Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

OBJECTIVE: This study explored the job choice preferences of Center for Disease Prevention and Control (CDC) workers to provide CDC management information and recommendations for optimizing employee retention and motivation policies. METHODS: A discrete choice experiment was conducted in nine provinces across China. Seven key attributes were identified to analyze the job preferences of CDC workers. Mixed logit models, latent class models, and policy simulation tools were used. RESULTS: A valid sample of 5,944 cases was included in the analysis. All seven attributes significantly influenced the job choices of CDC workers. Heterogeneity analyses identified two main groups based on different levels of preference for attribute utility. Income-prioritizers were concerned with income and opportunities for career development, whereas bianzhi-prioritizers were concerned with bianzhi and welfare benefits. The policy simulation analysis revealed that income-prioritizers had a relatively higher sensitivity to multiple job preference incentives. CONCLUSION Income and bianzhi were the two key attributes influencing the job choices and retention preferences of CDC workers. Heterogeneity in job preferences was also identified. Based on the preference characteristics of different subgroups, policy content should be skewed to differentiate the importance of incentives.
China ; Humans ; Male ; Female ; Adult ; Centers for Disease Control and Prevention, U.S. ; Middle Aged ; Choice Behavior ; Career Choice ; Motivation

Objective To analyze the current status and influencing factors of occupational health literacy (OHL) among noise-exposed workers in the automotive manufacturing industry. Methods A total of 1 188 front-line workers in noise-exposed positions in the automotive manufacturing industry were selected by judgment sampling method. The OHL status of the workers was investigated using the Occupational Health Literacy Questionnaire of National Key Population, and the influencing factors of OHL were analyzed. Results The overall OHL level was 30.13% (358/1 188). The result of binary logistic regression analysis showed that marital status, educational level, personal monthly income, household registration, enterprise scale and weekly working hours were influencing factors of OHL level (all P<0.05). Specifically, being married, having a high school education or higher, monthly personal income >5 000 yuan, being from a non-agricultural household, working in a medium-sized enterprise, and working more than >40-48 hours per week were protective factors for high OHL levels (all P<0.05). Conclusion There is considerable room for improvement in the OHL of noise-exposed workers in the automotive manufacturing industry. Focus should be placed on workers who are unmarried, widowed, or divorced, have educational levels below high school, earn less than 5 000 yuan per month, have agricultural household registrations, work in small or micro-sized enterprises, or work ≤40 hours per week, with targeted strategies to improve their overall OHL level.

Objective:To discuss the anti-inflammatory and antioxidant effect of mesalazine(MSZ)in the RAW264.7 cell model,and to elucidate its therapeutic effect on periodontitis in the rats.Methods:The proliferation rates of RAW264.7 cells stimulated by different concentrations(0,62.5,125.0,250.0,500.0,1 000.0,and 2 000.0 mg·L-1)of MSZ were detected by CCK-8 method to determine the optimal concentration of MSZ for cell treatment.Porphyromonas gingivalis lipopolysaccharide(P.g-LPS)and MSZ were used to treat the RAW264.7 cells,and the cells were divided into control group,P.g-LPS group,and MSZ+P.g-LPS group.The levels of reactive oxygen species(ROS)in the cells in various groups were detected by the DCFH-DA fluorescent probe assay;the malondialdehyde(MDA)levels,glutathione(GSH)levels and superoxide dismutase(SOD)activities in the cells in various groups were detected by ELISA method;the expression levels of inflammatory factors interleukin-8(IL-8)and interleukin-1β(IL-1β)mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.The periodontitis rat model was established by the ligation method combined with the injection of P.g bacterial fluid.A total of 18 rats were randomly divided into control group(without treatment),model group(making period ontits model),and drug administration group(making periodontits model and given MSZ),and there were 6 rats in each group.Micro-CT was used to assess the alveolar bone destruction of the rats in various groups;HE staining was used to observe the morphology of periodontal tissue of the rats in various groups.Results:Compared with control group,the proliferation rate of the cells in 500.0 mg·L-1 MSZ group was significantly increased(P＜0.01),so 500.0 mg·L-1 MSZ was subsequently selected to treat the cells.Compared with control group,the levels of ROS and MDA in the cells in P.g-LPS group were significantly increased(P＜0.01),and the level of GSH and activity of SOD were significantly decreased(P＜0.01),and the expression levels of IL-1β and IL-8 mRNA were significantly increased(P＜0.01);compared with P.g-LPS group,the levels of ROS and MDA in the cells in MSZ+P.g-LPS group were significantly decreased(P＜0.01),the level of GSH and activity of SOD were significantly increased(P＜0.01),and the expression levels of IL-1β and IL-8 mRNA were significantly decreased(P＜0.01).The micro-CT assay results showed that compared with control group,the distance from the cemento-enamel junction to alveolar bone crest(CEJ-ABC)of the rats in model group was significantly increased(P＜0.01),and the bone volume fraction(BV/TV)was significantly decreaced(P＜0.05);compared with model group;the CEJ-ABC of the rats in drug administration group was decreased(P＜0.01),and the BV/TV was increased(P＜0.05).The HE staining results showed that the inflammatory cell infiltration in periodontal tissue of the rats in drug administration group was reduced,and epithelial attachment was restored.Conclusion:MSZ effectively inhibits the production of pro-inflammatory factors and peroxides in the P.g-LPS-induced RAW264.7 cells,improves the cellular anti-inflammatory and antioxidant capacity,inhibits the alveolar bone resorption,and alleviates the inflammation of periodontal tissues in the periodontitis rats.

Objective:To discuss the effects of superelastic nickel-titanium archwires(SENT)and heat-activated nickel-titanium archwires(HANT)on the initial alignment efficiency of mandibular anterior teeth and pain levels of the patients with extraction orthodontic treatment and non-extraction orthodontic treatment by using low-friction self-ligating brackets,and to provide the basis for the selection of the most suitable archwire in orthodontic clinical practice.Methods:Eighty patients underwent fixed orthodontic treatment with self-ligating brackets were randomly assigned to SENT or HANT subgroups,and there were 40 patients in extraction orthodontic treatment group and 40 patients in non-extraction orthodontic treatment group.A single operator fully engaged a 0.014-inch straight archwire into the brackets.The patients,operators,and data measurers were all blinded;the initial clinical alignment efficiency of the archwires of the patients in various groups was observed,and the Little's index was calculated;the visual analog scale(VAS)scores and pain perception of the patients in various groups were recorded 4 h after initial bonding of the appliances and every day before breakfast during the first week of orthodontic treatment;multivariate regression analysis was performed for the initial Little's index,gender,and age,and the influence factors of pain in the patients was analyzed.Results:There were no significant differences in age,gender,and initial Little's index among the patients in extraction group and non-extraction group(P＞0.05).Compared with before treatment,the Little's indexes of the patients in both HANT and SENT subgroups in non-extraction orthedontic treatment group were decreased 4 weeks after treatment,but the difference between groups was not significant(P＞0.05).Compared with SENT subgroup in non-extraction orthodontic treatment group,the Little's index of the patients in HANT subgroup was decreased(P＜0.05).In extraction orthodontic treatment group,there were no significant differences in Little's indexes of the patients between the HANT and SENT subgroups before and after treatment(P＞0.05).The pain perception peaked on the first day after initial bonding and gradually decreased to baseline levels.The patients in SENT and HANT subgroups in both extraction and non-extraction orthodontic treatment groups showed the similar patterns of pain change.There were no significant differences in the average VAS scores and maximum pain intensity scores between the patients in SENT and HANT subgroups at different time points(P＞0.05).The type of archwire had no significant effect on the degree of pain,while time significantly affected the degree of pain.The multivariate regression analysis results showed a significant correlation between initial Little's index and maximum VAS scores of the patients in extraction orthodontic treatment group(b=0.359,P=0.033).Gender and age did not affect the degree of pain of the patients in either group.Conclusion:When applying low-friction self-ligating brackets for orthodontic treatment,the initial alignment efficiency with 0.014-inch HANT archwires is superior to 0.014-inch SENT archwires in non-extraction treatment group,while both archwires show the same efficiency in extraction patients.SENT and HANT archwires do not affect the initial degrees of pain of the orthodontic patients.