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:The purpose of this study was to investigate the diagnostic value and clinical significance of cochlear microphonics (CM) combined with otoacoustic emission (OAE) in patients with auditory neuropathy (AN).Methods:The study included patients who were diagnosed with bilateral AN and had CM originating from both sides. The CM amplitude, latency, duration and intensity-amplitude (I/O) function curve were recorded by CM test. According to whether the distortion product otoacoustic emissions (DPOAE) passed through, the patients were divided into three groups: bilateral OAE passed group (OAE PP Group), bilateral OAE failed group (OAE RR Group), and unilateral OAE passed through one side failed group (OAE PR Group). OAE was elicited by four or more frequencies of 750-8 000 Hz. The characteristics of CM and its related influencing factors were analyzed, and data were processed and analyzed by SPSS 26.0 software. Results:(1) A total of 256 patients (512 ears) with AN were enrolled, including 161 patients (322 ears) in OAE PP group, 32 patients (64 ears) in OAE PR group and 63 patients (126 ears) in OAE RR group. OAE failed in 30.9% of patients with AN. (2) When the stimulation intensity was 100 dB nHL, the CM amplitude of OAE passing ear (OAE P+CM P group) in AN patients aged 3 years was 0.43±0.17μV, which was significantly higher than that of OAE not passing ear (OAE R+CM P group) (0.29±0.15) μV ( t=4.876， P<0.001). The CM duration of the OAE P+CM P group was (5.18±1.04) ms, which was longer than that of the OAE R+CM P group at 4.60±1.12 ms ( P=0.005). The I/O function curve of OAE P+CM P group showed a nonlinear trend, while, that of OAE R+CM P group showed a linear trend. (3) In the OAE P+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, disease course, PTA, and ASSR threshold ( P<0.001), with correlation coefficients of r=-0.475, r=-0.519, r=-0.367, r=-0.374, and r=-0.494, respectively. In the OAE R+CM P group of AN patients, the amplitude of CM was negatively correlated with the onset age, test age, and ASSR threshold ( P<0.05), with correlation coefficients of r=-0.271, r=-0.240, and r=-0.287, respectively. Conclusions:Excluding patients with high-frequency steeply sloping hearing loss, when ABR is absent or abnormal and OAE is absent, CM detection can reduce the rate of missed diagnosis of AN. The analysis of CM amplitude and I/O function curve is helpful to determine the lesion site of AN patients, which is convenient for early diagnosis and effective intervention.

Objective:To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation.Methods:A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241).Results:MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c. 1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c. 2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP1) and likely pathogenic (PM2_Supporting+ PM3+ PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.

Reconstruction of low-dose CT image faced problems such as low resolution,blurred artifacts and strong noise.Deep learning reconstruction met the needs of reducing radiation dose and improving imaging quality,promoted reconstruction of CT image towards high efficiency,intelligence and integration of clinical diagnosis and treatment.The research progresses in deep learning low-dose CT imaging reconstruction were reviewed in this article.

Objective To explore the value of quantitative analysis of perirenal fat combined with Mayo adhesive probability(MAP)score in predicting the WHO/International Society of Urological Pathology(ISUP)nuclear grade of renal cell carcinoma(RCC).Methods The imaging data of 139 pathologically confirmed RCC patients were retrospectively analyzed.The patients were divided into low-grade group(grade Ⅰ-Ⅱ,n=112)and high-grade group(grade Ⅲ-Ⅳ,n=27)according to the WHO/ISUP nuclear grade.Spearman correlation analysis was used to assess the relationship between fat features and WHO/ISUP nuclear grade.The multivariate logistic regression model was used to detemine the related factors of high-grade RCC,and the area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of each parameter.Results The AUC of perirenal adipose tissue(PAT)％alone for evaluating high-grade RCC was the highest,at 0.77[95％confidence interval(CI)0.69-0.83].The stepwise multivariate logistic regression model showed that perinephric fat stranding(PFS)[odds ratio(OR)=34.54,95％CI 7.60-156.87,P＜0.001],PAT％(OR=0.46,95％CI 0.32-0.66,P＜0.001),and tumor location(OR=0.26,95％CI 0.07-0.92,P=0.037)were related factors of high-grade RCC,with an AUC of 0.90(95％CI 0.84-0.94).Conclusion Quantitative analysis of perire-nal fat combined with MAP score can effectively predict the WHO/ISUP nuclear grade of RCC,providing a novel approach for per-sonalized treatment strategies to improve prognosis.

OBJECTIVE: To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation. METHODS: A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241). RESULTS: MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c.1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c.2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+PM2_Supporting+PM3+PP1) and likely pathogenic (PM2_Supporting+PM3+PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.
Humans ; Male ; Pedigree ; Cholestasis, Intrahepatic/diagnostic imaging* ; Adenosine Triphosphatases/genetics* ; Female ; Adult ; Exome Sequencing ; Mutation ; East Asian People

Objective To investigate the research hotspot and development trend of noise-induced hearing loss(NIHL)in the past 30 years.Methods The CNKI(China national knowledge infrastructure)database,Wanfang Medical network and VIP database.NoteExpress were used for literature screening.CiteSpace 6.1.R6 software were used for bibliometric analysis and data visualization.Results A total of 3 823 articles were included for analy-sis.The top 3 keywords were:"noise","hearing loss",and"noise-induced deafness".A total of 358 literatures were published on the pathogenesis of NIHL.The pathogenesis included oxidative stress,genetic susceptibility,mechanical damage,microcirculation disturbance,calcium overload,etc.Conclusion The number of papers pub-lished in the field of NIHL has increased year by year,and the overall development can be divided into three stages:exploration of the influence of noise,research on etiology,and prevention and assessment of occupational noise-in-duced hearing loss.In terms of pathogenesis,the oxidative stress mechanism has been widely recognized by schol-ars,and genetic susceptibility has become a research hotspot.