The spine is the most common site of skeletal metastasis in lung cancer, which frequently leads to severe complications such as pathological fracture and neurological compromise and is associated with poor prognosis. The development and progression of spinal metastasis from lung cancer are linked to the unique local microenvironment and tumor microenvironment (TME) of the vertebral column. During metastatic evolution, the dense vascular network of the spine and a plethora of signaling molecules, together with the complex cellular constituents and their intricate interactions within the TME, all cooperate to facilitate the tumor invasion and colonization of the vertebral compartment. Mechanistic studies delineating the role of the TME in spinal metastasis from lung cancer have markedly expanded, fostering the emergence of innovative therapeutic strategies—including nanomedicines, sono-photodynamic therapy, gene therapy, and combination regimens. These strategies demonstrate remarkably potential for clinical translation and offer new directions for the precision management of spinal metastasis from lung cancer.

Objective To investigate the impact of intraoperative red blood cell (RBC) transfusion volume on the postoperative oxygenation index in lung transplant recipients. Methods This retrospective study analyzed the clinical data of patients who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from 2021 to 2023. Patients were divided into a non-severe primary graft dysfunction (PGD) group and a severe PGD group based on whether their postoperative oxygenation index was>200 mm Hg at 0, 24, and 48 h. General patient data and intraoperative RBC transfusion volumes were compared between the two groups. A binary logistic regression model was constructed to explore the effect size (OR and its 95%CI) of RBC transfusion volume on postoperative oxygenation status at different time points (0, 24, and 48 h). The area under the receiver operating characteristic curve was calculated to evaluate the model's diagnostic performance. Results A total of 351 patients were included (260 males, 91 females), with ages ranging from 20 to 77 years. The OR for the effect of intraoperative RBC transfusion on poor oxygenation was 1.486 (95%CI 0.982 to 2.248, P=0.061) at 0 h postoperatively, 3.111 (95%CI 1.793 to 5.399, P<0.001) at 24 h, and 1.583 (95%CI 1.026 to 2.442, P=0.038) at 48 h. This indicated that as time progressed, the postoperative oxygenation status of lung transplant recipients was affected by the intraoperative transfusion volume. Furthermore, an RBC transfusion volume>975 mLhad a significant impact on patient oxygenation at 24 and 48 h postoperatively. Conclusion The volume of intraoperative RBC transfusion has a significant impact on the oxygenation status at 24 and 48 h postoperatively. Intraoperative RBC transfusion volume is associated with the occurrence of severe PGD after lung transplantation. Controlling the volume of RBC transfusion during lung transplantation may help reduce the incidence of severe PGD.

Background Di(2-ethylhexyl) phthalate (DEHP) is the most prevalent environmental endocrine disruptor among phthalate acid esters (PAEs) worldwide. Previous studies have indicated that exposure to DEHP may disrupt glucose metabolism. Objective To investigate the impact of DEHP on glucose homeostasis in rats, focusing on oxidative stress-induced impairment of autophagy in islet β cells. Methods Forty male SD rats were randomly assigned to four groups, receiving DEHP doses of 0, 187, 375, and 750 mg·kg⁻¹ for 12 weeks. Oral glucose tolerance (OGTT) and insulin tolerance tests (ITT) were conducted 24 h after the final exposure. Pancreatic microstructural alterations were assessed using hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Commercial ELISA kits were employed to quantify the levels of insulin, adenosine triphosphate (ATP), and adenosine monophosphate (AMP) in rat serum, as well as the protein expression level of activated caspase-3 in pancreatic tissue. Additionally, commercial microplate kits were utilized to measure the concentration of reduced glutathione (GSH) in serum, the activity of superoxide dismutase (SOD) using water-soluble tetrazolium salt-1, the content of malondialdehyde (MDA) by thiobarbituric acid method, and the level of reactive oxygen species (ROS) in pancreatic tissue by chemical fluorescence method. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure sequestosome1 (SQSTM1/p62), Beclin1, microtubule-associated protein 1 light chain 3 (LC3), and cysteinyl aspartate specific proteinase-8 (Caspase-8) mRNA levels. Western blot analysis was applied to detect the protein relative expression levels of p62, Beclin-1, LC3-I, LC3 II, AMPK, p-AMPK, mTOR, p-mTOR, ULK1, and Caspase-8. Results Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited a significant increase in fasting blood glucose levels at 2, 4, 6, and 12 weeks (P<0.05). The OGTT showed that, following high-glucose gavage, the 187 mg·kg⁻¹ DEHP group had elevated blood glucose at 30 min (P<0.05), the 375 mg·kg⁻¹ DEHP group showed increased glucose levels at 15, 30, and 180 min (P<0.05), and the 750 mg·kg⁻¹ DEHP group exhibited elevated levels at 15, 30, 60, and 180 min (P<0.05). The 375 and 750 mg·kg⁻¹ DEHP groups demonstrated significantly increased OGTT area under the curve (AUC) values (P<0.05). In contrast, ITT results indicated no significant differences in blood glucose levels or AUC among the DEHP exposure groups at all time points (P>0.05). Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited significantly higher HOMA-IR levels and markedly lower HOMA-ISI values (P<0.05). HE and TEM showed that in each DEHP exposure group, the number of islet cells decreased, the islet area reduced, and chromatin condensation occurred. The endocrine granules in the cytoplasm of islet β cells decreased, and there were varying degrees of widening of the nuclear membrane gap, flattening and expansion of the Golgi complex, and expansion of the endoplasmic reticulum. Ribosome separation was observed, and autophagosomes were visible. In the 375 and 750 mg·kg⁻¹ DEHP groups, the mitochondria were deformed to varying degrees, and some cristae structures disappeared, presenting vacuolization. Moreover, the chromatin condensation in the nuclei was more severe in the 750 mg·kg⁻¹ DEHP group. The serum SOD activity was significantly elevated in the 750 mg·kg⁻¹ DEHP group (P<0.05). Both the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP groups exhibited a significant increase in the relative ROS content in pancreatic tissue (P<0.05). In DEHP-treated groups, the MDA content increased (P<0.05), while the GSH content decreased (P<0.05). Additionally, in the 750 mg·kg⁻¹ DEHP group, the AMP/ATP ratio in serum was significantly raised (P<0.05), and the expression of cleaved Caspase-3 protein in pancreatic tissue was also significantly increased (P<0.05). The relative mRNA levels of p62, Beclin-1, LC3, and Caspase-8 in the pancreatic tissue of rats exposed to DEHP were significantly elevated (P<0.05). The relative expression levels of p-AMPK/AMPK, p-ULK1/ULK1, and Beclin-1 proteins in the DEHP-treated groups were significantly increased (P<0.05). In the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP treatment groups, the relative expression levels of p62, LC3 II/LC1, and Caspase-8 proteins were significantly increased (P<0.05), while the relative expression level of p-mTOR/mTOR was significantly decreased (P<0.05). Conclusion DEHP can disrupt glucose homeostasis by inducing oxidative stress, which subsequently activates autophagy via the ROS/AMPK/ULK1 pathway, impairing autophagic flux and promoting apoptosis of islet β cells, ultimately decreasing their function and number.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

OBJECTIVE: To investigate the effectiveness of the suture anchor technique without knots for reconstruction of the anterior talofibular ligament (ATFL) combined with the reinforcement of the inferior extensor retinaculum in treating chronic lateral ankle instability (CLAI). METHODS: The clinical data of 31 patients with CLAI who were admitted between August 2017 and December 2023 and met the selection criteria were retrospectively analyzed. There were 18 males and 13 females, with an age range from 20 to 48 years (mean, 34.6 years). All patients had a history of repeated ankle sprain, with a disease duration of 6-18 months (mean, 9.65 months). The anterior drawer test and inversion stress test were positive, and tenderness was present in the ligament area. Stress X-ray films of the ankle joint showed a talar tilt angle of (10.00±2.78)° and an anterior talar displacement of (9.48±1.96) mm on the affected side. MRI revealed discontinuity, tortuosity, or disappearance of the ATFL structure. Preoperatively, the visual analogue scale (VAS) score was 5.2±2.1, and the American Orthopaedic Foot and Ankle Society (AOFAS) score was 62.9±7.1. All patients underwent arthroscopic debridement of the ankle joint followed by reconstruction of the ATFL using the suture anchor technique without knots combined with reinforcement of the inferior extensor retinaculum. Postoperatively, pain and function were assessed using the VAS and AOFAS scores. Stress X-ray films were taken to measure the talar tilt angle and anterior talar displacement to evaluate changes in ankle joint stability. Patient satisfaction was assessed according to the Insall criteria. RESULTS: All 31 surgeries were successfully completed. One case had wound exudation, while the remaining surgical incisions healed by first intention. Two cases experienced numbness on the lateral aspect of the foot, which disappeared within 1 month after operation. All patients were followed up 15-84 months (mean, 47.2 months). No complication such as anchor loosening, recurrent lateral ankle instability, superficial peroneal nerve injury, rejection reaction, or wound infection occurred postoperatively. The anterior drawer test and inversion stress test were negative at 3 months after operation. Stress X-ray films taken at 3 months after operation showed the talar tilt angle of (2.86±1.72)° and the anterior talar displacement of (2.97±1.32) mm, both of which were significantly different from the preoperative values ( t=12.218, P<0.001; t=15.367, P<0.001). At last follow-up, 2 patients had ankle swelling after exercise, which resolved spontaneously with rest; all 31 patients returned to their pre-injury level of sports or had no significant discomfort in daily activities. At last follow-up, 25 patients were pain-free, 4 had mild pain after exercise, and 2 had mild pain after walking more than 2 000 meters. The VAS score was 0.8±0.9 and the AOFAS score was 91.6±4.1, both of which were significantly different from the preoperative scores ( t=10.851, P<0.001; t=-19.514, P<0.001). According to the Insall criteria, 24 patients were rated as excellent, 4 as good, and 3 as fair, with a satisfaction rate of 90.3%. CONCLUSION The suture anchor technique without knots for reconstruction of the ATFL combined with reinforcement of the inferior extensor retinaculum provides satisfactory short- and mid-term effectiveness in treating CLAI.
Humans ; Male ; Adult ; Female ; Joint Instability/surgery* ; Lateral Ligament, Ankle/surgery* ; Retrospective Studies ; Middle Aged ; Ankle Joint/diagnostic imaging* ; Young Adult ; Suture Anchors ; Treatment Outcome ; Suture Techniques ; Plastic Surgery Procedures/methods* ; Chronic Disease ; Ankle Injuries/surgery*

Objective:To investigate the clinical characteristics and treatment outcomes of patients with blast-induced hearing loss（BIHL）. Methods:The clinical features, laboratory parameters, audiometric profiles, and treatment efficacy of patients with blast induced hearing loss and those with idiopathic sudden hearing loss（ISHL） were analyzed using t-tests, Wilcoxon rank-sum tests, and chi-square tests, with a significance level set at P<0.05. Results:A total of 59 patients in the BIHL group and 117 patients in the ISHL group were included in this study. The mean age of the BIHL group was（39.07±14.49） years, comprising 45 males and 14 females. After the blast, 21 patients went to the hospital within the initial 14-day period, and an additional 38 patients seeking admission thereafter. In the BIHL group, 33 patients had unilateral hearing loss with PTA of （50.30±28.85） dB HL, while 26 had bilateral hearing loss with a PTA of（44.54±26.22） dB HL. In comparison, among the ISHL group, 112 patients had unilateral hearing loss with a PTA of（56.28±14.19） dB HL, and 5 had bilateral involvement with a PTA of（56.25±35.14） dB HL. The effective treatment rate within 14 days for the BIHL group was 31.8%, while for the ISHL group, the effective rate within 14 days was 77.0%. Conclusion:Blast-induced hearing loss is caused by exposure to high-intensity noise. The overall treatment effectiveness during hospitalization is lower compared to idiopathic sudden hearing loss, and the treatment window is shorter. Therefore, greater emphasis should be placed on prevention.
Humans ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Blast Injuries/therapy* ; Treatment Outcome ; Hearing Loss, Sudden/etiology* ; Adolescent ; Hearing Loss, Noise-Induced/diagnosis*

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

Objective:To prepare pullulan-spermine (PS)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated with CD3 antibody, and to investigate their effects on T cell proliferation and cytokine secretion.Methods:Purulan polysaccharide was sperminized to synthesize PS, hydrophobically modified, and then grafted with PLGA to synthesize PS-PLGA. Infrared spectroscopy and nuclear magnetic resonance hydrogen spectrum were used to characterize the structure of PS-PLGA. PS-PLGA NPs were prepared by ultrasonic dialysis method and then coupled with CD3 antibody to prepare PS-PLGA-CD3 NPs. The morphological features of PS-PLGA-CD3 NPs were observed by the transmission electron microscope. The particle sizes, Zeta potential and dispersive coefficient of the NPs were measured using the dynamic laser particle size analyzer. The amount of coupled CD3 antibody on the surface of the NPs was determined using quantitative fluorescence analysis method. The effects of 1, 10, 50, 100, and 200 μg/ml PS-PLGA-CD3 NPs on T-cell proliferation were determined using cell counting kit-8 method. The effects of 1, 10, 50, 100, 200 μg/ml PS-PLGA-CD3 NPs on secretion of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-β (TNF-β) by T cell were determined by enzyme-linked immunosorbent assay. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:Pullulan and PS showed strong absorption at 2 939 cm ?1, and PS had a weaker absorption peak at 3 384 cm ?1 than pullulan. The proton peaks of spermine appeared at chemical shifts of 1.25 to 1.50, 1.63, and 2.25 to 2.75. The characteristic peaks of PLGA appeared at chemical shifts of 1.50, 3.40, and 4.80 to 5.30. Compared to pullulan, the characteristic peaks of both PS and PLGA appeared in the corresponding intervals for PS-PLGA. The morphology of PS-PLGA-CD3 NPs with spermine substitution at 9.7% was all regular and circular, with a mean particle size of (173.3±24.5) nm, a Zeta potential of (?12.78±3.68) mV, the dispersive coefficient of 0.254±0.101, and the CD3 antibody mass fraction of (52.1±9.4) μg/mg. The differences in cell survival were statistically significant for PS-PLGA-CD3 NPs and PS-PLGA NPs, respectively, after co-incubation with T cell after 24, 48, and 72 h at concentrations of 50, 100, and 200 μg/ml, respectively (all P<0.05). The results of the three concentration comparisons after 24 h of co-incubation were [(129.8±23.1)% vs (95.5±8.9)%, (137.5±22.7)% vs (95.1±15.8)%, and (142.3±25.6)% vs (93.2±9.2)%]; and the results after 48 h were [(145.9±23.7)% vs (95.8±10.6)%, (149.3±23.5)% vs (94.9±16.3)%, and (161.2±26.9)% vs (91.5±8.3)%]; and the results after 72 h were [(147.6±20.1)% vs (95.9±17.8)%, (152.4±22.3)% vs (92.7±16.5)%, and (167.7±25.4)% vs (90.8±17.4)%]. The differences in the levels of IFN-γ, IL-2 and TNF-β were statistically significant (all P<0.05 or 0.01) at 50, 100 and 200 μg/ml concentrations for PS-PLGA-CD3 NPs and PS-PLGA NPs, respectively. For IFN-γ, the results of the comparison of the three concentrations were [(35.7±3.1) ng/ml vs (16.4±6.9) ng/ml, (67.3±5.2) ng/ml vs (19.6±2.8) ng/ml, and (79.0±4.2) ng/ml vs (19.3±2.3) ng/ml]; and for IL-2, the results were [(43.5±8.2) ng/ml vs (12.6±1.9) ng/ml, (53.5±7.8) ng/ml vs (15.8±3.3) ng/ml, and (64.0±8.2) ng/ml vs (17.4±3.8) ng/ml]; and for TNF-β, the results were [(108.4±18.9) pg/ml vs (40.8±1.3) pg/ml, (152.3±28.3) pg/ml vs (56.4±3.7) pg/ml and (185.0±33.6) pg/ml vs (81.6±10.2) pg/ml]. Conclusions:PS-PLGA-CD3 NPs are successfully prepared, which have the function of effectively promoting T cell proliferation and cytokine sectetion.

Objective:To establish fingerprints and method for determining the content of two components of Qigong Pills.Methods:High performance liquid chromatography (HPLC) was used to establish the fingerprints of 10 batches of Qigong Pills and common peaks were identified. TCM Chromatographic Fingerprint Similarity Evaluation System (2012 Edition) was used for similarity analysis; the common peaks area was used as indicators, and SIMCA 14.1 was used for cluster analysis and principal component analysis for quality evaluation; a content analysis method was established using hesperidin and Atractylodes macrocephala as indicator components.Results:21 common peaks in the 10 batches of Qigong Pills were identified with the similarity greater than 0.952 (except for the sample S6); the clustering analysis results showed that at a measurement distance of 8, S6 was clustered into one category alone, S1 and S2 were clustered into one category, and the remaining samples were clustered into one major category. The content of hesperidin and Atractylodes macrocephala in 10 batches of Qigong Pills was 3.61-8.92 mg/g and 0.07-0.72 mg/g, respectively.Conclusion:The established HPLC fingerprints and content determination method in this study are stable, reliable, and reproducible, which can provide reference for quality control and evaluation of Qigong Pills.

Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data（including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography）, imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
Humans ; Connexins/genetics* ; Connexin 26/genetics* ; Hearing Loss, Central/genetics* ; Deafness/genetics* ; Mutation