Background Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents. Current research suggests that environmental factors, such as per- and polyfluoroalkyl substances (PFAS), may be associated with an increased risk of ADHD in offspring. However, most epidemiological evidence originates from non-Chinese populations, with limited research investigating the association between prenatal PFAS and ADHD-like symptoms in Chinese school-aged children. Objective To examine the association between prenatal PFAS exposure and ADHD-like symptoms in 7-year-old children. Methods Based on the Shanghai Birth Cohort, this study included 488 mother-child pairs. PFAS were measured in maternal serum during the second trimester using ultra-performance liquid chromatography-tandem mass spectrometry. The analysis focused on eight specific compounds from three PFAS categories [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS)]. The hyperactivity subscale of the Strengths and Difficulties Questionnaire (SDQ) was used to assess ADHD-like symptoms in children at age 7. Basic demographic information was collected via questionnaires and medical records. Negative binomial regression models were used to evaluate the relationship between individual exposures to the three typical PFAS categories (PFOA, PFOS, and PFHxS) and children's ADHD-like symptoms, while the bayesian kernel machine regression (BKMR) mixture model was employed to assess the overall effect of PFAS mixture exposure on ADHD-like symptoms. Results The detection rates of the eight target PFAS in maternal second-trimester serum were all above 85%, with PFOA exhibiting the highest median concentration (10.21 ng·mL⁻¹). Overall, 14.75% of the children exhibited ADHD-like symptoms. Results from the negative binomial regression models showed that second-trimester exposures to PFOA (IRR=1.15, 95%CI: 1.05, 1.26), n-PFOS (IRR=1.08, 95%CI: 1.01, 1.15), 6m-PFOS (IRR=1.13, 95%CI: 1.05, 1.21), and 1m-PFOS (IRR=1.11, 95%CI: 1.03, 1.18) were associated with an increased risk of ADHD-like symptoms in 7-year-old children. Stratified analyses suggested potentially statistically significant associations in girls [e.g., for PFOA, boys vs. girls: 1.09 (0.96, 1.23) vs. 1.25 (1.09, 1.44), P-int=0.31]. The BKMR mixture model indicated that the risk of ADHD-like symptoms trended upward with increasing PFAS mixture concentrations, although this association was statistically significant only among girls (P < 0.05). Conclusion Prenatal PFAS exposure may be associated with an increased risk of ADHD-like symptoms in 7-year-old children, and this adverse association appears to be more prominent in girls.

AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective To analyze the epidemiological characteristics of acute respiratory infections(ARIs)during the autumn-winter season in Beijing,providing evidence for the prevention,control,diagnosis,and treatment of ARIs.Methods A convenience sampling method was employed,enrolling patients who visited Peking Union Medical College Hospital(PUMCH)between September 2023 and February 2024 due to ARIs.Na-sopharyngeal swabs were collected,and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus(FluA),influenza B virus(FluB),human rhinovirus(HRV),Myco-plasma pneumoniae(MP),respiratory syncytial virus(RSV),and adenovirus(ADV)],as well as SARS-CoV-2 infection.The distribution patterns of pathogen infections were analyzed.Results A total of 5556 eligible patients were included.The overall positivity rate for the six common respiratory pathogens was 63.7％,with sin-gle-pathogen positivity at 54.0％,dual-pathogen positivity at 8.9％,and triple or more pathogen positivity at 0.7％.The predominant pathogens detected were FluA(16.1％)and RSV(15.7％),followed by ADV(11.1％),MP(11.1％),HRV(10.0％),and FluB(10.0％).No significant difference in overall pathogen positivity was observed between genders.However,significant differences were found between autumn and winter(x2=34.617,P＜0.001)and among pediatric,young/middle-aged,and elderly patients(x2=422.38,P＜0.001).Specifically,MP(x2=8.647,P=0.003),FluA(x2=131.932,P＜0.001),and HRV(x2=174.199,P＜0.001)exhibited significantly higher positivity rates in autumn than in winter,whereas FluB was more prevalent in winter(x2=287.894,P＜0.001).In pediatric patients,MP,RSV,HRV,and ADV positivity rates were significantly higher than in young/middle-aged and elderly patients(all P＜0.001),whereas FluB was more common in young/middle-aged patients(both P＜0.001).The positivity rates of the six common respiratory pathogens significantly declined during the SARS-CoV-2 epidemic period,exhibiting an asynchronous seasonal pattern.Conclusions The prevalence of respiratory pathogens in Beijing is associated with age and season.Tar-geted preventive measures should be implemented in different seasons and for key populations.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Objective To construct a Gabra3 gene knockout cell model and explore transcriptomic and proteomic alterations in murine neuronal cells,in order to investigate the molecular mechanisms underlying the increased depth of slow-wave sleep observed following Gabra3 deletion.Methods Multiple sgRNA sequences were designed,and the CRISPR/Cas9 system was used to knock out the Gabra3 gene in the murine GT1-7 neuronal cell line.Gene sequencing was performed to assess knockout efficiency,and TA cloning was used to validate the knockout results.Protein immunoblotting experiments were conducted to confirm the knockout,while cell proliferation assays were used to validate the knockout phenotype.Total RNA and protein were extracted for transcriptomic and proteomic sequencing,respectively.A range of bioinformatics analyses was conducted to assess the functional consequences of Gabra3 knockout in GT1-7 neuronal cells.Results Following Gabra3 gene knockout,pathways related to cortisol and aldosterone synthesis and secretion,as well as circadian rhythm,were significantly enriched.Three key genes,BMP2,GLI2,and DLL1,were identified.Proteomic profiling revealed widespread disturbances in protein expression following Gabra3 knockout.Conclusion Gabra3 gene knockout may increase slow-wave sleep depth by modulating the expression of hormone secretion-related genes and altering circadian regulatory pathways.

OBJECTIVE: To observe the clinical efficacy and safety of acupuncture combined with blade needle therapy for knee osteoarthritis (KOA). METHODS: A total of 60 patients with KOA were randomly divided into an observation group and a control group, 30 cases each group. The control group received acupuncture at Neixiyan (EX-LE4)，Dubi (ST35), Yinlingquan (SP9), Liangqiu (ST34), Xuehai (SP10), Yanglingquan (GB34) and Zusanli (ST36) on the affected side, once every other day, 3 times a week. The observation group received blade needle therapy on the basis of the treatment in the control group, once every 3 days, 2 times a week. Both groups were treated for 4 weeks. Before treatment, after 2, 4 weeks of treatment, and after 1 month of treatment completion (in follow-up), the scores of pain visual analogue scale (VAS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and Lequesne index were observed in the two groups, and the clinical efficacy and safety were evaluated. RESULTS: After 2, 4 weeks of treatment and in follow-up, the pain VAS scores, Lequesne index scores, and pain, stiffness, function scores of WOMAC in both groups were decreased compared with those before treatment (P<0.05), and the VAS scores, Lequesne index scores and pain, function scores of WOMAC in the observation group were lower than those in the control group (P<0.05). The effective response rate in the observation group was 76.7% (23/30), while that in the control group was 70.0% (21/30), there was no statistically significant difference in the effective response rates between the two groups (P>0.05). No adverse reactions were observed in either group. CONCLUSION Acupuncture combined with blade needle therapy could alleviate pain and promote functional recovery in KOA patients, and achieve long-lasting improvements.
Humans ; Osteoarthritis, Knee/physiopathology* ; Acupuncture Therapy/instrumentation* ; Male ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Needles ; Combined Modality Therapy

BACKGROUND: Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults. METHODS: By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs . with offspring; more than one vs . one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models. RESULTS: Among 210,129 men and 302,284 women aged 30-79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men ( vs . one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87-0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89-0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78-0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02-1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28-1.47]) and women (aHR [95% CI] = 1.27 [1.15-1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95-0.98]), while for women, the lowest risk was observed among those with three to four offspring ( Pnonlinear <0.0001). CONCLUSIONS Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Morbidity ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Family Characteristics ; Mortality ; East Asian People

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.