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

With the advance of research, non-coding RNA has been found to surpass the traditional definition to directly code functional proteins by coding sequence elements and binding with ribosomes. Among the non-coding RNAs, the function of circRNA encoded proteins has been most extensively studied. This study has used "circRNA", "encoded", and "translation" as the key words to search the PubMed and Web of Science databases. The retrieved literature was screened and traced, with the translation mechanism, related research methods, and correlation with diseases of circRNA reviewed. CircRNA can translate proteins through a non-cap-dependent pathway. Multiple molecular techniques, in particular mass spectrometry analysis, have important value in identifying unique peptide segments of circRNA encoded proteins for confirming their existence. The proteins encoded by the circRNA are involved in the pathogenesis of diseases of the digestive, neurological, urinary systems and the breast, and have the potential to serve as novel targets for disease diagnosis and treatment. This article has provided a comprehensive review for the basic theory, experimental methods, and disease-related research in the field of circRNA translation, which may provide clues for the identification of new diagnostic and therapeutic targets.

BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.
Humans ; Depressive Disorder, Major/pathology* ; Brain/pathology* ; Antidepressive Agents/therapeutic use* ; Visual Cortex/pathology*

In this paper, the current situation and existing problems of spinal surgery practice are analyzed and summarized. Combined with the review of the structure and function of spinal region, we have expounded the application and advantages of Essential Anatomy software in the clinical practice teaching of spinal surgery. This software has a friendly interface, simple operation, real content, intuitive and visual model, and it can provide videos and slice function, which makes the original complex and abstract spinal anatomy practice content become novel and vivid, and greatly deepens doctors' understanding of the structure, function, movement and the disease pathogenesis of spinal region. At the same time, it also greatly mobilizes the learning interest and initiative of the clinical practice doctors, and improves the effect of clinical practice.

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

Objective To explore the effect of the combination of Tuina and treadmill training on denervation skeletal muscle atrophy. Methods A total of 80 Sprague-Dawley rats (one month old) were randomly divided into control group (n=40) and manipulation group (n=40). Their sciatic nerves were transected, and the manipulative group accepted treadmill training and kneading of Tuina, while the control group accepted no intervention. Their muscle wet weight ratio, muscle satellite cells and insulin-like growth factor I (IGF-I) positive cells count were measured, and HE staining of gastrocnemius muscle were observed one, two, three and four months after intervention, ten rats in each group. Results Compared with the control group, the muscle wet weight ratio decreased three months after intervention (F=4.590, P<0.05), muscle satellite cells increased three months after intervention (F=12.466, P<0.01), and IGF-I positive cells increased two, three and four months after intervention (F>6.489, P<0.05). HE staining showed the skeletal muscle injury relieved somehow.Conclusion The combination of Tuina and treadmill training can relieve denervation skeletal muscle injury, but it is not enough for skeletal muscle atrophy, which may associate with promoting the expression of muscle satellite cells and IGF-I.

Objective To compare sinus tarsi approach(STA) and extensile L shape approach (ELA) in the surgical treatment of calcaneal fractures. Methods A total of 51 cases of calcaneal fractures treated from May 2014 to December 2016 were enrolled. Twenty of them were performed ORIF via the sinus tarsi approach, while the other 31 cases were performed ORIF via lateral extensile L shape approach. X-ray films were taken postoperatively to record the changes of B?hler angle and Gissane angle. The AOFAS, VAS and SF-36 scores were adopted to assess the therapeutic effect. Results The average follow-up period of STA group was 15.5 months. And patients in ELA group were followed up for an average period of 18.4 months. All the fractures in the series had a boney union at or before the final follow-up. The final correction of B?hler angle (34.60 ± 2.91)° , and Gissane angle (114.45 ± 2.91)° was significantly increased in the STA group; and the final correction of B?hler angle (33.55 ± 2.73)° , and Gissane angle (112.81 ± 4.15)° was also significantly increased in the ELA group; while there was no significant difference between the two groups. The final AOFAS scores , VAS scores and SF-36 scores of the STA were (83.56 ± 7.13), (1.78 ± 0.89), (88.95 ± 4.31) scores, while those in ELA group were (81.91 ± 9.89), (2.01 ± 1.33) and (86.65 ± 4.95) scores. There was no significant difference between the two groups (P>0.05). No wound problem happened in STA group, but there were 2 cases who had wound complications in ELA group. Conclusions No significant difference is found between the two groups in the short-term efficacy of the treatment for calaneal fracture. However, STA has the advantages of lower soft tissue complication rate.

Objective To explore the treatment experience and surgical strategy in papillary thyroid carcinoma (PTC) patients with parapharyngeal lymph node metastasis. Methods A retrospective review was performed on ten patients with PTC metastasis to parapharyngeal lymph node from January 2005 to August 2014. The treatment experience and surgical strategy were analyzed. Results Three patients accepted initial treatment and 7 patients had a history of surgical treatment prior to PTC. Parapharyngeal lymph node metastasis was diagnosed by imaging examination or fine needle aspiration cytology. Resection of lymph node metastasis was performed via transcervical approach and transmandibular approach. Total thyroidectomy and neck dissection were performed synchronously. All patients received 131I therapy after surgery and did not have recurrence in neck or parapharyngeal space. During follow-up, 3 patients died in 5 years because of lung metastasis, 3 patients survived with tumor , and 4 patients survived without recurrence. The 5-year overall survival rate was 7/10 and the 5-year disease-free was 4/10. Conclusions Parapharyngeal lymph node metastasis from PTC may occur in patients with previous neck dissection or widespread cervical metastases. CT and MRI is helpful for establishing the diagnosis. Surgical resection remains the mainstay of treatment for this disease. PTC patients with parapharyngeal lymph node metastasis have a poor prognosis.

Objective To investigate the application value of transcystic choledochoscopy combined with holmium laser for common bile duct stones . Methods Clinical data of 16 patients with common bile duct stones who underwent transcystic choledochoscopy and holmium laser cholelithotripsy between March 2012 and December 2013 in this hospital were retrospectively analyzed.During holmium laser cholelithotripsy (1.0 J/10 Hz, 400 μm fiber), the stones were fragmented under direct vision of choledochoscopy and were extracted by using water flushing or a stone basket . Results The stones were successfully removed in 15 patients, including 6 cases of laparoscopic operation and 9 cases of open operation .The operation time was (132 ±27) min for open surgery and (156 ±33) min for laparoscopic surgery .The stone fragment and removal time was (30.2 ±8.5) min for open surgery and (45.6 ±10.4) min for laparoscopic surgery .The hospital stay was (9.7 ±1.4) d.There was 1 case of failed cholelithotripsy due to obstructed water flow and blurry vision .Follow-up examinations in 14 cases for 2-24 months found no recurrence of stones or biliary strictures. Conclusion Transcystic choledochoscopy and holmium laser cholelithotripsy is intuitive , accurate, and effective, being a safe and reliable alternative for choledocholithiasis .