Effect of sternocleidomastoid flap repair and endoscopic injection of emulsified adipose tissue stromal vascular fraction in the treatment of refractory cervical anastomotic leak contaminating mediastinum.

Mediastinal infection caused by anastomotic leak is hard to cure, mainly because the poor drainage at the site of mediastinal infection leads to persistent cavity infection, which in turn becomes a refractory mediastinal abscess cavity after minimally invasive esophagectomy (MIE)-McKeown. Herein, we explored sternocleidomastoid (SCM) muscle flaps and emulsified adipose tissue stromal vascular fraction containing adipose-derived stem-cells to address this issue. We studied 10 patients with esophageal cancer who underwent MIE-McKeown + 2-field lymphadenectomy and developed anastomotic and mediastinal leak and received new technology treatment in the Affiliated Cancer Hospital of Zhengzhou University from June 2018 to March 2022. The clinical data and prognosis of the patients were collected and analyzed. A total of 5 patients received this surgery, and no other complications occurred during the perioperative period. Among the 5 patients, 1 patient was partially cured, and 4 patients were completely cured. During the follow-up 3 months postoperatively, all these 5 patients could eat regular food smoothly, and no relapse of leak and mediastinal infection occurred. The new surgical method has achieved good results in the treatment of anastomotic leak. Compared with the traditional thoracotomy, it is a less invasive and feasible surgical approach, which can be used as a supplement to the effective surgical treatment of cervical anastomotic leak contaminating the mediastinum.

A new, potential and safe neoadjuvant therapy strategy in epidermal growth factor receptor mutation-positive resectable non-small-cell lung cancer-targeted therapy: a retrospective study.

Background: Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC. Method: This retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital. Results: Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3-4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea. Conclusion: Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.

Tumor-suppressive E3 ubiquitin ligase CHIP inhibits the PBK/ERK axis to repress stem cell properties and radioresistance in non-small cell lung cancer.

Recently, radioresistant cancer cells surviving radiotherapy have been suggested to show more aggressive phenotypes than parental cells, and the underlying mechanisms may be associated with cancer stem cells. This study provided novel mechanistic insights for E3 ubiquitin ligase CHIP in stem cell properties and radioresistance of non-small cell lung cancer (NSCLC). After bioinformatic prediction for key genes involved, NSCLC tissues and cells were collected to measure the expression of CHIP and PBK. E3 ubiquitin ligase CHIP was poorly expressed, while PBK was highly expressed in NSCLC tissues and cells. CHIP reduced the protein stability of PBK through the ubiquitin-protease pathway to repress the activation of ERK pathway. Based on the gain- or loss-of-function experiments, it was noted that restoration of CHIP curtailed stem cell properties and radioresistance in NSCLC, as manifested by inhibited sphere formation and cell proliferation, decreased number of CD133+CD44+ cells and expression of OCT4, SOX2, and NANOG, as well as facilitated apoptosis of NSCLC cells. Besides, in vivo animal experiments further confirmed that CHIP restrained tumorigenic ability and improved radiosensitivity of NSCLC cells by inhibiting PBK/ERK axis. Collectively, CHIP suppressed stem cell properties and radioresistance of NSCLC cells by inhibiting PBK/ERK axis, therefore offering a potential therapeutic target for enhancing efficacy of radiotherapy.

CircSCN8A suppresses malignant progression and induces ferroptosis in non-small cell lung cancer by regulating miR-1290/ACSL4 axis.

Circular RNAs (CircRNAs) are reported to exert vital regulatory roles in the occurrence and development of various human malignancies, including non-small cell lung cancer (NSCLC). Bioinformatics methods identified the down-regulation of circSCN8A (circBase ID: hsa_circ_0026337) in NSCLC tissues. However, its biological functions and molecular mechanisms in NSCLC remain unknown. In this study, we found that circSCN8A expression was down-regulated in NSCLC tissues and cells. Low circSCN8A expression was positively associated with aggressive clinicopathological characteristics and poor prognosis in NSCLC patients. CircSCN8A suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and blocked tumor growth in vivo. Moreover, circSCN8A promoted cell ferroptosis in NSCLC. Mechanistically, circSCN8A acted as a competing endogenous RNA (ceRNA) by sponging miR-1290 to enhance the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Furthermore, the knockdown of ACSL4 or overexpression of miR-1290 reversed the effect of circSCN8A on facilitating ferroptosis and inhibiting cell proliferation and metastasis. In summary, circSCN8A represses cell proliferation and metastasis in NSCLC by regulating the miR-1290/ACSL4 axis to induce ferroptosis. Thus, circSCN8A may represent a promising therapeutic target against NSCLC.

E3 Ubiquitin Ligase CHIP Inhibits the Interaction between Hsp90ß and MAST1 to Repress Radiation Resistance in Non-Small-Cell Lung Cancer Stem Cells.

The radiation resistance of cancer stem cells poses a critical obstacle for management of non-small-cell lung cancer (NSCLC). It is interesting to note that E3 ubiquitin ligase CHIP is involved in radiation resistance and stemness phenotypes in NSCLC, while the downstream mechanisms remain elusive. Therefore, this study is aimed at exploring the possible molecular mechanism of E3 ubiquitin ligase CHIP in radiation resistance of NSCLC stem cells. Cancer and adjacent normal tissues of NSCLC patients were collected to determine expression of CHIP, Hsp90ß, and MAST1. CD133+ cells were isolated from the NSCLC tissues and the lung cancer cell line A549 by flow cytometric sorting. Accordingly, downregulated CHIP and upregulated Hsp90ß and MAST1 were observed in cancer tissues from NSCLC patients and in NSCLC stem cells. Sphere formation assay, colony formation assay, and flow cytometry were performed to examine self-renewal ability, survival, and apoptosis of NSCLC stem cells. An animal model of tumor xenograft was developed in nude mice to observe the tumorigenic ability and radiation resistance of NSCLC stem cells. CHIP overexpression was demonstrated to inhibit the NSCLC stem cell properties and radiation resistance in vitro and in vivo. Mechanistically, CHIP promoted MAST1 ubiquitination by blocking Hsp90ß interaction with MAST1, thus inhibiting MAST1 protein stability. Furthermore, CHIP-mediated downregulation of MAST1 protein stability inhibited the NSCLC stem cell properties and radiation resistance. Collectively, CHIP promotes the ubiquitination of MAST1 by blocking the interaction of Hsp90ß with MAST1, leading to decreased MAST1 protein stability, which suppressed NSCLC stem cell properties and radiation resistance.

Circ_0007624 suppresses the development of esophageal squamous cell carcinoma via targeting miR-224-5p/CPEB3 to inactivate the EGFR/PI3K/AKT signaling.

Circular RNAs (circRNAs) have been confirmed to be involved in the regulation of esophageal squamous cell carcinoma (ESCC) progression. According to GEO datasets (GSE112496 and GSE150476), we identified that circ_0007624 was abnormally down-regulated in ESCC. However, there is still no reports regarding the function and mechanism of circ_0007624 in ESCC development. Here, we found that circ_0007624 was significantly underexpressed in ESCC tissues, and low expression of circ_0007624 was indicative of a poor prognosis. Overexpressing circ_0007624 or silencing miR-224-5p suppressed cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro. Also, circ_0007624 up-regulation slowed ESCC tumor growth in vivo. Mechanistically, circ_0007624 could serve as a competing endogenous RNA (ceRNA) by sponging miR-224-5p to antagonize its inhibitory effect on the target cytoplasmic polyadenylation element binding protein 3 (CPEB3). Rescue experiments showed that the anti-cancer properity role of circ_0007624 in ESCC is partly reversed by the restoration of miR-224-5p or down-regulation of CPEB3. Furthermore, EGFR/PI3K/AKT pathway was involved in the regulation of circ_0007624/miR-224-5p/CPEB3 axis in ESCC. Together, our findings demonstrate for the first time that circ_0007624/miR-224-5p/CPEB3 suppresses ESCC progression by inactivating EGFR/PI3K/AKT signaling, providing a basis for developing circ_0007624-targeted therapies for ESCC patients.

Transplantation of human cord blood-derived multipotent stem cells (CB-SCs) enhances the recovery of Parkinson in rats.

Earlier published research showed that cord blood-derived multipotent stem cells (CB-SCs) exhibited the intrinsic expression of specific transcription factors (e.g., En1, Nurr1 and Wnt1) and seems to be induced to form dopamine neurons in vitro. In this research, we further investigated the therapeutic potential of CB-SCs in 6-hydroxydopamine lesioned Parkinson's disease (PD) rats. The results of PCR analysis showed that CB-SCs could express transcription factors associated with pluripotentiality and dopaminergic differentiation (e.g., Klf4, c-Myc, Nanog, Sox2, Ngn2, and Nurr1). After being transplanted into the striatum and substantia nigra of PD rats, most of CB-SCs (>90%) developed a fate commitment to dopaminergic differentiation, expressed as the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). The improvement effect of cell transplantation on dyskinesia in PD rats was better than that in sham control group. Moreover, higher levels of TH protein in brain homogenates further demonstrated that there were more surviving dopamine neurons in the brain of transplanted PD rats. Study concluds, CB SCS transplantation could promote the regeneration of dopamine neurons and behavioral recovery of PD rats.

Older patients more likely to die from cancer-related diseases than younger with stage IA non-small cell lung cancer: a SEER database analysis.

Background: Various reports showed some conflicting data on survival at different ages. This study aimed to investigate the main cause of death in older patients with lung cancer and to perform a comparison with younger patients in order to observe the differences between these two cohorts. Methods: Outcomes of patients with stage IA non-small cell lung cancer (NSCLC) ≤3 cm who underwent lobectomy without induction therapy in the Surveillance, Epidemiology, and End Results-18 (SEER-18; January 2004 to December 2016) database were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Results: A total of 16,672 eligible NSCLC cases were found in the SEER database. The number of patients aged ≤60, 61-70, and ≥71 years was 3,930, 6,391, and 6,351, respectively. Among these patient groups, 527 (13.4%), 1,018 (15.9%), and 1,235 (19.4%) died of lung cancer during follow-up, while 357 (9.1%), 964 (15.1%) and 1,579 (25.2%) died of non-lung cancer diseases, respectively. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of younger patients showed a significant survival advantage over older patients. After propensity-score matching (PSM) of patients aged ≤60 and ≥71 years using a ratio of 1:1, we found that 403 (12.9%) and 584 (18.7%) patients in the ≤60 and ≥71 years age groups died of lung cancer, respectively. The OS and LCSS rates of younger patients still exhibited a significant survival advantage over older patients. Conclusions: Older patients with stage IA NSCLC have a worse prognosis compared with younger patients. Also, cancer-related causes were more frequent in older patients than non-cancer-related causes.

A clinical nomogram for predicting tumor regression grade in esophageal squamous-cell carcinoma treated with immune neoadjuvant immunotherapy.

Background: There are various treatment options for esophageal squamous cell cancer. including surgery, peri-operative chemotherapy, and radiation. More recently, neoadjuvant immunotherapy has also been shown improve outcomes. In this study, we addressed the question, "Can we predict which patients with esophageal squamous cell cancer will benefit from neoadjuvant immunotherapy?". Methods: All patients with thoracic esophageal squamous-cell carcinoma (T2N+M0-T3-4N0/+M0) (according to the eighth edition of the National Comprehensive Cancer Network guidelines) who underwent immune neoadjuvant immunochemotherapy with programmed cell death protein 1 (PD-1) combined with paclitaxel plus cisplatin or nedaplatin in the Affiliated Cancer Hospital of Zhengzhou University, China, between November 2019 and August 2021 were included in this study. All patients underwent surgical resection. We developed a response [tumor regression grade (TRG)] prediction model using the least absolute shrinkage and selection operator (LASSO) regression incorporating factors associated with response. The accuracy of the prediction model was then validated. Results: We included 79 patients who underwent neoadjuvant immunotherapy combined with chemotherapy, aged 48-78 years (62.05±6.67), including 21 males and 58 females. There were five cases of immune-related pneumonia, of which three cases were diagnosed as immune-related pneumonia during the perioperative period, and one case of immune-related thyroid dysfunction changes. After LASSO regression, the factors that were independently associated with TRG were clinical T stage before neoadjuvant therapy, clinical N stage before neoadjuvant therapy, albumin level difference from before to after neoadjuvant therapy, white blood cell (WBC) count before neoadjuvant therapy, and T stage before surgery. We constructed a prediction model, plotted the nomogram, and verified its accuracy. Its Brier score was 0.13, its calibration slope was 0.98, and its C-index was 0.90 (95% CI: 0.82-0.97). Conclusions: Our prediction model can predict the likelihood of TRG in patients with esophageal squamous cell cancer after immunotherapy combined with neoadjuvant chemotherapy. Using this prediction model, we plan to conduct a subsequent neoadjuvant radiotherapy in patients with of TRG 2-3 patients with neoadjuvant radiotherapy.

THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the digestive system with a high incidence and poor prognosis. Long non-coding RNAs (LncRNA) have been reported to be closely associated with the occurrence and development of various human cancers. Data from GSE89102 shows an increase of THAP9-AS1 expression in ESCC. However, its functions and mechanisms underlying ESCC progression remain to be investigated. In this study, we found that THAP9-AS1 was overexpressed in ESCC tissues and cells. High THAP9-AS1 expression was positively correlated with tumor size, TNM stage, lymph node metastasis, and worse prognosis. Functionally, depletion of THAP9-AS1 suppressed cell proliferation, migration, and invasion, while enhanced apoptosis in vitro. Consistently, knockdown of THAP9-AS1 inhibited xenograft tumor growth in vivo. Mechanistically, THAP9-AS1 could serve as a competing endogenous RNA (ceRNA) for miR-133b, resulting in the upregulation of SOX4. Reciprocally, SOX4 bound to the promoter region of THAP9-AS1 to activate its transcription. Moreover, the anti-tumor property induced by THAP9-AS1 knockdown was significantly impaired due to miR-133b downregulation or SOX4 overexpression. Taken together, our study reveals a positive feedback loop of THAP9-AS1/miR-133b/SOX4 to facilitate ESCC progression, providing a potential molecular target to fight against ESCC.

Adjuvant treatment can improve prognosis in patients with non-small cell lung cancer ≤3 cm after sublobectomy: a propensity score analysis.

BACKGROUND: Numerous retrospective studies have reported that sublobectomy has a poorer prognosis than lobectomy in patients with early-stage lung cancer. The purpose of this study was to determine whether adjuvant treatment could improve the prognosis of patients with non-small cell lung cancer (NSCLC) ≤3 cm after sublobectomy. METHODS: We collected data from 17,763 patients with T1N0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Kaplan-Meier curves were generated to compare the overall survival (OS) rates and the lung cancer-specific survival (LCSS) rates. Cox proportional hazards regressions were performed to discover the independent risk factors for both the OS and LCSS rates. RESULTS: Lobectomy was performed in 12,428 cases and sublobectomy was performed in 5,335 cases. In the sublobectomy group, among the 394 patients treated with adjuvant therapy, larger tumor diameter, a lower number of lymph node dissections, and more wedge resections were observed in the patients treated with adjuvant therapy. In the subsequent survival analysis, the OS and LCSS rates of adjuvant therapy patients showed a significant survival advantage over those treated with sublobectomy alone (P<0.05). The survival analysis was performed again after propensity match scoring, generating similar results (P<0.05). There was still a significant difference in OS between adjuvant therapy and lobectomy alone (P<0.05). CONCLUSIONS: Chemoradiotherapy can improve the OS of patients with NSCLC ≤3 cm after sublobectomy and reduce death caused by tumors. Therefore, when patients cannot tolerate lobectomy or are given inappropriate sublobectomy, adjuvant therapy can improve the prognosis of patients.

Aerial View of the Association Between m6A-Related LncRNAs and Clinicopathological Characteristics of Pancreatic Cancer.

Pancreatic cancer is a highly malignant tumor with a poor survival prognosis. We attempted to establish a robust prognostic model to elucidate the clinicopathological association between lncRNA, which may lead to poor prognosis by influencing m6A modification, and pancreatic cancer. We investigated the lncRNAs expression level and the prognostic value in 440 PDAC patients and 171 normal tissues from GTEx, TCGA, and ICGC databases. The bioinformatic analysis and statistical analysis were used to illustrate the relationship. We implemented Pearson correlation analysis to explore the m6A-related lncRNAs, univariate Cox regression and Kaplan-Meier methods were performed to identify the seven prognostic lncRNAs signatures. We inputted them in the LASSO Cox regression to establish a prognostic model in the TCGA database, verified in the ICGC database. The AUC of the ROC curve of the training set is 0.887, while the validation set is 0.711. Each patient has calculated a risk score and divided it into low-risk and high-risk subgroups by the median value. Moreover, the model showed a robust prognostic ability in the stratification analysis of different risk subgroups, pathological grades, and recurrence events. We established a ceRNA network between lncRNAs and m6A regulators. Enrichment analysis indicated that malignancy-associated biological function and signaling pathways were enriched in the high-risk subgroup and m6A-related lncRNAs target mRNA. We have even identified small molecule drugs, such as Thapsigargin, Mepacrine, and Ellipticine, that may affect pancreatic cancer progression. We found that seven lncRNAs were highly expressed in tumor patients in the GTEx-TCGA database, and LncRNA CASC19/UCA1/LINC01094/LINC02323 were confirmed in both pancreatic cell lines and FISH relative quantity. We provided a comprehensive aerial view between m6A-related lncRNAs and pancreatic cancer's clinicopathological characteristics, and performed experiments to verify the robustness of the prognostic model.

Hand-assisted sputum excretion can effectively reduce postoperative pulmonary complications of esophageal cancer.

BACKGROUND: This study explores whether postoperative hand-assisted expectoration can reduce postoperative pulmonary complications (PPCs) in patients with esophageal cancer. METHODS: A retrospective analysis was performed on 543 patients undergoing radical esophageal cancer (EC) surgery in our hospital from October 2018 to August 2019, 156 of whom received postoperative handassisted sputum excretion (pulmonary rehabilitation, PR) and 387 of whom who did not receive postoperative hand-assisted sputum excretion (no pulmonary rehabilitation, NPR). Because the clinical characteristics of the two groups were not balanced, we used propensity score matching (PSM) to account for the variable factors of age, gender, body mass index (BMI), chronic respiratory comorbidity, smoking index, operation time, operation method, pathological stage. The main observation index used was PPCs. RESULTS: Among these 543 patients, 365 were male (67.2%), while 178 were female (32.8%). The age ranged from 30 to 82 years, with an average of 63.6±7.5 years old. In all, 342 patients (63%) underwent video-assisted thoracic surgery (VATS) surgery, while 201 patients (37%) underwent thoracotomy. Furthermore, 72 patients in the PR group received preoperative rehabilitation training and postoperative hand-assisted sputum excretion (combination pulmonary rehabilitation, CPR), while 87 patients only received postoperative hand-assisted sputum excretion (postoperative pulmonary rehabilitation, PPR). The patients in the PR group and the NPR group were uneven in terms of clinical characteristics, and we performed PSM as a result. After matching, PPC incidence in patients in the PR group was lower than that in the NPR group (P<0.05). CONCLUSIONS: Our results show that hand-assisted sputum excretion after EC surgery can reduce PPCs.

LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis.

BACKGROUND: Osteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed. METHODS: Cell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo. RESULTS: Autophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo. CONCLUSIONS: SNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

Chin-down-plus-larynx-tightening maneuver improves choking cough after esophageal cancer surgery.

BACKGROUND: Esophageal cancer patients can benefit from dissection of the recurrent laryngeal nerve (RLN) lymph node (LN); however, this procedure increases the risk of RLN injury. After nerve injury, many complications can occur, including choking cough, which can affect patients' quality of life. This study examined the effectiveness of the chin-down-plus-larynx-tightening maneuver for improving choking cough after radical thoracic esophageal cancer surgery. METHODS: Sixty-two patients with resectable thoracic esophageal cancer presented with choking cough, hoarseness or vocal cord paralysis after radical operations. Twenty-two patients who choked on water were guided to swallow 1 mL of warm water using a chin-down-plus-larynx-tightening maneuver. Choking cough relief results and their relationships with clinical factors were analyzed. RESULTS: No correlation was found between the occurrence of post-operative choking cough and gender, age, surgical method, hoarseness, vocal cord fixation type, vocal cord fixation, or glottal closure. Multivariate regression analysis revealed no independent risk factors associated with choking cough. Choking cough was completely relieved in 17 of 22 (77.3%) patients. Fifteen of 19 (78.9%) patients with choking cough and hoarseness, and 2 of 3 patients with only choking cough reported complete relief when they tried the new maneuver. The chin-down-plus-larynx-tightening maneuver was more effective for males than for females. CONCLUSIONS: The chin-down-plus-larynx-tightening maneuver significantly relieved choking cough; thus, this maneuver can aid in managing choking cough after radical thoracic esophageal cancer surgery.

Comparative study of esophagectomy, endoscopic therapy, and radiotherapy for cT1N0M0 esophageal cancer in elderly patients: A SEER database analysis.

BACKGROUND: The number of patients diagnosed with early stage disease (T1a or T1b) has been increasing. This study was conducted to investigate the effect of esophagectomy (ES), endoscopic therapy (ET), and radiotherapy (RT) on long-term survival in elderly patients with cT1N0M0 esophageal cancer. METHODS: We searched the Surveillance, Epidemiology, and End Results (SEER) database to identify the records of elderly patients (≥ 75 years) with cT1N0M0 esophageal cancer between 2004 and 2014. Patient demographics and esophageal cancer parameters were compared among ES, ET, and RT groups. The Kaplan-Meier method and Cox proportional hazard modeling were used to compare long-term survival. RESULTS: Data from 954 esophageal cancer patients (ES: n = 196; ET: n = 224; RT: n = 534) were identified. Multivariate Cox regression analysis showed that five-year survival in the ET and ES groups was significantly higher than in the RT group. After propensity score matching, we found no difference in five-year survival between ES and ET. CONCLUSION: Using SEER data, we identified a significant survival advantage with the use of ES and ET compared to RT in patients with cT1N0M0 esophageal cancer aged > 75 years, while the long-term survival of patients after ET and ES was not significantly different.

microRNA-301b-3p downregulation underlies a novel inhibitory role of long non-coding RNA MBNL1-AS1 in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the second most prevalent cause of cancer-related fatality. Long non-coding RNAs (lncRNAs) have been observed to exercise functions in NSCLC. Here, the current study aimed to explore the potential mechanism of lncRNA MBNL1-AS1 in NSCLC. METHODS: Microarray analysis was performed to screen the differentially expressed lncRNA associated with NSCLC and its potential mechanism. The lncRNA MBNL1-AS1 expression was quantified in 56 paired NSCLC and adjacent normal tissue samples. In an attempt to outline the function of lncRNA MBNL1-AS1 in NSCLC and to identify the interaction among lncRNA MBNL1-AS1, microRNA-301b-3p (miR-301b-3p) and TGFBR2, ectopic expression, depletion, and reporter assay experiments were conducted to detect CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. RESULTS: Initially, the intersection among lncRNA MBNL1-AS1, miR-301b-3p, and TGFBR2 was observed in NSCLC. While a poor expression of lncRNA MBNL1-AS1 and TGFBR2, along with a high expression of miR-301b-3p was observed in NSCLC tissues. A demonstration of lncRNA MBNL1-AS1 restoration significantly decreased CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 functioned as a sponge of miR-301b-3p, which inverted the inhibitory role of lncRNA MBNL1-AS1 in CSC proliferation, migration, invasion, drug resistance, and sphere formation in NSCLC. LncRNA MBNL1-AS1 positively regulated TGFBR2 which was a target gene of miR-301b-3p. At last, upregulated lncRNA MBNL1-AS1 or depleted miR-301b-3p suppressed the xenograft tumor formation in vivo. CONCLUSION: Collectively, the present study suggests an inhibitory role of lncRNA MBNL1-AS1 in CSC drug resistance of NSCLC by upregulating miR-301b-3p-targeted TGFBR2.

Unexpected solvent effects on the UV/Vis absorption spectra of o-cresol in toluene and benzene: in contrast with non-aromatic solvents.

Cresol is a prototype molecule in understanding intermolecular interactions in material and biological systems, because it offers different binding sites with various solvents and protonation states under different pH values. It is found that the UV/Vis absorption spectra of o-cresol in aromatic solvents (benzene, toluene) are characterized by a sharp peak, unlike the broad double-peaks in 11 non-aromatic solvents. Both molecular dynamics simulations and electronic structure calculations revealed the formation of intermolecular π-complexation between o-cresol and aromatic solvents. The thermal movements of solvent and solute molecules render the conformations of o-cresol changing between trans and cis isomers. The π-interaction makes the cis configuration a dominant isomer, hence leading to the single keen-edged UV/Vis absorption peak at approximately 283 nm. The free conformation changes between trans and cis in aqueous solution rationalize the broader absorption peaks in the range of 260-280 nm. The pH dependence of the UV/Vis absorption spectra in aqueous solutions is also rationalized by different protonation states of o-cresol. The explicit solvent model with long-ranged interactions is vital to describe the effects of π-complexation and electrostatic interaction on the UV/Vis absorption spectra of o-cresol in toluene and alkaline aqueous (pH > 10.3) solutions, respectively.

Single-Molecule Mechanics of Catechol-Iron Coordination Bonds.

Metal coordination bonds are widely found in natural adhesives and load-bearing and protective materials, in which they are thought to be responsible for the high mechanical strength and toughness. However, it remains unknown how metal-ligand complexes could give rise to such superb mechanical properties. Here, we developed a single-chain nanoparticle based force spectroscopy to directly quantify the mechanical properties of individual catechol-Fe3+ complexes, the key elements accounting for the high toughness and extensibility of byssal threads of marine mussels. We found that catechol-Fe3+ complexes possess a unique combination of mechanical features, including high mechanical stability, fast reformation kinetics, and stoichiometry-dependent mechanics. Therefore, they can serve as sacrificial bonds to efficiently dissipate energy in the materials, quickly recover the mechanical properties when load is released, and respond to pH and Fe3+ concentrations. Especially, we revealed that the bis-catechol-Fe3+ complex is mechanically ∼90% stronger than the tris-catechol-Fe3+ complex. Quantum calculation study suggested that the distinction between mechanical strength and thermodynamic stability of catechol-Fe3+ complexes is due to their different mechanical rupture pathways. Our study provides the nanoscale mechanistic understanding of the coordination bond-mediated mechanical properties of biogenetic materials, and could guide future rational design and regulation of the mechanical properties of synthetic materials.

Photodynamic therapy versus endoscopic submucosal dissection for management of patients with early esophageal neoplasia: a retrospective study.

BACKGROUND: Photodynamic therapy (PDT) and endoscopic submucosal dissection (ESD) have been proposed as a treatment for early esophageal neoplasia. The objective of this study is to compare between the clinical outcome after ESD and PDT to reach the best management for early esophageal neoplasia. METHODS: All patients undergoing ESD or PDT for early esophageal neoplasia between 2014 and 2015 were eligible for the study. A retrospective analysis for comparison between the results of ESD and PDT was done. RESULTS: 36 patients underwent ESD and Thirty PDT. No significant difference was found between the two groups regarding the demographic or pathologic data. Also, there was no significant difference regarding the length of hospital stay, presence of hydrothorax, fever, and pain. Operative time was significantly longer in ESD than in PDT (72 vs. 8 minutes, P<0.001). In addition, bleeding was significantly lower in ESD than PDT (12 vs. 2, P<0.05). There was a significant difference regarding stricture and cost which were less in ESD (6 vs. 15, P<0.05). However, perforation was much more in ESD (6 vs. 0, P<0.05). There was no significant difference between the two groups regarding the disease free survival (DFS), but it was observed that patients who underwent PDT had more favorable 2-year DFS rates than patients received ESD. CONCLUSIONS: The PDT may be comparable to the ESD. With the exception of esophageal stenosis, PDT could reduce many complications and have longer DFS in comparison with ESD. PDT is feasible for patients with early esophageal neoplasia confined to the mucosal layer without regional lymph nodal or distant metastasis.