[Retracted] Chronic oxymatrine treatment induces resistance and epithelial­mesenchymal transition through targeting the long non­coding RNA MALAT1 in colorectal cancer cells.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the cell migration and invasion assay data featured in Figs. 2B, 5C, 6B and C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been submitted elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (one of which has been retracted). In view of the fact that certain of these data had already apparently been submitted for publication prior to the submission of this article to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 967­976, 2018; DOI: 10.3892/or.2018.6204].

SMAD2/3 Phosphorylation is correlated with matrix metalloproteinase 9 expression in human periapical lesions.

OBJECTIVE: The aim of this study was to investigate the presence of phosphorylated SMAD2/3 (P-SMAD2/3) in periapical lesions in humans and its possible correlation with matrix metalloproteinase 9 (MMP9) during the development of apical periodontitis. DESIGN: In this study, a total of 38 samples were collected, consisting of 16 healthy controls and 22 periapical lesions. These samples underwent fixation, dehydration, and embedding for further histologic and immunochemical analysis. The expression of phosphorylated SMAD2/3 and MMP9 was quantified using the average integrated optical density. Additionally, immunofluorescence analysis was conducted to investigate the colocalization of phosphorylated SMAD2/3 and MMP9. RESULTS: The study found that periapical lesions exhibited a stronger expression of MMP9 compared to healthy controls. Additionally, the expression of phosphorylated SMAD2/3 was observed to increase in the periapical granulomas and radicular cysts group, as compared to the normal group (P < 0.01). The results of the immunofluorescence test showed that phosphorylated SMAD2/3 was colocalized with MMP9. CONCLUSIONS: The study found that SMAD2/3 phosphorylation is correlated with matrix metalloproteinase 9 expression in human periapical lesions, suggesting its potential involvement in tissue destruction and immune cell infiltration in periapical lesions.

Machine learning prediction models for different stages of non-small cell lung cancer based on tongue and tumor marker: a pilot study.

OBJECTIVE: To analyze the tongue feature of NSCLC at different stages, as well as the correlation between tongue feature and tumor marker, and investigate the feasibility of establishing prediction models for NSCLC at different stages based on tongue feature and tumor marker. METHODS: Tongue images were collected from non-advanced NSCLC patients (n = 109) and advanced NSCLC patients (n = 110), analyzed the tongue images to obtain tongue feature, and analyzed the correlation between tongue feature and tumor marker in different stages of NSCLC. On this basis, six classifiers, decision tree, logistic regression, SVM, random forest, naive bayes, and neural network, were used to establish prediction models for different stages of NSCLC based on tongue feature and tumor marker. RESULTS: There were statistically significant differences in tongue feature between the non-advanced and advanced NSCLC groups. In the advanced NSCLC group, the number of indexes with statistically significant correlations between tongue feature and tumor marker was significantly higher than in the non-advanced NSCLC group, and the correlations were stronger. Support Vector Machine (SVM), decision tree, and logistic regression among the machine learning methods performed poorly in models with different stages of NSCLC. Neural network, random forest and naive bayes had better classification efficiency for the data set of tongue feature and tumor marker and baseline. The models' classification accuracies were 0.767 ± 0.081, 0.718 ± 0.062, and 0.688 ± 0.070, respectively, and the AUCs were 0.793 ± 0.086, 0.779 ± 0.075, and 0.771 ± 0.072, respectively. CONCLUSIONS: There were statistically significant differences in tongue feature between different stages of NSCLC, with advanced NSCLC tongue feature being more closely correlated with tumor marker. Due to the limited information, single data sources including baseline, tongue feature, and tumor marker cannot be used to identify the different stages of NSCLC in this pilot study. In addition to the logistic regression method, other machine learning methods, based on tumor marker and baseline data sets, can effectively improve the differential diagnosis efficiency of different stages of NSCLC by adding tongue image data, which requires further verification based on large sample studies in the future.

A lung cancer risk warning model based on tongue images.

Objective: To investigate the tongue image features of patients with lung cancer and benign pulmonary nodules and to construct a lung cancer risk warning model using machine learning methods. Methods: From July 2020 to March 2022, we collected 862 participants including 263 patients with lung cancer, 292 patients with benign pulmonary nodules, and 307 healthy subjects. The TFDA-1 digital tongue diagnosis instrument was used to capture tongue images, using feature extraction technology to obtain the index of the tongue images. The statistical characteristics and correlations of the tongue index were analyzed, and six machine learning algorithms were used to build prediction models of lung cancer based on different data sets. Results: Patients with benign pulmonary nodules had different statistical characteristics and correlations of tongue image data than patients with lung cancer. Among the models based on tongue image data, the random forest prediction model performed the best, with a model accuracy of 0.679 ± 0.048 and an AUC of 0.752 ± 0.051. The accuracy for the logistic regression, decision tree, SVM, random forest, neural network, and naïve bayes models based on both the baseline and tongue image data were 0.760 ± 0.021, 0.764 ± 0.043, 0.774 ± 0.029, 0.770 ± 0.050, 0.762 ± 0.059, and 0.709 ± 0.052, respectively, while the corresponding AUCs were 0.808 ± 0.031, 0.764 ± 0.033, 0.755 ± 0.027, 0.804 ± 0.029, 0.777 ± 0.044, and 0.795 ± 0.039, respectively. Conclusion: The tongue diagnosis data under the guidance of traditional Chinese medicine diagnostic theory was useful. The performance of models built on tongue image and baseline data was superior to that of the models built using only the tongue image data or the baseline data. Adding objective tongue image data to baseline data can significantly improve the efficacy of lung cancer prediction models.

Case report: Response to endocrine therapy in triple-negative breast cancer metastases with altered hormone receptors.

Triple-negative breast cancer refers to breast cancer patients with negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2). Metastatic triple-negative breast cancer is predominantly treated with chemotherapy, but later-line treatment remains challenging. Breast cancer is highly heterogeneous, and the expression of hormone receptors is often inconsistent between primary and metastatic lesions. Here, we report a case of triple-negative breast cancer 17 years after surgery with lung metastases for 5 years that progressed to pleural metastases after multiple lines of chemotherapy. The pleural pathology suggested ER (+) and PR (+) and transformation to luminal A breast cancer. This patient received fifth-line letrozole endocrine therapy and achieved partial response (PR). The patient's cough and chest tightness improved after treatment, associated tumor markers decreased, and progression-free survival (PFS) exceeded 10 months. Our results may be of clinical relevance for patients with hormone receptor alterations in advanced triple-negative breast cancer and suggest that individualized regimens should be developed for breast cancer based on the molecular expression of tumor tissue at the primary and metastatic sites.

Effect of Fuzheng formulas on the level of soluble immune checkpoint protein molecules in peripheral blood of patients with advanced NSCLC and its clinical significance / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：观察扶正方药对晚期三线非小细胞肺癌（NSCLC）患者外周血中12种可溶性免疫检查点分子水平的影响，并分析可溶性免疫检查点基线水平与NSCLC患者无进展生存期（PFS）的关系。方法：纳入2020年10月至2023年4月在龙华医院肿瘤科接受三线治疗（扶正方药联合标准西医方案治疗）的72例晚期NSCLC患者，采用LEGENDplex™多因子试剂盒检测患者治疗前及治疗4疗程后可溶性免疫检查点分子的表达水平，分析基线水平与PFS预后的相关性。结果：治疗4个疗程后，sCD137、sTGF-β1、sPD-L1、sPD-L2等指标均明显下降（P<0.05或P<0.01），Kaplan-Meier生存分析表明sPD-L2高水平患者的PFS短于sPD-L2低水平患者的PFS（P<0.05），COX多因素分析表明sPD-L2水平是晚期三线NSCLC患者PFS的独立影响因子（P<0.05）。结论：扶正方药对外周血可溶性免疫检查点蛋白表达具有一定的调节作用，高水平的sPD-L2预示晚期NSCLC患者较短的PFS，sPD-L2可能是晚期三线治疗NSCLC患者PFS的独立影响因子。

Simultaneous development of pneumonitis and autoimmune diabetes secondary to immune checkpoint inhibitor treatment with durvalumab in an advanced small cell lung cancer patient: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various types of cancers worldwide, which is the most significant breakthrough in cancer therapy in recent years. Despite their excellent benefits in anti-tumor efficacy, a subset of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), which can affect almost any organ systems, but related to the pulmonary and pancreatic islets simultaneously has rarely been reported and discussed. PATIENT CONCERNS: In this report, we describe a rare case of a 65-year-old man patient with advanced small cell lung cancer (SCLC) who suffered general fatigue, dry cough, chest tightness, shortness of breath and polyuria-polydipsia syndrome after the eighth cycle treatment with programmed cell death ligand-1 (PD-L1) inhibitor durvalumab. DIAGNOSES: According to the results of laboratory tests, chest computed tomography and multidisciplinary discussion, the patient was eventually diagnosed with ICI-related pneumonitis and autoimmune diabetes mellitus. INTERVENTIONS: Multiple daily subcutaneous insulin injections, empirical anti-infection and immunosuppression treatment with corticosteroids were performed. OUTCOMES: After the cessation of durvalumab and comprehensive treatment, the patient's respiratory condition was relieved significantly and his blood glucose was well controlled with insulin therapy. LESSONS: With the widespread use of ICIs, there will be more patients developing these rare but severe irAEs in clinical practice, which should attract great attention of both clinicians and patients.

Mechanism underlying the effect of Liujunzi decoction on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy.

OBJECTIVE: To further clarify the anticancer mechanisms of Liujunzi decoction and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer (NSCLC) by re-analyzing differential gene expression profile of peripheral blood mononuclear cells (PBMCs) from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy. METHODS: The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database. Differentially expressed genes (DEGs) were screened by paired sample t-test and the multiple ratio method. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed using the DAVID database. The protein-protein interaction (PPI) network was constructed using interaction gene library retrieval tools and Cytoscape software. RESULTS: A total of 162 DEGs were identified, with 67 upregulated genes and 95 downregulated genes. The functional distribution of Gene Oncology (GO) genes showed that DEGs were mostly concentrated in extracellular regions, calcium ion binding, and transcriptase activity. KEGG pathway analysis showed that cytokine-cytokine receptor interactions were significantly enriched. PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree: IL2, PIWIL4, DICER1, PIWIL2, SAA1, XCL1, IL22RA1, ARHGAP11A, DCP1A, and GDNF. Among them, the central protein-coding gene with the highest node degree was IL2. In addition, the central protein-coding genes with high node degrees and high molecular complex detection (MCODE) scores were PIWIL4, DICER1, PIWIL2, and DCP1A, all of which are related to tumor development. CONCLUSIONS: One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data. IL2, PIWIL4, DICER1, PIWIL2, and DCP1A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC. Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases during Apical Periodontitis Development.

INTRODUCTION: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice. METHODS: AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. RESULTS: The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods. CONCLUSIONS: MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP.

Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation: A case report.

RATIONALE: Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. PATIENT CONCERNS: A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). DIAGNOSES: MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. INTERVENTIONS: Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. OUTCOMES: Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. LESSONS: As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.

Hypoxia and Porphyromonas gingivalis-lipopolysaccharide synergistically induce NLRP3 inflammasome activation in human gingival fibroblasts.

OBJECTIVE: To investigate the effects of hypoxia and Porphyromonas gingivalis- lipopolysaccharide (P. gingivalis-LPS) on activation of the NACHT leucine-rich repeat protein 3 (NLRP3) inflammasome in human gingival fibroblasts (HGFs). DESIGN: Periodontitis was optimally simulated using a hypoxic concentration of 1%. HGFs were stimulated using P. gingivalis-LPS (1.0 µg/ml) in normoxia and hypoxia for 3 h and 6 h, respectively. The expression levels of genes and proteins of hypoxia-inducible factor-1α (HIF-1α), interleukin-1ß, gasdermin D (GSDMD) and the NLRP3 inflammasome, including NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1 and its activated forms, were measured using quantitative real-time polymerase chain reaction and western blot. ELISA was used to detect and determine levels of the inflammatory factor interleukin-1ß in cell supernatants. Lactate dehydrogenase (LDH) release assay, caspase-1 activity assay and Hoechst 33342/Propidium Iodide (PI) staining were performed to further verify the presence of pyroptosis. RESULTS: The NLRP3 inflammasome (i.e., NLRP3, ASC, caspase-1) was not affected by individual stimulation using P. gingivalis-LPS or hypoxia. However, the combination of both hypoxia and P. gingivalis-LPS stimulation significantly enhanced inflammasome activation and promoted the expression of interleukin-1ß, gasdermin D and HIF-1α at gene and protein levels; PI positive cells and the release of LDH were also elevated. CONCLUSION: Hypoxia and P. gingivalis-LPS synergistically induced NLRP3 inflammasome activation in HGFs, and subsequently high levels of interleukin-1ß and GSDMD-mediated pyroptosis can cause an HGF inflammatory response, which plays an important role in the pathogenesis of periodontitis.

MMP9 protects against LPS-induced inflammation in osteoblasts.

The matrix metalloproteinase (MMP) family is widely involved in the destruction of the pulp and apical tissues in the inflammatory process. MMP9 is closely related to oral inflammation. Nevertheless, the specific function of MMP9 during oral inflammation, as well as its mechanism, is not well understood. Our previous studies found that in experimentally induced apical periodontitis, more severe inflammation occurred in MMP9 knockout mice compared with the wild type mice. Moreover, the pathology phenomenon of alveolar bone destruction was even more evident in MMP9 knockout mice compared with the wild type mice. We proposed that MMP9 has "anti-inflammatory" properties. We aimed to study the effects of MMP9 on inflammatory response as well as on bone formation and bone destruction. We found a specific relationship between MMP9 and inflammation. qRT-PCR and Western blot revealed that the production of IL-1ß, TNF-α, RANK, RANKL, TLR2, and TLR4 was reduced by MMP9 in LPS-stimulated MC3T3-E1 cells. Meanwhile, the expressions of OPG and OCN were increased by MMP9 in LPS-stimulated cells. MMP9 plays a protective role in LPS-induced inflammation, thereby providing new clues to the prevention and treatment of apical periodontitis.

TOB1-AS1 suppresses non-small cell lung cancer cell migration and invasion through a ceRNA network.

Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer-associated mortality. Recent studies revealed that long non-coding (lnc)RNAs have crucial roles in human cancers. The present study was the first, to the best of our knowledge, to indicate that the lncRNA transducer of ERBB2, 1-antisense 1 (TOB1-AS1) acts as a tumor suppressor in NSCLC. Knockdown of TOB1-AS1 significantly induced NSCLC cell migration, invasion and proliferation. It was also demonstrated that the higher expression of TOB1-AS1 in NSCLC samples was associated with longer overall survival time. Furthermore, a TOB1-AS1-mediated competing endogenous RNA network in NSCLC was constructed, including Homo sapiens (hsa)-microRNA (miR)-27a-3p, hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-27b-3p, hsa-miR-23c, dynein cytoplasmic 2 light intermediate chain 1, E4F transcription factor 1, TSPY-like 4, component of oligomeric Golgi complex 7, inositol hexakisphosphate kinase 2 and deltex E3 ubiquitin ligase 3. Of note, dysregulation of targets of TOB1-AS1 was associated with the prognosis of NSCLC patients. The present study suggested that TOB1-AS1 may serve as a novel biomarker for NSCLC.

Traditional Chinese Medicine Treatment as Adjuvant Therapy in Completely Resected Stage IB-IIIA Non-Small-Cell Lung Cancer: Study Protocol for a Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

Adjuvant chemotherapy (AC) has been proven to yield an approximately 5% improvement in 5-year survival for patients with early-stage non-small-cell lung cancer. With such small gains in survival, the optimal treatment regimen remains to be established. Traditional Chinese medicine (TCM) treatment in combination with AC is frequently used in China. The efficacy and safety of this integrated approach should be scientifically evaluated. We present the rationale and study design of the Combined Adjuvant Chemotherapy and Traditional Chinese Medicine (ACTCM) trial (ChiCTR-IPR-16009062). The ACTCM trial, a prospective multicenter double-blind randomized placebo-controlled study, will recruit 312 patients overall from 5 clinical research centers in China. Within 6 weeks of the thoracic surgery, eligible participants with stages IB-IIIA non-small-cell lung cancer will be randomly assigned in a 1:1 ratio to either the treatment or control group. Patients in the treatment group will receive AC combined with TCM herbal treatment for 4 cycles, then TCM herbal plus injection treatment for 4 cycles. Patients in the control group will receive AC combined with TCM placebo for 4 cycles and then TCM placebo for 4 cycles. Treatment will be discontinued if disease progression or unacceptable toxicity occurs. The primary end point is 2-year disease-free survival. Secondary end points include disease-free survival and quality of life. Other end points are TCM symptoms, performance status, and safety of the regimens. Recruitment started in October 2016 and is ongoing.

miR-139-5p reverses stemness maintenance and metastasis of colon cancer stem-like cells by targeting E2-2.

Colon cancer stem cells (CCSCs) stand for a critical subpopulation of colon cancer cells that possess self-renewal and multilineage differentiation potentials and drive tumorigenicity. Due to their impact on treatment tolerance, CCSCs have been a hot research topic in the past few years. We have previously reported that miR-139-5p is a vital tumor repressive noncoding RNA whose level decreases in the clinical colon cancer samples with the increase of tumor malignancy. This research discovered that miR-139-5p targets the Wnt/ß-catenin/TCF7L2 downstream effector E2-2 in CCSCs. E2-2 is a pivot molecule in the negative feedback loop of miR-139-5p/Wnt/ß-catenin/TCF7L2. Its small interfering RNA reverses the stemness maintenance and epithelial-mesenchymal transition of colon cancer CSCs. This study provides a theoretical foundation for the clinical diagnosis and medical treatment of recurrent or metastatic colon cancer with miR-139-5p and its target E2-2.

JAK2/STAT3 is associated with the inflammatory process in periapical granuloma.

OBJECTIVE: It has been shown that JAK2/STAT3 is involved in the occurrence of various inflammatory diseases. The purpose of this study was to associate the expression of Janus kinase 2 (JAK2) and its receptor signal transducer and activator of transcription 3 (STAT3) and suppressors of cytokine signaling 3 (SOCS3), to periapical granuloma. METHODS: Samples were collected from 40 patients who were divided into two groups, namely, healthy control (N=20) and periapical granuloma (N=20) groups in accordance with classified standards. The samples were prepared for histological analysis, immunohistochemistry, and double immunofluorescence staining. RESULTS: Only slight inflammatory cell infiltration was observed in the tissues from the healthy control group. Extensive infiltration of inflammatory cells was observed in patients with chronic periapical disease. The periapical granuloma group had higher levels of JAK2, STAT3, p-JAK2, p-STAT3 and SOCS3 (all P<0.05) than the control group. Double immunofluorescence staining results showed the presence of JAK2-positive and STAT3-positive cells in the periapical lesion areas. CONCLUSIONS: This study demonstrated that JAK2, STAT3, and SOCS3 can be observed and may be associated with the inflammatory process in periapical lesions. The results of this study will provide new insights into the pathological mechanisms of human periapical granuloma.

The influence of ProTaper and WaveOne on apically extruded debris: A systematic review and meta-analysis.

BACKGROUND: Apically extruded debris produced during root canal preparation can induce postoperative inflammation and subsequent failure of root canal treatment. Therefore, debris production must be reduced to improve the outcome of root canal treatment. AIM: This study aimed to provide a theoretical basis for the improvement of root canal treatment by comparing the difference in the amount of apically extruded debris produced during the root canal preparation of extracted human teeth with ProTaper Universal (PTU), ProTaper Next (PTN), and WaveOne (WO). MATERIALS AND METHODS: On March 30, 2017, three researchers searched five electronic databases (PubMed/Medline, Cochrane, Science Direct Online, Embase, and Web of Science) with no time limitations. Only articles written in English were retrieved, and 150 articles were obtained. Then, the three researchers independently selected articles in accordance with previously established inclusion and exclusion criteria, and inconsistent results were discussed. Data were analyzed through meta-analysis for standardized mean difference (SMD). RESULTS: Eight studies met the inclusion criteria and were subjected to qualitative analysis. Four articles showed that PTU produced higher amounts of apical debris than WO; two articles showed that PTU produced lower amounts of apical debris than WO; and three articles showed that PTN produced lower amounts of apical debris than WO. Moreover, one article demonstrated that PTU produced higher amounts of apical debris than PTN. A meta-analysis showed that PTU and WO did not produce significantly different amounts of apically extruded debris: SMD = -0.26, Z = 0.50 (P > 0.05). PTU produced lower amounts of apically extruded debris than WO: SMD = -4.98, Z = 2.79 (P < 0.05). However, results were significantly heterogeneous among all the included studies (I 2= 97%). No significant difference was found between PTU and WO in the amounts of apically extruded debris: SMD = 0.47, Z = 1.06 (P > 0.05). CONCLUSION: Currently available evidence shows that PTN can produce lower amounts of apical debris than WO (P < 0.05). Moreover, the amounts of apically extruded debris produced by PTU and WO are not significantly different (P > 0.05). Nevertheless, given the limited number of studies reviewed, a definitive conclusion cannot be reached.

Refinement and Evaluation of Modified Minimally Invasive Harvest Technique for Subepithelial Connective Tissue.

INTRODUCTION: The aim of this paper was to refine the modified minimally invasive single-incision technique (MSIT) into 6 steps that are easy to execute. The advantage of this modification was evaluated and compared with the traditional trap-door incision technique (TDIT). Several other harvesting techniques, suturing techniques, indications, contraindications, and limitations were also summarized. MATERIALS AND METHODS: A total of 40 patients presenting with multiple areas of gingival recession were recruited for this study. All patients were randomly assigned to either the MSIT or TDIT group. Standard periodontal instruments and crossed horizontal suspension sutures were used for both procedures. Harvesting and suturing time, verbal rating scale (VRS), and an early wound-healing index (EHI) were recorded. RESULTS: The total operating time, and particularly the suturing time, was shorter in the MSIT group (267.70 ±â€Š20.24 seconds) than the TDIT group (298.20 ±â€Š21.07 seconds), and the difference was statistically significant (P < 0.05). However, there was no significant difference in pain level between the 2 groups according to the VRS evaluation (P = 0.3658). One week postsurgery, the EHI of the MSIT group (2.00 ±â€Š0.95) was significantly lower than the TDIT group (2.85 ±â€Š1.15) (P < 0.05). DISCUSSION: The 6-step MSIT is more predictable and easy to execute, which decreases the challenge for both dentists and patients. Favorable outcomes occurred because of the streamlined minimally invasive procedure and favorable postoperative recovery.

Chronic oxymatrine treatment induces resistance and epithelial­mesenchymal transition through targeting the long non-coding RNA MALAT1 in colorectal cancer cells.

A major reason for colorectal cancer (CRC) chemoresistance is the enhanced migration and invasion of cancer cells, such as the cell acquisition of epithelial-mesenchymal transition (EMT). Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been considered as a pro-oncogene in multiple cancers. However, the precise functional mechanism of lncRNA MALAT1 in chemoresistance and EMT is not well known. In the present study, we focused on the effect of oxymatrine on CRC cells and further investigated the role of MALAT1 in oxymatrine-induced resistance and EMT process. The human CRC cell line HT29 was exposed to increasing doses of oxymatrine to establish stable cell lines resistant to oxymatrine. The established HT29 oxymatrine resistant cells showed an EMT phenotype including specific morphologic changes, enhanced migratory and invasive capacity, and downregulation of E-cadherin protein expression. Subsequently, high-throughput HiSeq sequencing and RT-qPCR showed that lncRNA MALAT1 was significantly upregulated in the oxymatrine resistant cells (P<0.01), while knockdown of MALAT1 partially reversed the EMT phenotype in HT29 resistant cells. Furthermore, oxymatrine treatment suppressed the migration and invasion ability of CRC cells, however, this effect was significantly reversed by overexpression of MALAT1. Finally, we investigated the clinical role of MALAT1 and found that high lncRNA MALAT1 expression level is associated with poor prognosis in CRC patients receiving oxymatrine treatment (P<0.01). In conclusion, we demonstrate that lncRNA MALAT1 is a stimulator for oxymatrine resistance in CRC and it may provide therapeutic and prognostic information for CRC patients.

High-mobility Group Box 1 Is Associated with the Inflammatory Infiltration and Alveolar Bone Destruction in Rats Experimental Periapical Lesions.

INTRODUCTION: This study was conducted to observe the immunohistochemical localization of high-mobility group box 1 (HMGB1) and its receptor, Toll-like receptor 4 (TRL4), in the development of periapical lesions induced in rats. The possible role of these molecules in the pathogenesis of periapical lesions was also explored. METHODS: Periapical lesions developed within 35 days after mandibular first molar pulp exposure in Wistar rats. The animals were randomly killed at 0, 7, 14, 21, 28, and 35 days after pulp exposure. The jaws that contained the first molar were obtained and prepared for histologic analysis, enzyme histochemistry, immunohistochemistry, and double immunofluorescence staining. RESULTS: From day 0 to 35, the areas of periapical bone loss increased and appeared to be stabilized on day 35. A few HMGB1-positive, TLR4-positive cells and osteoclasts could be observed on day 7. From day 7 to 28, the HMGB1 and TLR4 protein expression increased and subsequently remained stable. The number of osteoclasts multiplied from day 0 to 14 and then gradually decreased from day 14 to 35. Double immunofluorescence staining results showed HMGB1-positive, TLR4-positive cells around periapical lesions surrounding the apical foramen. CONCLUSIONS: Thus, HMGB1 and TLR4 may be associated with the pathogenesis of the periapical lesions.