Objective:To learn about the monitoring indicators and patient management in coal-burning-borne endemic arsenic poisoning areas in Shaanxi Province, and provide a basis for consolidating and improving the prevention and control achievements.Methods:From March to December 2023, in accordance with the requirements of the "Notice of the Office of Shaanxi Provincial Health Commission on Issuing of the Monitoring Plan for Key Endemic Diseases Such as Kashin-Beck Disease" and "The Monitoring Plan for Endemic Fluorosis and Arsenic Poisoning in Shaanxi Province", a basic situation investigation was conducted in the affected villages of all counties (districts) with coal-burning-borne endemic arsenic poisoning in Shaanxi Province, and on-site visits were conducted to check the management of high arsenic coal mines. Using the simple random sampling method, 30 families in each village were selected to investigate the use of stoves and the formation of health-related behaviors. A survey on arsenic poisoning was carried out among all populations in the affected villages. According to the requirements of the provincial monitoring program, 720 people were randomly selected from 12 affected villages in 3 monitoring counties to measure their urinary arsenic level. The determination was based on the "Guidelines for the Safety of Urinary Arsenic in Population" (WS/T 665-2019). The evaluation for elimination of disease areas was carried out in accordance with the "National Health Commission Issued the Evaluation Approach for Control and Elimination of Priority Endemic Diseases (2019 edition)".Results:A total of 2 cities, 8 counties (districts), 99 townships, and 1 414 affected villages were monitored. All 53 high arsenic coal mines had stopped mining. The rate of qualified improved stoves was 99.97%; the correct utilization rate of qualified improved stoves, and the correct drying rate of corn and chili peppers provided for human consumption in the affected villages were 100.00%. A total of 2 064 138 people were examined, and 2 682 cases of arsenic poisoning were detected, all of whom were historical patients. There were no new cases of arsenic poisoning or skin cancer. There were currently 2 682 arsenic poisoning patients who had received family doctor contract services and implemented follow-up management. The geometric mean of urinary arsenic was 0.016 7 mg/L, which was lower than the safety guideline value for human urinary arsenic (0.032 mg/L).Conclusions:The monitoring indicators in the coal-burning-borne endemic arsenic poisoning areas in Shaanxi Province have reached the elimination standards. In the future, we should continue to strengthen the management of high arsenic coal mines, implement comprehensive prevention and control measures mainly focused on furnace and stove renovation and health promotion, and do a good job in patient management to continuously consolidate and improve the prevention and control achievements.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

OBJECTIVES: Excessive production of AGEs in diabetic patients will affect the normal function of osteoblasts, and this process may be related to autophagy of osteoblasts. This study aims to explore the effect of advanced glycation end products (AGEs) on autophagic activity during osteogenic differentiation in rat bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated and cultured in vitro, treated with different concentrations (0, 50, 100, 200, and 400 mg/L) of AGEs for different time (3, 6, 12, 24, 48, and 72 h). The proliferation activity was detected by CCK-8 method. The mRNA and protein expression levels of Beclin1 and LC3 in cells were detected by real-time PCR and Western blotting, respectively.The autophagic vacuoles were observed under the transmission electron microscope. The cells were treated with autophagy promoter rapamycin or autophagy inhibitor 3MA. After 7 days of osteogenic induction, we performed alkaline phosphatase (ALP) staining and real-time PCR to detect the mRNA expression levels of osteogenesis-related genes. RESULTS: In the low-concentration groups, the proliferation activity in BMSCs was increased ( CONCLUSIONS Low concentration of AGEs can enhance the proliferative activity of BMSCs and promote osteogenic differentiation by accelerating autophagy. High concentration of AGEs can suppress the proliferation of BMSCs and inhibit osteogenic differentiation by reducing autophagy.
Animals ; Autophagy ; Bone Marrow Cells ; Cell Differentiation ; Cells, Cultured ; Glycation End Products, Advanced/pharmacology* ; Humans ; Osteoblasts ; Osteogenesis ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the effect of advanced glycation end products (AGEs) on osteoclasts at different stages of differentiation. METHODS: Raw264.7 cells cultured were induced for osteoclastogenesis using RANKL, and the stages of differentiation of the osteoclasts were determined with TRAP staining. The cells were then randomly divided into control group, early-stage AGEs intervention group and late-stage AGEs intervention group. The viability of the cells after AGEs treatment was assessed using CCK-8 method. The cells were examined after the induction for osteoclastogenesis using TRAP staining, and the expression levels of RANK, NFATC-1, TRAF-6, TRAP and CTSK mRNAs were tested with RT-PCR; the expressions of CTSK and RANK proteins were detected using Western boltting. RESULTS: We defined the initial 3 days of induction as the early stage of differentiation and the time beyond 3 days as the late stage of differentiation of Raw264.7 cells. Intervention with AGEs at 100 mg/L produced no significant effects on the viability of the cells, but AGEs suppressed the cell proliferation at a concentration exceeding 100 mg/L. The number of osteolasts in the early- and late-stage intervention groups was greater than that in the control group, but the cell count differed significantly only between the early-stage intervention group and control group ( < 0.05). The gene expressions of RANK, NFATC-1, TRAF-6, TRAP and CTSK all increased after the application of AGEs in both the early and late stages of differentiation, but the changes were significant only in the early-stage intervention group ( < 0.05). The changes in CTSK and RANK protein expressions were consistent with their mRNA expressions. CONCLUSIONS AGEs can affect the differentiation of osteoclasts differently when applied at different stages, and intervention with AGEs at the early stage produces stronger effect to promote osteoclast differentiation than its application at a late stage.
Animals ; Bone Resorption ; Cell Differentiation ; Mice ; Osteoclasts ; RANK Ligand ; RAW 264.7 Cells ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVES: To explore the difference in odontoblast differentiation capacity between stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs), and to examine the expression level of ephrinB1 in odontoblast differentiation of these stem cells. METHODS: The stems cells were divided into a SHED group and a DPSCs group. After odontoblast differentiation induction, the above 2 groups were also randomly divided into a 3 d group and a 7 d group, respectively.The calcium deposition was detected by alkaline phosphatase (ALP) staining and alizarin red staining.The mRNA and protein expressions of ephrinB1, dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) were detected by real-time PCR and Western blotting. RESULTS: ALP staining and alizarin red staining showed that there was stronger mineralization capacity in the SHED group than that in the DPSCs group. The relative mRNA and protein expressions of DMP-1, DSPP, and ephrinB1 in the SHED group were higher than those in the DPSCs group except for the protein expression of DMP-1 in the SHED 3 d group (all <0.05). CONCLUSIONS SHED has stronger odontoblast differentiation capacity than DPSCs. In addition, ephrinB1 may be involved in the processes of odontoblast differentiation in the SHED and DPSCs.
Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Dental Pulp ; Humans ; Odontoblasts ; Osteogenesis ; Stem Cells ; Tooth, Deciduous

Objective:To understand the molecular characteristics and correlation among isolated strains of Brucella melitensis (BM) so as to improve the strategies on prevention and control of the disease in Jiangxi province. Methods:A total of 25 strains of BM isolated from human in 17 counties of Jiangxi province were analyzed by multiple locus variable-number tandem repeat analysis (MLVA) method.Results:A total of 25 strains of BM were classified into 24 independent genotypes with similarities between 67.00% and 100.00% and Simpson index between 0.000 and 0.773. There were 3 genotypes in MLVA8, including 60.00% (15/25) as 42 genotype, 32.00% (8/25) as 43 genotype, and 8.00% (2/25) as 63 genotype, respectively. There were 7 genotypes in MLVA11 identified, with 116 genotype and 125 genotype the main genotypes, accounting for 56.00% (14/25) of all the identified strains.Conclusions:Genes from all the 25 strains of BM that isolated from human being were with high genetic diversities, and various, genotypes. However, no obvious epidemiological correlation was noticed among these strains, indicating the complexity of the source of infection on Brucella in Jiangxi province.

Objective: To investigate the effects and mechanism of Holothurian Glycosaminoglycan (hGAG) alone in combination with cisplatin (DDP) on apoptosis of pulmonary adenocarcinoma cell A549. Methods: A549 cells were separately treated with blank, hGAG, DDP and hGAG combined with DDP (hGAG + DDP). The cell morphology in 4 groups was observed using light microscope. CCK8 assay was used to determine the cell viability. Flow cytometry by Hoechst 33258 and AnnexinV-FITC/PI staining was applied to detect cell apoptosis. Western blot was then used to detect the protein expression of Bax, Bcl-2, survivin and caspase-3. Results: After treatment for 24 h, the inhibitory rates of A549 cells in control, hGAG, DDP and hGAG + DDP groups were 0, (19.74±5.39)%, (42.01±2.57)% and (53.89±4.58)%, respectively. Moreover, after treatment for 48 h and 72 h, the inhibitory rates in each group were 0, (23.17±4.78)% and (29.17±4.21 )%, (54.00±7.64)% and (59.35±7.31)%, as well as (77.58±4.26)% and (79.94±4.58)%, respectively. The cell viability was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Hochest 33258 staining showed that no obvious apoptotic cells were detected in the control group, while apoptotic cells were visible in hGAG, cisplatin and combination groups. Flow cytometry showed that cell apoptotic rates were (2.38±0.59)%, (12.59±4.22)%, (16.36±3.63)% and (44.60±5.45)% in the control, hGAG, DDP and hGAG + DDP groups, respectively. The cell apoptosis was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Furthermore, western blot results showed that the expression of Bax and caspase-3 protein was increased (P<0.05), whereas Bcl-2 and survivin was decreased (P<0.05) in the hGAG+ DDP group compared with cisplatin alone (P<0.05). Conclusions HGAG can inhibit the proliferation and promote the apoptosis of human lung adenocarcinoma A549 cells. Meanwhile, it can strengthen the chemosensitivity of A549 cells to DDP via up-regulation of Bax, caspase-3 and down-regulation of Bcl-2 and survivin.

BACKGROUND: The clinical features of patients with common single-mutation of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) has been well characterized. There is a high adenocarcinoma incidence rate among female patients with none or shorter smoking history. Those patients have higher objective response rate (ORR) and progression free survival (PFS) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, it is still unclear that the clinical features of patients with EGFR double mutation and the sensitivity towards EGFR-TKIs treatment. METHODS: We performed a retrospective cohort study of 1,238 primary NSCLC patients who had EGFR gene testing in Affiliated Hospital of Qingdao University from January 1, 2015 to December 31, 2016 and identified 603 patients with single mutation and 59 patients with double mutation. All genes were uniformly detected by using ARMS-PCR technology. We analyze the gene of 32 double-mutant patients with specific genotyping, and randomly selected 60 patients with single mutation and compared the clinical features with 59 patients with double mutation. Furthermore, we examined the efficacy of EGFR-TKIs treatment in lung cancer patients with double mutation and single mutation in EGFR. RESULTS: The rare single mutation gene is the most common in patients with double mutation of EGFR. There is no significant statistical difference in gender, smoking history, age, pathological type or tumor-node-metastasis (TNM) staging among patients with single and double EGFR mutantion. In the double mutation patients treated with EGFR-TKIs, the objective response rate was 36.80%, the disease control rate was 68.40%. The objective response rate was 60.00% and the disease control rate was 90.00% in the patients with single mutation. However, overall PFS was significantly higher in EGFR single mutation patients (P=0.003), with median PFS of 12.0 months compared with 6.0 months in EGFR double mutation patients. CONCLUSIONS There was no significant difference between the clinical features of patients with EGFR double mutation and single mutation. Patients with EGFR double mutation is associated with poor survival underwent the first generation of EGFR-TKIs treatment compared with patients with a single mutation.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Exons ; genetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Retrospective Studies ; Treatment Outcome

Objective To evaluate the effect of self-management program in patients with rheumatoid arthritis(RA).Methods Self-management of RA patients was performed using a chronic disease self-management program (CDSMP).The health status,overall function,disease activity index,joint swelling and tenderness,joint pain score were analyzed at 12 and 24 weeks.Results At 12 and 24 weeks,health status,overall function,disease activity index,joint swelling and tenderness,joint pain score showed significant differences in two groups.Conclusion Self-management program may reduce complications,restore joint functions and improve social interactions,and improve quality of life.