BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective:To explore the value of mitoxantrone hydrochloride injection for tracing in endoscopic thyroidectomy (ETE) via anterior chest approach for papillary thyroid carcinoma (PTC) .Methods:A retrospective analysis was conducted on patients undergoing ETE via anterior chest approach for PTC admitted to Beijing Longfu Hospital (Medical Treatment Combination with Peking Union Medical College Hospital) from Sep. 2022 to Mar. 2024. The patients were divided into two groups: the control group (without tracer) and the tracer group (with mitoxantrone hydrochloride injection for tracing). All surgeries were performed by the same thyroid surgical team. Baseline, postoperative pathologies and complications were compared between the 2 groups.Results:A total of 25 patients (13 in the control group and 12 in the tracer group) were included in this study, and the average dissection of unilateral central region lymph nodes in the tracer group was 7.4±4.6, significantly more than in the control group (2.4±1.9) ( P=0.004). There were no instances of mistakenly resected parathyroid gland in the postoperative pathology or accidental injury of recurrent laryngeal nerve in either group. The incidence of transient hypocalcemia did not significantly different between the two groups ( P=0.503). However, the incidence of transient hypoparathyroidism in the tracer group was 1 (1/12,8.3%), significantly lower than in the control group 4 (4/13,30.8%) ( P=0.009). The tracer group exhibited more impressive levels in parathyroid hormone (5.4±8.1) pg/mL compared to the control group (20.0±11.1) pg/mL ( P=0.001) .The total volume of postoperative drainage in the tracer group (142.9±71.7) mL was more than that of the control group (87.7±38.8) mL ( P=0.030). But It did not affect the extubation time in either group ( P=0.610). No residual tracer was observed at the skin puncture site in the tracer group after 2 weeks. Conclusions:Mitoxantrone hydrochloride injection for tracing as tracer in ETE via breast approach can increase the number of pathological lymph nodes dissection in cervical central region. Combined with negative development, identifying and protecting the function of parathyroid glands show feasible and potential application value to improve the safety of thyroidectomy. The use of mitoxantrone hydrochloride injection for tracer has the risk of increased exudation from the surgical area, but does not affect the time to remove the drain.

Apelin is an adipokine family which includes Apelin-13,Apelin-36 and other isoforms and regulates phys-iological functions by immunomodulation,oxidative stress,glycolipid metabolism,and apoptosis and so on.Apelin is closely related to polycystic ovary syndrome,ovarian cancer and other diseases of the female reproductive system so it is expected to be new target molecules and may orient the development of research and clinical treatment.

MiRNAs are a class of small non-coding RNAs,which regulate gene expression post-transcriptionally by partial complementary base pairing.Aberrant miRNA expressions have been reported in tumor tissues and peripheral blood of cancer patients.In recent years,artificial intelligence algorithms such as machine learning and deep learning have been widely used in bioinformatic research.Compared to traditional bioinformatic tools,miRNA target prediction tools based on artificial intelligence algorithms have higher accuracy,and can successfully predict subcellular localization and redistribution of miRNAs to deepen our understanding.Additionally,the construction of clinical models based on artificial intelligence algorithms could significantly improve the mining efficiency of miRNA used as biomarkers.In this article,we summarize recent development of bioinformatic miRNA tools based on artificial intelligence algorithms,focusing on the potential of machine learning and deep learning in cancer-related miRNA research.

Chondroitin sulfate sodium is a sulphated glycosaminoglycan composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-galactosamine,prepared from the cartilage tissue of land or marine animal by a specific extraction and purification process.Chondroitin sulfate sodium is considered to have anti-osteoarthritis effect and many other potential physiological activities.It has broad application prospects and development space in the fields of health food,cosmetics,and drugs.This paper reviews the preparation process of chondroitin sulfate sodium,development and problems of microbial synthesis technology and the research status of anti-osteoarthritis activity based on cells models,animal models and clinical randomized controlled trials(RCT).The limitations of current research are analyzed and corresponding strategies are proposed to provide reference for further standardization and development of chondroitin sulfate sodium.

Objective:To explore the optimal ratio of dihydrotestosterone and hydroxyflutamide (hereinafter referred to as DH), construct a dual release system of androgen and its antagonist, and analyze the application effect of this system in the repair of full-thickness burn wounds in mice.Methods:This study was an experimental study. The HaCaT cells were divided into blank group (without drug culture), low baseline group, medium baseline group, and high baseline group according to the random number table (the same grouping method below), and the last three groups of cells were cultured by adding three different ratios of DH. Under a medium ratio, the mass of dihydrotestosterone in the three baseline groups from low to high was 1.4, 2.8, and 4.0 μg, respectively, and the mass of hydroxyflutamide was 1.2, 1.6, and 2.0 μg, respectively. On this basis, under a small ratio, the mass of dihydrotestosterone was reduced by half and the mass of hydroxyflutamide was increased by half; under a large ratio, the mass of dihydrotestosterone was increased by half and the mass of hydroxyflutamide was reduced by half. After culture of 2 days, the cell proliferation level was detected by cell counting kit 8 ( n=4). Sixteen 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into blank group, small ratio group, medium ratio group, and large ratio group, with 4 mice in each group. On post injury day (PID) 7, normal saline containing different ratios of DH was locally dropped to the wounds of mice in the last three groups of mice (the total mass of DH in the three ratio groups from small to large was 127.5, 165.0, and 202.5 μg, respectively, and the mass ratios of dihydrotestosterone to hydroxyflutamide (hereinafter referred to as drug mass ratio) were 8∶9, 8∶3, and 8∶1, respectively), afterwards, the administration was repeated every 48 hours until PID 27; normal saline was dropped to the wound of mice in blank group at the aforementioned time points. The wound healing status on PID 0 (immediately), 7, 14, 21, and 28 was observed, and the wound healing rates on PID 7, 14, 21, and 28 were calculated ( n=4). On PID 28, the wound tissue was taken, which was stained with hematoxylin and eosin for observing re-epithelialization and with Masson for observing collagen fibers, and the proportion of collagen fibers was analyzed ( n=3). Twenty 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into ordinary scaffold group, small proportion scaffold group, medium proportion scaffold group, and large proportion scaffold group (with 5 mice in each group). On PID 7, the wound was continuously dressed with a polycaprolactone scaffold without drug and a polycaprolactone scaffold containing DH with a drug mass ratio of 1∶3, 1∶1, or 3∶1 (i.e. the dual release system of androgen and its antagonist, with total mass of DH being about 1.7 mg) prepared by using electrospinning technology until the end of the experiment. Histopathological analyses of tissue ( n=3) at the same time points as those in the previous animal experiment were performed. On PID 7 and 14, the wound exudates were collected and the relative abundance of bacterial communities was analyzed using 16S ribosomal RNA high-throughput sequencing ( n=3). Results:After culture of 2 days, under a small ratio, the proliferation levels of HaCaT cells in low baseline group and high baseline group were significantly higher than the level in blank group ( P<0.05). As the time after injury prolonged, the wounds of all four groups of mice continued to shrink. On PID 14, the wound healing rate of mice in large ratio group was 72.5% (61.7%, 75.1%), which was close to 53.3% (49.5%, 64.4%) in blank group ( P>0.05); the wound healing rates of mice in small and medium ratio groups were 74.2% (71.0%, 84.2%) and 70.4% (65.1%, 74.4%), respectively, which were significantly higher than the rate in blank group (with both Z values being -2.31, P<0.05). On PID 21, the wound healing rate of mice in small ratio group was significantly higher than that in blank group ( Z=-2.31, P<0.05). On PID 28, the wounds of mice in the three ratio groups were completely re-epithelialized and the epidermis was thicker than that in blank group; compared with that in blank group, the collagen fiber content in the wound tissue of mice in the three ratio groups was higher and arranged more orderly, and the proportions of collagen fibers in the wound tissue of mice in small and large ratio groups were significantly increased ( P<0.05). On PID 28, the wounds of mice in ordinary scaffold group were partially epithelialized, while the wounds of mice in the three proportion scaffold groups were almost completely epithelialized. Among them, the wounds of mice in small proportion scaffold group had the thickest epidermis. The proportion of collagen fibers in the wound tissue of mice in small proportion scaffold group was significantly increased compared with that in ordinary scaffold group ( P<0.05). On PID 7, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Corynebacterium, Staphylococcus, and Rhodococcus. On PID 14, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Stenotrophomonas, Rhodococcus, and Staphylococcus, and the number of bacterial species in the wound exudation of mice in the three proportion scaffold groups was more than that in ordinary scaffold group. Conclusions:When the drug mass ratio is relatively small, DH has the effect of promoting the proliferation of HaCaT cells. The ratio of 8∶9 is the optimal mass ratio of dihydrotestosterone to hydroxyflutamide, and DH with this mass ratio can promote re-epithelialization and collagen deposition of full-thickness burn wounds in mice, and promote wound healing. The constructed dual release system of androgen and its antagonist with DH in a 1∶3 drug mass ratio contributes to the re-epithelialization and collagen deposition of the full-thickness burn wounds in mice, and can improve the diversity of wound microbiota.

Adrenal epithelioid sarcoma is very rare in clinic. A case of epithelioid sarcoma of the right adrenal gland was reported in this paper. After physical examination, the patient was found to have a mass in the right adrenal area and underwent right adrenalectomy. The postoperative pathological diagnosis was right adrenal epithelioid sarcoma. Two months after adrenalectomy, positron emission tomography computed tomography(PET/CT) noted recurrence at the tumor bed and multiple metastases.The patient underwent chemotherapy combined with immunotherapy. After 16 months of follow-up, the disease was stable.

Objective:To analyze the electrophysiological characteristics of subacute combined degeneration of spinal cord in 10 patients with nitrous oxide poisoning.Methods:Ten patients with nitrous oxide poisoning (case group) and 20 controls (control group)treated in Dalian Municipal Central Hospital Affiliated of Dalian Medical University from January 2016 to January 2020 were included in this study. MRI and electrophysiological examinations were performed on the head, cervical spine and thoracic spine, including distal motor latency (DML), motor nerve amplitude (CMAP), motor conduction velocity (MNCV), sensory conduction velocity (SNCV), sensory nerve amplitude (SNAP), N20 latency of upper limb cortical somatosensory evoked potential and P40 latency of lower limb cortical somatosensory evoked potential. The above indexes were compared between the two groups.Results:In the case group, DML of motor nerve was prolonged, MNCV was slowed down, CMAP was decreased, SNCV was slowed down and SNAP was decreased compared with the control group, the differences were statistically significant ( P<0.05). The incubation periods of N20 and P40 in the case group were longer than those in the control group: (32.70 ± 3.34) ms vs. (18.85 ± 1.37) ms, (57.00 ± 4.08) ms vs. (38.40 ± 1.54) ms, the differences were statistically significant ( t = 16.20, 18.20, P<0.01). The inverted "V" type T 2 long signal of cervical spinal cord and thoracic spinal cord could be seen on MRI of cervical or cervical and thoracic vertebrae in 5 patients. Conclusions:Nitrous oxide poisoning can cause obvious subacute combined degeneration of spinal cord, involving peripheral nerve and spinal cord damage. Peripheral nerve damage can involve motor fibers and sensory fibers, mainly axonal damage, accompanied by demyelination damage, especially in both lower limbs.

Objective:To investigate the clinical value of fetal ultrasonography in the screening of congenital heart malformations in twins at 11-13 + 6 weeks of gestation. Methods:A retrospective cohort study method was used.Cases were collected from Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital (January 2012 to December 2016) and the Fourth Hospital of Shijiazhuang City (January 2014 to December 2018). The twins with singleton or twins with cardiac malformation were screened out as the cardiac malformation group, and the twins with normal delivery during the same period were selected as the control group. Ultrasound data such as the nuchal translucency (NT), crown-rump-length (CRL), chorionicity, conception method, NT discordance, CRL discordance, NT discordance ≥20% incidence rate between twins, and the CRL discordance ≥10% incidence rate between twins in the two groups at 11-13 + 6 weeks were compared and analyzed. Results:①There were 30 cases in the cardiac malformation group (including 27 twins with singleton cardiac malformation and 3 twins with twin cardiac malformation) and 1 906 cases in the control group. ②The incidence rates of NT value ≥95th percentile and NT value ≥99th percentile in one or two pregnancies were significantly higher in the cardiac malformation group than in the control group (20.00% vs 2.20%, P<0.001; 10.00% vs 0.63%, P=0.002), the area under the ROC curve (AUC) for cardiac malformation screening was 0.589 and 0.549, respectively; CRL discordance in cardiac malformation group was higher than that in control group ( P=0.018), the incidence of CRL discordance ≥10% in the cardiac malformation group was higher than that in the control group (26.67% vs 12.70%, P=0.024), the AUC of cardiac malformation screening was 0.570; there were no significant differences in the incidence of NT discordance, the incidence of NT discordance ≥20%, pregnancy pattern and chorionicity between the two groups (all P>0.05). ③Multivariate Logistic regression analysis was performed using the incidence rates of NT value ≥95% and NT value ≥99%, CRL discordance ≥10%, and NT discordance ≥20%. The incidences of fetal NT value ≥95% and NT value ≥99% were risk factors for cardiac malformation in twins ( OR=11.095, 105.778; 95% CI=4.311-28.558, 16.984-658.796). Conclusions:Ultrasound at 11-13 + 6 weeks of gestation showing thickened value of one or two fetuses, and the CRL discordance≥10%, indicates an increased risk of cardiac malformation in the twins; NT value ≥95% and NT value ≥99% is a risk factor for heart defects in twins.

Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 10⁸ μm³, 0.44 × 10⁸ μm³ and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 10⁸ μm³, 0.38 × 10⁸ μm³ and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.