Melatonin alleviates T-2 toxin-induced oxidative damage, inflammatory response, and apoptosis in piglet spleen and thymus.

T-2 toxin, an unavoidable contaminant in animal feeds, can induce oxidative stress and damage immune organs. Melatonin (MT), a natural and potent antioxidant, has shown promise as a detoxifier for various mycotoxins. However, the detoxifying effect of MT on T-2 toxin has not been previously reported. In order to investigate the protective effect of MT added to diets on the immune system of T-2 toxin-exposed piglets, twenty piglets weaned at 28d of age were randomly divided into control, T-2 toxin (1 mg/kg), MT (5 mg/kg), and T-2 toxin (1 mg/kg) + MT (5 mg/kg) groups(n = 5 per group). Our results demonstrated that MT mitigated T-2 toxin-induced histoarchitectural alterations in the spleen and thymus, such as hemorrhage, decreased white pulp size in the spleen, and medullary cell sparing in the thymus. Further research revealed that MT promoted the expression of Nrf2 and increased the activities of antioxidant enzymes CAT and SOD, while reducing the production of the lipid peroxidation product MDA. Moreover, MT inhibited the NF-κB signaling pathway, regulated the expression of downstream cytokines IL-1ß, IL-6, TNF-α, and TGF-ß1. MT also suppressed the activation of caspase-3 while down-regulating the ratio of Bax/Bcl-2 to reduce apoptosis. Additionally, MT ameliorated the T-2 toxin-induced disorders of immune cells and immune molecules in the blood. In conclusion, our findings suggest that MT may effectively protect the immune system of piglets against T-2 toxin-induced damage by inhibiting oxidative stress, inflammatory response, and apoptosis in the spleen and thymus. Therefore, MT holds the potential as an antidote for T-2 toxin poisoning.

Koumine inhibits IL-1ß-induced chondrocyte inflammation and ameliorates extracellular matrix degradation in osteoarthritic cartilage through activation of PINK1/Parkin-mediated mitochondrial autophagy.

Osteoarthritis (OA) is a degenerative joint disease, Increasingly, mitochondrial autophagy has been found to play an important regulatory role in the prevention and treatment of osteoarthritis. Koumine is a bioactive alkaloid extracted from the plant Gelsemium elegans. In previous research, Koumine was found to have potential in improving the progression of OA in rats. However, the specific mechanism of its action has not been fully explained. Therefore, the aim of this study was to investigate whether Koumine can alleviate OA in rats by influencing mitochondrial autophagy. In the in vitro study, rat chondrocytes (RCCS-1) were induced with IL-1ß (10 ng/mL) to induce inflammation, and Koumine (50 µg/mL) was co-treated. In the in vivo study, a rat OA model was established by intra-articular injection of 2% papain, and Koumine was administered orally (1 mg/kg, once daily for two weeks). It was found that Koumine effectively reduced cartilage erosion in rats with osteoarthritis. Additionally, it decreased the levels of inflammatory factors such as IL-1ß, IL-6, and extracellular matrix (ECM) components MMP13 and ADAMTS5 in chondrocytes and articular cartilage tissue, while increasing the level of Collagen II.Koumine inhibited the production of reactive oxygen species (ROS) in cartilage tissue and increased the number of autophagosomes in chondrocytes and articular cartilage tissue. Additionally, it upregulated the expression of mitochondrial autophagy proteins LC3Ⅱ/Ⅰ, PINK1, Parkin, and Drp1. The administration of Mdivi-1 (50 µM) reversed the enhanced effect of Koumine on mitochondrial autophagy, as well as its anti-inflammatory and anti-ECM degradation effects in rats with OA. These findings suggest that Koumine can alleviate chondrocyte inflammation and improve the progression of OA in rats by activating PINK1/Parkin-mediated mitochondrial autophagy.

Viola yedoensis Makino alleviates heat stress-induced inflammation, oxidative stress, and cell apoptosis in the spleen and thymus of broilers.

ETHNOPHARMACOLOGICAL RELEVANCE: Viola yedoensis Makino (VYM) is a traditional Chinese herbal medicine widely distributed in China. It has many pharmacological effects such as anti-inflammatory, immune regulation and anti-oxidation. However, the protective effect of VYM on the spleen and thymus of broilers induced by heat stress has rarely been reported. AIM OF THE STUDY: We established a heat stress model of broilers to explore the protective effect of VYM on spleen and thymus of broilers. MATERIALS AND METHODS: In this experiment, a heat stress model was made by adjusting the feeding temperature of broilers. The protective effect of VYM on the spleen and thymus of heat-stressed broilers were evaluated by detecting immune organ coefficient, histological observation, Enzyme-Linked Immunosorbent Assay, production of antioxidant enzymes and peroxides, TUNEL Staining, Quantitative Real-time PCR. RESULTS: In this study, 60 healthy male AA broilers were divided into 6 groups: Control, 4.5% VYM, HS, HS + 0.5% VYM, HS + 1.5% VYM, HS + 4.5% VYM. After 42 days of feeding, serum, spleen and thymus were collected for detection and analysis. The study revealed that heat stress can lead to pathological damage in the spleen and thymus of broilers, reduce the content of immunoglobulin and newcastle disease (ND), infectious bursal disease (IBD) antibody levels, increase the expression of inflammatory factors IL-1ß, INF-γ, heat shock 70 kDa protein (HSP70), heat shock 90 kDa protein (HSP90). Heat stress inhibits the activity of antioxidant enzymes CAT and SOD, promotes the production of MDA, and then lead to oxidative damage of the spleen and thymus. In addition, apoptotic cells and the ratio of Bax/Bcl-2 was increased. However, the addition of VYM to the feed can alleviate the adverse effects of heat stress on the spleen and thymus of broilers. CONCLUSIONS: This study showed that the addition of VYM to the diet could inhibit oxidative stress and apoptosis, and reduce the inflammatory damage of heat stress on the spleen and thymus of broilers. This study provides a basis for further exploring the regulatory role of VYM in heat stress-induced immune imbalance in broilers. In addition, this study also provides a theoretical basis for the development of VYM as a feed additive with immunomodulatory effects.

Refining postoperative monitoring of recurrent laryngeal nerve injury in esophagectomy patients through transcutaneous laryngeal ultrasonography.

BACKGROUND: Recurrent laryngeal nerve injury (RLNI) leading to vocal cord paralysis (VCP) is a significant complication following minimally invasive esophagectomy (MIE) with upper mediastinal lymphadenectomy. Transcutaneous laryngeal ultrasonography (TLUSG) has emerged as a non-invasive alternative to endoscopic examination for evaluating vocal cord function. Our study aimed to assess the diagnostic value of TLUSG in detecting RLNI by evaluating vocal cord movement after MIE. METHODS: This retrospective study examined 96 patients with esophageal cancer who underwent MIE between January 2021 and December 2022, using both TLUSG and endoscopy. RESULTS: VCP was observed in 36 out of 96 patients (37.5%). The incidence of RLNI was significantly higher on the left side than the right (29.2% vs. 5.2%, P < 0.001). Postoperative TLUSG showed a sensitivity and specificity of 88.5% (31/35) and 86.5% (45/52), respectively, with an AUC of 0.869 (P < 0.001, 95% CI 0.787-0.952). The percentage agreement between TLUSG and endoscopy in assessing VCP was 87.4% (κ = 0.743). CONCLUSIONS: TLUSG is a highly effective screening tool for VCP, given its high sensitivity and specificity. This can potentially eliminate the need for unnecessary endoscopies in about 80% of patients who have undergone MIE.

Clinical value of folate receptor-positive circulating tumor cells in patients with esophageal squamous cell carcinomas: a retrospective study.

BACKGROUND: The aim of the study is to explore the role of preoperative folate receptor-positive circulating tumor cell (FR+CTC) levels in predicting disease-free survival (DFS) and overall survival (OS) in patients with esophageal squamous cell carcinomas (ESCC). METHODS: Three ml blood samples were prospectively drawn from ESCC patients, and ligand-targeted polymerase chain reaction (LT-PCR) was used for the quantification of FR+CTCs. Other serum indicators were measured by traditional methods. Clinicopathological characteristics were obtained from the hospital medical record system, DFS and OS data were obtained by follow-up. The correlation between clinico-pathological characteristics, DFS, and OS and FR+CTCs were analyzed, respectively. Risk factors potentially affecting DFS and OS were explored by Cox regression analysis. RESULTS: there were no significant correlations between FR+CTCs and patient age, sex, albumin, pre-albumin, C-reactive protein (CRP), ferritin and CRP/Albumin ratio, tumor size, grade of differentiation, lymph node metastasis, TNM stage, perineural invasion/vessel invasion (all P > 0.05). Nevertheless, preoperative FR+CTCs were an independent prognostic factor for DFS (HR 2.7; 95% CI 1.31-, P = 0.007) and OS (HR 3.37; 95% CI 1.06-, P = 0.04). DFS was significantly shorter for patients with post-operative FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml (P = 0.0012). For OS, it was shorter for patients with FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml, however, the difference did not reach statistical significance (P = 0.51). CONCLUSIONS: ESCC patients with high FR+CTCs tend to have a worse prognosis. FR+CTCs may monitor the recurrence of cancers in time, accurately assess patient prognosis, and guide clinical decision-making. TRIAL REGISTRATION: The study was approved by the Sichuan Cancer Hospital & Institute Ethics Committee (No. SCCHEC-02-2022-050).

Mapping of Lymph Node Metastasis and Efficacy Index in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Retrospective Analysis.

BACKGROUND: Esophageal squamous cell carcinoma has a high mortality rate in China. The metastatic pattern in the lymph nodes and the value of their dissection on the overall survival of these patients remain controversial. The primary aim of this study was to provide a basis for accurate staging of esophageal cancer and to identify the relationship between esophageal cancer surgery, lymph node dissection, and overall survival rates. METHODS: We utilized our hospital database to retrospectively review the data of 1727 patients with esophageal cancer who underwent R0 esophagectomy from January 2010 to December 2017. The lymph nodes were defined according to Japanese Classification of Esophageal Cancer, 11th Edition. The Efficacy Index (EI) was calculated by multiplying the frequency (%) of metastases to a zone and the 5-year survival rate (%) of patients with metastases to that zone, and then dividing by 100. RESULTS: The EI was high in the supraclavicular and mediastinal zones in patients with upper esophageal tumors, and the EI of 101R was 17.39, which was the highest among the lymph node stations. In patients with middle esophageal tumors, the EI was highest in the mediastinal zone, followed by the celiac and supraclavicular zones. Furthermore, the EI was highest in the celiac zone, followed by the mediastinal zones in patients with lower esophageal tumors. CONCLUSIONS: The EI of resected lymph nodes was found to vary between stations and was related to the primary location of the tumor.

Resected lymph nodes and survival of patients with esophageal squamous cell carcinoma: an observational study.

BACKGROUND: The incidence and mortality of esophageal cancer are high. Therefore, the authors aimed to investigate how the number of dissected lymph nodes (LNs) during esophagectomy for esophageal squamous cell carcinoma impacts overall survival (OS), particularly that of patients with positive LNs. MATERIALS AND METHODS: Data from 2010 to 2017 were obtained from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database. Participants were divided into two groups: patients with negative lymph nodes (N0) and patients with positive lymph nodes (N+). The median number of resected LNs during surgery was 24; therefore, patients with 15-23 and those with 24 or more resected LNs were assigned to subgroups A and B, respectively. RESULTS: After a median follow-up of 60.33 months, 1624 patients who underwent esophagectomy were evaluated; 60.53 and 39.47% had a pathological diagnosis of N+ or N0, respectively. The median OS was 33.9 months for the N+ group; however, the N0 group did not achieve the median OS. The mean OS was 84.9 months. In the N+ group, the median OS times of subgroups A and B were 31.2 and 37.1 months, respectively. The OS rates at 1, 3, and 5 years were 82, 43, and 34%, respectively, for subgroup A of the N+ group; they were 86, 51, and 38%, respectively, for subgroup B of the N+ group. Subgroups A and B of the N0 group exhibited no statistically significant differences. CONCLUSION: Increasing the number of LNs harvested during surgery to 24 or more could improve the OS of patients with positive LNs but not that of patients with negative LNs.

Citrinin Exposure Induced Testicular Damage and Spermatogenesis Disorder by Triggering Endoplasmic Reticulum Stress.

Damage to the reproductive system is the key factor leading to male infertility. Citrinin (CTN) is produced by Penicillium and Aspergillus in nature, and is definitely found in food and animal feed. Studies have revealed that CTN can cause damage to male reproductive organs and reduce fertility, but the mechanism of toxicity has not been revealed. In the present study, male Kunming mice were given different doses of CTN (0, 1.25, 5 or 20 mg/kg BW) by intragastric administration. The results demonstrated that CTN exposure caused disorder of androgen, a decline in sperm quality, and histopathological damage of testis. The inhibition of the expression of ZO-1, claudin-1 and occludin suggests that the blood-testis barrier (BTB) was damaged. Simultaneously, CTN inhibited the activity of antioxidant enzymes such as CAT and SOD, and promoted the production of MDA and ROS, resulting in oxidative damage of testis. Additionally, apoptotic cells were detected and the ratio of Bax/Bcl-2 was increased. Not only that, CTN activated the expression of endoplasmic reticulum stress (ERS)-related proteins IRE1, ATF6, CHOP, and GRP78. Interestingly, 4-Phenylbutyric Acid (4-PBA, an ERS inhibitor) treatment blocked the adverse effects of CTN exposure on male reproduction. In short, the findings suggested that CTN exposure can cause damage to mouse testis tissue, in which ERS exhibited an important regulatory role.

PI3K/AKT/mTOR, NF-κB and ERS pathway participated in the attenuation of H2O2-induced IPEC-J2 cell injury by koumine.

ETHNOPHARMACOLOGICAL RELEVANCE: Koumine, an indole alkaloid extracted from Gelsemium elegans Benth, exerts anti-inflammation and antioxidant activities. However, the effects of koumine on intestinal injury induced by H2O2 and its potential molecular mechanisms need larger studies. AIM OF THE STUDY: We established an IPEC-J2 cell damage model induced by H2O2 to explore the protective mechanism of koumine on intestinal injury. MATERIALS AND METHODS: In the experiment, cell damage models were made with hydrogen peroxide. To assess the protective effect of koumine on H2O2-induced IPEC-J2 cell injury, CCK-8, the release of LDH and ROS, transmission electron microscopy and Annexin V-FITC/PI were employed. Western Blot and Quantitative Real-time PCR were used to determine the potential alleviated mechanism of koumine on H2O2-trigged IPEC-J2 cell damage. RESULTS: The results of CCK-8 and LDH implied that koumine has a mitigative effect on H2O2-induced cell damage via upregulating cell viability and suppressing cell membrane fragmentation. Simultaneously, koumine notably inhibited the level of pro-inflammatory factors (IL-1ß, IL-6, IL-8, TNF-α and TGF-ß), the over-production of ROS along with decreasing the injury of mitochondrion, endoplasmic reticulum and lysosome induced by H2O2. Moreover, koumine dramatically attenuated H2O2-triggered IPEC-J2 cell apoptosis and autophagy. Subsequently, Western blot analysis identified NF-ΚB, PI3K and ERS as possible pathway responsible for the protective effect of koumine on H2O2-stimulated IPEC-J2 cell inflammation. CONCLUSIONS: This in vitro experimental study suggests that koumine suppresses the H2O2-induced activation of inflammatory pathways, oxidative injury, ER stress, apoptosis and autophagy, which provide a rationale for therapeutically use in major intestinal diseases.

Betulinic acid alleviates zearalenone-induced uterine injury in mice.

Zearalenone (ZEA) is a mycotoxin with estrogen-like biological activity, which widely present in feed and raw materials, with strong reproductive system toxicity and a major threat to animal reproduction. Betulinic acid (BA) is a natural plant compound with antioxidant, anti-inflammatory and other pharmacological activities. However, the mechanism of ZEA-induced uterine injury and the protective effect of BA have not been reported. Our results show that ZEA could cause uterine histopathological damage and cellular ultrastructural damage, affecting the secretion of sex hormones, such as estradiol (E2) and progesterone (P4), and increase the mRNA and protein expression of estrogen receptor α (ERα). ZEA could inhibit the activities of catalase (CAT) and superoxide dismutase (SOD), increase the production of malondialdehyde (MDA) and reactive oxygen species (ROS), and cause uterine oxidative stress. Furthermore, ZEA affected the homeostasis of uterine cell proliferation and death by regulating the expression of proliferating cell nuclear antigen (PCNA) and activating the mitochondrial apoptotic pathway. ZEA-induced uterine injury might be related to the activation of p38/ERK MAPK signaling pathway. However, the regulatory effect of ZEA on the uterus was reversed after BA treatment. In conclusion, the uterus is an important target organ attacked by ZEA, and BA showed a good therapeutic effect.

Peripheral T lymphocyte and immunocyte subset dynamics: markers of neoadjuvant therapy outcomes in esophageal squamous cell carcinoma.

Purpose: In patients with resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant therapy increased the curative resection rate, disease-free survival, and overall survival for patients with resectable ESCC. However, the efficacy of neoadjuvant therapy varies among different patients. We aim to compare the differences in the characteristics of peripheral blood T lymphocyte subsets before and after neoadjuvant therapy in patients with different curative efficacy. Method: This study enrolled 266 ESCC patients who received neoadjuvant therapy and esophagectomy from August 2018 to August 2022. The postoperative pathological results divided patients into the major pathological response (MPR) and non-MPR groups. Compare the differences in peripheral blood T lymphocyte subsets and analyze the trend of changes in T lymphocyte subsets at different phases of treatment. Propensity score matching was used to reduce the influence of potential confounding factors. Results: Prior to the neoadjuvant therapy, particularly before the second cycle, the MPR group exhibited significantly higher ratios of CD4/CD8 (P=0.009) and helper T cells (TH ratio, P=0.030) compared to the non-MPR group. In contrast, the suppressor T cell ratio (TS ratio) was lower (P=0.016) in the MPR group. The difference in peripheral blood lymphocyte subsets between the two groups of patients who underwent neoadjuvant chemoradiotherapy is significant. Conclusion: In peripheral blood, T lymphocyte subsets varied significantly based on the effectiveness of neoadjuvant treatment. Prior to the second cycle of neoadjuvant therapy, a higher CD4/CD8 and TH ratio, coupled with a decreased TS ratio, might suggest enhanced treatment outcomes.

The role of ER stress and ATP/AMPK in oxidative stress meditated hepatotoxicity induced by citrinin.

Citrinin, a secondary metabolite, can pose serious risks to the environment and organisms, but its hepatotoxic mechanisms are still unclear. Histopathological and ultrastructural results showed that citrinin-induced liver injury in Kunming mice, and the mechanism of citrinin-induced hepatotoxicity was studied in L02 cells. Firstly, citrinin mades L02 cell cycle arrest in G2/M phase by inhibition of cyclin B1, cyclin D1, cyclin-dependent kinases 2 (CDK2), and CDK4 expression. Secondly, citrinin inhibits proliferation and promotes apoptosis of L02 cells via disruption of mitochondria membrane potential, increase Bax/Bcl-2 ration, activation of caspase-3, 9, and enhance lactate dehydrogenase (LDH) release. Then, citrinin inhibits superoxide dismutase (SOD) activity and increases the accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS), resulting oxidative damage in L02 cells; upregulates the protein expression of binding immunoglobulin protein (Bip), C/EBP homologous protein (CHOP), PKR-like ER kinase (PERK) and activating transcription factor6 (ATF6), inducing ER stress in L02 cells; increases the phosphorylation of AMP-activated protein kinase (AMPK) and decreases the content of adenosine-triphosphate (ATP), activating AMPK pathway in L02 cells. Eventually, pretreatment with NAC, an ROS inhibitor, alleviates citrinin-induced cell cycle G2/M arrest and apoptosis by inhibiting ROS-mediated ER stress; pretreatment with 4-PBA, an ER stress inhibitor, reversed ER stress and p-AMPK; pretreatment with dorsomorphin, an AMPK inhibitor, decreases citrinin-induced cell cycle G2/M arrest and apoptosis. In summary, citrinin induces cell cycle arrest and apoptosis to aggravate liver injury by activating ROS-ER stress-AMPK signaling pathway.

Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data. METHODS: In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored. RESULTS: Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03). CONCLUSIONS: The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC. CLINICAL TRIAL REGISTRATION: NCT04177797.

Identification of tumor-infiltrating lymphocyte subpopulations correlated with patient prognosis in esophageal squamous cell carcinoma.

OBJECTIVE: To identify biomarkers related to esophageal squamous cell carcinoma (ESCC) prognosis by analyzing genetic variations and the infiltration levels of tumor-infiltrating lymphocytes (TILs) in patients. METHODS: The clinical features of 61 patients with ESCC were collected. DNA panel sequencing was performed to screen differentially expressed genes (DEGs). Transcriptome sequencing was performed to identify gene expression profiles, and subsequent enrichment analysis of DEGs was conducted using Metascape. RESULTS: We identified 488 DEGs between patients with ESCC with distinct prognoses that were mainly enriched in the human immune response, fibrinogen complex, and protein activation cascade pathways. Among patients with ESCC treated with postoperative chemotherapy, those with a high infiltration level of myeloid-derived suppressor cells (MDSCs) had longer overall survival (OS), and OS was positively correlated with the infiltration level of T helper type 2 (Th2) cells among patients treated without chemotherapy after surgery. Additionally, in the case of MDSCs >0.7059 or Th2 cells <0.6290, patients receiving postoperative chemotherapy had a longer OS than those treated without chemotherapy following surgery. CONCLUSION: The level of MDSCs or Th2 cells can be used as a biomarker for assessing the prognosis of patients with ESCC treated with or without postoperative chemotherapy, respectively.

Controlling Electrode Spacing by Polystyrene Microsphere Spacers for Highly Stable and Flexible Transparent Supercapacitors.

Transparent polymer electrolytes such as poly(vinyl alcohol)-based H+, Li+, K+, and Na+ gels have been widely used as both an electrolyte and a separator for flexible transparent supercapacitors (FTSCs). However, these gels sandwiched between the electrodes in FTSCs are easily compressed under bending and compression due to their viscous flow behavior, resulting in the deformation of electrode spacing and the unstable capacitance performance. To resolve this issue, herein, we introduce monodispersed polystyrene (PS) microspheres into PVA-LiCl polymer gel electrolytes as spacers to precisely control the electrode spacing during the assembly of FTSCs using single-walled carbon nanotubes/indium tin oxide-polyethylene terephthalate (ITO-PET) or MnO2/multiwalled carbon nanotubes/ITO-PET as transparent electrodes. The electrode spacing could be tuned by varying the diameter of PS microspheres, for example, 20, 40, and 80 µm. More importantly, the PS microsphere spacers protect the gel electrolyte from the squeeze when bending takes place, allowing the stable performance output by FTSCs under a bending state. After repeating bending tests, the capacitance remains 95.6%, indicating the high stability and flexibility of the devices with the assistance of PS microsphere spacers.

Genomic characteristics in neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: The response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal squamous cell carcinoma (ESCC) can vary, but there is still no biomarker that can identify the benefiting population. Therefore, biomarkers to predict the outcome of nCRT are needed, as well as elucidation of the mechanism of resistance therapy. We investigated differences of genomic characteristics between patients with a pathologic complete response (pCR) and those with little or no response (pathologic stable disease: pSD) before and after nCRT. METHODS: Fourteen subjects with locally advanced ESCC (7 cases of pCR and 7 of pSD) who received nCRT before undergoing esophagectomy were enrolled. An analysis of whole-exome sequencing (WES) data from 27 ESCC tissue samples obtained from the subjects pre and post nCRT was performed. RESULTS: The number of pretherapy samples displaying loss of chromosome 19p13.11 was higher in the pCR group than in the pSD group (5/6) (P=0.0291, Fisher's exact test). Gain of 19q13.31 was observed significantly more often in the samples obtained following nCRT (5/14). KMT2A missense mutation was found more frequently in the pSD group's pre-nCRT samples than in those of the pCR group (3/6), and following nCRT, new genes such as NF1, KMT2D, NOTCH2, and NIPBL were detected new variations. C/G>G/C (P=0.003) and C/G>A/T (P=0.002) transitions were statistically significantly reduced in every patient after nCRT, with similar observations made in both groups (pCR group: C/G>G/C, P=0.027; C/G>A/T, P=0.004; and pSD group: C/G>G/C, P=0.032; C/G>A/T, P=0.017). CONCLUSIONS: Biomarkers to predict pCR might include 19p13.11 copy number loss and KMT2A missense mutation. Further validation in a prospective study of a larger sample is required.

[Comparison of thoracoscopic esophagectomy and traditional esophagectomy in radical mediastinal lymphadenectomy for esophageal cancer].

OBJECTIVE: To compare thoracoscopic esophagectomy with traditional esophagectomy in radical mediastinal lymphadenectomy for esophageal cancer, and to explore the feasibility and safety of thoracoscopic mediastinal lymphadenectomy for esophagectomy. METHODS: Clinical data associated with perioperation and mediastinal lymph nodes clearance of 304 patients undergoing radical operation of esophageal cancer via left neck-right chest-upper abdomen in our department from June 2009 to June 2011 were analyzed retrospectively. Among 304 cases, 199 received traditional open radical resection and 105 thoracoscopic esophagectomy. The intrathoracic mediastinal lymph node metastasis rate, extent of metastasis, time of operation, blood loss and complications between two groups were compared. RESULTS: All the 304 cases completed their operations successfully. A total of 3724 mediastinal lymph nodes were removed, mean 12.3±7.0 per case, including 1065 in thoracoscopic group, mean 10.1±5.5 per case, and 2659 in open group, mean 13.3±7.5 per case, whose difference was significant. But further analysis according to the postoperative pathologic staging showed no significant difference of above lymph nodes removed between two groups. Mediastinal lymph node metastasis was found in 126 patients with a rate of 41.4%, which was 35.6% and 44.7% in thoracoscopic and open groups respectively without significant difference(P>0.05). The left laryngeal recurrent nerve lymph node metastasis rate in open group and thoracoscopic group was 16.1% and 6.7% respectively, and the difference was significant(P<0.05). Differences of lymph node metastasis rate in other regions were not significant between the two groups. There were 365 positive lymph nodes, and the lymph node metastasis degree was 9.8%. which was 8.2% and 10.5% in thoracoscopic group and open group respectively(P<0.05), besides metastasis degree of open group was much higher in right laryngeal recurrent nerve and subcarinal lymph node region. The overall complication rate was 36.8%, which was 28.6% in thoracoscopic group and 41.2% in open group respectively with significant difference(P<0.05). There were no significant differences in operative time and blood loss between the two groups(both P>0.05). CONCLUSION: Radical mediastinal lymphadenectomy with thoracoscopic esophagectomy is technically safe and feasible for early to moderate stage esophageal cancer with similar lymph nodes removed and lower complication morbidity. In the early period of carrying out thoracoscopic radical mediastinal lymphadenectomy, laryngeal recurrent nerve and subcarinal lymph node region should be identified to prevent incidental injury.

[Characteristics of lymphatic metastasis and surgical approach of adenocarcinoma of the esophagogastric junction].

OBJECTIVE: To investigate the characteristics of lymphatic metastasis in different types of adenocarcinoma of the esophagogastric junction (AEG) and provide guidance for surgical approach adoption. METHODS: Clinical data of 228 patients with AEG undergoing surgery were analyzed retrospectively. According to Siewert classification, there were 9 cases of type I (3.9%) who all underwent left thoracoabdominal approach procedures. A total of 121 patients belonged to type II (53.1%), of whom 12 underwent left transthoracic approach, 48 left thoracoabdominal approach, and 61 transabdominal approach. Ninety-eight patients belonged to type III (43%), of whom 22 underwent left thoracoabdominal approach procedures and 76 transabdominal. The pattern of lymph node metastasis was analyzed and the association between surgical approach and oncological clearance was examined. RESULTS: The resection margin was positive in 20(8.8%) patients, including 10 with type II (8.3%) and 10 with type III (10.2%), and the difference was not statistically significant (P>0.05). The rate of positive resection margin was 12.4%(17/137) in the transabdominal group and 16.7%(2/12) in the left transthoracic group, both significantly higher than the left thoracoabdominal group (1.1%, 1/88) (both P<0.05). Lymph node metastasis was found in 159(69.7%) patients. The metastasis was found in 4 of 9 patients with type I cancer and two were thoracic metastasis, no metastasis was found in the upper mediastinum. For type II cancer, the rate of lymph node metastasis was 66.9%(81/121), including thoracic metastasis ( n=32, 26.4%) and abdominal metastasis (n=81, 66.9%). For type III cancer, the rate of lymph node metastasis was 66.9%(81/121), including thoracic metastasis (n=15, 15.3%) and abdominal metastasis (n=69, 70.4%). CONCLUSIONS: For type I AEG, left thoracoabdominal approach should be used because the pattern of lymph node metastasis is similar to that of the distal esophageal carcinoma. For type II , left thoracoabdominal approach should be used to ensure adequate resection of the tumor and clearance of lymph node in the lower esophagus and upper mediastinum because of high rate of intrathoracic lymph node metastasis. For type III cancer, transabdominal incision offers better benefit with less impact on respiratory function. However, thoracic incision should be used to ensure adequate clearance for tumors of larger size and significant external invasion.

[Clinical outcomes and selection conditions of three-field lymph node dissection for thoracic esophageal squamous cell carcinoma].

OBJECTIVE: To analyze the efficiency of cervical lymph node metastasis dissection and postoperative morbidity after selective three-field lymph node dissection (3FLND) for thoracic esophageal squamous cell carcinoma, and explore the proper selection conditions. METHODS: According to the conditions as follows: systemic evaluation, tumor T staging, tumor location, cervical CT and ultrasonography and the number of lymph nodes metastases, 85 patients with thoracic esophageal squamous cell carcinoma were selected and received 3FLND. RESULTS: In the same period 45.5% (85/187) of the patients received 3FLND selectively based on the conditions. The rate of the cervical lymph nodes metastasis was 40.0% (34/85). The rate of the cervical positive lymph nodes of the upper, middle and lower thoracic esophageal carcinomas with enlarged lymph nodes suggested by cervical CT and ultrasonography was 68.4% (13/19), 41.7% (20/48) and 16.7% (1/6), respectively. Twelve patients with upper thoracic esophageal carcinoma with enlarged lymph nodes unrevealed by cervical CT and ultrasonography showed no histopathological lymph node metastasis. In the same period 17.1% (32/187) of the patients were selectively not undergone three-field lymph node dissection. The cervical lymph node metastasis rates in patients with upper and middle mediastinal lymph node metastasis were 79.3% (23/29) and 58.6% (17/29), significantly higher than 8.9% (5/56) and 7.1% (4/56) in the patients without upper and middle mediastinal lymph node metastasis (P<0.05). There was no in-hospital mortality in the group. The incidence of pulmonary complications and over-all postoperative morbidity was 24.7% and 42.4%, respectively. CONCLUSIONS: Selective 3FLND based on certain conditions can reduce the risk of postoperative morbidity and improve the efficiency of metastatic cervical lymph node dissection in thoracic esophageal squamous cell carcinoma. The thoracic tracheoesophageal groove positve lymph node indicated by CT scans should be one of selective conditions for 3FLND. The upper thoracic esophageal carcinoma should selectively receive 3FLND. The selection standards should be more strict for the lower thoracic esophageal carcinoma.