The impact of mindfulness intervention on negative emotions and quality of life in malignant tumor patients: a systematic review and meta-analysis.

Objective: This study aims to assess the effect of mindfulness intervention on negative emotions (anxiety and depression) and quality of life in malignant tumor patients. Methods: The databases, including CNKI, VIP, Wanfang, Chinese Biomedical Literature Database disc (CBMdisc), PubMed, Embase, Cochrane Library, and Web of Science (WoS), were searched from inception to January 2024. Randomized controlled trials examining the effects of mindfulness intervention on negative emotions and quality of life in malignant tumor patients were selected. Meta-analysis was conducted using RevMan 5.1. Results: A total of 11 studies involving 993 patients were included. Compared with usual care, mindfulness intervention effectively reduced anxiety [SMD = -0.81, 95% CI (-1.01, -0.60), p < 0.00001], depression [SMD = -0.86, 95% CI (-1.01, -0.70), p < 0.00001], and improved patients' quality of life [SMD = 0.64, 95% CI (0.50, 0.78), p < 0.00001]. Conclusion: Mindfulness intervention can effectively alleviate negative emotions such as anxiety and depression in malignant tumor patients and positively impact their quality of life.

Successful laparoscopic resection for giant mature cystic teratoma of the pancreas: a case report and surgical refinements.

BACKGROUND: Mature cystic teratomas or dermoid cysts of the pancreas complicate surgical approaches because of their anatomical position and ever-growing size. Herein, we report a case of a giant mature cystic teratoma of the pancreas that was successfully resected via complete laparoscopic distal pancreatectomy (LDP). CASE PRESENTATION: A 39-year-old female patient was referred to our hospital for the evaluation of a pancreatic tumor. Three years of follow-up revealed that the tumor had increased in size to 18 cm, with hyperintense solid components on diffusion-weighted magnetic resonance imaging. Considering the possibility of malignancy, we decided to perform an LDP. The capsule appeared solid enough to withstand the retraction of the endoscopic forceps. Tumor size made it difficult to dissect the dorsal side of the tumor from the caudal to the cranial side. Early transection of the pancreas and additional ports facilitated dissection of the dorsal side of the tumor. We completed the LDP without intraoperative cyst rupture. On pathological examination, the tumor was diagnosed as a mature cystic teratoma originating from the pancreatic tail. The patient was discharged on postoperative day 13 with no complications. CONCLUSION: LDP may be an option for surgical procedures in patients with large cystic lesions of the pancreatic body or tail. Intraoperative observation of the tumor and surgical refinement are necessary to complete the laparoscopic procedure without tumor rupture.

TFEB and TFE3 cooperate in regulating inorganic arsenic-induced autophagy-lysosome impairment and immuno-dysfunction in primary dendritic cells.

Arsenic (As) is a prevalent and hazardous environmental toxicant associated with cancer and various health problems, which has been shown suppressive effects on dendritic cells (DCs). Autophagy is essential for the innate and adaptive immune responses of DCs, and the transcription factors TFEB and TFE3 are key regulators of autophagic and lysosomal target genes. However, the detrimental alterations of the autophagy-lysosome pathway in As-exposed DCs and the possible coordinating roles of TFEB and TFE3 in the immune dysfunction of this cell are less understood. In this paper, we found that As exposure significantly impaired lysosomal number, lysosomal acidic environment, and lysosomal membrane permeabilization, which might lead to blocked autophagic flux in cultured DCs. Furthermore, our results confirmed that TFEB or TFE3 knockdown exacerbated the disorders of lysosome and the blockade of autophagic flux in As-exposed DCs, and also enhanced the inhibitory expression of co-stimulatory molecules Cd80 and Cd83; adhesion molecule Icam1; cytokines TNF-α, IL-1ß, and IL-6; chemokine receptor Ccr7; and antigen-presenting molecules MHC II and MHC I. By contrast, overexpression of TFEB or TFE3 partially alleviated the above-mentioned impairment of DCs by inorganic As exposure. In conclusion, these findings reveal a previously unappreciated inhibition of lysosome-mediated degradation and damage of lysosomal membrane integrity leading to dysregulated autophagy and impaired immune functions of DCs by arsenicals, and also suggest TFEB and TFE3 as potential therapeutic targets for ameliorating As toxicity.

Comparison of clinical, imaging and second-look arthroscopic outcomes between varus knee patients with and without preoperative tibial varus deformity after medial opening-wedge high tibial osteotomy.

PURPOSE: This study aimed to compare the regeneration status of articular cartilage, clinical, and radiologic outcomes between varus knee patients with and without preoperative tibial varus deformity (PTVD) after medial opening-wedge high tibial osteotomy (OWHTO) METHODS: Varus knee patients who had undergone OWHTO were divided into two groups according to preoperative medial proximal tibial angle (MPTA): a great varus (GV) group (MPTA <85°) and a mild varus (MV) group (85°≤preoperative MPTA <87°). The hip-knee-ankle (HKA) angle, weight-bearing line ratio (WBL%), MPTA, joint line convergence angle and joint line obliquity were measured. Second-look arthroscopy was undertaken 24 months after HTO. The Knee Society (KS) function score and knee score, and Lysholm score were used to evaluate the functional outcomes. All parameters were evaluated preoperatively and 24 months after HTO. RESULTS: The GV group had greater varus than the MV group in HKA and WBL% before surgery, but greater valgus after surgery. The arthroscopic probe before HTO revealed the advanced chondral damage in the GV group and lighter chondral damage in the MV group. The regeneration of medial femoral condyle was considerably more frequent in the GV group (72.5%, 45/62) than in the MV group (50.0%, 27/54) (P = 0.030). No significant differences were observed in all functional outcomes preoperatively and 24 months after HTO. CONCLUSION: The extent of cartilage regeneration in patients without PTVD was inferior to that in those with PTVD, but the functional outcomes were comparable. OWHTO may be a treatment option in a selected subset of varus knee patients without PTVD.

Effect of tibial rotation after uniplane medial open-wedge high tibial osteotomy in genu varum patients: An observational study.

The change in axial tibial rotation after uniplane medial open-wedge high tibial osteotomy (uniplane OWHTO) and its relevant influence factor is not known. Therefore, the aim of this study was to evaluate the change in axial tibial rotation after uniplane OWHTO, and the factors affecting tibia rotational change were analyzed. Between January 2022 and April 2022, the study was retrospectively conducted on genu varum patients who underwent uniplane OWHTO. In the weight-bearing anteroposterior long leg view, the hip-knee-ankle angle and medial proximal tibial angle (MPTA) were evaluated. The posterior tibial slope were measured from the lateral view. A CT scan of the knee joint was performed to evaluate the distal tibial rotation angle (TRA), femorotibial rotation angle and tibial tuberosity-trochlear groove distance. In addition, the foot morphology was assessed by the ankle deformity angle and ankle rotation angle using an angle measuring instrument. All parameters were measured preoperatively and 14 days after surgery. The mean change in hip-knee-ankle, MPTA was 10.5°±2.9°, 8.8°±2.6°. The mean preoperative and postoperative TRA were 25.1°±6.9° and 22.2°±6.2° respectively (P = .007). Thus, the mean ∆TRA was -3.0°±3.4° (IR) with a range of -9.6° to +2.8° after surgery. No significant differences were found in the femorotibial rotation angle and tibial tuberosity-trochlear groove distance before and after surgery (P > .05). The postoperative ankle rotation angle and ankle deformity angle changed significantly compared with preoperative values (P < .001). In the multiple regression analysis, ∆MPTA was the only predictor of distal tibial rotation (ß = 0.667, P = .003). The current study confirms an unintended internal rotation in the distal tibia following uniplane MOWHTO and the rotation in the distal tibia was influenced by the opening width. Surgeron should keep in mind to avoid the osteotomy complication leading to excessive rotation change during surgery.

Comparison of the plantar pressure distribution and mechanical alignment in patients with varus knee osteoarthritis following high tibial osteotomy.

PURPOSE: The changes in the lower limb alignment were vitally important after high tibial osteotomy (HTO). Therefore, the purpose of present study was to analyze the characteristics of plantar pressure distribution after HTO, and to investigate the effect of plantar pressure distribution on postoperative limb alignment. METHODS: Between May 2020 and April 2021, varus knee patients undergoing HTO were evaluated in the present study. The peak pressure of plantar regions, medial-lateral pressure ratio (MLPR), foot progression angle (FTA), anteroposterior COP (AP-COP), lateral symmetry of COP (LS-COP), and the radiographic parameters were evaluated preoperatively and at the final follow-up. Compared among the slight valgus (SV), moderate valgus (MV) and large valgus (LV) groups at the final follow-up, the peak pressure of HM, HC and M5 regions, and the MLPR were compared; the Knee Injury and Osteoarthritis Outcome Score4 (KOOS4) including four subscales, and the American of orthopedic foot and ankle society (AOFAS) were evaluated. RESULTS: The WBL%, HKA and TPI angle changed significantly after HTO (P < 0.001). The preoperative group exhibited a lower peak pressure in the HM region (P < 0.05) and higher peak pressure in the M5 region (P < 0.05); the pre- and postoperative groups exhibited a lower peak pressure in the HC region (P < 0.05); the rearfoot MLPR was significantly lower and LS-COP was significantly higher in the preoperative group (P = 0.017 in MLPR and 0.031 in LS-COP, respectively). Comparison among the SV, MV and LV groups, the SV group indicated a lower peak pressure in the HM region (P = 0.036), and a lower MLPR in the rearfoot (P = 0.033). The KOOS Sport/Re score in the MV and LV groups increased significantly compared with the SV group (P = 0.042). CONCLUSION: Plantar pressure distribution during the stance phase in patients with varus knee OA following HTO exhibited a more medialized rearfoot plantar pressure distribution pattern than that before surgery. Compared with the small valgus alignment, a moderate to large valgus alignment allows patients to walk with a more even medial and lateral plantar pressure distribution, which is more similar to healthy adults.

Liposomes trigger bone marrow niche macrophage "foam" cell formation and affect hematopoiesis in mice.

Liposomes are the most widely used nanocarrier platform for the delivery of therapeutic and diagnostic agents, and a number of liposomes have been approved for use in clinical practice. After systemic administration, most liposomes are cleared by macrophages in the mononuclear phagocyte system, such as the liver and bone marrow (BM). However, the majority of studies have focused on investigating the therapeutic results of liposomal drugs, and too few studies have evaluated the potential side effects of empty nanocarriers on the functions of macrophages in the mononuclear phagocyte system. Here, we evaluate the potential effects of empty liposomes on the functions of BM niche macrophages. Following liposome administration, we observed lipid droplet (LD) accumulation in cultured primary macrophages and BM niche macrophages. We found that these LD-accumulating macrophages, similar to foam cells, exhibited increased expression of inflammatory cytokines, such as IL-1ß and IL-6. We further provided evidence that liposome deposition and degradation induced LD biogenesis on the endoplasmic reticulum membrane and subsequently disturbed endoplasmic reticulum homeostasis and activated the inositol-requiring transmembrane kinase/endoribonuclease 1α/NF-κB signaling pathway, which is responsible for the inflammatory activation of macrophages after liposome engulfment. Finally, we also showed the side effects of dysfunctional BM niche macrophages on hematopoiesis in mice, such as the promotion of myeloid-biased output and impairment of erythropoiesis. This study not only draws attention to the safety of liposomal drugs in clinical practice but also provides new directions for the design of lipid-based drug carriers in preclinical studies.

Treatment of Elderly Patients with Acute Symptomatic OVCF: A Study of Comparison of Conservative Treatment and Percutaneous Kyphoplasty.

Objective: The present study was designed for the contrastive analysis of conservative and percutaneous kyphoplasty (PKP) on pain severity and recovery of injured vertebrae in elderly patients with acute symptomatic osteoporotic vertebral compression fracture (OVCF). Methods: A total of 60 elderly patients with acute symptomatic OVCF were divided into two groups according to different treatment protocols, with 30 patients in each group. Patients in the Con group received conservative treatment, while patients in the PKP group received percutaneous kyphoplasty treatment. Clinical evaluation included the visual analogue scale (VAS), the Dallas pain questionnaire, the vertebral body leading edge height, the Cobb angle of injured vertebrae, the MOS item short-form health survey (SF-36), the Barthel index, and the mini-mental state examination (MMSE). Results: At 3 days, 3 months, and 6 months post-treatment, the score of VAS and the Cobb angle of injured vertebrae in patients of the PKP group were all significantly lower than those in the Con group (P < 0.05), while the height of vertebral body leading edge in patients of the PKP group was significantly longer than that in the Con group (P < 0.05). At 6 months post-treatment, the scores of the four dimensions of the Dallas pain questionnaire scale in the PKP group were all significantly lower than those in the Con group (P < 0.05), while the score of SF-36 (PCS), SF-36 (MCS), and Barthel index in patients of the PKP group were all significantly lower than those in the Con group (P < 0.05), and there was no significant difference in the scores of MMSE between these two groups (P > 0.05). Conclusion: Compared with conservative treatment, PKP treatment of elderly patients with acute symptomatic OVCF provides rapid pain relief, restoration of damaged vertebral body height, correction of Cobb's angle, and improved quality of life.

Mandibular Buccal Bifurcation Cyst: Report of Two Cases.

Mandibular buccal bifurcation cyst is a rare inflammatory odontogenic cyst. We reported two cases who complained of painful swelling of extraoral soft tissue. Intraoral examination revealed the partially erupted mandibular first molar. Cone beam computed tomography showed a well-defined cystic lesion surrounding the first molar. Histopathologic images showed the cyst wall was infiltrated by a large number of plasma cells, neutrophils and eosinophils, and lined with a thin layer of non-keratinized stratified squamous epithelium. Finally, the two patients were diagnosed as mandibular buccal bifurcation cyst and treated with cyst enucleation and curettage.

Intravital lipid droplet labeling and imaging reveals the phenotypes and functions of individual macrophages in vivo.

Macrophages play pivotal roles in the maintenance of tissue homeostasis. However, the reactivation of macrophages toward proinflammatory states correlates with a plethora of inflammatory diseases, including atherosclerosis, obesity, neurodegeneration, and bone marrow (BM) failure syndromes. The lack of methods to reveal macrophage phenotype and function in vivo impedes the translational research of these diseases. Here, we found that proinflammatory macrophages accumulate intracellular lipid droplets (LDs) relative to resting or noninflammatory macrophages both in vitro and in vivo, indicating that LD accumulation serves as a structural biomarker for macrophage phenotyping. To realize the staining and imaging of macrophage LDs in vivo, we developed a fluorescent fatty acid analog-loaded poly(lactic-co-glycolic acid) nanoparticle to label macrophages in mice with high efficiency and specificity. Using these novel nanoparticles, we achieved in situ functional identification of single macrophages in BM, liver, lung, and adipose tissues under conditions of acute or chronic inflammation. Moreover, with this intravital imaging platform, we further realized in vivo phenotyping of individual macrophages in the calvarial BM of mice under systemic inflammation. In conclusion, we established an efficient in vivo LD labeling and imaging system for single macrophage phenotyping, which will aid in the development of diagnostics and therapeutic monitoring. Moreover, this method also provides new avenues for the study of lipid trafficking and dynamics in vivo.

Analysis on the Effect of Different Surgical Methods on the Treatment of Senile Osteoporotic Spinal Compression Fractures and the Influencing Factors of Complications.

Osteoporotic fractures are a common type of fractures in the elderly, among which spinal compression fractures are more common. After the occurrence of fractures, due to the compression and burst of the vertebral body, this will lead to local kyphosis deformity and even affect the balance of the sagittal spine. In the past, conservative treatments were used for osteoporotic spinal compression fractures. Although it can relieve pain symptoms, it can easily lead to complications such as aggravation of osteoporosis and deep vein thrombosis of the lower extremities. At present, percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are the main clinical surgical treatments, both of which are minimally invasive surgery, short operation time, effective pain relief, and rapid postoperative recovery. Although both of them are effective, there is still controversy over the efficacy of both in the treatment of osteoporotic spinal compression fractures. The purpose of this study was to investigate the efficacy of PVP and PKP in the treatment of elderly osteoporotic spinal compression fractures and to analyze the related factors that affect the occurrence of postoperative complications. The results show that both PVP and PKP can effectively improve the pain and dysfunction of elderly patients with osteoporotic spinal compression fracture, restoration of vertebral height, and correct kyphosis, but PKP has better effect and higher safety and is worth promoting. Postoperative complications of patients are related to their age, bone mineral density, use of hormones, and antiosteoporosis treatment.

Treatment of Perianal Abscess and Fistula in Infants and Young Children: From Basic Etiology to Clinical Features.

Perianal abscess and anal fistula are 2 common anorectal diseases in infants and young children. However, their causes, clinical diagnosis, and treatment remain controversial. Compared to adults, infants with these 2 diseases exhibit unique clinical characteristics. Blind pursuit of conservative treatment or surgery may worsen the condition, resulting in increased pain in young patients and greater economic burden and psychological harm to parents. Therefore, it is crucial to select correct and effective treatments. This review summarizes the relevant literature from the past 10 years and systematically explains the pathogenesis, clinical characteristics, and treatment measures of perianal abscess and anal fistula in infants with the goal of providing clinicians a deeper understanding of perianal abscess and anal fistula in infants and summarizing safe and effective treatment methods.

Bone mesenchymal stem cells transplantation combined with mild hypothermia improves the prognosis of cerebral ischemia in rats.

Bone marrow mesenchymal stem cells (BMSCs) are used as a great promising choice for the treatment of cerebral ischemia. Herein, we discuss the neuroprotective effects of the combination of BMSCs transplantation and mild hypothermia (MH) in an ischemia-reperfusion rat model. First, BMSCs were isolated using density gradient centrifugation and the adherent screening method, followed by culture, identification and labeling with DAPI. Second, adult male SD rats were divided into 5 groups: sham group (surgery without blockage of middle cerebral artery), model group (middle cerebral artery occlusion (MCAO) was established 2h prior to reperfusion), BMSCs group (injection of BMSCs via the lateral ventricle 24h after MCAO), MH group (mild hypothermia for 3h immediately after MCAO) and combination therapy group (combination of BMSCs and MH). Finally, the modified neurological severity score (mNSS) test was performed to assess behavioral function at different time points (before MCAO, before transplantation, at day 1, day 5 and day 10 after transplantation). After that, the brain was subjected to TTC staining, and the homing and angiogenesis were evaluated by immumofluorescence and immunohistochemistry. Immunofluorescence staining and Western Blot analysis were performed to calculate the percentage of the infarct area and explore glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF). Our results showed that the combination therapy significantly decreased mNSS scores (P<0.01) and reduced the percentage of the infarct area (P<0.01) than a single treatment. Moreover, the expression of GFAP and VEGF increased significantly in the combination therapy group (at day 5, day 10 after transplantation; at all time points after transplantation, respectively) compared to the single treatment groups. Taken together, it was suggested that the combination of BMSCs transplantation and MH can significantly reduce the percentage of the infarct area and improve functional recovery by promoting homing and angiogenesis, which may be a beneficial treatment for cerebral ischemia.

Potential Mechanism of Detoxification of Cyanide Compounds by Gut Microbiomes of Bamboo-Eating Pandas.

Gut microbes can enhance the ability of hosts to consume secondary plant compounds and, therefore, expand the dietary niche breadth of mammalian herbivores. The giant and red pandas are bamboo-eating specialists within the mammalian order Carnivora. Bamboo contains abundant plant secondary metabolites (e.g., cyanide-containing compounds). However, Carnivora species, including the giant panda, have deficient levels of rhodanese (one of the essential cyanide detoxification enzymes) in their tissues compared with the same tissues of herbivores. Here, we make a comparative analysis of 94 gut metagenomes, including 25 from bamboo-eating pandas (19 from giant pandas and 6 from red pandas), 30 from Père David's deer, and 39 from published data for other mammals. The bamboo-eating pandas' gut microbiomes had some common features, such as high proportions of Pseudomonas bacteria. The results revealed that bamboo-eating pandas' gut microbiomes were significantly enriched in putative genes coding for enzymes related to cyanide degradation (e.g., rhodanese) compared with the gut microbiomes of typical herbivorous mammals, which might have coevolved with their special bamboo diets. The enrichment of putative cyanide-digesting gut microbes, in combination with adaptations related to morphology (e.g., pseudothumbs) and genomic signatures, show that the giant panda and red panda have evolved some common traits to adapt to their bamboo diet.IMPORTANCE The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens), two obligate bamboo feeders, have distinct phylogenetic positions in the order Carnivora. Bamboo is extraordinarily rich in plant secondary metabolites, such as allied phenolic and polyphenolic compounds and even toxic cyanide compounds. Here, the enrichment of putative cyanide-digesting gut microbes, in combination with adaptations related to morphology (e.g., pseudothumbs) and genomic signatures, show that the giant panda and red panda have evolved some common traits to adapt to their bamboo diet. Thus, here is another story of diet-driven gut microbiota in nature.

Combined overexpression of cadherin 6, cadherin 11 and cluster of differentiation 44 is associated with lymph node metastasis and poor prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly invasive lesion that frequently metastasizes to the cervical lymph nodes and is associated with a poor prognosis. Several adhesion factors, including cadherin 6 (CDH6), cadherin 11 (CDH11) and cluster of differentiation 44 (CD44), have been reported to be involved in the invasion and metastasis of multiple types of cancer. Therefore, the aim of the present study was to determine the expression of CDH6, CDH11 and CD44 in tumor tissues from patients with OSCC, and whether this was associated with the metastasis and survival of OSCC. The mRNA expression of the human tumor metastasis-related cytokines was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in OSCC tumors with or without lymph node metastasis (n=10/group). The expression of CDH6, CDH11 and CD44 in 101 OSCC and 10 normal oral mucosa samples was examined by immunohistochemical staining. The association between overall and disease-specific survival times of patients with OSCC and the expression of these three proteins was evaluated using Kaplan-Meier curves and the log-rank test. RT-qPCR results indicated that the mRNA expression of CDH6, CDH11 and CD44 was increased in OSCC patients with lymph node metastasis (2.93-, 2.01- and 1.92-fold; P<0.05). Overexpression of CDH6, CDH11 and CD44 was observed in 31/35 (89%), 25/35 (71%) and 31/35 (89%) patients, respectively. The number of OSCC patients with lymph node metastasis exhibiting CDH6, CDH11 and CD44 overexpression was significantly higher than the number of patients without lymph node metastasis exhibiting overexpression of these proteins (P=0.017, P=0.038 and P=0.007, respectively). OSCC patients with high co-expression of CDH6, CDH11 and CD44 exhibited lower disease-specific survival times (P=0.047; χ2=3.933) when compared with OSCC patients with low co-expression of these adhesion factors. CDH6, CDH11 and CD44 serve important roles in OSCC metastasis and the combined use of these factors as biomarkers may improve the accuracy of the prediction of cancer metastases and prognosis.

Xerophilusin B induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma cells and does not cause toxicity in nude mice.

Esophageal cancer is the eighth most common cancer in the world and ranks as the sixth leading cause of cancer-related mortality. Esophageal cancer has a poor prognosis partially due to its low sensitivity to chemotherapy agents, and the development of new therapeutic agents is urgently needed. Here, the antitumor activity of a natural ent-kaurane diterpenoid, xerophilusin B (1), which was isolated from Isodon xerophilus, a perennial herb frequently used in Chinese folk medicine for tumor treatment, was investigated. Compound 1 exhibited antiproliferative effects against esophageal squamous cell carcinoma (ESCC) cell lines in a time- and dose-dependent manner with lower toxicity against normal human and murine cell lines. In vivo studies demonstrated that 1 inhibited tumor growth of a human esophageal tumor xenograft in BALB/c nude mice without significant secondary adverse effects, indicating its safety in treating ESCC. Furthermore, 1 induced G2/M cell cycle arrest and promoted apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway in ESCC cell lines. In conclusion, the observations herein reported showed that 1 is a potential chemotherapeutic agent for ESCC and merits further preclinical and clinical investigation for cancer drug development.

Genetic landscape of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

MiRNA expression profile reveals a prognostic signature for esophageal squamous cell carcinoma.

In this study, we analyzed the microRNA (miRNA) expression profile of 119 paired ESCC samples by microarray and identified a four-miRNA signature that predicted patient survival. The signature derived from the training set (n=60) had a good prognostic value in the test set (n=59) and the independent cohort (n=58), indicating the replicability of its prognostic value. Furthermore, the stratified analysis showed that the signature could predict the survival of TNM stage II and stage III patients, indicating that the four-miRNA signature could help to more accurately predict ESCC patient survival.

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.

BACKGROUND: Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles. OBJECTIVE: To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs. METHOD: LncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis. RESULTS: LncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p<0.0001). The signature was applied to the test group (median survival 21.5 months vs >60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages. CONCLUSIONS: Our results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.

Identification of somatic alterations in stage I lung adenocarcinomas by next-generation sequencing.

Adenocarcinoma is the most common type of lung cancer. Somatic mutations in the early stage of this disease have a tight relationship with tumor initiation and potentially activate downstream pathways that are implicated in tumor progression. In this study, we performed whole genome and exome sequencing of tumor and adjacent normal tissue from 10 patients with stage I lung adenocarcinoma. EGFR (4/10 tumors), BCHE (3/10), and TP53 (2/10) were identified recurrently with validated tumor-specific non-synonymous mutations; and the remaining mutations were specific to individual tumors. Computational methods were used to evaluate the potential effect of non-synonymous mutations on protein function, and putative driver mutation in genes such as SDK1 was predicted. Cell adhesion was the most enriched biological process in gene set analysis using the DAVID database. Copy number amplification at 12q15, which includes MDM2, was identified as a recurrent somatic alteration in 4 of 10 tumors. These findings provided additional information for understanding early-stage lung adenocarcinomas.