Mitochondria, ubiquitous energy-producing organelles in eukaryotic cells, can have their normal functions disrupted by bacterial infections, leading to mitochondrial dysfunction. This dysfunction is closely associated with inflammatory diseases. Periodontitis, a chronic inflammatory disorder of periodontal tissues caused by pathogenic microorganisms, has been increasingly linked to mitochondrial dysfunction in its pathogenesis and progression. Compared to healthy periodontal tissues, inflammatory lesions exhibit more pronounced mitochondrial dysfunction—a pathological process that is strongly correlated with periodontal pathogen infection. Studies reveal that these pathogens disrupt mitochondrial homeostasis in host cells (e.g., gingival epithelial cells and fibroblasts) through multiple mechanisms, including disrupting mitochondrial biogenesis, altering mitochondrial dynamics (promoting excessive fission), inhibiting mitophagy, impairing mitochondrial dysfunction-associated apoptosis, and inducing endogenous oxidative stress, which upregulates pro-inflammatory cytokines. Collectively, these processes drive the establishment and persistence of an inflammatory microenvironment. This review explores how periodontal pathogens affect mitochondrial function and their mechanistic contributions to periodontitis progression, with the goal of providing novel insights for developing mitochondria-targeted therapeutic strategies.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

OBJECTIVE To explore the practice pathway and evaluate the effectiveness of the resident pharmacists stationed in the Drug Clinical Trial Institution Office （hereinafter referred to as the “GCP resident pharmacist”） in the management of dermatological drug clinical trials. METHODS The practical approach of GCP resident pharmacists participating in dermatological drug clinical trials at our hospital was introduced. A retrospective analysis was conducted on the data of dermatological drug clinical trials from 2021 to 2024， comparing efficiency and quality indicators between dermatological clinical trials and those of other specialties. RESULTS With the involvement of our hospital’s GCP resident pharmacists throughout, the process for dermatology drug clinical trials was constructed and optimized， a dedicated quality control system was established， and the acceleration strategy for subject enrollment was optimized. The number of dermatological drug clinical trials at our hospital showed a compound annual growth rate of 69.56% from 2021 to 2023. In terms of efficiency indicators， the approval waiting time for dermatological drug clinical trials was （12.31±4.99） days， which was significantly shorter than that of other specialties （[ 19.68±6.09） days， P＜0.05]. Regarding quality indicators， the enrollment rate for dermatological drug clinical trials was 75.71%（50.00%，114.48%）， which was significantly higher than that of other specialties [51.00%（25.00%，174.17%）， P＜0.05]. The numbers of first quality control issues （[ 8.31±3.25）items vs.（ 11.68±4.49）items] and protocol deviations [5.5（2.0，11.0）times vs. 11.0（5.5，17.5）times] were significantly lower than those of other specialties （P＜0.05）. CONCLUSIONS GCP resident pharmacists significantly enhance the overall efficiency of dermatological drug clinical trials， playing a crucial role in ensuring the reliability and authenticity of drug clinical trials， as well as safeguarding the rights and safety of trial subjects.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Objective:To study the relationship between fluoride exposure and adrenocorticotropic hormone (ACTH)/cortisol (CORT) in rural children in eastern Henan, and to reveal the modifying effect of brain-derived neurotrophic factor (BDNF) gene polymorphism.Methods:A total of 463 children aged 7 - 12 (245 boys and 218 girls) from 4 primary schools in Tongxu County, Henan Province were recruited by a cluster sampling method for questionnaire survey, physical examination, and collection of morning urine and fasting venous blood. The concentrations of urinary fluoride and creatinine were determined by a fluoride ion selective electrode method and picric acid method, respectively. Serum ACTH and CORT levels were determined with a fully automated biochemical analyzer, and the genotyping of BDNF gene loci of single nucleotide polymorphism was conducted by a customized 48-Plex SNPscan TM reagent kit. Besides, the relationships between urinary fluoride concentrations and serum ACTH/CORT levels in children were analyzed by multiple linear regression models. The interaction term between urinary fluoride concentration and BDNF gene polymorphism was established, and the interaction between unit point gene polymorphism and environment on serum ACTH or CORT levels of children was analyzed by multiple linear regression. Results:For every 1 mg/L increase in urinary fluoride concentration, serum ACTH level in girls increased by 1.98 pg/ml [95% confidence interval ( CI): 0.71, 3.24; P = 0.002], while serum CORT level in boys decreased by 37.48 ng/ml (95% CI: - 63.99, - 10.97; P = 0.006). Regardless of stratified analysis, the urinary fluoride concentration of individuals carrying the TA genotype at the rs6484320 locus was positively correlated with serum ACTH level (β > 0, P < 0.05); in addition, there was a positive correlation between urinary fluoride concentration and serum ACTH level in the total population and boys carrying the CC genotype of rs7103873 locus (β > 0, P < 0.05); and the serum ACTH and CORT levels in girls carrying the AA genotype of rs12291186 locus were positively correlated with urinary fluoride concentration (β > 0, P < 0.05). The interaction analysis showed that there was an interaction between urinary fluoride concentrations and rs6484320/rs7103873 loci polymorphisms on serum ACTH level in the total population and boys ( Pinteraction < 0.1), as well as urinary fluoride concentrations and rs12291186 locus polymorphism on serum CORT level in girls ( Pinteraction = 0.035). Conclusions:Urinary fluoride concentration is associated with increased serum ACTH level in girls and decreased serum CORT level in boys. BDNF gene polymorphism can modify the association between fluoride exposure and serum ACTH or CORT levels in children, and the modification effect varies by gender.

Objective:To compare image quality and diagnostic parameters of whole-brain CT perfusion scans under different scanning conditions and assess the utility of deep learning image reconstruction algorithm (DLIR) in reducing tube current during low-dose scans.Methods:Method A total of 105 patients with suspected acute ischemic stroke (AIS) were prospectively enrolled in the First Affiliated Hospital of Zhengzhou University from March, 2022 to March, 203 and their baseline information was recorded. All patients underwent head non-contrast CT and CT perfusion (CTP) examinations. CTP scanning was performed at 80 kV in two groups with the tube current of 150 mA (regular dose) and 100 mA (low dose), respectively. The CTP images of 150 mA group were reconstructed using filtered back-projection algorithm as well as adaptive statistical iterative reconstruction-V (ASIR-V) at 40% and 80% strength levels, which were denoted as groups A-C. The CTP images of 100 mA group were reconstructed using ASIR-V80%, DLIR-M, and DLIR-H, which were denoted as groups D-F. Clinical baseline characteristics and radiation doses were compared between the two groups under different scanning conditions. Furthermore, we assessed the subjective and objective image quality, conventional perfusion parameters, and abnormal perfusion parameters of AIS patients across the six groups of reconstructed CTP images.Results:Under the scanning conditions of 150 mA and 100 mA, 47 and 48 patients were diagnosed with AIS, respectively. There were no significant differences in the baseline characteristics between the two groups. However, there was a significant difference in the mean effective radiation dose (5.71 mSv vs. 3.80 mSv, t = 2 768.30, P < 0.001). The standard deviation (SD) of noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of gray matter (GM) and white matter (WM) were significantly different among the six groups of reconstructed images ( F = 40.58-212.13, P < 0.001). In GM, the SD values in groups C, D, and F were lower than those in other groups ( P < 0.05), and the SNR values in groups C and F were higher than those in other groups ( P < 0.05). In WM, the SD and SNR values in groups C and F were significantly different from those in other groups ( P < 0.05). Additionally, CNR values in groups C and F were higher than those in other groups ( P < 0.05). There was no significant difference in subjective scores among groups B, C, and F ( P > 0.05). Regarding perfusion parameters in the brain GM, groups D and E had lower cerebral blood volume (CBV) values compared to groups A to C ( P < 0.05), and group F had lower CBV values than group B ( P < 0.05). In the brain WM, group D had consistently lower mean transit time (MTT) values compared to the other groups ( P < 0.05). Notably, there were no significant differences in AIS lesion detection rates and relevant diagnostic parameters across the six image groups. Conclusions:Low-tube current CTP scan combined with the DLIR-H algorithm can enhance image quality without affecting perfusion parameters such as CBV and MTT, while reducing radiation dose by 30%. This algorithm can be routinely applied in brain CTP examinations.

Abstract During the peirod of Republic of China, the rural economy in China was in a state of decline, with poor hygiene conditions and extremely low levels of physical health among children. Under such circumstances, Professor Chen Zhiqian established the first rural health pilot zone in China and created the Dingxian Model,and explored a path suitable for the development of rural school health services by conducting health education courses, cultivating good hygiene habits,examining and improving students physical health status, and carrying out health surveys among teachers and students. The above actions has accumulated valuable experiences for the exploration and practice of contemporary rural school health services.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

BACKGROUND:Abnormal activation of osteoclasts plays an important role in the bone destruction due to spinal tuberculosis.During the pathogenesis of osteoporosis,miR-155 knockdown activates adenosine phosphate-dependent protein kinase(AMPK)by increasing the expression of leptin receptors,thereby inhibiting osteoclast differentiation and bone resorption.However,the role of miR-155/leptin receptor(LEPR)/AMPK axis in the bone destruction due to spinal tuberculosis remains unclear. OBJECTIVE:To investigate the role and mechanism of miR-155/LEPR/AMPK axis in tuberculin-induced osteoclast formation. METHODS:RAW264.7 cells were cultured and treated with different concentrations of purified protein derivative(PPD)(1.0,2.5,5.0,10.0 IU/mL)and transfected with negative control(NC)sequence or miR-155 inhibitor,NC siRNA sequence or LEPR siRNA sequence.Tartrate resistant acid phosphatase staining was used to detect the number of osteoclasts.Fluorescence quantitative PCR was used to detect the expression of miR-155.Western blot was used to detect the expression of LEPR and p-AMPK.Double luciferase reporter gene was used to verify miR-155 targeting LEPR. RESULTS AND CONCLUSION:Compared with the control group,the number of osteoclasts and the expression level of miR-155 significantly increased,while the expression level of LEPR and p-AMPK significantly decreased in 2.5,5.0,and 10.0 IU/mL PPD groups(P＜0.05).Compared with NC+5.0 IU/mL PPD group,the number of osteoclasts and the expression level of miR-155 significantly decreased,while the expression level of LEPR and p-AMPK significantly increased in the miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).Compared with the NC group,the fluorescence activity of LEPR wild-type double luciferase reporter gene was increased in the miR-155 inhibitor group,and decreased in the miR-155 mimic group(P＜0.05).Compared with si-NC+miR-155 inhibitor+5.0 IU/mL PPD group,the expression level of miR-155 had no significant change,the number of osteoclasts significantly increased,and the expression levels of LEPR and p-AMPL significantly decreased in si-LEPR+miR-155 inhibitor+5.0 IU/mL PPD group(P＜0.05).To conclude,tuberculin can induce osteoclast formation by increasing miR-155 expression and inhibiting downstream LEPR expression and AMPK activation.