BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female

Objective: To investigate the influencing factors of depressive symptoms and to construct and verify the prediction model of depressive symptoms in middle school students, so as to provide risk assessment tools for effectively screening depressive symptom. Methods: Physical examination and questionnaire survey were conducted among middle school students in one city in Guangdong Province from September to October in 2021 ( n =2 376) and from September to October in 2022 ( n =4 344) by a multistage cluster sampling method, and a nomographic prediction model of depressive symptoms in middle school student was constructed. The questionnaire survey was conducted using the student health status and influencing factors questionnaire (secondary school version) and the Center for Epidemiological Studies Depression Scale (CES-D) to measure the lifestyle and depressive symptom of middle school students. Results: The detection rate of depressive symptoms in 2021 was 23.3%. Multivariate Logistic regression analysis showed that irregular breakfast ( OR =2.64), school bullying ( OR =4.28), being beaten by parents ( OR =2.86), using mobile devices for a long time ( OR =1.08) and sitting for a long time ( OR =1.05) were positively related to depressive symptoms in middle school students ( P <0.05). Long sleep duration ( OR =0.78) and outdoor activity durations of 1-<2, 2-<3 and ≥3 h/d (compared with <1 h/d, OR =0.63, 0.61, 0.49) were negatively related to depressive symptoms in middle school students ( P < 0.05 ). Multivariate Logistic regression analysis showed that 7 statistically signifucant predictive factors constructed a nomogram, and the AUC of the nomogram was 0.77, which had been verified internally and externally with good differentiation and reliability. Conclusions The nomogram prediction model of depressive symptoms provides a convenient and effective risk assessment tool for depressive symptoms among middle school students. The life behavior, diet behavior and injury behavior of middle school students play an important role in the formation of depressive symptoms. It should pay attention to the impact of the behavioral factors on the mental health of middle school students.

Objective:To explore the application value and surgical experience of neuroendoscopic resection for pediatric patients with cerebellar tumors.Methods:This was a case series study.The clinical data and outcomes of 30 pediatric patients with cerebellar tumors treated through neuroendoscopic surgery in the Department of Neurosurgery, the Guizhou Hospital of Shanghai Children′s Medical Center and Guizhou Provincial People′s Hospital from January 2021 to January 2024 were retrospectively analyzed.Results:Twenty-six patients underwent total resection, 3 patients underwent subtotal resection, and 1 patient underwent biopsy.Postoperative pathological findings showed 9 cases of medulloblastoma, 3 cases of ependymoma, 17 cases of astrocytoma (5 cases of World Health Organization Grade Ⅰ, 3 cases of Grade Ⅱ, and 9 cases of Grade Ⅲ), and 1 case of cerebellar benign lesion.During the perioperative period, malignant arrhythmia occurred and induced death in 1 case, cerebellar mutism occurred in 12 cases, and ataxia occurred in 22 cases.During the 1-36 months of follow-up, 2 cases developed communicating hydrocephalus at the 2 nd and the 6 th month, respectively, and improved after ventriculoperitoneal shunt; cerebellar mutism was relieved to varying degrees after an average postoperative follow-up period of (115±23) days(46-194 days), and ataxia was alleviated after an average postoperative follow-up period of (127±42) days(27-173 days).Tumors relapsed in 5 cases during the last follow-up. Conclusions:Neuroendoscopy provides an alternative to the microscope for experienced operators to achieve the surgical exposure requirements during the resection of pediatric cerebellar vermis tumors.

Objective:To investigate the effectiveness, safety, and advantages of modified radical neck dissection by gasless unilateral axillary approach (GUA-MRND) in the surgical management of selected patients with papillary thyroid cancer.Methods:We retrospectively analyzed patients with papillary thyroid cancer who underwent GUA-MRND (endoscopic group, n=16) versus unilateral open modified radical neck dissection (MRND) (open group, n=32) during the period from Jan. 2019 to Jun. 2021, including the differences in surgical efficiency, complication rate, and incisional satisfaction.Results:Compared MRND with GUA-MRND, the patients were younger ( P<0.05) , operative time and postoperative drainage anterior ( P<0.01) were slightly inferior in the latter, but it had obvious advantages in cervical swallowing discomfort and incision satisfaction evaluation ( P<0.05) . There was no significant difference in the incidence of temporary recurrent laryngeal nerve injury, intraoperative and postoperative bleeding, hematoma, infection, lymphatic or chylous leakage and supraclavicular numbness after surgery ( P>0.05) . The number of dissected lymph nodes in area II in the GUA-MRND was lower ( P<0.05) , but it was significantly higher ( P<0.01) in area III. And the average regional cleaning efficiency in the GUA-MRND was level Ⅲ (35.5%) , level Ⅵ (28.59%) , level Ⅳ (23.21%) , level Ⅱ (7.18%) and level Ⅴ (7.12%) , suggested that GUA-MRND had higher efficacy for level III, level Ⅵ and Level IV. Conclusion:GUA-MRND is safe, effective, and has high cosmetic satisfaction in the treatment of selected patients with lateral cervical lymph node metastases from papillary thyroid cancer.

The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.
Animals ; Rats ; PC12 Cells ; Ferroptosis/genetics* ; Reactive Oxygen Species ; Transcription Factors ; Glutathione

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

Animals ; Genomics ; Humans ; Serogroup ; Streptococcal Infections ; Streptococcus suis/isolation & purification* ; Swine ; Swine Diseases

Objective: To investigate the molecular mechanisms of Gupi Xiaoji decoction on apoptosis of human hepatoma cells HepG2. Methods: HepG2 cells were divided into 4 groups: control group (Control), blank serum group (Blank), Gupi Xiaoji Yin serum group (GPXJY) and cisplatin group (Positive). Eight duplicate holes were set in each group. After treated with Gupi Xiaoji Decoction-containing serum or cisplatin for 24 hours, the cell viability, the number of viable cells, the state of apoptosis, the cell cycle and the mitochondrial membrane potential were detected, and the level of lipid peroxidation (MDA) and glycolysis rate of the cells were detected. The expressions of apoptotic Bax, Bcl-2, and Caspase-3 proteins, and the contents of triacylglycerol (TG), cholesterol (TC), pyruvate and glucose in the cell supernatant were detected. Results: Compared with the control group, in the GPXJY group, the inhibition rate was increased (P＜0.05), the number of cells was decreased, the number of apoptosis-positive cells was increased (P＜0.01), the number of cells in the G1 phase was increased significantly (P＜0.05), and the cell membrane potential was decreased (P＜0.05,P＜0.01), the glycolytic function was inhibited significantly, the MDA level was increased, the expressions of Bax and Caspase-3 in the GPXJY group were increased, and the expression of Bcl-2 was decreased (P＜0.05, P＜0.01). In cell supernatant, the TC, TG and glucose contents were decreased significantly, and the pyruvate content was increased significantly (P＜0.05,P＜0.01). Conclusion: Gupi Xiaoji Decoction can induce apoptosis of HepG2 cells and may play a role in energy metabolism.
Apoptosis ; Carcinoma, Hepatocellular ; Caspase 3/metabolism* ; Cisplatin ; Drugs, Chinese Herbal ; Glucose ; Hep G2 Cells ; Humans ; Liver Neoplasms ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Pyruvates ; bcl-2-Associated X Protein/metabolism*

ObjectiveTo screen the active antitumor components of Gupi Xiaoji decoction by network pharmacology and molecular docking based on the pyroptosis mediated by cysteinyl aspartate-specific protease 1 （Caspase-1） and explore its molecular mechanism in intervening in the pyroptosis of HepG2.2.15 cells through in vitro experiments. MethodThe compounds and targets of Gupi Xiaoji decoction were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） to obtain the corresponding gene symbols. The targets of Caspase-1 were collected from GeneCards，online mendelian inheritance in man（OMIM），PharmGKB，and TTD，and the compound-gene target regulatory network was constructed by Cytoscape. The protein-protein interaction（PPI） network was established and analyzed by STRING. The mechanism of the effective components of Gupi Xiaoji decoction on Caspase-1 was predicted by gene ontology（GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The molecular docking was verified with AutoDock Vina. The plasma medicated with Gupi Xiaoji Decoction was prepared and HepG2.2.15 cells were cultured in vitro. HepG2.2.15 cells were divided into a blank plasma group，a VX-765 group，a VX-765+medicated plasma group， and a medicated plasma group. After 48 hours of intervention with 15% medicated plasma， the expression and distribution of gasdermin D-N （GSDMD-N） on the surface of the cell membrane were detected by immunofluorescence staining. The release of lactic dehydrogenase （LDH）， interleukin（IL）-1β，and IL-18 in the cell supernatant was measured by enzyme-linked immunosorbent assay（ELISA） kits. The expression of Caspase-1 and GSDMD-N was measured by Western blot. ResultThe mitogen-activated protein kinase 14 （MAPK14），MAPK1，protein kinase B1 （Akt1）， MAPK8， V-Jun sarcoma virus oncogene homolog （JUN）， and TP53 screened by network pharmacology were the main targets. The compounds 7-hydroxy-5，8-dimethoxy-2-phenyl-chromone，wogonin，rhamnazin，moslosooflavone，isorhamnetin，7-O-methylisomucronulatol，formononetin，calycosin，luteolin，quercetin，kaempferol，β-sitosterol，and baicalein screened by network pharmacology were the main active components of Gupi Xiaoji decoction. Go enrichment analysis showed that multiple biological processes were involved， including responses to oxidative stress and metal ions，ubiquitin-like protein ligase binding，and phosphatase binding. KEGG pathway enrichment analysis showed MAPK pathway，nuclear factor（NF）-κB pathway，p53 pathway， and hypoxia-inducible factor-1（HIF-1） pathway were involved. Molecular docking showed that the targets had good binding with the components. In vitro experiments displayed that compared with the blank plasma group，the VX-765 group showed weakened GSDMD-N fluorescence signal，reduced release of LDH，IL-1β，and IL-18，and declining expression of Caspase-1 and GSDMD-N（P<0.01）， and the medicated plasma group showed increased GSDMD-N fluorescence signal， increased release of LDH，IL-1β，and IL-18，and up-regulated expression of Caspase-1 and GSDMD-N（P<0.01）. ConclusionGupi Xiaoji Decoction can induce the pyroptosis of HepG2.2.15 cells by regulating Caspase-1 through multiple targets and multiple pathways.

Studies have shown that ABO blood group is related to the susceptibility and disease progression of SARS-CoV-2 infection, and most studies indicated that group O individuals were less likely to get infected while group A conferred a higher susceptibility to infection and propensity to severe disease. ABO blood group antigens are oligosaccharides expressed on red cells and other tissues. People with different ABO blood type have different susceptibility to a variety of pathogens, including SARS-CoV-2. There are several hypotheses to explain the differences in SARS-CoV-2 infection between ABO blood group individuals. Firstly, anti-A and/or anti-B antibodies could bind to corresponding antigens on the viral envelope and contribute to viral neutralization, thereby preventing target cell from being infected. The SARS-CoV-2 virus and SARS-CoV spike (S) proteins may be bound by anti-A isoagglutinin, which may block interactions between virus and angiotensin-converting-enzyme-2-receptor, thereby preventing entering into lung epithelial cells. Secondly, the receptor binding domain (RBD) of S protein domain can bind to antigen A expressed in respiratory epithelium and promote its infection to respiratory epithelial cells. In conclusion, most studies indicated that group O may be associated with a lower risk of SARS-CoV-2 infection while group A with a higher risk along with severe disease, and the related mechanism needs to be further studied.