What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.

BACKGROUND: Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on LCBM, problems have emerged, such as confusing research structures. AIM: To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation, clinical treatment, and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research. METHODS: We used tools, including R, VOSviewer and CiteSpace software, to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection. We also performed enrichment and protein-protein interaction analyses of gene expression datasets from LCBM cases worldwide. RESULTS: Research on LCBM has received extensive attention from scholars worldwide over the last 20 years. Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions. The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis. The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence. CONCLUSION: Novel therapies for LCBM face animal testing and drug resistance issues. Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma.

BACKGROUND: The role of HOXA family genes in the occurrence and progression of a variety of human cancers has been scatteredly reported. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD. METHODS: In-house immunohistochemistry (IHC), multi-center microarrays, RT-qPCR and RNA-seq data were incorporated for comprehensively evaluating the expression and prognostic value of HOXA4 and HOXA5 in LUAD. The mechanism of HOXA4 and HOXA5 in the formation and development of LUAD was analyzed from multiple aspects of immune correlations, upstream transcriptional regulation, functional states of single cells and co-expressed gene network. The functional roles of HOXA4 and HOXA5 in LUAD were validated by in vitro experiments. RESULTS: As a result, in 3201 LUAD samples and 2494 non-cancer lung samples, HOXA4 and HOXA5 were significantly downexpressed (P < 0.05). The aberrant expression of HOXA5 was significantly correlated with the clinical progression of LUAD (P < 0.05). HOXA5 showed remarkable prognostic value for LUAD patients (P < 0.05). The expression of HOXA4 and HOXA5 in LUAD were negatively correlated with tumor purity and positively correlated with the infiltration of various immune cells such as B cells, T cells and macrophages. HOXA4 and HOXA5 overexpression had notable inhibitory effect on the proliferation, migration and invasion of LUAD cells. CONCLUSIONS: In conclusion, the identified downexpressed HOXA4 and HOXA5 had significant distinguishing ability for LUAD samples and affected the cellular functions of LUAD cells. The low expression of HOXA5 indicated worse overall survival of LUAD patients. Therefore, the two HOXA family genes especially HOXA5 may serve as potential biomarkers for LUAD.

Downregulation of miR-125b-5p and Its Prospective Molecular Mechanism in Lung Squamous Cell Carcinoma.

Background: To explore the clinical significance of miR-125b-5p and its potential mechanisms in lung squamous cell carcinoma (LUSC). Materials and Methods: An integrated analysis of data from in-house quantitative real-time polymerase chain reaction (qRT-PCR), microRNA-sequencing, and microarray assays to appraise the expression level of miR-125b-5p in LUSC tissues compared to adjacent noncancerous controls. The authors identified the candidate targets of miR-125b-5p and conducted functional analysis using computational biology strategies from gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, disease ontology (DO), and protein-protein interaction (PPI) network analyses to investigate the prospective mechanisms. Results: According to qRT-PCR results, the expression level of miR-125b-5p was markedly decreased in LUSC tissues compared to noncancerous control tissues. Receiver operating characteristic and summary receiver operating characteristic analyses showed that miR-125b-5p had good specificity and sensitivity for distinguishing LUSC tissue from noncancerous lung tissue. The standard mean difference revealed that men and women with lower expression levels of miR-125b-5p may have a higher risk for LUSC. KEGG analysis and DO analysis intimated that target genes were evidently enriched in pyrimidine metabolism and pancreatic carcinoma. The PPI network of the top assembled KEGG pathway indicated that RRM2, UMPS, UCK2, and CTPS1 were regarded as crucial target genes for miR-125b-5p, and RRM2 was eventually deemed a key target. Conclusions: The authors' findings implicate a low expression level of miR-125b-5p in LUSC. A tumor-suppressive role of miR-125b-5p is proposed, based on its effects on LUSC tumor growth, clinical stage progression, and lymph node metastasis.

Clinical significance of transcription factor RUNX2 in lung adenocarcinoma and its latent transcriptional regulating mechanism.

RUNX family transcription factor 2 (RUNX2) overexpression has been found in various human malignancies. However, the expression levels of RUNX2 mRNA and protein in lung adenocarcinoma (LUAD) were not investigated. This study aims to thoroughly analysis the expression level and potential mechanisms of RUNX2 mRNA in LUAD. We applied in-house immunohistochemistry, high-throughput RNA-sequencing, and gene microarrays to comprehensively investigate the expression level of RUNX2 in LUAD. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to assess the integrated expression value of RUNX2 in LUAD. The hazard ratios (HRs) were integrated to evaluate the overall prognostic effect of RUNX2 on the LUAD patients. The differentially expressed genes (DEGs) of LUAD, the potential target genes of RUNX2, and its co-expressed genes were overlapped to obtain a set of specific genes for GO and KEGG enrichment analyses. RUNX2 overexpression in LUAD was validated using a large number of cases (2 418 LUAD and 1 574 non-tumor lung samples). The pooled SMD was 0.85 (95 % CI: 0.64-1.05) and the area under the curve (AUC) of the SROC was 0.86 (95 %CI: 0.83-0.89). The integrated HR was 1.20 [1.04-1.38], indicating that increased expression of RUNX2 was an independent risk factor for the poor survival of the LUAD patients. RUNX2 and its transcriptionally regulates potential target genes may promote cell proliferation and drug resistance of LUAD by modulating the cell cycle and MAPK signaling pathways. RUNX2 can provide new research directions for targeted drug therapy and drug resistance for LUAD treatment.

Integrated expression analysis revealed RUNX2 upregulation in lung squamous cell carcinoma tissues.

This study aimed to investigate the clinicopathological significance and prospective molecular mechanism of RUNX family transcription factor 2 (RUNX2) in lung squamous cell carcinoma (LUSC). The authors used immunohistochemistry (IHC), RNA-seq, and microarray data from multi-platforms to conduct a comprehensive analysis of the clinicopathological significance and molecular mechanism of RUNX2 in the occurrence and development of LUSC. RUNX2 expression was significantly higher in 16 LUSC tissues than in paired non-cancerous tissues detected by IHC (P < 0.05). RNA-seq data from the combination of TCGA and genotype-tissue expression (GTEx) revealed significantly higher expression of RUNX2 in 502 LUSC samples than in 476 non-cancer samples. The expression of RUNX2 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples (P = 0.031). The pooled standardised mean difference (SMD) for RUNX2 was 0.87 (95% CI, 0.58-1.16), including 29 microarrays from GEO and one from ArrayExpress. The co-expression network of RUNX2 revealed complicated connections between RUNX2 and 45 co-expressed genes, which were significantly clustered in pathways including ECM-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection and PI3K-Akt signalling pathway. Overexpression of RUNX2 plays an essential role in the clinical progression of LUSC.

Downregulation of miRNA-126-3p is associated with progression of and poor prognosis for lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is the main pathological type of pulmonary malignant tumors; at present, less than 10% of patients with advanced metastatic LUSC live for more than 5 years. We previously reported that low expression of miRNA-126-3p is associated with the occurrence and progression of lung adenocarcinoma (LUAD). Here, we examined expression of miRNA-126-3p in 23 samples from patients with LUSCs and 23 normal control specimens by quantitative real-time PCR (RT-qPCR). Associations between miRNA-126-3p expression and clinical features were studied from materials derived from Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) database. Twelve online platforms were used to identify candidate target genes of miRNA-126-3p. Further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) network were performed on the target genes. GEO microarray analysis, TCGA data mining, RT-qPCR, and integration analysis consistently reported low expression of miRNA-126-3p in LUSC. A total of 42 genes were identified as potential target genes of miRNA-126-3p from online platforms, GEO microarrays, and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in several biological processes that promote the progression of LUSC. SOX2, E2F2, and E2F3 were selected as hub genes from the PPI network for further analysis. In summary, our results suggest that the low expression of miRNA-126-3p may play a role in promoting the development of LUSC and miRNA-126-3p may be a biomarker for LUSC early diagnosis and prognosis.

Facial Resurfacing With Prefabricated Induced Expanded Skin Flap.

Massive facial damages extremely affect the facial appearance and function. In existing publications, the surgical flap transfer was still prior to other methods in repairing the facial injury. Among them, the prefabricated induced expanded skin flap seems more effective based on the facial specific features and damage range. In this study, a literature research was carried out in the database of PubMed. A total of 85 patients were included and all of them underwent the method of prefabricated expanded flap to reconstruct the massive facial defects. The prefabricated induced expanded skin flaps harvested from the neck and chest area have prominent advantage in resetting massive facial deformities. All the flaps survived demonstrated an excellent texture and color match with the facial defects areas. However, the unsolved problems are still existed in these flaps and further research is necessary to obtain a satisfactory outcome for both patients and surgeons.

Comparison between laparoscopy and laboratory tests for the diagnosis of tuberculous peritonitis

Background/aim: Our study aimed to investigate a reliable diagnostic approach for tuberculous peritonitis (TBP) by comparing the commonly used diagnostic tools. Materials and methods: Fifty-one patients had received a series of diagnoses, including laparoscopy, erythrocyte sedimentation rate (ESR), cancer antigen 125 (CA125), tuberculin skin test, tuberculosis antibody in serum (TB-Ab), the T-SPOT.TB test, or adenosine deaminase (ADA) in ascitic fluid. The positive rate of each method was calculated and the differences of positive rates between laparoscopy and laboratory tests that had higher positive rates were analyzed by McNemar chi-square test. Results: The most common symptoms and signs of 51 patients were fever (86.3%), abdominal mass (78.4%), abdominal distension (62.7%), abdominal pain (74.5%), and weight loss (66.7%). Furthermore, the positive rates of CA125, laparoscopy, T-SPOT.TB test, and ESR were relatively higher than those of the other three methods (tuberculin skin test, TB-Ab, and ascitic ADA). Additionally, there was no significant difference (P > 0.05) in the positive rates between the diagnoses of laparoscopy and those three laboratory tests. Conclusion: CA125, laparoscopy, T-SPOT.TB test, and ESR had a stronger diagnostic power for TBP, and they are reliable alternatives for the diagnosis of TBP.

A systematic review of p53 as a biomarker of survival in patients with osteosarcoma.

Osteosarcoma is the most common malignant bone tumor, and the prognosis of patients with osteosarcoma is still unsatisfactory with low survival rates. There are many studies assessing the prognostic role of upregulated p53 in patients presenting osteosarcoma, and there is no consistent finding. To summarize the existing evidence about whether the presence of upregulated p53 was a biomarker of survival in patients with osteosarcoma, we performed a systematic review and meta-analysis of relevant publications. We assessed the effect of upregulated p53 on the 3-year overall survival and the 3-year disease-free survival by calculating the pooled odds ratio (OR) with corresponding 95% confidence interval (95%CI). Fifteen studies with a total of 609 patients with osteosarcoma were finally included into the systematic review and meta-analysis. Compared with osteosarcoma patients with low or undetectable p53, patients with upregulated p53 were obviously associated with decreased 3-year overall survival (OR = 0.29, 95 %CI 0.19-0.43, P < 0.001). In addition, patients with upregulated p53 were obviously associated with decreased 3-year disease-free survival (OR = 0.06, 95 %CI 0.02-0.23, P < 0.001). The results from the systematic review and meta-analysis highlight that p53 is an effective biomarker of survival in patients with osteosarcoma. In addition, more studies with a large sample size are needed to identify the effect of p53 expression in osteosarcoma patients.

[An experimental study of small-caliber tissue engineering vessels with acellular matrix].

OBJECTIVE: To observe the mechanical properties of the prefabricated connective tissue tube as blood vessel substitute and its changes after implantation at the femoral artery. METHODS: The acellular matrix tube of 8-12 cm in length with a silicone rod inside it was implanted into dog peritoneal cavity. 3 weeks later, a new formed tube around the silicone rod was transferred to the femoral artery as blood vessel substitute. The mechanical properties and histological examination of the blood vessel substitute were assessed and compared to those of the carotid artery and vein. 6 months after transfer, the patency of the blood vessels substitute was observed. The histological change was studied by light microscopy, scanning and transmitting electron microscopy. RESULTS: (1) The mechanical properties of blood vessel substitute was not as strong as artery, but better than the vein. (2) There were elastic and collagen fibers with many fibroblasts around the tube wall, but few mesothelial cells around the inner wall. All of the blood vessel substitutes (n = 6) were found to keep patency and the structure of the blood vessels substitutes became similar to femoral artery 6 months after they had been grafted to the femoral artery. CONCLUSIONS: These results suggest that tissue engineering in vivo is a good approach to construct vessels substitute. The tissue tubes made in dog's peritoneal cavity have good condition when it is used as a blood vessel substitutes.

[Reconstruction of skin defect at frontal hair line with mastoid fasciocutaneous island flap].

OBJECTIVE: To investigate the reconstruction of skin defect at frontal and temporal hair line. METHODS: 5 cases with skin defect at frontal and temporal hair line were treated with mastoid fasciocutaneous island flap pedicled with parietal branch of superficial temporal artery. RESULTS: All the flaps survived completely. Hair grew up 5 - 7 days after operation, showing good reconstructed hair line. CONCLUSIONS: Mastoid fasciocutaneous island flap is a reliable method for reconstruction of skin defect at frontal and temporal hair line.

[Biocompatibility of decellularized canine carotid artery allograft cross-linked by carbodiimide].

UNLABELLED: OBJECTIVE Crosslink decellularized canine carotid artery allograft by EDC [1-3-(dimethylamino)propyl-3-ethylcarbodiimide methiodide] and evaluate the biocompatibility of it. METHODS: Use the multi-step detergent-enzyme method to construct decellularized canine carotid artery allograft and cross-link it by EDC with the weight ratio of decellularized artery to EDC 1:1 and 1:2. Evaluate the biocompatibility of it by the cytotoxical MTT test and the rat subdermal bury test. RESULTS: Decellularized canine carotid artery cross-linked by EDC has a lower degradation rate treated by collagenase type II, the result of MTT test show that the EDC cross-linked decellularized artery has no cytotoxity and the rat subdermal bury test show that crosslinking greatly enhance the ability of decellularize artery to resist the enzyme degradation and lower the immune reaction. The more the artery was cross-linked , the more effects it has. CONCLUSIONS: Decellularized canine carotid artery cross-linked by EDC has fairly good biocompatibility and ability to resist the collagenase degradation.

[Vascular anatomy and clinical applications of the distally based superficial sural artery island flap].

OBJECTIVE: To document the vascular anatomy of the distally based superficial sural artery flap and to study the vascular anastomoses between the superficial sural artery and the septocutaneous perforators of the peroneal artery. METHODS: Ten fresh human cadavers were injected with lead oxide, gelatin and water. Twenty lags were then dissected and an overall map of the cutaneous vasculature was constructed. Vascular communications between the superficial sural artery and the lowest septocutaneous perforator of the peroneal artery was evaluated to determine the cutaneous vascular territory of the superficial sural flap. The distally based superficial sural artery island flap was used in 26 cases. RESULTS: There is constant vascular anastomosis between the superficial sural artery and the lowest septocutaneous perforator of the peroneal artery. The 26 flaps survived uneventfully except for two of partial fat necrosis. CONCLUSION: The anatomic information enhances our understanding of flap design.

[Transferring neurovascular rectus femoris muscle segment for treatment of facial paralysis].

OBJECTIVE: To investigate a new technique for functional treatment of chronic facial paralysis. METHODS: Based on anatomy of intramuscular neurovascular structure in the rectus femoris muscle, 7 consecutive patients with facial paralysis were treated by using a technique of microsurgically free-transferring neurovascular rectus femoris muscle segment to the face in one-stage. Follow-ups were 10 to 24 months. RESULTS: All of the 7 patients showed significantly improvement in the appearance of the oral commissure and oral competence. No complications occurred in the donor site. CONCLUSIONS: The above mentioned technique may have the advantages of preventing the intramuscular nerve and vessel from the surgical injury during splitting the muscle. It could also maintain the transferred muscular segment in a proper tension in the recipient site.

[The neurovascular anatomy and its clinical implication of the rectus femoris muscle].

OBJECTIVE: The objective of this anatomic study was to investigate the intramuscular neurovascular configuration and to evaluate whether the muscle could be split into two functional units in transplantation. METHODS: Ten fresh cadavers and ten preserved cadavers were used in the study. A mixture of lead oxide, gelatin and water was injected to the femoral artery of the fresh cadaver. The rectus femoris muscle with its neurovascular pedicles was dissected and radiographed. RESULTS: Three vascular patterns of the rectus femoris muscle were found in the 40 cadaver legs. The muscle received its blood supply through a single vascular pedicle (12.5%), or a dominant pedicle with 1-2 ramified (80%), or two dominant vascular pedicles (7.5%). CONCLUSIONS: The study provided a detailed description on the intramuscular neurovascular territories of the rectus femoris muscle. Based on the neurovascular supply of the muscle, it is possible to subdivide the muscle into two functional units for segmental muscle transfer.