Objective:To investigate the relationship between individual and combined exposure to ambient air pollutants and vitamin D, as well as the potential role of ultraviolet radiation (UVR) in mediating the relationships.Methods:This study included 6 967 participants from the China Kadoorie Biobank, whose baseline (2004-2008) blood 25-hydroxyvitamin D had been tested. The average monthly concentrations of pollutants (PM 2.5, PM 10, NO 2, O 3) and the UVR estimates in the month of blood sample collection were derived from the ChinaHighAirPollutants and ultraviolet datasets covering China, respectively. Linear models and multinomial logistic regression models were used to analyze the associations of each air pollutant with vitamin D concentrations and groups. Principal component analysis integrated with quantile-based g-computation was applied to evaluate the co-effects and relative contribution weights of air pollutants. Mediation analyses were performed to investigate the potential role of UVR. Results:PM 2.5, PM 10, NO 2, and O 3 were individually associated with vitamin D concentrations, as well as vitamin D groups: insufficiency (20-30 ng/ml) and deficiency (<20 ng/ml). For each 10 μg/m3 increase in monthly PM 2.5, PM 10, NO 2, and O 3, the percentage changes (95% CIs) in vitamin D concentrations were -1.71% (-2.16% - -1.26%), -1.30% (-1.60% - -1.00%), -3.77% (-4.60% - -2.93%), and 1.27% (0.91%-1.63%), respectively, with corresponding ORs (95% CIs) for vitamin D deficiency of 1.17 (1.06-1.29), 1.12 (1.05-1.19), 1.66 (1.38-2.00), and 0.81 (0.74-0.89). The mixture of the first principal component of PM 2.5 and PM 10 (PM), along with NO 2 and O 3, was negatively correlated with vitamin D. The percentage change (95% CI) in vitamin D concentrations for a one-quintile increase in the mixture was -2.20% (-3.56%- -0.82%), with NO 2 contributing the most (83%), followed by PM (17%). UVR-mediated association was 12.2% (95% CI：2.5%-23.0%) for PM 2.5 and 4.9% (95% CI：2.2%-8.0%) for PM 10 with vitamin D concentrations, respectively. Conclusion:Higher concentrations of particulate matter, NO 2, and a mixture of air pollutants were associated with lower vitamin D concentrations in Chinese adults, with reduced UVR acting as a partial mediator in the particulate matter-vitamin D relationship.

Objective To construct a risk score model for basement membrane-related genes(BMRGs)in triple-negative breast cancer(TNBC).Methods The TNBC risk score model based on BMRGs was established in the cancer genome atlas(TCGA)cohort by the LASSO-COX regression machine learning method,and verified in the Yau-2010 cohort and the molecular taxonomy of breast cancer international consortium(METABRIC)cohort.A nomogram containing BMRG risk score and clinical factors was constructed to predict the survival prognosis of TNBC patients.Based on the functional annotations of gene ontology(GO)and the Kyoto encyclopedia of genes and genomes,KEGG and Gene Set Enrichment Analysis(GSEA)were used to explore differences in protein functional enrichment in risk subgroups.The Immuno-Oncology Biological Research(IOBR)package was used to explore differences in immune infiltration based on risk subgroups.The Mutation Annotation Format Tools(Maltools)package was used to explore genomic changes.Finally,based on the cancer therapeutics response portal(CTRP)and the cancer single-cell expression map(CSEP)to explore differences in drug sensitivity and single-cell expression status in risk score subgroups.Results Six BMRGS-constructed risk subgroups were identified by Kaplan-Meier(KM)survival analysis and LASSO-COX regression analysis and were closely related to the prognosis of TNBC patients(all P<0.001).Among them,SDC1 and ADAM9 were poor prognostic factors,HAPLN1,FREM1,FBLN5 and ITGB4 were protective prognostic factors.The combination of BMRGs risk score and TNM tumor stage has excellent predictive ability for the prognosis of TNBC patients.Protein function analysis showed that the up-regulated genes in the high-risk group were enriched in the pathways and biological functions of neuroactive ligand-receptor interactions,synthesis of various biological complexes,and participation in immune defense responses.Compared with the high-risk group,the infiltration degree of mast cells and cytotoxic lymphocytes was higher in the low-risk group.The genetic map revealed that the most frequently mutated genes in the high-low-risk subgroups were not identical Drug sensitivity analysis showed that patients in the high-risk group had higher sensitivity to bortezomib,fluvastatin,and ouabain(all P<0.05).Patients in the low-risk group had higher sensitivity to nintedanib,BRD-A86708339,and vandetanib(all P<0.05).Single-cell analysis showed that the above six genes were highly expressed in TNBC tumor cells.Conclusion The risk score based on BMRGs was constructed and validated to provide effective biological indicators for predicting the survival and prognosis of TNBC patients.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Objective:To explore the current implementation status and challenges of family doctor contract services (FDCS) from the perspective of contracted residents.Methods:This qualitative study used purposive sampling to select contracted residents from 11 primary healthcare institutions across five cities in China. Semi-structured interviews were conducted from March to December 2024, covering topics such as awareness of contracting, service experience, health needs, service continuity, and policy recommendations. Thematic framework analysis was applied to organize, code, and summarize the data.Results:A total of 25 contracted residents were interviewed (6 men, 19 women; 11 from central urban areas, 14 from suburban or rural towns; 8 with chronic diseases). Three main themes and ten sub-themes emerged: Theme Ⅰ: Pathways to improved service accessibility (optimized chronic disease management, more efficient referrals, and improved health education). Theme Ⅱ: Structural misalignment between supply and demand (limited specialty services despite patient needs, insufficient coverage and public awareness of home-based medical care, imbalanced human resources, and service disruption due to clinician turnover). Theme Ⅲ: Challenges in service awareness and communication mechanisms (information asymmetry and public misperception regarding FDCS, perverse incentives in administrative performance evaluation, and communication barriers in building patient-doctor trust).Conclusions:While FDCS has shown progress in chronic disease management, referral coordination, and health education, structural supply-demand gaps and communication challenges continue to hinder service quality. Improvements in resource allocation and service models are needed to support high-quality development.

Objective:To investigate the relationship between individual and combined exposure to ambient air pollutants and vitamin D, as well as the potential role of ultraviolet radiation (UVR) in mediating the relationships.Methods:This study included 6 967 participants from the China Kadoorie Biobank, whose baseline (2004-2008) blood 25-hydroxyvitamin D had been tested. The average monthly concentrations of pollutants (PM 2.5, PM 10, NO 2, O 3) and the UVR estimates in the month of blood sample collection were derived from the ChinaHighAirPollutants and ultraviolet datasets covering China, respectively. Linear models and multinomial logistic regression models were used to analyze the associations of each air pollutant with vitamin D concentrations and groups. Principal component analysis integrated with quantile-based g-computation was applied to evaluate the co-effects and relative contribution weights of air pollutants. Mediation analyses were performed to investigate the potential role of UVR. Results:PM 2.5, PM 10, NO 2, and O 3 were individually associated with vitamin D concentrations, as well as vitamin D groups: insufficiency (20-30 ng/ml) and deficiency (<20 ng/ml). For each 10 μg/m3 increase in monthly PM 2.5, PM 10, NO 2, and O 3, the percentage changes (95% CIs) in vitamin D concentrations were -1.71% (-2.16% - -1.26%), -1.30% (-1.60% - -1.00%), -3.77% (-4.60% - -2.93%), and 1.27% (0.91%-1.63%), respectively, with corresponding ORs (95% CIs) for vitamin D deficiency of 1.17 (1.06-1.29), 1.12 (1.05-1.19), 1.66 (1.38-2.00), and 0.81 (0.74-0.89). The mixture of the first principal component of PM 2.5 and PM 10 (PM), along with NO 2 and O 3, was negatively correlated with vitamin D. The percentage change (95% CI) in vitamin D concentrations for a one-quintile increase in the mixture was -2.20% (-3.56%- -0.82%), with NO 2 contributing the most (83%), followed by PM (17%). UVR-mediated association was 12.2% (95% CI：2.5%-23.0%) for PM 2.5 and 4.9% (95% CI：2.2%-8.0%) for PM 10 with vitamin D concentrations, respectively. Conclusion:Higher concentrations of particulate matter, NO 2, and a mixture of air pollutants were associated with lower vitamin D concentrations in Chinese adults, with reduced UVR acting as a partial mediator in the particulate matter-vitamin D relationship.

Objective To construct a risk score model for basement membrane-related genes(BMRGs)in triple-negative breast cancer(TNBC).Methods The TNBC risk score model based on BMRGs was established in the cancer genome atlas(TCGA)cohort by the LASSO-COX regression machine learning method,and verified in the Yau-2010 cohort and the molecular taxonomy of breast cancer international consortium(METABRIC)cohort.A nomogram containing BMRG risk score and clinical factors was constructed to predict the survival prognosis of TNBC patients.Based on the functional annotations of gene ontology(GO)and the Kyoto encyclopedia of genes and genomes,KEGG and Gene Set Enrichment Analysis(GSEA)were used to explore differences in protein functional enrichment in risk subgroups.The Immuno-Oncology Biological Research(IOBR)package was used to explore differences in immune infiltration based on risk subgroups.The Mutation Annotation Format Tools(Maltools)package was used to explore genomic changes.Finally,based on the cancer therapeutics response portal(CTRP)and the cancer single-cell expression map(CSEP)to explore differences in drug sensitivity and single-cell expression status in risk score subgroups.Results Six BMRGS-constructed risk subgroups were identified by Kaplan-Meier(KM)survival analysis and LASSO-COX regression analysis and were closely related to the prognosis of TNBC patients(all P<0.001).Among them,SDC1 and ADAM9 were poor prognostic factors,HAPLN1,FREM1,FBLN5 and ITGB4 were protective prognostic factors.The combination of BMRGs risk score and TNM tumor stage has excellent predictive ability for the prognosis of TNBC patients.Protein function analysis showed that the up-regulated genes in the high-risk group were enriched in the pathways and biological functions of neuroactive ligand-receptor interactions,synthesis of various biological complexes,and participation in immune defense responses.Compared with the high-risk group,the infiltration degree of mast cells and cytotoxic lymphocytes was higher in the low-risk group.The genetic map revealed that the most frequently mutated genes in the high-low-risk subgroups were not identical Drug sensitivity analysis showed that patients in the high-risk group had higher sensitivity to bortezomib,fluvastatin,and ouabain(all P<0.05).Patients in the low-risk group had higher sensitivity to nintedanib,BRD-A86708339,and vandetanib(all P<0.05).Single-cell analysis showed that the above six genes were highly expressed in TNBC tumor cells.Conclusion The risk score based on BMRGs was constructed and validated to provide effective biological indicators for predicting the survival and prognosis of TNBC patients.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Objective:To explore the current implementation status and challenges of family doctor contract services (FDCS) from the perspective of contracted residents.Methods:This qualitative study used purposive sampling to select contracted residents from 11 primary healthcare institutions across five cities in China. Semi-structured interviews were conducted from March to December 2024, covering topics such as awareness of contracting, service experience, health needs, service continuity, and policy recommendations. Thematic framework analysis was applied to organize, code, and summarize the data.Results:A total of 25 contracted residents were interviewed (6 men, 19 women; 11 from central urban areas, 14 from suburban or rural towns; 8 with chronic diseases). Three main themes and ten sub-themes emerged: Theme Ⅰ: Pathways to improved service accessibility (optimized chronic disease management, more efficient referrals, and improved health education). Theme Ⅱ: Structural misalignment between supply and demand (limited specialty services despite patient needs, insufficient coverage and public awareness of home-based medical care, imbalanced human resources, and service disruption due to clinician turnover). Theme Ⅲ: Challenges in service awareness and communication mechanisms (information asymmetry and public misperception regarding FDCS, perverse incentives in administrative performance evaluation, and communication barriers in building patient-doctor trust).Conclusions:While FDCS has shown progress in chronic disease management, referral coordination, and health education, structural supply-demand gaps and communication challenges continue to hinder service quality. Improvements in resource allocation and service models are needed to support high-quality development.

Objective:To study the role of ML-SA5, an agonist of the lysosomal Ca 2+ channel transient receptor potential mucolipin 1 (TRPML1), in promoting lysosomal exocytosis to facilitate intracellular uranium removal and alleviate uranium-induced cellular damage for human renal proximal tubule epithelial cells (HK-2) exposed to uranyl acetate. Methods:HK-2 cells were divided into the following groups to be exposed to uranyl acetate at either 0 or 300 μmol/L for 24 h, followed by treatment with ML-SA5 and/or the lysosomal exocytosis inhibitor vacuolin-1 for 0.5 h: control group (Ctrl group), ML-SA5 group (M group), vacuolin-1 group (V group), ML-SA5 plus vacuolin-1 group (M+ V group), uranium exposure group (U group), uranium exposure plus ML-SA5 group (U+ M group), uranium exposure plus vacuolin-1 group (U+ V group), and uranium exposure plus ML-SA5 plus vacuolin-1 group (U+ M+ V group). We localized lysosome-associated membrane protein-1 (LAMP-1) on the plasma membrane (surface LAMP-1) by immunofluorescence assay; measured intracellular uranium content by inductively coupled plasma mass spectrometry; measured the level of kidney injury molecule-1 (KIM-1) by immunofluorescence assay; measured the rate of cell death with Calcein-AM/PI double staining; determined the subcellular localization of transcription factor EB (TFEB) and the levels of LAMP-1 and TRPML1 proteins by immunofluorescence assay; and measured the number of lysosomes using LysoTracker probes.Results:Compared with the Ctrl group, the U group showed significant increases in the surface LAMP-1 protein level ( t = 12.86, P < 0.05), KIM-1 protein level ( t = 18.86, P < 0.05), cell death rate ( t = 38.53, P < 0.05), TFEB nuclear translocation ( t = 9.12, P < 0.05), the protein expression levels of TFEB’s downstream target genes LAMP-1 ( t = 16.47, P < 0.05) and TRPML1 ( t = 32.33, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 7.75, P < 0.05). Compared with the U group, the U+ M group showed a significantly increased surface LAMP-1 level ( t = 3.33, P < 0.05) and significant decreases in the intracellular uranium level ( t = 5.01, P < 0.05), KIM-1 protein expression level ( t = 3.81, P < 0.05), and cell death rate ( t = 3.24, P < 0.05); all these effects in the U+ M group could be neutralized by the lysosomal exocytosis inhibitor vacuolin-1; and in addition, ML-SA5 significantly increased TFEB nuclear translocation ( t = 9.20, P < 0.05), the protein expression levels of LAMP-1 ( t = 3.05, P < 0.05) and TRPML1 ( t = 3.17, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 3.13, P < 0.05). Conclusions:The TRPML1 agonist ML-SA5 can promote lysosomal exocytosis to enhance intracellular uranium clearance and reduce uranium-induced cellular damage/death in uranium-loaded HK-2 cells, through activating TFEB to up-regulate lysosome biogenesis and TRPML1 protein expression.

Objective:To analyze the clinical characteristics and neurophysiological features of patients with neuralgic amyotrophy (NA) and explore their neurological function status.Methods:Clinical data and neurophysiological findings of 90 patients diagnosed with NA at Beijing Tsinghua Changgung Hospital from September 2016 to January 2024 were collected and their clinical phenotypes and neurophysiological characteristics were systematically summarized and analyzed.Results:Among the 90 patients, males accounted for 60.0% (54 cases) and females accounted for 40.0% (36 cases). The duration of the disease was 12 (3, 36) months (ranged from 1 week to 5 years). The onset age of the patients was 58 (30, 70) (21-87) years. Unilateral involvement was noted in 94.4% (85/90) of patients, exhibiting a left-to-right ratio of 1∶1.3, while only 5.6% (5/90) had bilateral involvement. The majority of patients demonstrated a monophasic clinical course with a recurrence rate of just 2.2% (2/90). The primary clinical manifestations included upper limb pain in 70.0% (63/90) of patients, which progressed to muscle weakness and atrophy within 1 day to 1 month, whereas 30.0% (27/90) of patients without significant pain symptoms. Lesions predominantly affected the upper trunk of the brachial plexus, which accounted for 64.4% (58/90) of patients. Distal nerve injuries in the upper limb were observed in 14.4% (13/90) of patients, with 6.7% (6/90) demonstrating isolated anterior interosseous nerve involvement and another 6.7% (6/90) exhibiting isolated posterior interosseous nerve involvement; 1 case had concurrent anterior and posterior interosseous nerve damage. Additionally, 1 case presented with bilateral phrenic nerve involvement, and another patient had isolated posterior tibial nerve injury. Electrophysiological evaluations of patients with NA revealed that axonal damage to motor nerve fibers was a hallmark feature of the condition. Among patients undergoing motor nerve conduction studies, 68.8% (55/80) exhibited decreased compound muscle action potential amplitude, and 31.3% (25/80) had prolonged latency. Sensory nerve conduction was normal in 60.0% (48/80) of patients, while abnormalities included prolonged latency in 15.0% (12/80), reduced amplitude in 12.5% (10/80), slowed conduction velocity in 8.8% (7/80), and absent waveforms in 3.8% (3/80) of patients. The rates of abnormal nerve conduction findings in motor nerves were the highest in the suprascapular nerve (70.6%, 36/51), followed by the axillary nerve (58.3%, 35/60), musculocutaneous nerve (50.7%, 35/69), long thoracic nerve (6/17), and both anterior and posterior interosseous nerves (7.5%, 6/80 each). In sensory nerves, abnormalities were predominantly noted in the lateral antebrachial cutaneous nerve (30.0%, 12/40). Needle electromyography demonstrated neurogenic damage, most frequently affecting the infraspinatus muscle (69.2%, 18/26), biceps brachii (68.1%, 49/72), and deltoid muscle (65.3%, 47/72). The positive rate of magnetic resonance neurography (MRN) for NA was 62.1% (41/66), among which 63.4% (26/41) showed localized swelling of the brachial plexus, 51.2% (21/41) exhibited T 2 hyperintensity, and 4.9% (2/41) demonstrated denervated changes in the muscles. The positive rate of ultrasound for NA was 71.1% (59/83), with 91.5% (54/59) showing nerve swelling and 8.5% (5/59) exhibiting hourglass constriction .Conclusions:NA is a peripheral neuropathy characterized by spontaneous pain, limb weakness, and (or) muscle atrophy primarily. Its clinical phenotype predominantly involves damage to the upper trunk of the brachial plexus, which can also manifest as isolated mononeuropathy. Neurophysiological findings most commonly reveal the neurogenic damage to the muscles innervated by the upper trunk of the brachial plexus, mainly characterized by the axonal damage to the motor nerves, and pure motor nerve damage may also be observed. MRN and neuroultrasound can assist in qualitative diagnosis.