contained 30 compounds, and the identified components accounted for 90.26% of the total peak area. The volatile oil of Pelargonium graveolens L'Herit. has a certain inhibitory effect on Candida albicans and Staphylococcus aureus, especially on Candida albicans. The diameter of the bacteriostatic zone is 15.55±1.53 mm by using the oxford cup method. Dexamethasone and low, middle and high doses of volatile oils of Pelargonium graveolens L'Herit. were given after the RAW264. 7 cell inflammatory model and was induced by lipopolysaccharide (LPS = 10.0 μg/mL). ELISA assays showed that it could effectively reduce the expression of IL-1β and TNF-α in inflammatory cells, and the effect of high doses was similar to that of IL-1β and TNF-α in the dexamethasone group. GC-MS was successfully used to determine and identify the chemical constituents of volatile oils from Pelargonium graveolens L'Herit. in this study. We show that the volatile oil of Pelargonium graveolens L'Herit. had certain bacteriostatic activity and effectively reduces the secretion of IL-1β and TNF-α by inflammatory cells. It provides an experimental basis for the development and utilization of volatile oils from Pelargonium graveolens L'Herit.

An assessment of sensitivity biomarkers for urinary cadmium burden.

BACKGROUND: Excess cadmium (Cd) intake poses a general risk to health and to the kidneys in particular. Among indices of renal dysfunction under Cd burden measures are the urinary N-acetyl-ß-D-glucosidase (UNAG) and urinary ß2-microglobulin (Uß2-MG) enzymes. However, the end-pointed values and the Cd burden threshold remain controversial because the scopes fluctuate widely. METHODS: To ascertain the clinical benchmark dose of urinary Cd (UCd) burden for renal dysfunction, 1595 residents near a Cd site were surveyed. Urine was sampled and assayed. A benchmark dose low (BMDL) was obtained by fitting UCd levels and index levels. RESULTS: We found that over 50% of the subjects were suffering from Cd exposure as their UCd levels far exceeded the national standard threshold of 5.000 µg/g creatinine (cr). Further analysis indicated that Uß2-MG was more sensitive than UNAG for renal dysfunction. The BMDL for UCd was estimated as 3.486 U/g cr (male, where U is unit of enzyme) and 2.998 U/g cr (female) for UNAG. The BMDL for Uß2-MG, which is released into urine from glomerulus after Cd exposure, was found to be 2.506 µg/g cr (male, where µg is the unit of microglobulin) and 2.236 µg/g cr (female). CONCLUSIONS: Uß2-MG is recommended as the sensitivity index for renal dysfunction, with 2.2 µg/g cr as the threshold for clinical diagnosis. Our findings suggest that Uß2-MG is the better biomarker for exposure to Cd.

A Reflection on the 2017 Nobel Prize for Physiology and Chinese Medicine.

Research on the molecular mechanisms controlling circadian rhythm in Western medicine is comparable to the study of a day-night rhythm in Chinese medicine (CM), as also focus on the same life phenomenon. By comparing the two, this paper elaborates on the differences between them in their respective issues of consciousness, ways of thinking, research methods and research results. Relatively speaking, Nobel Prize research has a stronger sense of the problems and concerns about the essence of "what", while CM focuses on "how a thing functions". The former mainly adopts experimental and mathematical methods, while the latter primarily depends on observation and understanding. The natural philosophy and natural science eventually lead to the results and the inevitable, quantitative and qualitative differences. Research on the life rhythm in CM should be proposed, scientific problems should be fully grasped, and research should be carried out with the aid of multidisciplinary new knowledge and new achievements through cross-disciplinary studies. On the basis of clinical epidemiological research and experimental research, a systematic review should be made of the human physiology of CM and the pathological rhythm model to explore the regulatory mechanism of time rhythm and create a new theory of time medicine.

A Reflection on the 2017 Nobel Prize for Physiology and Chinese Medicine / 中国结合医学杂志

Research on the molecular mechanisms controlling circadian rhythm in Western medicine is comparable to the study of a day-night rhythm in Chinese medicine (CM), as also focus on the same life phenomenon. By comparing the two, this paper elaborates on the differences between them in their respective issues of consciousness, ways of thinking, research methods and research results. Relatively speaking, Nobel Prize research has a stronger sense of the problems and concerns about the essence of "what", while CM focuses on "how a thing functions". The former mainly adopts experimental and mathematical methods, while the latter primarily depends on observation and understanding. The natural philosophy and natural science eventually lead to the results and the inevitable, quantitative and qualitative differences. Research on the life rhythm in CM should be proposed, scientific problems should be fully grasped, and research should be carried out with the aid of multidisciplinary new knowledge and new achievements through cross-disciplinary studies. On the basis of clinical epidemiological research and experimental research, a systematic review should be made of the human physiology of CM and the pathological rhythm model to explore the regulatory mechanism of time rhythm and create a new theory of time medicine.

KangFuXin Liquid in the Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most common complications of diabetes mellitus, with the wound not healing as expected and healing slowly. Poor control can develop into gangrene and even amputation. Currently, the existing treatments are not satisfactory enough. In China, KangFuXin liquid (KFXL) has been clinically used to treat DFU and has shown good clinical efficacy. In order to provide more reference to clinicians and experts, evidence of efficacy for it needs to be further rigorously evaluated. METHODS: Eight electronic databases were searched to identify eligible randomized clinical trials (RCTs) published from construction of the library to April 2019. There is no language or data restriction; 11 trials involving 889 participants met the inclusion criteria. These RCTs compared the total effective rate, cure rate, cure time, and adverse events associated with KFXL. The Cochrane Handbook guidelines were used to assess the risk of bias and to evaluate the methodological quality of eligible studies. The methodological quality of included studies was generally low. Dichotomous and continuous data were presented using risk ratios (RRs) and mean differences (MDs), respectively. RESULTS: Compared with the basic treatment, meta-analyses showed that KFXL combined with basic treatment can improve the total effective rate (RR = 1.38; 95% CI = 1.23-1.54; P < 0.00001; fixed effect model: I 2 = 32%) and cure rate (RR = 1.67; 95% CI = 1.17-2.38; P=0.005; random effect model: I 2 = 65%), and shorten the healing time (MD = -5.73; 95% CI = -6.95 to -4.52; P < 0.00001; random effect model). Moreover, under the same basic treatment, KFXL had a better effect than external use of pharmaceutical medications (RR = 1.95; 95% CI = 1.30-2.93; P=0.001), but the cure rate was not significantly different. Also, KFXL had nothing to do with adverse reactions. CONCLUSION: The evidence confirms that KFXL is an effective treatment for DFU. However, further large-scale, rigorously designed trials and high-quality studies are needed to confirm the role of KFXL in the treatment of DFU.

Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association With Alzheimer's Disease Risk.

To determine the role of A disintegrin and metalloproteinase 10 (ADAM10) in genetic susceptibility to Alzheimer's disease (AD) in a representative Chinese sample, we genotyped 362 AD patients and 370 healthy controls for the rs514049A/C and rs653765C/T polymorphisms in the ADAM10 promoter using the SNaPshot technique. We also examined the potential impact of these polymorphisms on the plasma level of soluble receptor for advanced glycation end products (sRAGE), a decoy receptor whose reduction has been associated with a higher risk of AD. Additionally, a meta-analysis was performed using the present study and the largest GWAS from the International Genomics of Alzheimer's Project (IGAP). No significant differences were found in the distributions of genotypes or alleles between AD patients and control subjects. However, age-at-onset stratification analysis revealed that there were significant differences in the genotypes (P = 0.015) and alleles (P = 0.006) of the rs653765 SNP. Furthermore, patients with the rs653765 CC genotype showed a lower ADAM10 level and a faster cognitive deterioration than those in patients with the CT/TT genotype in late-onset AD (LOAD), and the rs653765 CC polymorphism was able to regulate the production of the ADAM10 substrate sRAGE. In contrast, the rs514049 polymorphism was not statistically associated with AD. In the meta-analysis, we observed that both rs514049 (A allele vs. C allele, P = 0.002) and rs653765 (C allele vs. T allele, P = 0.004) were associated with AD risk. The present study indicated that the rs653765 polymorphism might be associated with the risk and development of LOAD; in particular, the risk genotype, CC, may decrease the expression of ADAM10, influencing the plasma levels of sRAGE, and thus may be correlated with the clinical progression of AD.

Effect of inflammatory factor and neurotransmitter of Yizhi Xingnao Fang combined with western medicine for patients with alzheimer's disease / 中国免疫学杂志

Objective:To study the effect of inflammatory factor and neurotransmitter of Yizhi Xingnao Fang combined with western medicine for patients with alzheimer's disease. Methods:124 cases alzheimer's patients from October 2014 to October 2016 were divided into observation group and control group,the control group given donepezil etc conventional western medicine therapy,ob-servation group given Yizhi Xingnao Fang combinde with western medicine therapy. 12 weeks after treatment,cerebrospinal fluid in-flammatory factors,neurotransmitter and clinical efficacy were compared between two groups. Results:Observation group effective rate 80.65% was significantly higher than control group 64.52% (X2= 4.052 9,P<0.05);cerebrospinal fluid TNF-α,IL-6 were significantly lower than control group,IL-4,IL-10 were significantly higher than control group (t=10.911,8.739,5.000,4.046,P<0.05,P<0.01);DA,5-HT,NE were significantly higher than control group(t=9.435,7.916,5.985,P<0.05,P<0.01). Conclusion:Yizhi Xingnao Fang combined with western medicine therapy help to improve the clinical symptoms and therapeutic effect,which may be related to the suppression of inflammatory symptoms,regulation of neurotransmitter expression level.

Analyzing the role of soil and rice cadmium pollution on human renal dysfunction by correlation and path analysis.

The aim of this study was to investigate the role of soil and rice pollution on human renal dysfunction. The participants were 97 inhabitants (46 men and 51 women) who are aged 50 to 60 years old and have been living in Xiaogan (Hubei, China) from birth. We collected samples of soil, rice, and urinary correspondingly. Urinary N-acetyl-ß-D-glucosaminidase (NAG) and ß-2-microglobulin (ß2MG) were used as indicators of renal dysfunction, and urinary cadmium (U-Cd) was used as indicator of total internal cadmium exposure. We made a hypothesis that soil cadmium concentration (S-Cd) and rice cadmium concentration (R-Cd) could be used as indicators of environmental cadmium exposure. Correlation and path analysis were used to estimate the relationships among the levels of rice cadmium (R-Cd), soil cadmium (S-Cd), urinary cadmium (U-Cd), and renal damage indicators (NAG and ß2MG). Our results showed that there was positive significant relationship between S-Cd (R-Cd, U-Cd), and U-NAG (U-ß2MG). The standard multiple regression describing the relationship between S-Cd (R-Cd, U-Cd) and U-NAG was Y1 = 1.26X1-6.53X2 + 9.32, where Y is U-NAG, X1 is U-Cd, X2 is S-Cd. The equation of U-ß2MG was Y = 49.32X1 + 3085.99X2 + 143.42, where Y is U-ß2MG, X1 is U-Cd, X2 is R-Cd. It is obvious that the effect of S-Cd and R-Cd on NAG or U-ß2MG cannot be ignored. Through our study, we can find that the effects of S-Cd on renal health even as significant as R-Cd. To protect people from the damage of cadmium pollution, it is vital to monitor the situation of soil and rice cadmium pollution.

Association between Polymorphisms of the AKT1 Gene Promoter and Risk of the Alzheimer's Disease in a Chinese Han Population with Type 2 Diabetes.

AIMS: Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with type 2 diabetes (T2D) where the v-akt murine thymoma viral oncogene homolog 1 (AKT1) plays an important role in the protein synthesis pathways and cell apoptosis processes. Evidence has been shown that AKT1 protein may be related to AD risk among patients with T2D. The aim of this study was to analyze the potential association between single nucleotide polymorphisms of AKT1 promoter and the risk of AD among patients with T2D. METHODS: The association between AKT1 polymorphisms and AD risk in patients with T2D was assessed among 574 consecutive unrelated subjects including 112 AD patients with T2D, 231 patients with AD, and 231 healthy controls in a case-control study. The cognitive function of all subjects was assessed using MMSE. Six single nucleotide polymorphisms with minor allele frequency >0.2 (rs2498786, rs74090038, rs2494750, rs2494751, rs5811155, and rs2494752) in AKT1 promoter were analyzed by polymerase chain reaction (PCR), and the concentration of AKT1 protein in serum was tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: Overall, there was statistically significant difference in AKT1 rs2498786 polymorphism. The CC frequency of AKT1 rs2498786 polymorphism in AD with T2D group and AD control group was significantly higher than that in healthy control group (PAD+T2D vs. health < 0.0001, PAD vs. health < 0.0001). However, the difference was not found between AD with T2D group and AD control group. Compared with healthy control group, the plasma levels of AKT1 protein in AD with T2D group (PAD+T2D vs. health < 0.0001) and AD control group (PAD vs. health = 0.0003) decreased significantly. Among genotypes of AKT1 rs2498786 polymorphism, the AKT1 protein level in GG genotype was significantly higher than that in GC genotype (PGG vs. GC < 0.0001) and CC genotype (PGG vs. CC < 0.0001). CONCLUSION: The study suggests that AKT1 rs2498786 polymorphism in insulin signaling pathway may be associated with AD risk and different genotypes may affects levels of protein expression. However, the polymorphism is not shown to be exclusive in AD patients with T2D.

Estimation of the benchmark dose of urinary cadmium as the reference level for renal dysfunction: a large sample study in five cadmium polluted areas in China.

BACKGROUND: Itai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey. METHODS: A total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary ß2-microglobulin (Uß2-MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10% additional risk above the background. RESULTS: There was a positive correlation between the UCd levels and the prevalence of Uß2-MG. The BMD of UCd for Uß2-MG was estimated for each province. The findings showed that the BMD levels were related to the participants' geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uß2-MG with an excess risk of 10% were 2.00 µg/g creatinine (µg/g cr) in males and 1.69 µg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 µg/g cr for Cd-related renal effects. CONCLUSIONS: The selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uß2-MG in males with BMRs at 10% were 2.00 µg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.