Parkinson's disease （PD） is a neurological degenerative disease with a high clinical incidence， unclear etiology， and incurability. The main pathological features of PD are the loss of dopaminergic neurons in the midbrain substantia nigra and the formation of Lewy bodies. At present， the anti-parkinsonism drugs used in clinical practice have problems， such as decreasing efficacy and severe toxic side effects in the late stage of the disease. Mitochondrial autophagy is a self-regulation mode in which cells automatically remove damaged and aging mitochondria to maintain mitochondrial homeostasis. It is generally believed that the degree of mitochondrial autophagy is weakened in PD state， and this process mainly progresses through the ubiquitin-dependent pathway， non-ubiquitin-dependent pathway， and α-Synuclein-mediated mitochondrial autophagy pathway. Abnormal accumulation of damaged mitochondria will cause further damage to nerve cells and accelerate PD process. Therefore， restoring the mitochondrial autophagy balance， reducing the excessive accumulation of abnormal mitochondria， and reducing the damage of dopaminergic neurons in the substantia nigra are particularly important for the treatment of PD. Traditional Chinese medicine （TCM） has definite effect in the clinical prevention and treatment of PD， and studies have been carried out targeting the intervention of mitochondrial autophagy. A large number of studies have confirmed that single herbs and compound prescriptions of TCM can relieve nerve function defects and delay degenerative changes of nerve cells by restoring the balance of mitochondrial autophagy， thus playing a role in the treatment of PD. This paper systematically summarized the regulatory mechanisms of mitochondrial autophagy in the pathogenesis of PD and the influences of active ingredients from single herbs and compound prescriptions of TCM on mitochondrial autophagy. Furthermore， this paper explored the pathogenesis of PD and the basis of the therapeutic role of TCM through the intervention of mitochondrial autophagy， providing references for promoting the application of TCM in the prevention and treatment of PD.

ObjectiveTo investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease （AD） comorbid with apathy （AD-A）. MethodsThe study included 30 patients with AD-A， 30 AD disease patients without apathy （AD without apathy， AD-NA）， and 30 healthy controls （HCs） matched in gender， age， and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging （MRI） scans. Voxel-based morphometry （VBM） was used to analyze changes in gray matter volume among the three groups. Additionally， the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. ResultsThere were no statistically significant differences among the three groups in terms of age， gender， years of education， or total intracranial volume. Compared with the HCs group， both the AD-A and AD-NA groups showed significantly lower scores in cognitive function （P<0.001）. The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group （P<0.001）. Compared with the AD-NA group， the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus， left orbitofrontal cortex， lingual gyrus， inferior frontal gyrus， superior frontal gyrus， entorhinal cortex， right middle frontal gyrus and posterior cingulate cortex （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus， left fusiform gyrus， calcarine sulcus， postcentral gyrus， right inferior frontal gyrus and supramarginal gyrus （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-NA group showed reduced gray matter volume in the left precuneus， inferior temporal gyrus， and right inferior temporal gyrus （FWE-corrected， P<0.05 for all）. In the AD-A group， changes in the gray matter volume of the left caudate nucleus （r= -0.557， P=0.002） and right middle frontal gyrus （r=-0.620， P=0.001） were negatively correlated with the apathy evaluation scale （AES） scores. ConclusionPatients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit， and the degree of gray matter atrophy was correlated with the severity of apathy.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Background Lead smelting workers are exposed to mixed heavy metals such as lead (Pb) and cadmium (Cd). However, the specific associations and molecular mechanisms by which their combined exposure induces genetic damage remain unclear. Objective To clarify the association between combined Pb-Cd exposure and genetic damage and to explore the possible biological mechanisms through occupational epidemiological investigations and animal experiments. Methods (1) Population study: A cross-sectional study was conducted on 374 lead smelting workers in northern China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary levels of 8 metals including Pb and Cd, and graphite furnace atomic absorption spectroscopy (GFAAS) was used to quantify blood levels of Pb and Cd. The cytokinesis-block micronucleus assay (CBMN) was used to assess genetic damage. Poisson regression was used to analyze the association between metal exposure and micronucleus rates. (2) In vivo experiment: Thirty SD rats were randomly assigned to five groups: control (pure water), Pb (300 mg·L⁻¹ lead acetate), Cd (50 mg·L⁻¹ cadmium chloride), combined exposure (Pb + Cd), and resveratrol intervention (Pb + Cd + 50 mg·L⁻¹ resveratrol). After 8 weeks of ad libitum drinking water exposure, liver pathology, oxidative stress indicators [reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD)], genetic damage (Comet assay and γ-H2AX) were evaluated. Furthermore, cell cycle distribution, apoptosis rates, and mRNA expression of DNA damage response (DDR), DNA repair, and apoptosis-related genes were measured. Results (1) The geometric mean (GM, 95%CI) of urinary Pb and Cd were 14.69 (13.14, 16.51) µg·L⁻¹ and 2.11 (1.90, 2.33) µg·L⁻¹, respectively; the blood Pb and Cd levels were 117.10 (105.59, 129.87) µg·L⁻¹ and 4.55 (4.23, 4.89) µg·L⁻¹, respectively among the 374 workers. The mean micronucleus rate was (1.64±0.081) ‰, with significantly higher rates in males (1.65±0.083) ‰ than females (1.53±0.334) ‰ (U=4.166, P=0.041). All Pb and Cd biomarkers were positively correlated with micronucleus rate (FR>1, P<0.05), with a significant interaction effect observed between Pb and Cd (FR>1, P<0.05). (2) In rats, co-exposure to Pb and Cd caused liver tissue damage and inflammatory infiltration. Significant increases were observed in lymphocyte ROS; GSSG and MDA in lung tissue increased, while GSH and CAT activity decreased. Comet assay indicators and γ-H2AX levels were significantly elevated. Co-exposure induced S-phase arrest and increased apoptosis. mRNA levels of DDR (ATM, ATR, Chk2, and P53) and pro-apoptotic genes (Bax and Caspase-3) were upregulated, while the anti-apoptotic gene Bcl-2 and DNA repair genes (BRCA1, BRCA2, RAD51, RAD52, and CtIP) were downregulated. Two-way ANOVA confirmed synergistic effects on GSSG, Comet assay indicators, and ATR/Chk2 mRNA expression. Conclusion Occupational co-exposure to Pb and Cd synergistically induces genetic damage. This damage is mediated by oxidative stress and DNA damage, which activates the DDR pathway and inhibits the expression of DNA repair genes, ultimately leading to cell cycle arrest and apoptosis.

Objective: This review aimed to synthesize and critically appraise the existing evidence on endoscopic-assisted anterior odontoid screw fixation, with the objectives of clarifying its current clinical utility and identifying priorities for future optimization of the technique. Methods: A systematic review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines and registered with PROSPERO (registration number: CRD420251251051). Searches of PubMed/MEDLINE, Embase, Scopus, Web of Science, and Google Scholar identified studies reporting the use of endoscopic visualization during anterior odontoid screw placement. Eligible study designs included clinical reports and cadaveric investigations. Extracted data encompassed patient demographics, fracture subtype, operative technique, radiological alignment, fusion status, perioperative complications, and risk of bias, which was assessed using the modified Joanna Briggs Institute checklist. Results: Eight studies met the inclusion criteria, comprising 6 clinical reports and 2 cadaveric feasibility studies. The extent of endoscopic assistance ranged from hybrid mini-open approaches to fully endoscopic uniportal techniques. Reported fusion rates ranged from 80% to 100%, with fully endoscopic procedures demonstrating the most consistent radiological consolidation and anatomical reduction. No major neurovascular, aerodigestive, or implant-related complications were reported. Cadaveric evidence confirmed enhanced visualization of the C2 odontoid entry point and validated safe screw entry-point orientation with acceptable screw trajectories. Risk-of-bias assessment indicated low risk in 5 studies and moderate risk in 3. Small sample sizes, heterogeneous fracture morphology, and modest follow-up durations limited the overall quality of the evidence. Conclusion Endoscopic-assisted anterior odontoid screw fixation appears to be a technically feasible and biologically favorable minimally invasive option for selected odontoid fractures. Its potential advantages include improved visualization and reduced approach-related morbidity. Further prospective, multicenter investigations, particularly those integrating navigation systems, are required to define its definitive role in the management of cervical spine trauma.

Objective To investigate the current status of adverse drug reaction(ADR)monitoring in medical institu-tions under China's pharmacovigilance framework in Guangdong Province,and to propose evidence-based strategies for enhancing institutional monitoring capabilities.Methods A cross-sectional survey was conducted using a structured questionnaire devel-oped in alignment with national regulatory requirements and expert consensus.Data were collected from 65 medical institutions,including general hospitals,traditional Chinese medicine hospitals,and maternal/children's hospitals,across 21 prefecture-level cities in Guangdong.Descriptive and comparative analyses were performed to evaluate institutional practices.Results All 65 in-stitutions submitted valid responses.Among them,63(96.9％)had established standardized ADR reporting protocols,with 93.8％(61/65)delegating oversight to pharmacy departments.ADR data were predominantly collected via institutional informa-tion systems(67.7％,44/65),though these systems focused on passive reporting and basic data aggregation,lacking functional-ities for active signal detection or risk alert mechanisms.Significant disparities(P＜0.05)were observed across hospitals of dif-ferent tiers in reporting modalities,system sophistication,analytical frequency,and early warning implementation.Notably,mo-nitoring practices for conditionally approved drugs(e.g.,emergency-authorized therapeutics)exhibited systemic deficiencies.Conclusions To address these gaps,the following measures are recommended:Accelerating the adoption of intelligent monito-ring systems to enable real-time ADR detection and predictive analytics;Implementing tiered resource allocation policies to ensure equitable capability development;Establishing specialized protocols for high-risk pharmaceuticals,particularly conditionally ap-proved and fast-tracked drugs;Strengthening interdisciplinary training programs to improve pharmacovigilance literacy among healthcare practitioners.These interventions aim to foster a proactive risk management culture and advance patient safety within China's evolving healthcare landscape.

Aim To study whether intravenous injec-tion of miR-129-3p mimetic(agomir)can resist bone loss caused by hind limb disuse,and to provide new i-deas for preventing bone loss in microgravity environ-ment.Methods Forty-eight C57BL/6J male mice were randomly divided into the control group(CON),tail suspension model group(TS),tail suspension+miR-129-3p agomir administration group(miRNA)and tail suspension+miR-129-3p negative sequence agomir control group(NC).The miRNA group was given 4 mg·kg-1 miR-129-3p agomir by intravenous injection into the medial canthus twice a week.The NC agomir group were consistent with those in the miR-129-3p agomir group,and the CON and TS groups were given only equal volumes of normal saline.After four weeks,all mice were sacrificed and samples were collected.Micro-CT scan of femur,three-point femur bending test,serum bone metabolism index detection,oxidative stress index detection and osteogenesis-related protein expression analysis in bone tissue were per-formed.Results After four weeks,the number of tra-becular bone in the TS group was significantly re-duced,and Tb.BMD,Tb.Th,Tb.N,Tb.BS/TV and Tb.BV/TV were significantly lower than those in the CON group(P＜0.01).While Tb.Sp TS group was significantly higher than the CON group(P＜0.05),the maximum load and flexural strength of the femur significantly decreased(P＜0.01),the content of ser-um bone formation index PINP was significantly lower than that of the CON group(P＜0.01),and the con-tent of bone resorption index CTX-I was significantly higher than that of the CON group(P＜0.01),the content of serum oxidative damage indexes 8-iso-PGF2α and 8-OHdG significantly increased(P＜0.01),and the expression of osteogenesis-related pro-teins in bone tissue markedly decreased(P＜0.01).However,the increase or decrease of all indexes in miRNA group was significantly lower than that in TS group.Conclusions miR-129-3p mimetic can signifi-cantly reduce bone loss caused by hind limb disuse.This experiment provides a new idea and method for preventing bone loss in microgravity environment.