Genome-wide identification of Shaker K+ channel family in Nicotiana tabacum and functional analysis of NtSKOR1B in response to salt stress.

Soil salinization poses a mounting global ecological and environmental threat. The identification of genes responsible for negative regulation of salt tolerance and their utilization in crop improvement through gene editing technologies emerges as a swift strategy for the effective utilization of saline-alkali lands. One efficient mechanism of plant salt tolerance is maintaining the proper intracellular K+/Na+ ratio. The Shaker K+ channels play a crucial role in potassium absorption, transport, and intracellular potassium homeostasis in plant cells. Here, the study presents the first genome-wide identification of Shaker K+ channels in Nicotiana tabacum L., along with a detailed bioinformatic analysis of the 20 identified members. Transcriptome analysis revealed a significant up-regulation of NtSKOR1B, an outwardly-rectifying member predominantly expressed in the root tissue of tobacco seedlings, in response to salt stress. This finding was then confirmed by GUS staining of ProNtSKOR1B::GUS transgenic lines and RT-qPCR analysis. Subsequently, NtSKOR1B knockout mutants (ntskor1) were then generated and subjected to salt conditions. It was found that ntskor1 mutants exhibit enhanced salt tolerance, characterized by increased biomass, higher K+ content and elevated K+/Na+ ratios in both leaf and root tissues, compared to wild-type plants. These results indicate that NtSKOR1B knockout inhibits K+ efflux in root and leaf tissues of tobacco seedlings under salt stress, thereby maintaining higher K+/Na+ ratios within the cells. Thus, our study identifies NtSKOR1B as a negative regulator of salt tolerance in tobacco seedlings.

Comparison of ethanol-soaked gelatin sponge and microspheres for hepatic arterioportal fistulas embolization in hepatic cellular carcinoma.

BACKGROUND: Hepatic arterioportal fistulas (APFs) are common in hepatocellular carcinoma (HCC). Moreover, correlated with poor prognosis, APFs often complicate anti-tumor treatments, including transarterial chemoembolization (TACE). AIM: To compare the efficacy of ethanol-soaked gelatin sponges (ESG) and microspheres in the management of APFs and their impact on the prognosis of HCC. METHODS: Data from patients diagnosed with HCC or hepatic APFs between June 2016 and December 2019 were retrospectively analyzed. Furthermore, APFs were embolized with ESG (group E) or microspheres (group M) during TACE. The primary outcomes were disease control rate (DCR) and objective response rate (ORR). The secondary outcomes included immediate and first follow-up APF improvement, overall survival (OS), and progression-free survival (PFS). RESULTS: Altogether, 91 participants were enrolled in the study, comprising 46 in group E and 45 in group M. The DCR was 93.5% and 91.1% in groups E and M, respectively (P = 0.714). The ORRs were 91.3% and 66.7% in groups E and M, respectively (P = 0.004). The APFs improved immediately after the procedure in 43 (93.5%) patients in group E and 40 (88.9%) patients in group M (P = 0.485). After 2 mo, APF improvement was achieved in 37 (80.4%) and 33 (73.3%) participants in groups E and M, respectively (P = 0.421). The OS was 26.2 ± 1.4 and 20.6 ± 1.1 mo in groups E and M, respectively (P = 0.004), whereas the PFS was 16.6 ± 1.0 and 13.8 ± 0.7 mo in groups E and M, respectively (P = 0.012). CONCLUSION: Compared with microspheres, ESG embolization demonstrated a higher ORR and longer OS and PFS in patients of HCC with hepatic APFs.

The impact of surgery and age on mortality with primary trachea malignant tumors: a retrospective study based on propensity-score matching analysis.

PURPOSE: This study aimed to explore the survival significance of surgery and age on the prognosis of patients with primary trachea malignancies. METHODS: The entire cohort of 637 patients with primary malignant trachea tumors was used to perform the main analyses. The data of those patients were from a public database. Overall survival (OS) curves were drawn by the Kaplan-Meier method and compared by the Log-rank test. The univariable and multivariable Cox regression analyses calculated the hazard ratio (HR) and 95% confidence interval (CI) for overall mortality. The propensity-score matching analysis was used to reduce the selection bias. RESULTS: Age, surgery, histological type, N classification, M classification, marital status, and tumor grading were identified as independent prognostic factors after eliminating confounding factors. The results of the Kaplan-Meier method revealed that patients with age < 65 had a survival advantage over those with age ≥ 65 (HR = 1.908, 95% CI 1.549-2.348, P < 0.001). The 5-year OS rates were 28% and 8% in the group with age < 65 and age ≥ 65, respectively (P < 0.001). Cases with surgery had better survival over patients without surgery (HR = 0.372, 95% CI 0.265-0.522, P < 0.001). Compared with patients who did not undergo operations, patients with surgery had a higher median survival time (20 vs. 174 months). For patients with surgery, young age was considered a survival-promoting factor (HR 2.484; 95% CI 1.238-4.983, P = 0.010). CONCLUSION: We suggested that age and surgery were the independent prognostic factors in patients with primary malignant trachea tumors. Besides, age serves as an essential indicator for evaluating the prognosis of postoperative patients.

Carbon dot decorated Co3O4 nanozymes responsive to the NIR-II window for mild photothermal-enhanced nanocatalytic therapy.

Although NIR-II laser-mediated photothermal therapy (PTT) is considered as an emerging strategy for tumor therapy, its therapeutic effects are still seriously hampered by low photothermal conversion efficacy, limited tissue penetration depth, and inevitable damage to adjoining healthy tissues. Herein, we report a mild second-near-infrared (NIR-II) photothermal-augmented nanocatalytic therapy (NCT) nanoplatform based on CD@Co3O4 heterojunctions by depositing NIR-II-responsive carbon dots (CDs) onto the surface of Co3O4 nanozymes. The as-prepared Co3O4 nanozymes possess multi-enzyme-mimicking catalytic activity including peroxidase, catalase, and glutathione-peroxidase to realize the cascade amplification of ROS levels owing to the presence of multivalent Co2+ and Co3+. CDs with a high NIR-II photothermal conversion efficiency (PCE) (51.1%) enable the realization of mild PTT (∼43 °C), which could not only avoid damage to adjoining healthy tissues but also enhance the multi-enzyme-mimic catalytic activity of Co3O4 nanozymes. More importantly, the NIR-II photothermal properties of CDs and the multi-enzyme-mimicking catalytic activity of Co3O4 nanozymes are greatly augmented by the fabrication of heterojunctions due to the induced localized surface plasmonic resonance (LSPR) and accelerated carrier transfer. On the basis of these advantages, satisfactory mild PTT-amplified NCT is accomplished. Our work presents a promising approach for mild NIR-II photothermal-amplified NCT based on semiconductor heterojunctions.

Degradation of Aflatoxin B1 in Peanut Oil by Ultraviolet-LED Cold-Light Irradiation and Structure Elucidation of the Degradation Products.

This study aimed to determine the efficiency of ultraviolet (UV)-LED cold light treatment on the degradation of aflatoxin (AF)B1 in peanut oils. The peanut oil samples obtained from different places in China and abroad were determined for AFB1 degradation efficiency of the UV-LED cold-light irradiation method. The degradation products were analyzed by ultra-high performance liquid chromatography coupled to quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive MS). The results indicated that the AFB1 content in all peanut oil samples decreased rapidly after 5 min of irradiation. Four main photodegradation products (C18H16O7, C17H14O7, C17H14O7, and C17H14O8) were identified using the established LC-MS method. Their chemical structures were postulated based on the LC-MS data. Also, the degradation pathways were proposed based on the data obtained. Oxidation and reduction reactions were mainly responsible for AFB1-decomposition. The reactions occurred at the furan and lactone rings. These findings demonstrated that UV-LED cold-light irradiation was an effective method for treating AFB1- contaminated peanut oil.

Differential Effects of Ammonium (NH4+) and Potassium (K+) Nutrition on Photoassimilate Partitioning and Growth of Tobacco Seedlings.

Plants utilize carbohydrates as the main energy source, but much focus has been on the impact of N and K on plant growth. Less is known about the combined impact of NH4+ and K+ nutrition on photoassimilate distribution among plant organs, and the resultant effect of such distribution on growth of tobacco seedlings, hence this study. Here, we investigated the synergetic effect of NH4+ and K+ nutrition on photoassimilate distribution, and their resultant effect on growth of tobacco seedlings. Soluble sugar and starch content peaks under moderate NH4+ and moderate K+ (2-2 mM), leading to improved plant growth, as evidenced by the increase in tobacco weight and root activity. Whereas, a drastic reduction in the above indicators was observed in plants under high NH4+ and low K+ (20-0.2 mM), due to low carbohydrate synthesis and poor photoassimilate distribution. A strong positive linear relationship also exists between carbohydrate (soluble sugar and starch) and the activities of these enzymes but not for invertase. Our findings demonstrated that NH4+ and K+-induced ion imbalance influences plant growth and is critical for photoassimilate distribution among organs of tobacco seedlings.

Biopsy of paediatric brainstem intrinsic tumours: Experience from a Singapore Children's Hospital.

BACKGROUND: Biopsy of intrinsic brainstem tumours presumed to be diffuse midline gliomas (previously known as DIPG) is controversial. Surgery has risks of injury to the eloquent brainstem and may not have direct benefit to the patient. Technological improvements in operative adjuncts have allowed the role of biopsy for paediatric brainstem lesions to be revisited with new insights. This study aims to evaluate our institutional experience in brainstem biopsy. METHODS: This is an ethics-approved retrospective study based in KK Women's and Children's Hospital. Patients diagnosed with intrinsic brainstem tumours and managed by the Neurosurgical Service were included. Variables of interest included patient demographics, neuroimaging features, type of surgery, histological and molecular diagnosis, treatment, and outcomes. RESULTS: From 2006 to 2021, a total of 27 brainstem intrinsic tumours were referred to the Neurosurgical Service. Eleven (40.7 %) patients underwent stereotactic biopsy and 10 (37 %) had open biopsies. Histologically, 10 (37 %) were confirmed to be high grade gliomas, eight (29.6 %) were low grade gliomas and 3 (11.1 %) were malignant embryonal tumours. No negative diagnostic results or permanent postoperative complications were encountered. Five patients went on to have their tumours interrogated via next-generation sequencing to look for targetable mutations. The remaining 6 (22.2 %) patients did not undergo biopsy, whereby 1 of them is still alive after 6 years. CONCLUSION: Biopsy of paediatric brainstem intrinsic tumours is a safe procedure that concurrs with accurate tissue diagnosis. This option can be offered to affected patients, especially to identify relevant markers for targeted therapy.

Comprehensive Analysis and Experimental Validation of a Novel Estrogen/Progesterone-Related Prognostic Signature for Endometrial Cancer.

Estrogen and progesterone are the major determinants of the occurrence and development of endometrial cancer (EC), which is one of the most common gynecological cancers worldwide. Our purpose was to develop a novel estrogen/progesterone-related gene signature to better predict the prognosis of EC and help discover effective therapeutic strategies. We downloaded the clinical and RNA-seq data of 397 EC patients from The Cancer Genome Atlas (TCGA) database. The "limma" R package was used to screen for estrogen/progesterone-related differentially expressed genes (DEGs) between EC and normal tissues. Univariate and multivariate Cox proportional hazards regression analyses were applied to identify these DEGs that were associated with prognosis; then, a novel estrogen/progesterone-related prognostic signature comprising CDC25B, GNG3, ITIH3, PRXL2A and SDHB was established. The Kaplan-Meier (KM) survival analysis showed that the low-risk group identified by this signature had significantly longer overall survival (OS) than the high-risk group; the receiver operating characteristic (ROC) and risk distribution curves suggested this signature was an accurate predictor independent of risk factors. A nomogram incorporating the signature risk score and stage was constructed, and the calibration plot suggested it could accurately predict the survival rate. Compared with normal tissues, tumor tissues had increased mRNA levels of GNG3 and PRXL2A and a reduced mRNA level of ITIH3. The knockdown of PRXL2A and GNG3 significantly inhibited the proliferation and colony formation of Ishikawa and AN3CA cells, while the inhibition of PRXL2A expression suppressed xenograft growth. In this study, five estrogen/progesterone-related genes were identified and incorporated into a novel signature, which provided a new classification tool for improved risk assessment and potential molecular targets for EC therapies.

Relevance of presenting risks of frailty, sarcopaenia and osteopaenia to outcomes from aneurysmal subarachnoid haemorrhage.

INTRODUCTION: Aneurysmal subarachnoid haemorrhage (aSAH) is a condition with significant morbidity and mortality. Traditional markers of aSAH have established their utility in the prediction of aSAH outcomes while frailty markers have been validated in other surgical specialties. We aimed to compare the predictive value of frailty indices and markers of sarcopaenia and osteopaenia, against the traditional markers for aSAH outcomes. METHODS: An observational study in a tertiary neurosurgical unit on 51 consecutive patients with ruptured aSAH was performed. The best performing marker in predicting the modified Rankin scale (mRS) on discharge was selected and an appropriate threshold for the definition of frail and non-frail was derived. We compared various frailty indices (modified frailty index 11, and 5, and the National Surgical Quality Improvement Program score [NSQIP]) and markers of sarcopaenia and osteopaenia (temporalis [TMT] and zygoma thickness), against traditional markers (age, World Federation of Neurological Surgery and modified Fisher scale [MFS]) for aSAH outcomes. Univariable and multivariable analysis was then performed for various inpatient and long-term outcomes. RESULTS: TMT was the best performing marker in our cohort with an AUC of 0.82, Somers' D statistic of 0.63 and Tau statistic 0.25. Of the frailty scores, the NSQIP performed the best (AUC 0.69), at levels comparable to traditional markers of aSAH, such as MFS (AUC 0.68). The threshold of 5.5 mm in TMT thickness was found to have a specificity of 0.93, sensitivity of 0.51, positive predictive value of 0.95 and negative predictive value of 0.42. After multivariate analysis, patients with TMT ≥ 5.5 mm (defined as non-frail), were less likely to experience delayed cerebral ischaemia (OR 0.11 [0.01 - 0.93], p = 0.042), any complications (OR 0.20 [0.06 - 0.069], p = 0.011), and had a larger proportion of favourable mRS on discharge (95.0% vs. 58.1%, p = 0.024) and at 3-months (95.0% vs. 64.5%, p = 0.048). However, the gap between unfavourable and favourable mRS was insignificant at the comparison of 1-year outcomes. CONCLUSION: TMT, as a marker of sarcopaenia, correlated well with the presenting status, and outcomes of aSAH. Frailty, as defined by NSQIP, performed at levels equivalent to aSAH scores of clinical relevance, suggesting that, in patients presenting with acute brain injury, both non-neurological and neurological factors were complementary in the determination of eventual clinical outcomes. Further validation of these markers, in addition to exploration of other relevant frailty indices, may help to better prognosticate aSAH outcomes and allow for a precision medicine approach to decision making and optimization of best outcomes.

Transanal vs laparoscopic total mesorectal excision for rectal cancer: a multicenter randomized phase III clinical trial (TaLaR trial) protocol.

BACKGROUND: Total mesorectum excision (TME) is considered the standard surgical procedure for rectal-cancer treatment. Transanal TME (taTME) is a new procedure to treat low rectal cancer. Some published studies have proven that taTME can provide a better-quality resected specimen in low-rectal-cancer patients in comparison to the transabdominal procedure, yet long-term outcomes must be investigated. We designed this non-inferiority trial (TaLaR trial) to compare short-term and long-term outcomes between taTME and laparoscopic TME (lapTME) for rectal cancer. METHODS: The TaLaR trial is a phase III open-labeled multicenter randomized-controlled trial. Patients who are diagnosed with rectal cancer with no more than T3N2 stage, and with the tumor location below the peritoneal reflection by magnetic resonance imaging scan, digital rectal examination, or colonoscopy, qualify for this study. After calculating, a total of 1,114 patients (557 per group) will be randomly allocated to either the taTME or the lapTME group. Primary endpoints are the 3-year disease-free survival (DFS) rate and the 5-year overall survival (OS) rate. Secondary endpoints include specimen quality, perioperative results, pelvic and anal function, and quality of life. DISCUSSION: The TaLaR trial is expected to clarify whether taTME can achieve comparable oncological outcomes, as well as improve specimen quality and recovery conditions in rectal-cancer patients compared with lapTME.

Identification of MicroRNAs as Potential Biomarkers in Ovarian Endometriosis.

Endometriosis, as a prevalent gynecological disease, is characterized by the presence of endometrial-like tissue outside the uterus, causing infertility and considerable pain and affecting the quality of life of women. The pathogenic mechanism has not been fully elucidated, and there are no effective biomarkers for endometriosis. In our study, microRNA (miRNA) expression profiling of 10 ectopic endometrial plasma from patients with ovarian endometriosis and 10 normal plasma from healthy controls was analyzed using a microarray. As a result, 114 differentially expressed miRNAs were identified. Among them, 14 miRNAs were significantly downregulated in patients with ovarian endometriosis, which matched the microarray results. The diagnostic value of the 14 downregulated miRNAs in ovarian endometriosis was evaluated by receiver operating characteristic (ROC) curve analysis, and hsa-let-7i-5p showed the highest area under the ROC curve (AUC) with a value of 0.900. The target genes of the 14 miRNAs were predicted by miRWalk2.0, and the genes that were targeted by at least 2 of the 14 miRNAs were analyzed by function enrichment. The target genes were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as microRNAs in cancer, bladder cancer, and endocrine resistance pathways, and the Gene Ontology (GO) terms such as nucleobase-containing compound metabolic process, cellular nitrogen compound biosynthetic process, and heterocycle metabolic process. The identified 14 differentially expressed miRNAs could be potential biomarkers and therapeutic targets for the diagnosis and treatment of endometriosis.

Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies.

Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg-1·d-1, ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5'-nucleotidase (NT5E), guanidinoacetate N-methyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases.

Transanal total mesorectal excision for rectal cancer: a multicentric cohort study.

BACKGROUND: Transanal total mesorectal excision (taTME) has recently emerged as a promising novel surgical procedure for rectal cancer. It is believed to hold the potential advantage of providing better access to mobilize the distal rectum and achieving better pathologic results. This study aimed to evaluate the feasibility of taTME for rectal cancer and summarize the preliminary experience in 10 Chinese hospitals. METHODS: A total of 211 patients were enrolled in this study. Variables for evaluation of safety, feasibility, and oncologic outcomes were retrospectively collected and analysed. RESULTS: The median distance between the tumor and the anal verge was 5.9 cm (range, 1.5-12 cm). The median operating time was 280 min (range, 70-600 min) and the median estimated intra-operative blood loss was 50 mL (range, 10-1,500 mL). The overall rate of complication was 27.9%. Among the 211 patients, 175 (82.9%) had complete TME and 33 (15.6%) had near complete TME. The circumferential resection margin was negative in 97.7% of patients. The patients were followed for a median of 35 months (range, 2-86 months). There was 7.6% (16) mortality, 6.2% (13) had local recurrence, and 12.8% (27) had systemic recurrence. Kaplan-Meier survival analysis showed that 1-, 2-, and 3-year disease-free survival rates were 94.8%, 89.3%, and 80.2%, respectively, and 1-, 2-, and 3-year OS rates were 97.4%, 95.7%, and 92.9%, respectively. CONCLUSIONS: Although limited by its retrospective nature, taTME was safe and feasible in selected patients. Future work with rigorous data recording is warranted.

Comparative analysis of robotic vs laparoscopic radical hysterectomy for cervical cancer.

BACKGROUND: Cervical cancer is the most common gynecological malignancy, ranking first in female reproductive malignancies with more than 500000 new cases and 275000 deaths each year. Traditionally, open radical hysterectomy is considered the standard surgical procedure for the treatment of resectable cervical cancer. The latest guidelines from the National Comprehensive Cancer Network and the European Society of Gynecological Oncology suggest that open surgery and laparoscopic surgery (using traditional laparoscopic or robotic techniques) are the main surgical approaches for radical hysterectomy for patients with stage IA2-IIA cervical cancer. Robotic surgery has been increasingly used in abdominal surgery and has shown more beneficial effects. AIM: To analyse the perioperative conditions, complications, and short-term and long-term effects in patients undergoing robotic radical hysterectomy (RRH) and laparoscopic radical hysterectomy (LRH) to compare their clinical efficacy, safety, and feasibility. METHODS: The perioperative data of patients undergoing RRH and LRH were extracted and collected from the database of surgical treatments for cervical cancer for statistical analysis. RESULTS: Of the patients, 342 underwent LRH for cervical cancer, and 216 underwent RRH. The total complication rate was 9.65% (20 patients) in the RRH group and 17.59% (60 patients) in the LRH group. The complication rate was significantly lower in the RRH group than in the LRH group. There was no significant difference in the follow-up period (P = 0.658). The total recurrence rates were 15.7% and 12% in the RRH and LRH groups, respectively. The progression-free survival time was 28.91 ± 15.68 mo and 28.34 ± 15.13 mo in the RRH and LRH groups, respectively (P = 0.669). The overall survival (OS) rates were 92.13% and 94.45% in the RRH and LRH groups, respectively (P = 0.292). The OS time was 29.87 ± 15.92 mo and 29.41 ± 15.14 mo in the RRH and LRH groups, respectively (P = 0.732). The survival curves and the progression-free survival curves were not statistically significantly different between the two groups (P = 0.407 and 0.28, respectively). CONCLUSION: RRH is associated with significantly less operative time and blood loss than LRH. The two procedures have similar complication rates, OS, and progression-free survival time.

Establishment of the PDTX model of gynecological tumors.

OBJECTIVE: Fresh tumor tissues from patients with gynecological tumors were obtained by surgery or biopsy, and transplanted into NOD-Prkdcem26ll2rgem26Nju (NCG) mice to establish a patient-derived tumor xenograft (PDTX). MATERIALS AND METHODS: A total of 15 patients with gynecologic tumors were enrolled into the present study. Among these patients, 12 patients had epithelial fallopian tube/ovarian/peritoneal cancer, one patient had metastatic ovarian cancer, and two patients had cervical cancer. Furthermore, among these patients, three patients were treated with puncture or microscopy biopsy, six patients underwent laparoscopic surgery, and six patients underwent robotic surgery. The tumor formation latency, tumor formation rate, tumor volume, tumor invasion and metastasis of the transplanted tumor were observed, the consistency of the PDTX model tumor tissue and patient's primary tumor tissue was compared by pathological H&E staining, and pharmacodynamics testing was performed. RESULTS: Seven of 15 PDTX models were successfully established, with a success rate of 46.7%. The tumor formation time ranged within 21-130 days, with a median tumor formation time of 73 days. The PDTX model maintained the differentiation, morphological and structural characteristics of tumor cells, and the pharmacodynamic test was completed in five patients. CONCLUSION: The PDTX model is highly consistent with the pathology of the patient's tumor, and can be used as a substitute for clinical patients to guide the accurate treatment and scientific research of gynecological tumors.

Comparison of integrated PET/MRI with PET/CT in evaluation of endometrial cancer: a retrospective analysis of 81 cases.

BACKGROUND: The objective of this study was to compare the diagnostic value of integrated PET/MRI with PET/CT for assessment of regional lymph node metastasis and deep myometrial invasion detection of endometrial cancer. METHODS: Eighty-one patients with biopsy-proven endometrial cancer underwent preoperative PET/CT (n = 37) and integrated PET/MRI (n = 44) for initial staging. The diagnostic performance of PET/CT and integrated PET/MRI for assessing the extent of the primary tumor and metastasis to the regional lymph nodes was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. McNemar's test was employed for statistical analysis. RESULTS: Integrated PET/MRI and PET/CT both detected 100% of the primary tumors. Integrated PET/MRI proved significantly more sensitivity and specificity than PET/CT in regional lymph node metastasis detection (P = 0.015 and P < 0.001, respectively). The overall accuracy of myometrial invasion detection for PET/CT and Integrated PET/MRI was 45.9% and 81.8%, respectively. Integrated PET/MRI proved significantly more accurate than PET/CT (P < 0.001). CONCLUSION: Integrated PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for the assessment of the lymph node metastasis and myometrial invasion in patients with endometrial cancer.

Dolyemycins A and B, two novel cyclopeptides isolated from Streptomyces griseus subsp. griseus HYS31.

Two novel cyclopeptides with special skeleton, namely, dolyemycins A (1) and B (2) were isolated from Streptomyces griseus subsp. griseus HYS31 by bio-guided isolation. Their structures were elucidated by detailed analysis of spectroscopic data. These two compounds were cyclopeptides containing eleven amino acids including five unusual amino acids (hydroxyglycine, 3-hydroxyleucine, 3-phenylserine, ß-hydroxy-O-methyltyrosine, 2,3-diaminobutyric acid) in both of them and an extra nonprotein amino acids (3-methylaspartic acid) in Dolyemycin B only. Dolyemycins A and B performed antiproliferative activity against human lung cancer A549 cells with IC50 values of 1.0 and 1.2 µM, respectively.

Nedaplatin and paclitaxel compared with carboplatin and paclitaxel for patients with platinum-sensitive recurrent ovarian cancer.

This retrospective cohort study was designed to evaluate the efficacy and safety of nedaplatin plus paclitaxel (NP) compared with carboplatin plus paclitaxel (CP) in platinum-sensitive recurrent ovarian cancer. Patients with histologically proven epithelial ovarian cancer with recurrent interval ≥6 months after finishing platinum-based therapies between January 1, 2009 and December 31, 2014 were investigated. Patients received an intravenous infusion of NP (nedaplatin 80 mg/m2 plus paclitaxel 175 mg/m2) or CP (carboplatin at an area under the curve of 5 plus paclitaxel 175 mg/m2) protocols every 3 weeks for at least 6-8 cycles or until disease progression. Primary end point was progression-free survival (PFS); secondary end points were toxicity and overall survival (OS). 436 patients were included in the study, containing 241 cases receiving CP regimen and 195 cases receiving NP regimen, who were all contained in safety analysis. Because of 61 patients with unbearable toxicity and poor compliance, 375 patients were finally included in the efficacy analysis. With median follow-up of 63.5 months, PFS was 11.0 months with NP regimen versus 9.5 months with CP regimen (P=0.109). Subgroup analysis indicated that PFS of the NP arm was statistically superior to the CP arm when recurrent interval was 6-12 months (P=0.048); median PFS was 10.0 versus 8.0 months, respectively. There was no significant difference in overall survival between two groups. More frequent grade 3-4 neutropenia (13.3% vs 33.6%), thrombocytopenia (5.6% vs 14.5%) and hypersensitivity reactions (5.6% vs 21.9% ) were observed in CP arm (P<0.01). Compared to the CP, NP regimen did not improve 5-year overall survival in platinum-sensitive recurrent ovarian cancer, but it had better tolerance. NP obtained significant benefit in progression-free survival when the recurrent interval was between 6 and 12 months, although the efficacy of two regimens were similar when the recurrent interval ≥12 months.

Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells.

AIM: To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism. METHODS: Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species (ROS) were quantified using the fluorescent probe DCFH-DA. RESULTS: Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation. CONCLUSION: Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.

Homeobox­containing protein 1 loss is associated with clinicopathological performance in glioma.

Homeobox-containing protein 1 (HMBOX1) is a novel member of the homeobox family, and abnormal expression of HMBOX1 has been observed in several types of carcinoma. A total of 144 cases of confirmed glioma diagnoses were included in the present study. Grading was performed according to the World Health Organization (WHO) grading system for central nervous system neoplasm. Immunohistochemical staining of HMBOX1, proliferation marker protein Ki­67 (Ki­67) and microvessel density (MVD) was performed, and scores were calculated. HMBOX1 mRNA levels were detected using the reverse transcription quantitative polymerase chain reaction. It was identified that the expression of HMBOX1 was reduced in glioma tissue compared with normal brain tissue (P<0.05). The expression of HMBOX1 was downregulated significantly in WHO grade IV tumors compared with WHO grades II and III (P<0.05). HMBOX1 expression was significantly correlated with WHO grade, Karnofsky Performance Score, MVD and Ki­67 expression; however, not associated with age or gender. Log­rank testing did not demonstrate that HMBOX1 expression was associated with prognosis. In conclusion, HMBOX1 may be a potential diagnostic marker in glioma.