Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM: To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS: Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS: LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. CONCLUSION: The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Two new species and one new combination of Ophiocordyceps (Hypocreales, Ophiocordycipitaceae) in Guizhou.

Ophiocordyceps is the largest genus in Ophiocordycipitaceae and has a broad distribution with high diversity in subtropical and tropical regions. In this study, two new species, pathogenic on lepidopteran larvae are introduced, based on morphological observation and molecular phylogeny. Ophiocordycepsfenggangensissp. nov. is characterised by having fibrous, stalked stroma with a sterile tip, immersed perithecia, cylindrical asci and filiform ascospores disarticulating into secondary spores. Ophiocordycepsliangiisp. nov. has the characteristics of fibrous, brown, stipitate, filiform stroma, superficial perithecia, cylindrical asci and cylindrical-filiform, non-disarticulating ascospores. A new combination Ophiocordycepsmusicaudata (syn. Cordycepsmusicaudata) is established employing molecular analysis and morphological characteristics. Ophiocordycepsmusicaudata is characterised by wiry, stipitate, solitary, paired to multiple stromata, yellowish, branched fertile part, brown stipe, immersed perithecia, cylindrical asci and cylindrical-filiform, non-disarticulating ascospores.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Short-term Outcomes of Elective Surgery Following Self-Expandable Metallic Stent and Neoadjuvant Chemotherapy in Patients With Left-Sided Colon Cancer Obstruction.

BACKGROUND: Colonic stenting reduces morbidity and stoma formation for left-sided colon cancer obstruction, and a prolonged interval between stenting and surgery with neoadjuvant chemotherapy administered might result in a lower stoma rate and tumor reduction. OBJECTIVE: The study aimed to evaluate the short-term outcomes of elective surgery following colonic stenting compared with elective surgery following colonic stenting and neoadjuvant chemotherapy in patients with left-sided colon cancer obstruction. DESIGN: This is a prospective multicenter cohort study. SETTINGS: This study was conducted at 5 medical centers. PATIENTS: Patients ( n = 100) with acute left-sided colon cancer obstruction undergoing colonic stenting between December 2015 and December 2019 were included. INTERVENTIONS: Patients were assigned to the stenting-alone or chemotherapy group. MAIN OUTCOME MEASURES: The primary outcomes measured were laparoscopic surgery and stoma rate. RESULTS: Of the 100 patients who underwent colonic stenting, 52 were assigned to the stenting group and 48 were assigned to the chemotherapy group. No statistically significant differences were detected in stent-related complications. The adverse events associated with neoadjuvant chemotherapy were well tolerated. The level of hemoglobin (117.2 vs 107.6 g/L; p = 0.008), albumin (34.2 vs 31.5 g/L; p < 0.001), and prealbumin (0.19 vs 0.16 g/L; p = 0.001) was significantly increased, and the bowel wall thickness (1.09 vs 2.04 mm; p < 0.001) was significantly decreased preoperatively in the chemotherapy group compared with the stenting group. The number of mean harvested lymph nodes was greater in the chemotherapy group than in the stenting group (25.6 vs 21.8; p = 0.04). Laparoscopic surgery was performed more frequently (77.1% vs 40.4%; p < 0.001) and a stoma was created less frequently (10.4% vs 28.8%; p = 0.02) in the chemotherapy group than in the stenting group. LIMITATIONS: This trial was limited by the nonrandomized design and a short follow-up period. CONCLUSIONS: This study suggests that elective surgery following neoadjuvant chemotherapy and colonic stenting is a safe, effective, and well-tolerated treatment approach with a high laparoscopic resection rate and a low stoma rate. See Video Abstract at http://links.lww.com/DCR/B980 . RESULTADOS A CORTO PLAZO DE LA CIRUGA ELECTIVA SEGUIDO DE STENT METLICO AUTOEXPANDIBLE Y QUIMIOTERAPIA NEOADYUVANTE EN PACIENTES CON OBSTRUCCIN POR CNCER DE COLON IZQUIERDO: ANTECEDENTES:La colocación de stents colónicos reduce la morbilidad y la formación de estomas por obstrucción por cáncer de colon izquierdo, y el intervalo prolongado entre la colocación de stents y la cirugía con quimioterapia neoadyuvante administrada podría resultar en una menor tasa de estomas y reducción del tumor.OBJETIVO:Evaluar los resultados a corto plazo de la cirugía electiva después de la colocación de stent en el colon en comparación con la cirugía electiva después de la colocación de stent en el colon y la quimioterapia neoadyuvante en pacientes con obstrucción por cáncer de colon izquierdo.DISEÑO:Estudio prospectivo de cohorte multicéntrico.ENTORNO CLINICO:Este estudio se realizó en 5 centros médicos.PACIENTES:Se incluyeron pacientes (n=100) con obstrucción aguda por cáncer de colon izquierdo que se sometieron a colocación de stent colónico entre diciembre de 2015 y diciembre de 2019.INTERVENCIONES:Los pacientes fueron asignados al grupo de stent solo o quimioterapia.MEDIDAS DE RESULTADO PRINCIPALES:Los resultados primarios medidos fueron la cirugía laparoscópica y la tasa de ostomía.RESULTADOS:De los 100 pacientes que se sometieron a la colocación de stent colónico, 52 fueron asignados al grupo de colocación de stent y 48 al grupo de quimioterapia. No se detectaron diferencias estadísticamente significativas en las complicaciones relacionadas con el stent. Los eventos adversos asociados con la quimioterapia neoadyuvante fueron bien tolerados. Hemoglobina (117,2 g/l vs. 107,6 g/l; p = 0,008), albúmina (34,2 g/l vs. 31,5 g/l; p < 0,001) y prealbúmina (0,19 g/l vs. 0,16 g/l; p = 0,001) aumentaron significativamente y el grosor de la pared intestinal (1,09 mm vs. 2,04 mm; p < 0,001) disminuyó significativamente antes de la operación en el grupo de quimioterapia en comparación con el grupo de colocación de stent. El número medio de ganglios linfáticos extraídos fue mayor en el grupo de quimioterapia que en el grupo de stent (25,6 vs. 21,8; p = 0,04). La cirugía laparoscópica se realizó con mayor frecuencia (77,1 % vs. 40,4 %; p < 0,001) y se creó un estoma con menos frecuencia (10,4 % vs. 28,8 % ; p = 0,02) en el grupo de quimioterapia que en el grupo de colocación de stent.LIMITACIONES:Este ensayo estuvo limitado por el diseño no aleatorio y el corto período de seguimiento.CONCLUSIONES:Este estudio sugiere que la cirugía electiva después de la quimioterapia neoadyuvante y la colocación de stent colónico es un tratamiento seguro, efectivo y bien tolerado, con una alta tasa de resección laparoscópica y una baja tasa de estoma. Consulte Video Resumen en http://links.lww.com/DCR/B980 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Inhibition of glutamatergic neurons in layer II/III of the medial prefrontal cortex alleviates paclitaxel-induced neuropathic pain and anxiety.

Paclitaxel-treated patients frequently experience chemotherapy-induced peripheral neuropathy (CIPN) and mood changes, such as anxiety. Layer II/III of the medial prefrontal cortex (mPFC) is vital for generating pain and emotions. However, it is unclear whether glutamatergic neurons in layer II/III of the mPFC are involved in regulating paclitaxel-induced neuropathic pain and anxiety. Here, we determined the role of glutamatergic neurons in layer II/III of the mPFC in paclitaxel (4 mg/kg/d, consecutive 8 days, intraperitoneal injection, cumulative dose: 32 mg/kg)-induced pain and anxiety by using a combination of behavior testing's, immunostaining, chemogenetics, optogenetics, fiberphotometry, and morphological approaches. The number of c-Fos-positive neurons expressing calcium/calmodulin-dependent protein kinase II (CaMKII) (CaMKII-positive neurons) were increased in layer II/III of the mPFC in paclitaxel-treated mice. Selectively inhibiting CaMKII-positive neurons in layer II/III of the mPFC with chemogenetic or optogenetic approaches relieved paclitaxel-induced neuropathic pain and anxiety. Furthermore, paclitaxel treatment increased calcium signals in layer II/III of the mPFC CaMKII-positive neurons expressed GCaMP6m. In addition, Golgi staining was performed to analyze that basal and apical dendrites of pyramidal neurons in layer II/III of the mPFC. Compared with vehicle-treated mice, paclitaxel-treated mice displayed longer and more branches and increased spine density in layer II/III of the mPFC. Further electron microscopy analysis revealed that asymmetrical synapses and postsynaptic density 95 thickness were significantly increased in layer II/III of the mPFC in paclitaxel-treated mice. These data suggest that CaMKII neurons in the mPFC layer II/III are importantly involved in paclitaxel-induced pain and anxiety.

Paclitaxel induces cognitive impairment via necroptosis, decreased synaptic plasticity and M1 polarisation of microglia.

CONTEXT: Paclitaxel (PTX) leads to chemotherapy brain (chemo-brain) which is characterised by cognitive impairment. It has been reported that necroptosis is associated with cognitive impairment in some neurodegenerative diseases, but it is not clear whether it is related to the development of chemo-brain. OBJECTIVE: To investigate the role of necroptosis and related changes in PTX-induced cognitive impairment. MATERIALS AND METHODS: C57bl/6n mice were randomly divided into five groups: control, vehicle, and different concentrations of PTX (6, 8, 10 mg/kg). Two additional groups received pre-treatment with Gdcl3 or PBS through Intracerebroventricular (ICV) injection before PTX-treatment. Cognitive function, necroptosis, synaptic plasticity and microglia polarisation were analysed. RESULTS: PTX (10 mg/kg) induced significant cognitive impairment, accompanied by changes in synaptic plasticity, including decreased density of PSD95 (0.65-fold), BDNF (0.44-fold) and dendritic spines (0.57-fold). PTX induced necroptosis of 53.41% (RIP3) and 61.91% (MLKL) in hippocampal neurons, with high expression of RIP3 (1.58-fold) compared with the control group. MLKL (1.87-fold) exhibited the same trend, reaching a peak on the 14th day. The increased expression of iNOS (1.63-fold) and inflammatory factors such as TNF-α (1.85-fold) and IL-ß (1.89-fold) compared to the control group suggests that M1 polarisation of microglia is involved in the process of cognitive impairment. Pre-treatment with Gdcl3 effectively reduced the number of microglia (0.50-fold), inhibited the release of TNF-α (0.73-fold) and IL-ß (0.56-fold), and improved cognitive impairment. CONCLUSION: We established a stable animal model of PTX-induced cognitive impairment and explored the underlying pathophysiological mechanism. These findings can guide the future treatment of chemo-brain.

A comparative genomic database of skeletogenesis genes: from fish to mammals.

Skeletogenesis is a complex process that requires a rigorous control at multiple levels during osteogenesis, such as signaling pathways and transcription factors. The skeleton among vertebrates is a highly conserved organ system, but teleost fish and mammals have evolved unique traits or have lost particular skeletal elements in each lineage. In present study, we constructed a skeletogenesis database containing 4101, 3715, 2996, 3300, 3719 and 3737 genes in Danio rerio, Oryzias latipes, Gallus gallus, Xenopus tropicalis, Mus musculus and Homo sapiens genome, respectively. Then, we found over 55% of the genes are conserved in the six species. Notably, there are 181 specific-genes in the human genome without orthologues in the other five genomes, such as the ZNF family (ZNF100, ZNF101, ZNF14, CALML6, CCL4L2, ZIM2, HSPA6, etc); and 31 genes are identified explicitly in fish species, which are mainly involved in TGF-beta, Wnt, MAPK, Calcium signaling pathways, such as bmp16, bmpr2a, eif4e1c, wnt2ba, etc. Particularly, there are 20 zebrafish-specific genes (calm3a, si:dkey-25li10, drd1a, drd7, etc) and one medaka-specific gene (c-myc17) that may alter skeletogenesis formation in the corresponding species. The database provides the new systematic genomic insights into skeletal development from teleosts to mammals, which may help to explain some of the complexities of skeletal phenotypes among different vertebrates and provide a reference for the treatment of skeletal diseases as well as for applications in the aquaculture industry.

Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement.

METHOD: Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-κB, SIRT1, and PGC-1α in the skeletal muscles were detected by western blot. Blood TNF-α levels, gastrocnemius muscle contractile force, and ATP concentration were examined. RESULTS: Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF-α levels, and inhibited the expression levels of TLR4/NF-κB in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels. CONCLUSION: Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-κB-dependent inflammatory response and protects SIRT1/PGC-1α-dependent mitochondrial function.

[Irreducible Indirect Inguinal Hernia Caused by Sigmoid Colon Cancer Entering Right Groin:A Case Report].

We reported a case of irreducible indirect inguinal hernia caused by sigmoid colon cancer entering the right groin.The patient complained about a right groin mass for more than 60 years with progressive enlargement for 3 years and pain for half a month.Abdominal CT examination at admission showed rectum and sigmoid colon hernia in the right inguinal area and thickening of sigmoid colon wall.Electronic colonoscopy and pathological diagnosis showed sigmoid colon cancer.Therefore,the result of preliminary diagnosis was irreducible indirect inguinal hernia caused by sigmoid colon cancer entering the right groin.We converted laparoscopic exploration to laparotomy followed by radical sigmoidectomy and employed end-to-end anastomosis of descending colon and rectum in combination with repair of right inguinal hernia.The patient recovered well after operation and was discharged.

Molecular characterization of a cyprinid fish (Ancherythroculter nigrocauda) TBK1 and its kinase activity in IFN regulation.

TANK-binding kinase 1 (TBK1) plays a vital role in activating interferon (IFN) production and positively regulating antiviral response in mammals. Research on more species of fish is necessary to clarify whether the function of fish TBK1 is conserved compared to that in mammals. Here, a cyprinid fish (Ancherythroculter nigrocauda) TBK1 (AnTBK1) was functionally identified and characterized. The full-length open reading frame (ORF) of AnTBK1 consists of 2184 nucleotides encoding 727 amino acids and contains a conserved Serine/Threonine protein kinase catalytic domain (S_TKc) in the N-terminal, similar to TBK1 in other species. The transcripts of AnTBK1 were found in all the tissues evaluated and the cellular distribution indicated that AnTBK1 was localized in the cytoplasm. In terms of functional identification, AnTBK1 induced a variety of IFN promoter activities as well as the expression of downstream IFN-stimulated genes (ISGs). In addition, AnTBK1 interacted with and significantly phosphorylated IFN regulatory factor 3 (IRF3), exhibiting the canonical kinase activity of TBK1. Finally, AnTBK1 presented strong antiviral activity against spring viremia of carp virus (SVCV) infection. Taken together, our research on the features and functions of AnTBK1 demonstrated that AnTBK1 plays a central role in IFN induction against SVCV infection.

Gunsight Procedure Versus the Purse-String Procedure for Closing Wounds After Stoma Reversal: A Multicenter Prospective Randomized Trial.

BACKGROUND: Stoma reversal is associated with a high risk of wound infection. The gunsight and purse-string closure techniques are both effective alternatives for stoma reversal, but comparative studies are lacking. OBJECTIVE: The purpose of this study was to compare the gunsight procedure with the purse-string closure technique when closing wounds after loop stoma reversal. DESIGN: This was a nonblinded, multicenter prospective randomized study (clinicaltrials.gov No. NCT02053948). SETTINGS: The study was conducted at a general surgery unit of 7 tertiary academic medical centers. PATIENTS: A total of 143 patients undergoing loop stoma reversal were included in the study (72 in the gunsight group and 71 in the purse-string group) between November 2013 and December 2017. INTERVENTION: Patients were randomly assigned to undergo either gunsight or purse-string closure procedure. MAIN OUTCOME MEASURES: Primary outcome was wound healing time. Secondary outcomes were the incidence of surgical site infection, morbidity, and patient satisfaction. RESULTS: No differences were found between the 2 groups in terms of surgical site infection, intraoperative blood loss, and postoperative hospital stay. The gunsight procedure had a shorter wound healing time compared with the purse-string procedure (17 vs 25 d; p < 0.001). A patient satisfaction questionnaire showed that the gunsight group had a higher score level of patient satisfaction with respect to wound healing time (p < 0.001) and total patient satisfaction score (p = 0.01) than the purse-string group. LIMITATIONS: Treatment teams were not blinded, and there was operator dependence of techniques. CONCLUSIONS: The gunsight and purse-string techniques are effective procedures for stoma reversal and both have a low incidence of surgical site infection. The gunsight technique is associated with shorter wound healing time, higher levels of patient satisfaction with regard to healing time, and overall final score and is recommended as the closure technique of choice. See Video Abstract at http://links.lww.com/DCR/B319. EL PROCEDIMIENTO DE GUNSIGHT VERSUS EL PROCEDIMIENTO DE JARETA, PARA EL CIERRE DE HERIDAS, DESPUéS DE REVERSIóN DE ESTOMA: UN ENSAYO, MULTICéNTRICO, PROSPECTIVO Y RANDOMIZADO: La reversión de estoma está asociada con un alto riesgo de infección de la herida. Las técnicas de gunsight y de jareta, son eficaces alternativas en la reversión de estoma, pero faltan estudios comparativos.Comparar el procedimiento de gunsight con la técnica de jareta, después de la reversión de estoma en asa.Estudio multicéntrico, prospectivo y randomizado ciego (NCT02053948).Realizado en la unidad de cirugía general, de siete centros médicos académicos terciarios.Se incluyeron en el estudio, un total de 143 pacientes sometidos a reversión de estoma de asa (72 en el grupo de gunsight y 71 en el grupo de jareta) entre noviembre de 2013 y diciembre de 2017.Los pacientes fueron asignados aleatoriamente, para someterse a un procedimiento de cierre de gunsight o de jareta.El resultado primario fue el tiempo de cicatrización de la herida. Los resultados secundarios fueron la incidencia de infección del sitio quirúrgico, morbilidad y satisfacción del paciente.No se encontraron diferencias entre los dos grupos en términos de infección del sitio quirúrgico, pérdida de sangre intraoperatoria o estadía hospitalaria postoperatoria. El procedimiento de gunsight tuvo un tiempo más corto en la cicatrización de la herida, en comparación con el procedimiento de jareta (17 días frente a 25 días, p <0,001). Un cuestionario de satisfacción del paciente, mostró que el grupo de gunsight tenía una puntuación más alta en relación al tiempo de cicatrización de la herida (p <0.001) y la puntuación total en satisfacción del paciente (p = 0.01), que en el grupo de jareta.Los equipos de tratamiento quirúrgico, no fueron cegados y hubo en los cirujanos, dependencia en las técnicas.Las técnicas de gunsight y de jareta son procedimientos efectivos para la reversión de estoma y ambas tienen una baja incidencia de infección en el sitio quirúrgico. La técnica de gunsight está asociada con un tiempo más corto en cicatrización de heridas, mejores niveles en satisfacción del tiempo de cicatrización y en la puntuación general final. Se recomienda como la técnica de cierre de elección. Consulte Video Resumen en http://links.lww.com/DCR/B319. (Traducción-Dr Fidel Ruiz Healy).

Combination of endoscopic submucosal dissection and laparoscopic sentinel lymph node dissection in early mucinous gastric cancer: Role of lymph node metastasis.

BACKGROUND: Recent evidence showed that combining endoscopic submucosal dissection (ESD) and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer (EMGC) patients with risks of positive lymph node metastasis (pLNM). AIM: To explore the predictive factors for pLNM in EMGC, and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC. METHODS: Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016. Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors, providing odds ratio (OR) with 95% confidence interval. And the association between the number of predictors and the pLNM rate was also investigated. RESULTS: Depth of invasion (OR = 7.342, 1.127-33.256, P = 0.039), tumor diameter (OR = 9.158, 1.348-29.133, P = 0.044), and lymphatic vessel involvement (OR = 27.749, 1.821-33.143, P = 0.019) turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis. For patients with 1, 2, and 3 risk factors, the pLNM rates were 9.1%, 33.3%, and 75.0%, respectively. pLNM was not detected in seven patients without any of these risk factors. CONCLUSION: ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size ≤ 2 cm, and when lymphatic vessel involvement is absent by postoperative histological examination. Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM.

Fetal growth restriction mice are more likely to exhibit depression-like behaviors due to stress-induced loss of dopaminergic neurons in the VTA.

Fetal growth restriction (FGR) is a severe perinatal complication that can increase risk for mental illness. To investigate the mechanism by which FGR mice develop mental illness in adulthood, we established the FGR mouse model and the FGR mice did not display obvious depression-like behaviors, but after environmental stress exposure, FGR mice were more likely to exhibit depression-like behaviors than control mice. Moreover, FGR mice had significantly fewer dopaminergic neurons in the ventral tegmental area but no difference in serotoninergic neurons in the dorsal raphe. RNA-seq analysis showed that the downregulated genes in the midbrain of FGR mice were associated with many mental diseases and were especially involved in the regulation of NMDA-selective glutamate receptor (NMDAR) activity. Furthermore, the NMDAR antagonist memantine can relieve the stress-induced depression-like behaviors of FGR mice. In summary, our findings provide a theoretical basis for future research and treatment of FGR-related depression.

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer.

Transcobalamin (TCN1) is a vitamin B12 (cobalamin)-binding protein that regulates cobalamin homeostasis. Recent studies and bioinformatic analyses have found that TCN1 is highly expressed in cancer tissues and is associated with tumour aggressiveness and poor prognosis. The present study aimed to detect TCN1 as a novel biomarker for prognosis and chemosensitivity of colon cancer. Next-generation sequencing showed that TCN1 was one of several upregulated mRNAs in colon cancer, which was verified by further bioinformatics analyses. Western blotting (n = 9) and quantitative real time polymerase chain reaction (qRT-PCR, n = 30) revealed that TCN1 was highly expressed in colon cancer tissues at both the protein and mRNA level. A total of 194 cases of colon cancer were examined by immunohistochemistry and revealed that TCN1 expression level was related to advanced stages (P < 0.005). Kaplan-Meier analysis verified that patients with lower TCN1 expression usually had longer overall survival (P = 0.008). In addition, TCN1 was highly expressed in pulmonary metastatic tumour tissues (n = 37, P = 0.025) and exhibited higher levels in right-sided colon cancer than in left-sided colon cancer (P = 0.029). TCN1 expression in specimens that had received neoadjuvant chemotherapy decreased compared with that in colonoscopy biopsy tissues (n = 42, P = 0.009). Further bioinformatics analyses verified that apoptosis pathways might have a role in high TCN1 expression. All the studies revealed that TCN1 expression in colon cancer was significantly associated with malignant biological behaviour. Therefore, TCN1 could be used as a novel biomarker for colon cancer aggressiveness and prognosis and might also be a potential biomarker for predicting neoadjuvant chemosensitivity.

Screening and Identification of Differentially Expressed Genes Expressed among Left and Right Colon Adenocarcinoma.

PURPOSE: Colon adenocarcinoma (COAD) is the third most common malignancy globally and is further categorized as left colon adenocarcinoma (LCOAD) or right colon adenocarcinoma (RCOAD) depending on the location of the primary tumor. The therapeutic outcome and long-term prognosis for patients with COAD are less than satisfactory, and this may be associated with tumor location. Therefore, it is important to investigate the genetic differences in COAD at different sites. Patients and Methods. Public data associated with COAD were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software (version 3.5.3), and functional annotation of DEGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction network was constructed, hub genes were identified and analyzed, and data mining using Gene Expression Profiling Interactive Analysis (GEPIA) was conducted. RESULTS: A total of 286 DEGs were identified between LCOAD and RCOAD. Additionally, 10 hub genes associated with COAD at different locations were screened, namely, CDKN2A, IGF1R, MDM2, SMAD3, SLC2A1, GRM5, PLCB4, FGFR1, UBE2V2, and TNFRSF10B. The expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and solute carrier family 2 member 1 (SLC2A1) was significantly associated with pathological stage (P < 0.05). COAD patients with high expression levels of CDKN2A exhibited poorer overall survival (OS) times than those with low expression levels (P < 0.05). CONCLUSION: CDKN2A expression was significantly different between LCOAD and RCOAD and was closely related to the prognosis of COAD. It is of great value for further understanding of the pathogenesis of LCOAD and RCOAD.

Genome-Wide Integrated Analysis Revealed Functions of lncRNA-miRNA-mRNA Interaction in Growth of Intermuscular Bones in Megalobrama amblycephala.

Intermuscular bone (IB) occurs in the myosepta of teleosts. Its existence has an adverse influence on the edible and economic value of fish, especially for aquaculture species belonging to Cypriniformes. The growth mechanism of IBs is quite lacking. In this study, we firstly used single molecular real-time sequencing (SMRT) technology to improve the draft genome annotation and full characterization of the transcriptome for one typical aquaculture species, blunt snout bream (Megalobrama amblycephala). The long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression profiles in two IB growth stages (1 and 3 years old) were compared through transcriptome and degradome analyses. A total of 126 miRNAs, 403 mRNAs, and 353 lncRNAs were found to be differentially expressed between the two stages. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the significantly upregulated map2k6 and cytc in the MAPK/p53 signaling pathway and the significantly downregulated lama3 and thbs4b in the extracellular matrix (ECM)-receptor pathway may play a key regulatory role in IB growth. Bioinformatics analysis subsequently revealed 14 competing endogenous RNA (ceRNA) pairs related to the growth of IBs, consisting of 10 lncRNAs, 7 miRNAs, and 10 mRNAs. Of these, dre-miR-24b-3p and dre-miR-193b-3p are core regulatory factors interacting with four lncRNAs and three mRNAs, the interaction mechanism of which was also revealed by subsequent experiments at the cellular level. In conclusion, our data showed that IBs had higher activity of cell apoptosis and lower mineralization activity in IB_III compared to IB_I via interaction of MAPK/p53 and ECM-receptor signaling pathways. The downregulated zip1 interacted with miR-24a-3p and lnc017705, decreased osteoblast differentiation and Ca2+ deposition in the IB_III stage. Our identified functional mRNAs, lncRNAs, and miRNAs provide a data basis for in-depth elucidation of the growth mechanism of teleost IB.

The lncRNA FEZF1-AS1 Promotes the Progression of Colorectal Cancer Through Regulating OTX1 and Targeting miR-30a-5p.

Long noncoding RNAs (lncRNAs) participate in and regulate the biological process of colorectal cancer (CRC) progression. Our previous research identified differentially expressed lncRNAs in 10 CRC tissues and 10 matched nontumor tissues by next-generation sequencing (NGS). In this study, we identified an lncRNA, FEZF1 antisense RNA 1 (FEZF1-AS1), and further explored its function and mechanism in CRC. We verified that FEZF1-AS1 is highly expressed in CRC tissues and cell lines. Through functional experiments, we found that reduced levels of FEZF1-AS1 significantly suppressed CRC cell migration, invasion, and proliferation and inhibited tumor growth in vivo. Mechanistically, we discovered that reduced levels of the lncRNA FEZF1-AS1 inhibited the activation of epithelial-mesenchymal transition (EMT); the overexpression of orthodenticle homeobox 1 (OTX1) partially rescued the FEZF1-AS1-induced inhibition of protein expression. It indicated that FEZF1-AS1 may play a role in the occurrence and development of CRC by regulating the FEZF1-AS1/OTX1/EMT pathway. Furthermore, it was reported that FEZF1-AS1 is located in both the nucleus and cytoplasm of HCT116 cells. Dual-luciferase reporter assays verified that FEZF1-AS1 directly binds miR-30a-5p and negatively regulated each other. Further, we showed that 5'-nucleotidase ecto (NT5E) is a direct target of miR-30a-5p, and the inhibition of miR-30a-5p expression partially rescued the inhibitory effect of FEZF1-AS1 on NT5E. Our results indicated that the mechanism by which FEZF1-AS1 positively regulates the expression of NT5E is through sponging miR-30a-5p. Our study demonstrated that lncRNA FEZF1-AS1 is involved in the development of CRC and may serve as a diagnostic and therapeutic target for CRC patients.

[Effects of moxibustion at 45 ℃ on blood lipoids and serum level of ox-LDL and NO in rats with hyperlipidemia].

OBJECTIVE: To observe the effects of moxibustion at different temperatures (38 ℃ and 45 ℃) on blood lipoids and serum level of oxidized low density lipoprotein (ox-LDL) and nitric oxide (NO) in rats with hyperlipidemia, and to explore the correlation between regulating blood fat and anti-oxidative stress and protection of vascular endothelium of moxibustion at 45 ℃. METHODS: According to random number table, 60 SD rats were randomly divided into a normal group, a model group, a moxibustion at 38 ℃ group and a moxibustion at 45 ℃ group, 15 rats in each group. The rats in the normal group received no treatment; the rats in the remaining three groups were fed with high-fat diet for 8 weeks to prepare rat models of hyperlipidemia. After successful modeling, the rats in the model group received no treatment; the rats in the moxibustion at 38 ℃ group and moxibustion at 45 ℃ group were treated with moxibustion at "Shenque" (CV 8) and "Zusanli" (ST 36), and the temperature was controlled at (38±1) ℃ and (45±1) ℃, respectively. The moxibustion was given for 10 min at each acupoint, once every two days, and totally 4-week treatment was given. After treatment, the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by using biochemical colorimetric method; the levels of ox-LDL and NO were measured by using ELISA method. RESULTS: ① Compared with the normal group, the levels of TC, TG and LDL-C were significantly increased in the model group (all P<0.01); compared with the model group and moxibustion at 38 ℃ group, the levels of TC, TG and LDL-C were significantly decreased in the moxibustion at 45 ℃ group (P<0.01，P<0.05); compared with the model group, the levels of TC, TG and LDL-C were insignificantly decreased in the moxibustion at 38 ℃ group (all P>0.05). ② Compared with the normal group, the level of ox-LDL was increased but that of NO was decreased in the model group (both P<0.01); compared with the model group and moxibustion at 38 ℃ group, the level of ox-LDL was decreased but that of NO was increased in the moxibustion at 45 ℃ group (P<0.01, P<0.05); compared with the model group, the level of ox-LDL was decreased but that of NO was increased in the moxibustion at 38 ℃ group (both P<0.05). CONCLUSION: Moxibustion at 45 ℃ has regulating effects on blood lipid in rats with hyperlipidemia, which can regulate blood lipid through various ways, such as anti-oxidative stress and protection of vascular endothelium.