Background Metals and metalloids in fine particulate matter (PM_2.5) may cause damage to the respiratory and circulatory systems of the human body, and long-term exposure is prone to causing chronic poisoning, cancer, and other adverse effects. Objective To assess the distribution characteristics of metals and metalloids in outdoor PM_2.5 in a southern city of China, conduct source apportionment, and evaluate the associated health risks, thereby providing theoretical support for further pollution control measures. Methods PM_2.5 samples were collected in districts A, B, and C of a southern China city, and the concentrations of 17 metals and metalloids were detected by inductively coupled plasma-mass spectrometry (ICP-MS). Pollution sources were assessed through enrichment factor and principal components analysis, and the main pollution sources were quantified using absolute principal component scores-multivariate linear regression (APCS-MLR). Health risks were evaluated based on the Technical guide for environmental health risk assessment of chemical exposure (WS/T777—2021). Results The ambient air PM_2.5 concentrations in the city were higher in winter and spring, and lower in summer and autumn. The annual average concentrations of ambient PM_2.5 in districts A, B, and C were 36.7, 31.9, and 24.4 μg·m⁻³, respectively. The ambient PM_2.5 levels in districts B and C were below the second-grade limit set by the Ambient air quality standards (GB 3095—2012). The enrichment factors of cadmium (Cd), aluminum (Al), and antimony (Sb) were greater than 10, those of copper (Cu), lead (Pb), arsenic (As), nickel (Ni), mercury (Hg), and molybdenum (Mo) fell between 1 and 10, and those of manganese (Mn), vanadium (V), chromium (Cr), cobalt (Co), barium (Ba), beryllium (Be), and uranium (U) were below or equal to 1. The comprehensive evaluation of source analysis showed that the main pollution sources in districts A and C and the whole city were coal-burning. In district B, the main pollution source was also coal combustion, followed by industrial process sources and dust sources. The carcinogenic risks of As and Cr were between 1×10⁻⁶ and 1×10⁻⁴. However, the hazard quotients for 15 metals and metalloids in terms of non-carcinogenic risk were below 1. Conclusion Cr and As in the atmospheric PM_2.5 of the city present a certain risk of cancer and should be paid attention to. In addition, preventive control measures should be taken against relevant pollution sources such as industrial emission, dust, and coal burning.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

ObjectiveThis study aimed to explore the effects of aerobic exercise on cognitive function in aging mice and to elucidate the underlying molecular mechanisms by which aerobic exercise ameliorates cognitive decline through the regulation of gut microbiota-metabolite network. By providing novel insights into the interplay between exercise, gut microbiota, and cognitive health, this research seeks to offer a robust theoretical foundation for developing anti-aging strategies and personalized exercise interventions targeting aging-related cognitive dysfunction. MethodsUsing naturally aged C57BL/6 mice as the experimental model, this study employed a multi-omics approach combining 16S rRNA sequencing and wide-targeted metabolomics analysis. A total of 18 mice were divided into 3 groups: young control (YC, 4-month-old), old control (OC, 21-month-old), and old+exercise (OE, 21-month-old with 12 weeks of moderate-intensity treadmill training) groups. Behavioral assessments, including the Morris water maze (MWM) test, were conducted to evaluate cognitive function. Histopathological examinations of brain tissue sections provided morphological evidence of neuronal changes. Fecal samples were collected for gut microbiota and metabolite profiling via 16S rRNA sequencing and ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS). Data were analyzed using a combination of statistical and bioinformatics tools to identify differentially abundant microbial taxa and metabolites and to construct interaction networks between them. ResultsBehavioral tests revealed that 12 weeks of aerobic exercise significantly improved spatial learning and memory capacity of aged mice, as evidenced by reduced escape latency and increased target area exploration and platform crossings in the MWM. Histopathological analysis demonstrated that exercise mitigated aging-related neuronal damage in the hippocampus, enhancing neuronal density and morphology. 16S rRNA sequencing indicated that exercise increased gut microbiota α‑diversity and enriched beneficial bacterial genera, including Bifidobacterium, Parabacteroides, and Rikenella. Metabolomics analysis identified 32 differentially regulated metabolites between OC and OE groups, with 94 up-regulated and 30 down-regulated in the OE group when compared with OC group. These metabolites were primarily involved in energy metabolism reprogramming (e.g., L-homocitrulline), antioxidant defense (e.g., L-carnosine), neuroprotection (e.g., lithocholic acid), and DNA repair (e.g., ADP-ribose). Network analysis further revealed strong positive correlations between specific bacteria and metabolites, such as Parabacteroides with ADP-ribose and Bifidobacterium with lithocholic acid, suggesting potential neuroprotective pathways mediated by the gut microbiota-metabolite axis. ConclusionThis study provides comprehensive evidence that aerobic exercise elicits cognitive benefits in aging mice by modulating the gut microbiota-metabolite network. These findings highlight three key mechanisms: (1) the proliferation of beneficial gut bacteria enhances metabolic reprogramming to boost DNA repair pathways; (2) elevated neuroinflammation-inhibiting factors reduce neurodegenerative changes; and (3) enhanced antioxidant defenses maintain neuronal homeostasis. These results underscore the critical role of the “microbiota-metabolite-brain” axis in mediating the cognitive benefits of aerobic exercise. This study not only advances our understanding of the gut-brain axis in aging but also offers a scientific basis for developing personalized exercise and probiotic-based interventions targeting aging-related cognitive decline. Future research should further validate these mechanisms in non-human primates and human clinical trials to establish the translational potential of exercise-induced gut microbiota-metabolite modulation for combating neurodegenerative diseases.

Objective To understand the equity and influencing factors of maternal health service utilization in Changning District, Shanghai. Methods A convenience sampling method was used to conduct a questionnaire survey among mothers of children aged 1 to 1.5 years old who received health services from the child health care clinics and EPI clinics of 10 community health service centers in Changning District, Shanghai from March to April 2022. Count data was expressed by frequency and percentage. Chi-square analysis, binomial logistic regression analysis, and multivariate logistic regression analysis were used to analyze fairness-related factors. Rate difference, rate ratio and concentration index were used to represent fairness. Results A total of 696 subjects were investigated, with an average age of (33.35±4.76) years. There were statistically significant differences in service utilization among women with different household registrations only in early pregnancy registration (χ²=11.026, P=0.001) and postpartum visits (χ²=4.989, P=0.026). Women with a career showed differently in folic acid supplement (χ²=6.247, P=0.012), early pregnancy registration (χ²=12.989, P=0.002), physical examination in 42 days postpartum (χ²=4.446, P=0.035) and postpartum contraception (χ²=4.061, P=0.044), and the differences were statistically significant. Women with different monthly family income had a statistically significant difference in pre-pregnancy examination (χ²=8.977, P=0.030) and postpartum visit (χ²=16.114, P=0.001). There was a statistically significant difference between women with maternity insurance or not in the early pregnancy registration (χ²=10.576, P=0.001) and physical examination in 42 days postpartum (χ²=8.166, P=0.004). The results of the multivariate analysis showed that occupation (OR=2.616, 95% CI: 1.142-5.990) and maternity insurance (OR=4.490, 95% CI: 1.992~10.120) affected the utilization of service in early pregnancy registration. The monthly household income (OR=0.278, 95% CI: 0.124-0.625) affected the utilization of services in postpartum visit. At the same time, the monthly household income (10,000-19,999: OR=0.286, 95% CI: 0.090-0.907; ≥30,000: OR=0.180, 95% CI: 0.041-0.801) also affected the utilization of service in physical examination in 42 days postpartum. Conclusion The equity of maternal health care service utilization overall is good in central area in Shanghai, but there is still room for improvement. It is necessary to strengthen community mobilization, propagandize maternal health services, and expand the coverage of maternity insurance to improve the equity of maternal health service utilization and provide equal access to maternity health services.

BACKGROUND: Neoadjuvant therapy enhances the possibility of achieving radical resection and improves the prognosis for locally advanced gastric cancer (GC). However, there is a lack of evidence regarding the optimal extent of resection for locally advanced proximal GC after neoadjuvant therapy. METHODS: In this study, 330 patients underwent resection in Peking University Cancer Hospital, with curative intent after neoadjuvant therapy for histologically confirmed proximal GC from January 2009 to December 2022. RESULTS: In this study, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). After propensity-score matching, 110 patients (71 TG and 39 PG) were included in the analysis. No significant differences between PG and TG regarding short-term outcomes and long-term prognosis were found. Specifically, PG demonstrated comparable overall survival to TG ( P = 0.47). Subgroup analysis revealed that although not statistically significant, PG showed a potential advantage over TG in overall survival for patients with tumor-long diameters less than 4 cm ( P  = 0.31). However, for those with a long diameter larger than 4 cm, TG had a better survival probability ( P  = 0.81). No substantial differences were observed in baseline characteristics, surgical safety, postoperative recovery, and postoperative complications. CONCLUSION For locally advanced proximal GC with objective response to neoadjuvant therapy (long diameter <4 cm), PG is an alternative surgical procedure.
Humans ; Stomach Neoplasms/drug therapy* ; Gastrectomy/methods* ; Neoadjuvant Therapy/methods* ; Male ; Female ; Middle Aged ; Propensity Score ; Aged ; Adult ; Retrospective Studies

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

Cinnabar(HgS) was widely used in ancient times for medicinal purposes, religious rituals, and pigments. A group of bright red powdery clumps was excavated from Mawangdui Tomb No.3 of the Han Dynasty. Early studies considered the clumps as evidence of cinnabar's medicinal use during the Qin-Han period. This study employed a range of archaeometric techniques, including extended-depth-of-field stereo imaging, micro-CT, scanning electron microscopy-energy dispersive spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrometry FTIR, to systematically analyze the material composition and structural characteristics of these remains. The results revealed that the cinnabar particles were granular, finely ground, and tightly bound to silk matrix, with no detectable excipients typically associated with medicinal formulations. Micro-CT imaging indicated a well-preserved textile structure, with clear signs of sedimentary accumulation and mechanical damage. Based on historical and archaeological studies, this study suggested that these remains were more likely degraded accumulations of cinnabar-colored silk textiles rather than medicinal cinnabar. By clarifying the diversity of ancient cinnabar applications and preservation states, this study provides new insights for the archaeological identification of mineral medicinal materials and contributes to the standardized study of Chinese medicinal materials and understanding of the historical use of cinnabar.
History, Ancient ; China ; Humans ; Medicine, Chinese Traditional/history* ; Archaeology ; Drugs, Chinese Herbal/history* ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; Mercury Compounds

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome