Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
.
Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

With the advancement of rigid endoscopic nasal surgery techniques, the indications for surgery have continued to expand, encompassing an increasing number of anatomical regions. As a surgical adjunct, imaging-guided system assists surgeons in identifying vital structures and mitigating surgical risks, and they are extensively employed in operations involving the nasal cavity, sinuses, and skull base. Nevertheless, existing imaging-guided system faces several unresolved challenges. With ongoing technological advancements and the integration of novel technologies, these systems are demonstrating renewed vigor.
Humans ; Skull Base/surgery* ; Endoscopy/methods* ; Surgery, Computer-Assisted/methods*

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Objective:To explore the clinical characteristics of pregnancy complicated by primary Sj?gren's syndrome (pSS) and the related factors of adverse outcomes in pregnant women with pSS.Methods:A retrospective analysis was conducted on the clinical data of 32 pregnancies complicated by pSS treated in the Department of Obstetrics at the Third Affiliated Hospital of Guangzhou Medical University from February 2017 to August 2022. The patients were divided into two groups according to whether they had perinatal adverse outcomes: an adverse outcome group ( n=20) and a favorable outcome group ( n=12). The clinical characteristics of the two groups were compared with two independant sample t-test, Mann-Whitney U test, and Fisher's exact test, and multivariate logistic regression analysis was used to analyze the related factors of adverse outcomes in pregnant women with pSS. Results:(1) The average maternal age of the 32 pSS pregnancies was (32.9±4.6) years, the pre-pregnancy body mass index was (21.1±3.8) kg/m 2, and the median gestational age at delivery was 37.8 (35.4-38.5) weeks. There were 18 women (56.3%, 18/32) were diagnosed before pregnancy and 14 women (43.7%, 14/32) during pregnancy. Out of the 32 pregnancies, 25 (79.1%, 25/32) received therapy with glucocorticoids and/or hydroxychloroquine during pregnancy, whereas seven (21.9%, 7/32) had no medication during pregnancy. (2) The main adverse maternal outcomes included oligohydramnios (25%, 8/32), hypertensive disorder of pregnancy (18.8%, 6/32), preterm birth (18.8%, 6/32), fetal growth restriction (15.6%, 5/32), miscarriage (12.5%, 4/32), gestational diabetes mellitus (9.4%, 3/32), and postpartum hemorrhage (3.1%, 1/32). (3) Adverse neonatal outcomes included low birth weight infants in seven cases (25.0%, 7/28), neonatal asphyxia in seven cases (25.0%, 7/28), and two cases of congenital heart block (7.1%, 2/28). (4) The rate of diagnosis before pregnancy in the favorable outcome group was higher than the adverse outcome group [10/12 vs. 40.0%(8/20), Fisher's exact test, P=0.028]. There were no significant differences between the two groups concerning maternal age, pre-pregnancy BMI, weight gain during pregnancy, parity, rates of positivity for autoantibodies (antinuclear antibody, Sj?gren-specific antibody A, Sj?gren-specific antibody B, anti-Ro-52), and proportion of drug treatment (glucocorticoids, hydroxychloroquine) (all P>0.05). (5) Multivariate logistic regression analysis showed that diagnosis before pregnancy ( OR=0.02, 95% CI: 0.00-0.62, P=0.024) and positive Sj?gren-specific antibody B ( OR=0.01,95% CI: 0.00-0.75, P=0.038) were the protective factors. Conclusions:The clinical manifestations of pSS among pregnant women are varied and atypical,often with insidious onset. For pregnant women with pSS, being diagnosed before pregnancy, positive Sj?gren-specific antibody B may reduce adverse outcomes. It is important to address pre-pregnancy examination, early diagnosis and timely intervention to reduce the occurrence of adverse outcomes in pregnant women with pSS.

Objective To investigate the composition of symptom clusters in early postoperative breast cancer patients and analyze the sentinel symptoms of each cluster of symptoms. Methods A total of 309 patients who underwent mastectomy were conveniently sampled and surveyed using the Chinese version of the Anderson Symptom Inventory. Principal component analysis and varimax orthogonal rotation were employed to analyze the symptom clusters, and their associations were analyzed using the Apriori algorithm model to identify the sentinel symptoms of each cluster of symptoms. Results Three symptom clusters were identified in early postoperative breast cancer patients: neuro-sleep symptom cluster [fatigue (weakness)-distress-pain-sleepiness-restless sleep], sensory-perception symptom cluster (numbness-forgetfulness-shortness of breath-sadness-dry mouth), and digestive system symptom cluster (nausea-vomiting-loss of appetite). Fatigue was the sentinel symptom of the neuro-sleep symptom cluster, numbness was the sentinel symptom of the sensory-perception symptom cluster, and nausea was the sentinel symptom of the digestive system symptom cluster. Conclusion Early postoperative breast cancer patients experience multiple symptom clusters, with sentinel symptoms existing in each cluster. Healthcare staff should develop intervention measures based on sentinel symptoms to improve the efficiency of symptom management and reduce the degree of symptom distress for patients.

BackgroundThere are differences in executive function between major depressive episode patients with or without psychotic symptoms， and childhood trauma may affect the executive function of patients with major depressive episode. Previous research studies predominantly focused on adult patients with major depressive episode， with a lack of studies specifically focusing on adolescent patients with major depressive episode. ObjectiveTo investigate the differences in executive function among adolescent patients with major depressive episode， with or without psychotic symptoms and childhood trauma. MethodsA total of 112 hospitalized adolescent patients with major depressive episode who met the criteria of the International Classification of Diseases， tenth edition （ICD-10） were included in the study. The participants were recruited from the Department of Child and Adolescent Psychiatry， Shenzhen Kangning Hospital during the period from August 2020 to November 2021. Additionally， 27 healthy controls were recruited through public advertisements. The Cambridge Neuropsychological Test Automated Battery （CANTAB） was used to assess executive function through the administration of the Motor Screening Task （MOT）， Spatial Working Memory（SWM） and Rapid Visual Information Processing （RVP） modules. Childhood Trauma Questionnaire-Short Form （CTQ-SF） was used to assess the trauma type. ResultsCompared with healthy controls， adolescent patients with major depressive episode had a longer mean delay （Z=-3.407， P=0.001） in the MOT task. In the SWM task， the patients had a higher total number of intergroup error responses （Z=-3.291， P=0.001）， a higher total number of intragroup error responses （Z=-3.461， P=0.001）， more total number of double error responses （Z=-3.218， P=0.001）， a higher total error responses （Z=-3.312， P=0.001）， higher strategy scores （Z=-2.437， P=0.015） and longer average delay time （Z=-2.055， P=0.040）. In the RVP task， the patients had fewer hits （Z=-3.196， P=0.001）， more misses （Z=-3.179， P=0.001）， fewer rejections （Z=-2.772， P=0.006）， lower hit probability （Z=-3.187， P=0.001） and lower A´ scores （Z=-3.070， P=0.002）.Compared with adolescent patients with major depressive episode without psychotic symptoms， those with psychotic symptoms had a lower total number of double error responses （Z=-2.566， P=0.010） in SWM task. Compared with adolescent patients with major depressive episode who did not experience emotional neglect， those who experienced emotional neglect had longer average delay time （Z=-3.183， P=0.001） in MOT task， fewer total hits （Z=-2.445， P=0.014）， more total missed reports （Z=-2.467， P=0.014）， lower hit probability （Z=-2.445， P=0.014） and lower A´scores （Z=-2.089， P=0.037） in RVP task. Adolescent patients with major depressive episode who had experienced emotional abuse had longer average delay time in MOT task than those who had not experienced emotional abuse （Z=-2.552， P=0.011）. ConclusionAdolescent patients with major depressive episode exhibit abnormalities in a majority of executive function domains. Specifically， those without psychotic symptoms and with childhood trauma demonstrate significantly impaired executive function. ［Funded by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties （number， SZGS013）， Basic and Applied Basic Research Fund of Guangdong Province （number， 2019A1515110047）， Shenzhen Science and Technology Planning Project （number， JCYJ20190809155019338）］

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

【Objective】 To evaluate the performance of the magnetic artificial blood vessel device for fast non-suture anastomosis of caval reconstruction with artificial blood vessel transplantation after resection in canines. 【Methods】 Sixteen adult mongrel dogs of either gender were randomly divided into two groups for vena cava reconstruction with artificial blood vessel transplantation after inferior vena cava (IVC) resection. Group MCA (n=8): magnetic artificial blood vessel device for IVC reconstruction; Group manual sewing (MS) (n=8): hand suturing for IVC reconstruction. Operation time and stoma errhysis were recorded during operation. Patency and stoma stenosis were confirmed via color Doppler ultrasound scanning and X-ray cholangiography at different time points as late as 4 weeks after surgery. 【Results】 The time required to perform the vascular anastomosis was significantly shorter for the magnetic artificial blood vessel device (6.25±2.25)min than for MS (27.32±5.12)min (P<0.001). There were four cases of stoma errhysis in MS group which had to be repaired (P=0.077). Vascular X-ray angiography and color Doppler ultrasound found normal blood flow and no stoma stenosis in MCA group, but three cases of stoma stenosis in MS groups (P=0.200). Compared with MS group, the magnetic ring device stoma was associated with smooth re-endothelialization and depressed infiltration of inflammatory cells at the anastomotic site. 【Conclusion】 The magnetic artificial blood vessel device offers a simple, fast, reliable, and efficacious technique for vena cava reconstruction with artificial blood vessel transplantation.

Objective:To compare the histological differences between magnetic anastomosis and traditional suture in canine portal vein (PV) .Methods:Eighteen healthy Chinese garden dogs, either gender, 8-12 months and weighing 13.5-18.9 kg, were randomly divided into magnetic compressive anastomats (MCA) group ( n=9) and hand-sewing (HS) group ( n=9) for PV reconstruction. The time of PV anastomosis was compared between the two groups. HE and Masson staining were performed immediately and at 4, 8, 12 and 24 weeks after operation. The ultrastructure of the anastomosis was observed using scanning and transmission electron microscopy. Results:All dogs survived. The PV anastomosis time was significantly shorter in MCA group (3.58±2.75) min than that HS group (12.89±3.12) min, P<0.01. In MCA group, the vascular wall of anastomotic stoma was well aligned immediately after operation, and the shrinkage was obvious in HS group by gross eyes. At 24 weeks, electron microscope scanning showed the re-endothelialization was smooth and endothelial cells arranged regularly at the anastomotic site of the MCA group, whereas different-sized and irregularly aligned endothelial cells and large collagenous fibers arranged in disorder were present at the HS anastomotic stoma. Representative HE and Masson staining confirmed that the magnetic device was associated with decreased infiltration of inflammatory cells and deposition of fibrotic collagen at 24 weeks explanted anastomotic stomas compared with the HS group. Conclusions:Compared with the HS, MCA produced shorter anastomosis time, smooth anastomotic intima, light fibrous tissue hyperplasia, no foreign body residue, mild inflammatory reaction and reliable technique for canines PV anastomosis.

Objective:To invent a set of novel magnetic anastomotic device based upon the technique of magnetic compression anastomosis(MCA)for rapid venous reconstruction during ex situ liver resection, and verify its clinical value and performance in animal models. Methods:Fiften adult mongrel dogs of either gender underwent the ex situ liver resection. The novel magnetic vessel anastomosis device for the venous reconstruction of liver autotransplantation procedure was performed on 8 mongrel dogs(MCA group), and the traditional handsewing technique was used on 5 additional dogs(THS group). Time for completing venous reconstruction and time of venous anastomosis, venous velocity, intraoperative and postoperative survival and complications were recorded. Patency was detected via color Doppler ultrasound scans and X-ray cholangiography after surgery. The changes of intestinal lumen and kidney were also observed. Results:The time required to perform IVC and PV reconstruction for liver autotransplantation was significantly shorter for the magnetic vessel anastomosis device(9.5±2.5) min than for THS(30.7±3.4) min. There was significant difference in anhepatic period( P=0.0000). After operation, except one died, other nine animals in group A survived after operation but all five cases died in the THS group during liver autotransplantation. Vascular X-ray angiography and color Doppler ultrasound found blood flow MCA group normal, and there wasn't stoma stenosis. Conclusions:MCA technique could be fast and efficacious to complete venous reconstruction for liver autotransplantation in ex situ liver resection operation, and helpful to reduce organ ischemia-reperfusion injury.