BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

Objective: To explore human papillomavirus (HPV) and vaccination related knowledge and vaccination willingness of college students in Guizhou Province and their related factors, so as to provide a basis for formulating targeted intervention strategies. Methods: From May to June 2025, by applying convenience sampling method,4 567 college students were selected from 8 universities in Guizhou Province to conduct a questionnaire survey. Awareness of HPV and vaccination related knowledge, vaccination willingness as well as related factors among college students were also analyzed. The t test and Chi square test were used for comparison between groups, and multifactor Logistic regression was employed to analyze the related factors of HPV vaccination willingness among college students. Results: The HPV and vaccine knowledge score of college students in Guizhou Province was ( 10.50 ±2.09), and the score of girls (10.81±1.82) was higher than that of boys (10.19±2.30) ( t=10.09, P <0.01). The HPV vaccination willingness rate of college students was 65.6%, and the rate was higher in girls than in boys (67.1%,64.1%, χ 2=4.75, P <0.05). Multi factor Logistic regression analysis showed that ethnicity and HPV testing were related factors that affected college students willingness to vaccinate (minority: OR boy =1.23, OR girl =1.35; previous HPV testing: OR boy =0.56, OR girl =0.59); boys willingness to vaccinate was related to the number of sexual partners ( OR =0.60), family history of cancer ( OR =0.65), and sexual behavior related HPV knowledge scores ( OR =0.89), while girls willingness to vaccinate was related to bisexual sexual orientation ( OR =0.59), previous HIV testing ( OR =0.60), and HPV and vaccine basic knowledge scores ( OR =0.86) (all P <0.05). Conclusions College students in Guizhou Province have higher HPV vaccine related knowledge scores and are more willing to vaccinate, and those above are higher in girls than in boys. Health education content should be optimized based on gender differences, and promote the willingness and behavior of HPV vaccination among college students.

Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

BACKGROUND:In the preparation of injectable extracellular matrix materials,most of the materials require pepsin digestion followed by combination with other matrix components like hydrogels for pulp tissue regeneration,which also means the destruction of the microenvironment retained by natural extracellular matrix materials.OBJECTIVE:To investigate the effect of injectable dental pulp extracellular matrix prepared by grinding treatment on the regeneration of dental pulp tissue.METHODS:(1)The dental pulp tissue from pig teeth was prepared into acellular dental pulp matrix materials after acellular treatment.After freezing in liquid nitrogen and high-speed grinding,the injectable dental pulp extracellular matrix was prepared.Then,the differences in cell adhesion efficiency and microstructure between the injectable dental pulp extracellular matrix and natural dental pulp extracellular matrix were compared.Immunohistochemical analysis was used to analyze extracellular matrix protein components in injectable dental pulp extracellular matrix.(2)Injectable dental pulp extracellular matrix material inoculated with dental pulp stem cells was injected into the dental pulp cavity constructed from the dentin matrix material.The samples were obtained after 1,3,and 5 weeks of subcutaneous implantation in nude mice to observe the in vivo conversion rate of injectable dental pulp extracellular matrix materials and the regeneration ability of ectopic dental pulp tissue under the skin of nude mice.RESULTS AND CONCLUSION:(1)Compared with the dental pulp extracellular matrix,the injectable dental pulp extracellular matrix significantly improved the cell adhesion rate and retained the porous collagen structure similar to that of natural dental pulp extracellular matrix.(2)Compared with the natural dental pulp extracellular matrix,immunohistochemical staining showed that there was no significant difference in the expression of fibronectin,collagen type Ⅰ,and integrin β1 in the injectable dental pulp extracellular matrix,while the expression of fibronectin was significantly decreased.(3)In vivo experiments show that the injectable dental pulp extracellular matrix has excellent angiogenesis ability and promotes the formation of pulp-like tissues.The results exhibit that the milled injectable dental pulp extracellular matrix can still be used as an effective scaffold for the regeneration of dental pulp.

Objective Aimed at investigating the effect and molecular mechanism of artemisinin on hemo-dynamics and vascular remodeling in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)rats.Methods 30 male SD rats were randomly divided into 3 groups(n=10):control group,MCT-induced PAH group(MCT group,60 mg/kg)and artemisinin intervention group(50 mg/kg).At 28 days after modeling,the right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),heart rate and right ventricular hypertrophy index(RVHI)were measured to evaluate the development of PAH.HE staining and α-SMA immuno-histochemistry were used to observe the morphology and assess muscularization of pulmonary arterioles,and the percentage of medial wall thickness(WT%),the percentage of vascular wall area(WA%)and the proportion of muscular vessels were calculated to evaluate the degree of pulmonary vascular remodeling.The mRNA and protein levels of HIF-1α and LDHA were detected by real-time PCR and Western blot,respectively.Pyruvate and lactate concentration in lung tissue was measured using pyruvate and lactateassay kit.Results Compared with the control group,the RVSP,mPAP,heart rate and RVHI were significantly increased in MCT-induced PAH rats(all P<0.05).Histological analysis showed that the increasedmedial wall thickness of small pulmonary arteries and vascular muscularization were observed in MCT-treated rats compared with control rats.WT%,WA%and muscularization degrees of pulmonary arterioles were higher in MCT-treated rats than those in the control group(all P<0.05),suggesting successful construction of PAH model.Compared with the MCT group,the RVSP,mPAP,heart rate and RVHI decreased in the rats treated with artemisinin(all P<0.05),accompanied with lower WT%and WA%(P<0.05),and muscularization of pulmonary arterioles was improved(P<0.05).Further study showed the mRNA and protein levels ofHIF-1α and LDHA in lung tissue of MCT-induced PAH rats were higher than those in the control group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were higher than that in the control group(all P<0.05).However,the mRNA and protein levels of HIF-1α and LDHA in lung tissue of rats treated with artemisinin were lower than those in the MCT group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were lower than that in the MCT group(all P<0.05).Conclusion Artemisinin improves hemodynamic and pulmonary vascular remodeling in PAH rats through inhibiting HIF-1α/LDHA signaling pathway-mediated glycolysis.

BACKGROUND:In the preparation of injectable extracellular matrix materials,most of the materials require pepsin digestion followed by combination with other matrix components like hydrogels for pulp tissue regeneration,which also means the destruction of the microenvironment retained by natural extracellular matrix materials.OBJECTIVE:To investigate the effect of injectable dental pulp extracellular matrix prepared by grinding treatment on the regeneration of dental pulp tissue.METHODS:(1)The dental pulp tissue from pig teeth was prepared into acellular dental pulp matrix materials after acellular treatment.After freezing in liquid nitrogen and high-speed grinding,the injectable dental pulp extracellular matrix was prepared.Then,the differences in cell adhesion efficiency and microstructure between the injectable dental pulp extracellular matrix and natural dental pulp extracellular matrix were compared.Immunohistochemical analysis was used to analyze extracellular matrix protein components in injectable dental pulp extracellular matrix.(2)Injectable dental pulp extracellular matrix material inoculated with dental pulp stem cells was injected into the dental pulp cavity constructed from the dentin matrix material.The samples were obtained after 1,3,and 5 weeks of subcutaneous implantation in nude mice to observe the in vivo conversion rate of injectable dental pulp extracellular matrix materials and the regeneration ability of ectopic dental pulp tissue under the skin of nude mice.RESULTS AND CONCLUSION:(1)Compared with the dental pulp extracellular matrix,the injectable dental pulp extracellular matrix significantly improved the cell adhesion rate and retained the porous collagen structure similar to that of natural dental pulp extracellular matrix.(2)Compared with the natural dental pulp extracellular matrix,immunohistochemical staining showed that there was no significant difference in the expression of fibronectin,collagen type Ⅰ,and integrin β1 in the injectable dental pulp extracellular matrix,while the expression of fibronectin was significantly decreased.(3)In vivo experiments show that the injectable dental pulp extracellular matrix has excellent angiogenesis ability and promotes the formation of pulp-like tissues.The results exhibit that the milled injectable dental pulp extracellular matrix can still be used as an effective scaffold for the regeneration of dental pulp.

Objective Aimed at investigating the effect and molecular mechanism of artemisinin on hemo-dynamics and vascular remodeling in monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH)rats.Methods 30 male SD rats were randomly divided into 3 groups(n=10):control group,MCT-induced PAH group(MCT group,60 mg/kg)and artemisinin intervention group(50 mg/kg).At 28 days after modeling,the right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),heart rate and right ventricular hypertrophy index(RVHI)were measured to evaluate the development of PAH.HE staining and α-SMA immuno-histochemistry were used to observe the morphology and assess muscularization of pulmonary arterioles,and the percentage of medial wall thickness(WT%),the percentage of vascular wall area(WA%)and the proportion of muscular vessels were calculated to evaluate the degree of pulmonary vascular remodeling.The mRNA and protein levels of HIF-1α and LDHA were detected by real-time PCR and Western blot,respectively.Pyruvate and lactate concentration in lung tissue was measured using pyruvate and lactateassay kit.Results Compared with the control group,the RVSP,mPAP,heart rate and RVHI were significantly increased in MCT-induced PAH rats(all P<0.05).Histological analysis showed that the increasedmedial wall thickness of small pulmonary arteries and vascular muscularization were observed in MCT-treated rats compared with control rats.WT%,WA%and muscularization degrees of pulmonary arterioles were higher in MCT-treated rats than those in the control group(all P<0.05),suggesting successful construction of PAH model.Compared with the MCT group,the RVSP,mPAP,heart rate and RVHI decreased in the rats treated with artemisinin(all P<0.05),accompanied with lower WT%and WA%(P<0.05),and muscularization of pulmonary arterioles was improved(P<0.05).Further study showed the mRNA and protein levels ofHIF-1α and LDHA in lung tissue of MCT-induced PAH rats were higher than those in the control group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were higher than that in the control group(all P<0.05).However,the mRNA and protein levels of HIF-1α and LDHA in lung tissue of rats treated with artemisinin were lower than those in the MCT group,the content of lactate and pyruvate and the ratio of lactate to pyruvate were lower than that in the MCT group(all P<0.05).Conclusion Artemisinin improves hemodynamic and pulmonary vascular remodeling in PAH rats through inhibiting HIF-1α/LDHA signaling pathway-mediated glycolysis.

Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.

Objective To compare the anesthetic effect of different doses of esketamine combined with propofol in elderly patients underwent endoscopic retrograde cholangiopancreatography(ERCP),and explore the appropriate dose.Methods 105 elderly patients were selected for ERCP.The patients were divided into 3 groups with 35 cases in each group by random number table method.E1 group,E2 group and E3 group were given esketamine 0.15,0.35 and 0.50 mg/kg,respectively,and were given propofol 1.00 mg/kg intravenous injection 15 s later.Heart rate(HR),mean arterial pressure(MAP),and percutaneous arterial oxygen saturation(SpO2)were recorded after left lateral position(T0),at successful induction(T1),endoscope through larynx(T2),sphincter insertion or incision(T3),and at recovery(T4).Operation duration,intraoperative propofol dosage,anesthesia recovery time,visual analogue scale(VAS)score 15 min after anesthesia recovery and occurrence of adverse reactions were recorded.Results Compared with T0,HR and MAP decreased at T1,T2,T3 and T4 time point in E1 group,HR and MAP increased at T1,T2,T3 and T4 time point in E3 group,the differences were statistically significant(P<0.05);HR and MAP had no significant changes at T1,T2,T3 and T4 time point in E2 group(P>0.05);Compared with group E3,HR and MAP decreased at T1,T2,T3 and T4 time point in E1 group and E2 group,and E1 group was lower than E2 group,the differences were statistically significant(P<0.05);There were no significant difference in SpO2 at different time points between the three groups(P>0.05);Compared with E1 group,the dosage of propofol in E2 group and E3 group was decreased,and E3 group was significantly less than E2 group,with statistical significance(P<0.05).Compared with E3 group,the recovery time of E1 group and E2 group was shorter,and E2 group was shorter than E1 group,the differences were statistically significant(P<0.05).Compared with E1 group,pain VAS score 15 min after recovery in E2 group and E3 group was lower,and E3 group was lower than E2 group,the differences were statistically significant(P<0.05).There was no significant difference in operation time among 3 groups(P>0.05).The incidence of hypoxemia,respiratory depression and hypotension in E1 group were higher than that in E2 group and E3 group,the difference was statistically significant(P<0.05).The incidence of psychomimetic symptoms and visual disturbance in E3 group was higher than that in E1 group and E2 group,the difference was statistically significant(P<0.05).There were no significant differences in the incidence of dizziness and nausea vomiting among the 3 groups(P>0.05).Conclusion 0.35 mg/kg esketamine combined with propofol in the operation of ERCP in elderly patients,respiratory circulation is more stable,and adverse reactions do not increase.

Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.