Objective: To assess the causal association between specific oral microbiota and the risk of oral leukoplakia (OLK) using a Mendelian randomization (MR) approach, and to elucidate the potential mediating role of immune cells. Methods: Summary statistics from genome-wide association studies (GWAS) of the oral microbiome, GWAS data for immune cell phenotypes, and GWAS summary statistics for OLK from FinnGen were used. The inverse variance weighted (IVW) method was adopted as the primary approach, and it was supplemented by MR Egger regression, simple mode, weighted median, and weighted mode methods for additional analyses, to investigate the causal relationship between 3 117 types of tongue coating and salivary microbiota, as well as 731 immune cell traits, and OLK. Furthermore, a two-step MR approach was applied to explore the potential mediating role of immune cells in the association between oral microbiota and OLK. Results: IVW analysis revealed causal associations between 15 oral microbial genera and OLK. Among these, Streptococcus, Neisseria, and Catonella were associated with a reduced risk of OLK, with Fusobacterium showing the most significant protective effect (OR = 0.41, P = 0.023). In contrast, genera, including Microbacterium, Campylobacter, and Haemophilus_A, were linked to an increased risk of OLK, with Lancefieldella exhibiting the strongest risk effect (OR = 2.66, P = 0.006). Eleven immune cell phenotypes with potential causal associations with OLK were identified, including four protective and seven risk-increasing factors. Mediation analysis further identified four key mediating pathways: pathogenic genera, particularly Campylobacter_A and Lancefieldella, may promote the development and progression of OLK by upregulating highly activated pro-inflammatory immune subsets such as activated monocytes, B cells, and myeloid cells. Conversely, the potentially protective genus Catonella appeared to exert inhibitory effects on OLK by significantly downregulating dendritic cell subsets. Conclusion This study is the first to reveal, at the genetic level, causal pathways through which specific oral microbial genera influence the risk of OLK by mediating immune cell responses. These findings provide novel insights into the immunopathological mechanisms underlying OLK and offer potential targets for intervention strategies aimed at modulating specific microbial genera or immune cell subsets.

To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

Background Diesel engines are widely used in transportation, agriculture, construction, industry, and other fields. Diesel exhaust, classified as a Group 1 carcinogen, emits particles (DEP) that can penetrate deep into the respiratory tract, posing significant health risks. DEP pollution is particularly severe in confined environments, necessitating effective control measures. Objective Under laboratory simulation conditions, to explore the spatiotemporal distribution characteristics of the mass and number concentrations of DEP as it diffuses indoors and to reveal the effects of ventilation and additional airflow on indoor DEP pollution levels. Methods A diesel engine was placed in a laboratory (length 3.39 m × width 2.85 m × height 2.4 m) with its exhaust emitted from east to west. An air purifier was installed 1 m south of the engine. Eight measurement points (1 m horizontal distance from the exhaust outlet, height: 1 m/1.5 m) were setup to monitor DEP concentrations using portable laser particle sizers. The effects of engine power (4.05 kW vs. 5.15 kW), ventilation (maximum airflow: 600 m³·h⁻¹), additional airflow intensity (low and high), and direction (forward/reverse) on DEP pollution were analyzed. DEP levels of 5 diesel vehicle models were also compared. Results The mass and number concentrations of DEP indoors increased immediately after the diesel engine started. The peak mass concentration time at the eastern measurement point (−1, 0) m opposite to the exhaust direction (17.70 min) was significantly longer than that at the western (1, 0) m (16.20 min), southern (0, -1) m (14.45 min), and northern (0, 1) m (12.70 min) points (P<0.05), with no significant differences between the other points (western, southern, and northern) (P>0.05). The northern point (0, 1) m exhibited the highest DEP mass and number concentration peaks (174.62 μg·m⁻³, 1319.85 p·cm⁻³), significantly exceeding those at the southern (0, −1) m (129.89 μg·m⁻³, 1175.24 p·cm⁻³), eastern (−1, 0) m (140.12 μg·m⁻³, 1120.53 p·cm⁻³), and western (1, 0) m (147.60 μg·m⁻³, 818.62 p·cm⁻³) points (P<0.05), and no significant differences were observed among other points (P>0.05). There were no significant differences in peak DEP mass and number concentrations by measurement heights (P>0.05). Diesel engine power, ventilation, airflow intensity, and airflow direction had no significant effect on the time of peak DEP concentration (P>0.05). However, higher engine power (5.15 kW) produced greater DEP peaks [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] than the 4.05 kW engine power [(168.41±12.65) μg·m⁻³, (1284.45±71.30) p·cm⁻³] (P<0.05). The peak mass concentration [(342.04±35.03) μg·m⁻³] and number concentration [(1886.87±57.91) p·cm⁻³] of DEP in the non-ventilated group were significantly higher than those in the ventilated group [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] (P<0.001). Forward airflow elevated DEP mass concentrations compared to reverse airflow (287.71 μg·m⁻³ vs. 243.74 μg·m⁻³, t=−2.592, P=0.009), but no effects on DEP number concentration (P>0.05). Significant differences in mass concentration were observed among selected 5 vehicle models (Z=38.109, P<0.001). Conclusion The operation of diesel engines will emit a large amount of particulate matter, causing pollution in enclosed spaces. Diesel engines with greater power have higher levels of DEP pollution emissions. Based on the spatiotemporal distribution characteristics, it is recommended to set the operation position in the reverse direction of exhaust emissions and close to air purifiers, while avoiding the use of additional air flow equipment.

Ferroptosis is a regulated form of cell death, with its core mechanism being intracellular iron overload-induced lipid peroxidation, leading to cellular dysfunction and mitochondrial structural abnormalities. Ferroptosis is closely related to various diseases including neurodegenerative disorders, tumors, and ischemia-reperfusion organ damage, and has become a potential therapeutic target. Iron is essential for life but can also cause cell death. Despite continuous progress in iron-related biomedical research, many questions remain unanswered. Advances in high-throughput technologies, genomics and proteomics are expected to reveal the cellular iron regulatory mechanism and open up new therapeutic approaches for ferroptosis-related diseases. This article reviews the research progress on iron in terms of its biology, metabolism, regulation, and related diseases, aiming to provide clues and references for developing new ferroptosis-targeted therapeutic strategies and facilitating more in-depth molecular studies from multiple perspectives.
Humans ; Ferroptosis/physiology* ; Iron/metabolism* ; Animals ; Neoplasms/metabolism* ; Neurodegenerative Diseases/metabolism*

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female

OBJECTIVES: This study aims to analyze the clinical symptoms and imaging manifestations in patients with temporomandibular disorder syndrome (TMD), who are sensitive to sudden temperature drop. METHODS: One hundred and nineteen patients with TMD who attended the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital from December 2022 to December 2023 were included, including 44 males and 75 females, with a mean age of 32.4±13.7 years.The questionnaire was used to determine whether they were sensitive to temperature drop, and the TMD patients were divided into a temperature plunge-sensitive group and a temperature drop insensitive group. The clinical symptoms and imaging manifestations of patients in the two groups were observed. SPSS 25.0 was used for statistical analysis. RESULTS: There was no statistically significant difference between the gender and age of patients in the temperature plunge-sensitive group (50 patients) and the insensitivity group (69 patients) (P>0.05). The percentage of patients with pain was slightly higher in the temperature plunge-sensitive group [86.0% (43/50)] than in the insensitive group [68.1% (47/69)], and the difference was statistically significant (χ²=5.031, P=0.025), while the differences in joint murmur and mouth opening limitation between the two groups were not statistically significant. A total of 238 lateral joints were detected in both groups, the percentage of osteoarthropathic imaging changes was significantly higher in the temperature plunge-sensitive group [82.0% (82/100)] than in the insensitive group [53.6% (74/138)] (χ²=20.675, P<0.001). Magnetic imaging showed that the percentage of joint effusion was higher in patients in the temperature plunge-sensitive group [66.0% (33/50)] than in the insensitive group [42.0% (29/69)], and the difference was statistically significant (χ²=5.602, P=0.018). CONCLUSIONS TMD patients with maxillofacial pain symptoms, joint effusions, and abnormal imaging of osteoarticular structures are more likely to be sensitive to sudden temperature drops.
Humans ; Male ; Female ; Adult ; Temporomandibular Joint Disorders/diagnosis* ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; Temperature ; Adolescent

OBJECTIVES: This study aimed to investigate the correlation between clinical symptoms and unilateral chewing habits in patients with temporomandibular disorder (TMD) accompanied by tinnitus. METHODS: A total of 285 patients diagnosed with TMD at the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital between December 2020 and May 2024 were included and divided into two groups: tinnitus group and non-tinnitus group. Analysis was conducted on the proportion of patients with unilateral chewing habits in both groups, the correlation between the side of tinnitus and the side of unilateral chewing, and the correlation of tinnitus with TMD clinical symptoms (joint clicking, joint pain, and limited mouth opening) and unilateral chewing habits. The correlation of the type of disc displacement with unilateral chewing and tinnitus was also examined. RESULTS: In the tinnitus group, the proportions of patients with and without unilateral chewing habits were 90.70% (39/43) and 9.30% (4/43), respectively. In the non-tinnitus group, the proportions of patients with and without unilateral chewing habits were 76.03% (184/242) and 23.97% (58/242), respectively. The proportion of patients with unilateral chewing habits in the tinnitus group was significantly higher than in the non-tinnitus group (χ²=4.613, P<0.05). Correlation analysis showed a positive correlation between tinnitus and unilateral chewing habits (P<0.05). In the left-sided tinnitus group, the proportion of left-sided unilateral chewers [54.55% (12/22)] was higher than that of right-sided unilateral chewers [45.45% (10/22)]. In the right-sided tinnitus group, the proportion of right-sided unilateral chewers [81.82% (9/11)] was higher than that of left-sided unilateral chewers [18.18% (2/11)]. The difference was statistically significant (χ²=7.282, P<0.05). A positive correlation was also found between the side of tinnitus and the side of unilateral chewing habits (P<0.05). The proportion of patients with pain was significantly higher in the tinnitus group than in the non-tinnitus group (P<0.05). No significant difference in the proportion of joint clicking or limited mouth opening and disc displacement (no disc displacement, unilateral disc displacement, bilateral disc displacement, reducible disc displacement, or irreducible disc displacement) was found between the tinnitus and non-tinnitus groups (P>0.05). CONCLUSIONS TMD with unilateral chewing habits may be a contributing factor to unexplained tinnitus. Unexplained tinnitus is correlated with joint pain in patients with TMD.
Humans ; Tinnitus/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Mastication ; Male ; Adult ; Female ; Middle Aged ; Habits

As the need for antibody production rises, there is an urgent need to lower the costs and enhance the efficiency of the separation process. Currently, the chromatographic media used for antibody separation and purification often focus on individual properties of antibodies, such as affinity, hydrophobicity, and charge, leading to issues like low purification efficiency or inadequate adsorption capacity. To address this, an electrostatically coupled polypeptide affinity medium (FD7-3, 5-diaminobenzoic acid n-sepharose, FD7-DA-Sepharose) was developed for rapid purification of antibodies from cell culture supernatant. This medium utilized 3, 5-diaminobenzoic acid as a spacer to attach the heptapeptide-affinity ligand (FYEILHD, FD7) to agarose microspheres. Antibodies could be adsorbed through charge interactions with the carboxyl functional group of the FD7-DA-Sepharose spacer, while FD7 enhanced electrostatic coupling and affinity adsorption through synergistic effects, significantly increasing the adsorption capacity while maintaining the affinity and specificity. The influences of pH and ionic strength on adsorption capacity were investigated with human immunoglobulin as a model protein. The static adsorption capacity (Q_m) of FD7-DA-Sepharose in the solution of pH 6.0 reached 67.73 mg/mL, representing a 52.68% increase compared with that (44.36 mg/mL) of the commercial Protein A affinity medium. Furthermore, the elution conditions for FD7-DA- Sepharose were mild (20 mmol/L PB, 0.5 mol/L NaCl, pH 6.0), in contrast to the harsh acidic elution (pH 2.7-3.6) typically associated with Protein A, which can damage antibody integrity. The FD7-DA-Sepharose medium was then employed to purify antibodies from cell culture supernatant, achieving the yield of 94.8% and the purity of 98.4%. The secondary structure of the purified antibody was determined by circular dichroism spectroscopy. The results demonstrated that FD7-DA-Sepharose enabled efficient purification of antibodies from cell culture supernatant, which provided a cost-effective solution (approximately one-third the price of commercial Protein A affinity medium) with gentle elution conditions that preserve the natural conformation of antibodies. This approach paves a novel, economical, and efficient way for the separation and purification of antibodies from cell culture supernatant.
Chromatography, Affinity/methods* ; Static Electricity ; Humans ; Sepharose/analogs & derivatives* ; Peptides/chemistry* ; Adsorption ; Antibodies/isolation & purification*

Objective To investigate the clinical features in children with invasive pneumococcal disease (IPD) and early warning indicators of severe case.Methods The case data of 101 children inpatients with IPD isolated Streptococcus pneumoniae (Sp) at least once blood culture in this hospital from January 2007 to De-cember 2021 were collected retrospectively.The children patients were divided into the pediatric intensive care unit (PICU) group (35 cases) and general ward group (66 cases) according to whether or not entering PICU during hospitalization.The general clinical data,infection types and results of drug sensitivity test and bacteri-al strain serotype identification were compared between the two groups and analyzed.Results Compared with the general ward group,the male proportion,proportions of complicating nervous system disease and iron-defi-ciency anemia,winter incidence rate,disturbance of consciousness,convulsion,dyspnea,heart rate increase,oc-currence rate of vomiting and diarrhea,proportion of peripheral blood neutrophilic granulocytes,C reactive protein (CRP),lactic dehydrogenase (LDH) level,Hb<90 g/L,LDH>700 U/L,creatine kinase isoenzyme-MB (CK-MB) abnomality,proportions of bacterial meningitis,sepsis and severe pneumonia in the PICU group were higher,the proportion of 3-97 percentile of body weight,bronchopneumonia and no-focus blood stream infection were lower,WBC,Hb and albumin level were lower,and the differences were statistically significant (P<0.05).Eleven kinds of serotypes were identified in this study,ranking the top five in order were 6B,14,19F,23F and 19A.Pneumococcal 13-valent conjugate vaccine (PCV13) could cover 96.9％ of the IPD sero-types.The multivariate logistic regression analysis showed that consciousness disturbance,convulsion,per-centage of neutrophils increase,Hb<90 g/L,LDH>700 U/L and CK-MB abnormality indicated the condition of IPD children patients was critical,which was the early-warning indicator of entering PICU (P<0.05).Con-clusion Severe IPD lacks the early specific early-warning indicator,and the cover rate of PCV13 is high.