BACKGROUND: Tissue engineering is increasingly viewed as a promising avenue for functional cartilage reconstruction.However, chondrocyte dedifferentiation during in vitro culture remains an obstacle for clinical translation of tissue engineered cartilage. Re-differentiated induction have been employed to induce dedifferentiated chondrocytes back to their original phenotype. Regrettably, these strategies have been proven to be only moderately effective. METHODS: To explore underlying mechanism, RNA transcriptome sequencing was conducted on primary chondrocytes (P0), dedifferentiated chondrocytes (P5), and redifferentiated chondrocytes (redifferentiation-induction of P5, P5.R). Based on multiple bioinformatics analysis, LGR5 was identified as a target gene. Subsequently, stable cell lines with LGR5 knocking-down and overexpression were established using P0 chondrocytes. The phenotypic changes in P1 and P5 chondrocytes with either LGR5 knockdown or overexpression were assessed to ascertain the potential influence of LGR5 dysregulation on chondrocyte phenotypes. Regulatory mechanism was then investigated using bioinformatic analysis, protein–protein docking, immunofluorescence co-localization and immunoprecipitation. RESULTS: The current study found that dysregulation of LGR5 can significantly impact the dedifferentiated phenotypes of chondrocytes (P5). Upregulation of LGR5 appears to activate the PI3K/AKT signal via increasing the phosphorylation levels of AKT (p-AKT1). Moreover, the increase of p-AKT1 may stabilize b-catenin and enhance the intensity of Wnt/b-catenin signal, and help to restore the dedifferentated phenotype of chondrocytes. CONCLUSION LGR5 can modulate the phenotypes of chondrocytes in P5 passage through PI3K/AKT signaling pathway.

Objective To analyze the related factors of esophageal squamous cell carcinoma and precancerous lesions among residents aged 40-69 years old in rural areas of Shandong Province. Methods In October 2018, 300 villages in 13 counties of the Shandong upper gastrointestinal cancerearly diagnosis and treatment projectin 2017 were selected as research areas, and 30 400 residents aged 40-69 were recruited in this study. The demographic characteristics, health status and lifestyle information were collected through the questionnaire survey, and endoscope iodine staining and indicative biopsy methods were used for cancer screening among eligible people.The multivariate logistic regression model was used to analyze the risk factors for esophageal cancer and precancerous lesions. Results The subjects in this study were (56.42±7.24) years old, including 13 193 males (43.40%).There were 936 cases of esophageal cancer and precancerous lesions (3.08%), including 521 males and 415 females.Compared with women, 40-49 years old, high level education, drinking tap water, regular intake of meat, eggs and milk, and family average annual income more than 30 000 RMB, men (OR=1.90, 95%CI : 1.65-2.19), 60-69 years old (OR=5.28, 95%CI : 4.11-7.30), primary school education or below ( OR=1.50, 95%CI : 1.20-1.89), drinking groundwater (OR=1.71, 95%CI: 1.38-2.13), never eating meat, eggs and milk (OR=1.48, 95%CI: 1.22-1.80), and family average annual income less than 30 000 RMB ( OR=1.41, 95%CI : 1.16-1.70) would increase the risk of esophageal cancer and precancerous lesions. Conclusion The gender, age, educational level, annual household income, drinking water source, the frequency of eating meat, egg and milk were related to the occurrence of esophageal cancer and precancerous lesions among 40-69 years old residents in rural areas of Shandong Province.

Objective:To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults.Methods:In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T 3), and thyroxine (T 4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results:Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M ( Q 1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M ( Q 1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M ( Q 1, Q3) for TSH, T 3, and T 4 was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95% CI:-15.17%, -4.36%) and 11.14% (95% CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion:Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

Objective To analyze the related factors of esophageal squamous cell carcinoma and precancerous lesions among residents aged 40-69 years old in rural areas of Shandong Province. Methods In October 2018, 300 villages in 13 counties of the Shandong upper gastrointestinal cancerearly diagnosis and treatment projectin 2017 were selected as research areas, and 30 400 residents aged 40-69 were recruited in this study. The demographic characteristics, health status and lifestyle information were collected through the questionnaire survey, and endoscope iodine staining and indicative biopsy methods were used for cancer screening among eligible people.The multivariate logistic regression model was used to analyze the risk factors for esophageal cancer and precancerous lesions. Results The subjects in this study were (56.42±7.24) years old, including 13 193 males (43.40%).There were 936 cases of esophageal cancer and precancerous lesions (3.08%), including 521 males and 415 females.Compared with women, 40-49 years old, high level education, drinking tap water, regular intake of meat, eggs and milk, and family average annual income more than 30 000 RMB, men (OR=1.90, 95%CI : 1.65-2.19), 60-69 years old (OR=5.28, 95%CI : 4.11-7.30), primary school education or below ( OR=1.50, 95%CI : 1.20-1.89), drinking groundwater (OR=1.71, 95%CI: 1.38-2.13), never eating meat, eggs and milk (OR=1.48, 95%CI: 1.22-1.80), and family average annual income less than 30 000 RMB ( OR=1.41, 95%CI : 1.16-1.70) would increase the risk of esophageal cancer and precancerous lesions. Conclusion The gender, age, educational level, annual household income, drinking water source, the frequency of eating meat, egg and milk were related to the occurrence of esophageal cancer and precancerous lesions among 40-69 years old residents in rural areas of Shandong Province.

Objective:To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults.Methods:In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T 3), and thyroxine (T 4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results:Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M ( Q 1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M ( Q 1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M ( Q 1, Q3) for TSH, T 3, and T 4 was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95% CI:-15.17%, -4.36%) and 11.14% (95% CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion:Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

Objective:To investigate the alterations of cholinergic and monoamine neurotransmitters in cerebrospinal fluid in patients with postoperative delirium.Methods:Sixty-eight patients with normal preoperative cognitive functions were enrolled.They were diagnosed with spinal extramedullary intradural space-occupying lesion and underwent surgical resection.Among these patients, 18 developed postoperative delirium (delirium group), 46 had no postoperative delirium (control group), and the diagnosis of delirium was unclear in four cases (excluded). Cerebrospinal fluid (CSF) was collected before the surgical resection of lesions and on the third day postoperatively.The concentrations of acetylcholine (Ach), norepinephrine (NE), adrenaline (E), dopamine (DA) and serotonin (5-HT) were measured using the high-performance liquid chromatography/electrochemical method.Results:Prior to the surgical resection, there were no significant differences in the Ach, NE, E, DA or 5-HT baseline levels in the CSF between the delirium group and the control group (all P>0.05). After surgery, the Ach level in the delirium group ((0.63±0.26) μmol/L) was significantly lower than that in the control group ((0.77±0.19) μmol/L) ( P=0.032), and there were no significant differences in other neurotransmitter levels (all P>0.05). In the delirium group, the level of Ach in the CSF after surgery ((0.63±0.26) μmol/L) was significantly lower than the baseline level ((0.75±0.19) μmol/L) ( P=0.021). The postoperative NE level ((1.58±0.28) μmol/L) was significantly higher than the baseline level ((1.49±0.21) μmol/L) ( P=0.036). There was no significant difference in the adrenaline level ( P=0.497). The postoperative DA level ((0.86±0.18) μmol/L) was significantly higher than the baseline level ((0.82±0.15) μmol/L) ( P=0.045), and the postoperative 5-HT level ((2.94±0.28) μmol/L) was also significantly higher than the baseline level ((2.75±0.35) μmol/L) ( P=0.022). In the control group, only the postoperative 5-HT level ((2.90±0.31) μmol/L) was significantly higher than the baseline level ((2.76±0.26) μmol/L) ( P=0.016), while the postoperative levels of other neurotransmitters were not significantly changed when compared to the baseline levels (all P>0.05). Conclusion:The cholinergic neurotransmitter levels were reduced while the monoamine neurotransmitter levels were increased in the cerebrospinal fluid in patients with postoperative delirium, which suggests that cholinergic hypoactivity and monoaminergic hyperexcitability may be important pathophysiological processes in the occurrence and development of postoperative delirium.

Objective: To analyze the related factors of esophageal squamous cell carcinoma and precancerous lesions among residents aged 40-69 years old in rural areas of Shandong Province. Methods: In October 2018, 300 villages in 13 counties of the Shandong upper gastrointestinal cancerearly diagnosis and treatment projectin 2017 were selected as research areas, and 30 400 residents aged 40-69 were recruited in this study. The demographic characteristics, health status and lifestyle information were collected through the questionnaire survey, and endoscope iodine staining and indicative biopsy methods were used for cancer screening among eligible people.The multivariate logistic regression model was used to analyze the risk factors for esophageal cancer and precancerous lesions. Results: The subjects in this study were (56.42±7.24) years old, including 13 193 males (43.40%).There were 936 cases of esophageal cancer and precancerous lesions (3.08%), including 521 males and 415 females.Compared with women, 40-49 years old, high level education, drinking tap water, regular intake of meat, eggs and milk, and family average annual income more than 30 000 RMB, men (OR=1.90, 95%CI: 1.65-2.19), 60-69 years old (OR=5.28, 95%CI: 4.11-7.30), primary school education or below (OR=1.50, 95%CI: 1.20-1.89), drinking groundwater (OR=1.71, 95%CI: 1.38-2.13), never eating meat, eggs and milk (OR=1.48, 95%CI: 1.22-1.80), and family average annual income less than 30 000 RMB (OR=1.41, 95%CI: 1.16-1.70) would increase the risk of esophageal cancer and precancerous lesions. Conclusion The gender, age, educational level, annual household income, drinking water source, the frequency of eating meat, egg and milk were related to the occurrence of esophageal cancer and precancerous lesions among 40-69 years old residents in rural areas of Shandong Province.