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Abstract Background The efficacy of prophylactic cranial irradiation (PCI) is still controversial in small cell lung cancer (SCLC) patients with pT1-2N0M0 disease after complete resection. The majority of previous studies haven’t discerned the potential benefit of PCI in this subgroup of patients, probably due to the paucity of these patients and distinct treating modalities. The aim of this study is to demonstrate the potential medical benefit of PCI in these patients. Methods A retrospective study was conducted to evaluate the potential benefit of PCI in pT1-2N0M0 SCLC patients after complete resection. We retrospectively reviewed 112 pT1-2N0M0 SCLCs after complete resection and adjuvant chemotherapy between January 2013 and January 2022. Survival and Cox regression analysis were conducted to elucidate the potential medical benefit of PCI in these patients. Results The median overall survival (OS) has not been reached. The 2-year, 5-year, 8-year OS rate was 93.7%, 73.2%, and 65.7%, respectively. Brain metastasis (BM) was observed in 17.0% (19/112) patients during the process of follow-up. PCI significantly decreased the BM actuarial risk from 23.9 to 4.9% (log-rank p = 0.0097, HR = 0.180, 95% CI: 0.041–0.778). The brain metastasis free survival (BMFS, log-rank p = 0.02) and OS (log-rank p = 0.05) in PCI cohort were also significantly longer than that of non_PCI group. Cox analysis demonstrated that PCI was an independent prognostic factor in both BM actuarial risk (HR = 0.198, 95% CI: 0.046–0.859, p = 0.031) and BMFS (HR = 0.387, 95% CI: 0.169–0.890, p = 0.025). Moreover, T2 patients showed a significant superior prognosis in terms of BM actuarial risk with comparison to those with T1 disease in non_PCI cohort (log-rank p = 0.016, HR = 3.345, 95% CI: 1.177–9.511), whereas the difference could not be observed in PCI cohort. Conclusions PCI was significantly associated with a better clinical outcome in pT1-2N0M0 SCLC patients who received complete resection and adjuvant chemotherapy, especially in T2 patients. more...

Abstract Bronchial carcinoid tumors are low‐grade malignant and lung‐sparing surgery is preferred for the removal of these tumors. We describe a surgical technique of robot‐assisted sleeve segmentectomy via single utility port approach with three robotic arms. This operation was performed in an aged patient with decreased pulmonary function, whose carcinoid tumor was located at the origin of the right superior segmental bronchus. A 1.5‐cm incision was performed in the eighth intercostal space of the midaxillary line and another 4‐cm incision was made in the fifth intercostal space of the anterior axillary line. Postoperative recovery of the patient was smooth without postoperative complications. more...

IntroductionThe efficacy of postoperative radiotherapy (PORT) is still unclear in non-small cell lung cancer (NSCLC) patients with pIIIA-N2 disease. Estrogen receptor (ER) was proven significantly associated with poor clinical outcome of male lung squamous cell cancer (LUSC) after R0 resection in our previous study.MethodsA total of 124 male pIIIA-N2 LUSC patients who completed four cycles of adjuvant chemotherapy and PORT after complete resection were eligible for enrollment in this study from October 2016 to December 2021. ER expression was evaluated using immunohistochemistry assay.ResultsThe median follow-up was 29.7 months. Among 124 patients, 46 (37.1%) were ER positive (stained tumor cells≥1%), and the rest 78 (62.9%) were ER negative. Eleven clinical factors considered in this study were well balanced between ER+ and ER- groups. ER expression significantly predicted a poor prognosis in disease-free survival (DFS, HR=2.507; 95% CI: 1.629-3.857; log-rank p=1.60×10-5). The 3-year DFS rates were 37.8% with ER- vs. 5.7% with ER+, with median DFS 25.9 vs. 12.6 months, respectively. The significant prognostic advantage in ER- patients was also observed in overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The 3-year OS rates were 59.7% with ER- vs. 48.2% with ER+ (HR, 1.859; 95% CI: 1.132-3.053; log-rank p=0.013), the 3-year LRFS rates were 44.1% vs. 15.3% (HR=2.616; 95% CI: 1.685-4.061; log-rank p=8.80×10-6), and the 3-year DMFS rates were 45.3% vs. 31.8% (HR=1.628; 95% CI: 1.019-2.601; log-rank p=0.039). Cox regression analyses indicated that ER status was the only significant factor for DFS (p=2.940×10-5), OS (p=0.014), LRFS (p=1.825×10-5) and DMFS (p=0.041) among other 11 clinical factors.ConclusionsPORT might be more beneficial for ER negative LUSCs in male, and the examination of ER status might be helpful in identifying patients suitable for PORT. more...

Abstract Background Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient. Methods We identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay. Results Twelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089–4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients’ OS after R0 resection (HR = 2.152, p = 0.037). Conclusion ERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data. more...

Background: 5-methylcytosine has a profound impact on the development and progression of hepatocellular carcinoma. The aim of this study was to investigate the usefulness of 5-methylcytosine in determining the prognosis, tumor microenvironment, and applicability of precision medicine in hepatocellular carcinoma.Methods: We collected data of seven hepatocellular carcinoma cohorts (The Cancer Genome Atlas, International Cancer Genome Consortium, GSE14520, GSE6764, GSE9843, GSE63898, GSE76427). An unsupervised clustering method was used to identify novel subtypes of hepatocellular carcinoma based on the expression 5-methylcytosine gene signatures. The 5-methylcytosine score was determined using the least absolute shrinkage and selection operator method based on the differential expression of genes in the identified subtypes. Subsequently, we investigated the association between 5-methylcytosine-based clusters (according to the 5-methylcytosine score) and clinical outcomes, immunophenotypes, classical molecular subtypes, and therapeutic opportunities in hepatocellular carcinoma. Finally, we examined the sensitivity of patients with high 5-methylcytosine score to drugs.Results: We identified two hepatocellular carcinoma-specific, 5-methylcytosine-based subtypes (clusters 1 and 2). Cluster 1 exhibited significantly higher 5-methylcytosine scores versus cluster 2. The 5-methylcytosine-based subtypes accurately predicted classical molecular subtypes, immunophenotypes, prognosis, and therapeutic opportunities for patients with hepatocellular carcinoma. Cluster 1 (high 5-methylcytosine score) was characterized by lower anticancer immunity and worse prognosis versus cluster 2 (low 5-methylcytosine score). Moreover, cluster 1 (high 5-methylcytosine score) exhibited low sensitivity to cancer immunotherapy, but high sensitivity to radiotherapy and targeted therapy with lenvatinib.Conclusion: The novel 5-methylcytosine-based subtypes (according to the 5-methylcytosine score) may reflect the prognosis, tumor microenvironment, and applicability of precision medicine in patients with hepatocellular carcinoma. more...

Osteoarthritis (OA) is a common degenerative joint condition associated with inflammation and characterized by progressive degradation of the articular cartilage and subchondral bone loss in the early stages. Inflammation is closely associated with these two major pathophysiological changes in OA. Velutin, a flavonoid family member, reportedly exerts anti-inflammatory effects. However, the therapeutic effects of velutin in OA have not yet been characterized. In this study, we explore the effects of velutin in an OA mouse model. Histological staining and micro-CT revealed that velutin had a protective effect against cartilage degradation and subchondral bone loss in an OA mouse model generated by surgical destabilization of the medial meniscus (DMM). Additionally, velutin rescued IL-1β-induced inflammation in chondrocytes and inhibited RANKL-induced osteoclast formation and bone resorption in vitro. Mechanistically, the p38 signaling pathway was found to be implicated in the inhibitory effects of velutin. Our study reveals the dual protective effects of velutin against cartilage degradation and subchondral bone loss by inhibiting the p38 signaling pathway, thereby highlighting velutin as an alternative treatment for OA. more...

Abstract Video‐assisted thoracoscopic surgery (VATS) subsegmentectomy has been widely used to resect small‐sized lung lesions in clinical practice. Precise identification of the subsegmental bronchus is one of the essential steps in performing thoracoscopic anatomic subsegmentectomy. Here, we report a thoracoscopic right S2a segmentectomy with preoperative electromagnetic navigational bronchoscopy (ENB)‐guided injection of methylene blue to identify the subsegmental bronchus in a 51‐year‐old male. We successfully performed complicated surgery using this method. This ENB‐guided dye marking method may accurately distinguish the subsegmental bronchus to effectively guide surgery. more...

Background and objective TRIM proteins are important members of E3 ubiquitin ligases, and many studies have confirmed that TRIM family members play an important role in the development of various tumors. We found that TRIM59 expression level in non-small cell lung cancer (NSCLC) was significantly increased through second-generation sequencing. The purpose of this study was to investigate the expression of TRIM59 in NSCLC and its relationship with the clinicopathological parameters as well as the prognosis of patients. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were excavated to analyze the expression of TRIM59 mRNA in NSCLC and its relationship with the prognosis of patients; The expression of TRIM59 protein in 90 tumor tissues and adjacent tissues was detected by immunohistochemical staining, and the relationship between the expression of TRIM59 protein and clinicopathological parameters and prognosis was analyzed. Results Overexpression of TRIM59 mRNA in tumor tissues predicted poor prognosis. The expression level of TRIM59 protein was significantly higher in tumor tissues than in adjacent tissues, and TRIM59 protein expression was correlated with tumor size (P=0.007), tumor differentiation (P=0.009), tumor-node-metastasis (TNM) stage (P=0.003) and lymph node metastasis (P=0.003). Multivariate Cox regression analyses showed that along with TNM stage, overexpression of TRIM59 could be considered an independent prognostic factor for NSCLC patients. Conclusion The expression of TRIM59 is closely related to the prognosis of NSCLC patients, and it is an independent risk factor for NSCLC patients. more...

Background: Post-stroke cognitive impairment (PSCI) is commonest clinical disorder in which peripheral cholinergic activity is important. Oleuropein (OLP) is polyphenol is present in olive oil. Here we evaluated the effect of OLP in cognitive dysfunction rats in post cerebral stroke model. Methods: The post cerebral stroke cognitive dysfunction PSD rat model was created by occlusion of transient middle cerebral artery. The rats were divided into 6 groups named, Sham + Vehicle, Sham + OLP (50 mg/kg), PSD rats + Vehicle, PSD rats + OLP (20, 50 or 100 mg/kg). The spatial learning was assessed by Morris water maze (MWM). The expression of choline acetyltransferase (ChAT), acetylcholine (ACH), extent of histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) were evaluated by Western blot assay and immunofluorescence staining. Results: Treatment of OLP at various doses showed higher number of spontaneous and rewarded alterations and lesser percentage bias compared to vehicle treated PSD rats. OLP resulted in decreased levels of ChAT and ACH, whereas the degree of histone acetylation and phosphorylation of CREB improved in dose dependent pattern. Conclusion: treatment of OLP improved PSCI via increasing the phosphorylation of CREB and histone acetylation, thus attenuating cholinergic activity. more...

Abstract Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pathogenesis. Emerging evidence shows microRNA (miRNA, or miR) can function as important regulators of many pathological processes, including osteogenic differentiation. Here, we aimed to explore the function of miR-449c-5p in CAVD pathogenesis. In this study, we demonstrated the role of miR-449c-5p in VICs osteogenesis. MiRNA microarray assay and qRT-PCR results revealed miR-449c-5p was significantly down-regulated in calcified aortic valves compared with non-calcified valves. MiR-449c-5p overexpression inhibited VICs osteogenic differentiation in vitro, whereas down-regulation of miR-449c-5p enhanced the process. Target prediction analysis and dual-luciferase reporter assay confirmed Smad4 was a direct target of miR-449c-5p. Furthermore, knockdown of Smad4 inhibited VICs osteogenic differentiation, similar to the effect observed in up-regulation miR-449c-5p. In addition, animal experiments proved indirectly miR-449c-5p could alleviate aortic valve calcification. Our data suggested miR-449c-5p could function as a new inhibitory regulator of VICs osteogenic differentiation, which may act by targeting Smad4. MiR-449c-5p may be a potential therapeutic target for CAVD. more...

A kind of digitally designing and manufacturing system for the gradient heterogeneous 3-D printing was designed. The molar model of PLY format was composed based on the CT images, and a novel method for the gradient heterogeneous material model designing based on the material distribution control function and the sliced edge rings was proposed. The point color slicing algorithm based on the topological structure was achieved. Based on the system, a gradient heterogeneous dental model was prepared. The algorithm used for constructing and slicing of the molar model could store the geometry and material information effectively, and maintain the compatibility for the heterogeneous 3-D printer. The system supplied a fast and integrating method for the heterogeneous 3-D bio-model printing. more...

The present study aimed to investigate the effect of laser therapy on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the plasma of infants diagnosed with cutaneous hemangioma, in order to identify biomarkers for assessing the clinical efficacy of laser therapy. In total, 109 infants with superficial abdominal hemangioma received laser treatment, of which 74 were diagnosed in the proliferation phase, 20 in the regression phase and 15 in the involution phase. In addition, 10 infants without cutaneous hemangioma were recruited as normal controls. The concentrations of VEGF and bFGF in peripheral plasma samples were measured using ELISAs. Dynamic changes in the VEGF and bFGF concentrations of 23 infants diagnosed in the proliferation phase were compared before and after laser therapy. The plasma concentration of VEGF in the proliferation phase group was significantly higher compared with that in the regression phase, involution phase and normal control groups (all P<0.01), whereas it did not differ significantly among the regression phase, involution phase and normal control groups (all P>0.05). The plasma concentration of bFGF in the proliferation phase group was significantly higher compared with that in the regression phase, involution phase and normal control groups (all P<0.01), while the bFGF level did not differ significantly among the regression phase, involution phase and normal control groups (all P>0.05). Following laser therapy, the plasma concentrations of VEGF and bFGF in infants with cutaneous hemangioma were significantly decreased (both P<0.01). These results suggested that VEGF and bFGF may serve as reliable indexes to evaluate the clinical efficacy of laser therapy for treating infantile cutaneous hemangioma. [ABSTRACT FROM AUTHOR] more...

Introduction: Pulsed dye laser (PDL) is an important treatment for superficial infantile hemangioma, but few studies report on its cellular mechanism. The aim of this study was to evaluate alterations of serum vascular endothelial growth factor (VEGF) level in infantile hemangioma (IH) patients after laser treatment and effects of PDL irradiation on human umbilical vein endothelial cells (HUVECs) in vitro, as well as to explore the biomolecular mechanisms and ultrastructure changes of the PDL effect. Methods: 74 children with infant hemangioma including 45 patients in proliferating phase, 18 patients in involuting phase, 11 patients in involuted phase and 10 healthy children were engaged in this study. The plasma VEGF levels of children were measured with the enzyme-linked immunosorbent assay (ELISA). 24 hours after, HUVECs cultured in vitro were irradiated with PDL, cell apoptosis, mRNA levels of VEGF, and changes of ultrastructure were evaluated using flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR), and transmission electron microscopy, respectively. Results: The serum VEGF concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting / involved hemangiomas and healthy patients. After receiving 3 laser treatments, the plasma VEGF levels of IH patients in proliferating hemangiomas decreased significantly. PDL irradiation could down-regulate VEGF mRNA expression of HUVECs, and increase cell apoptosis rate. Conclusion: The present study demonstrates that PDL irradiation imparts apoptosis induction effects on HUVECs in vitro. Furthermore, our results suggest that vascular endothelial growth factor may be of particular importance in pathophysiology and PDL treatment of hemangiomas, also serum VEGF levels may be used as an aid in the follow up of IH. This provides valuable evidence of the PDL effect on infantile hemangioma. [ABSTRACT FROM AUTHOR] more...