Predictive value of infiltrating tumor border configuration of rectal cancer on MRI.

BACKGROUND: Infiltrating tumor border configuration (iTBC) is assessed by postoperative pathological examination, thus, is not helpful for preoperative treatment strategies. The study aimed to detect iTBC by magnetic resonance imaging (MRI) and evaluate its predictive value. MATERIALS AND METHODS: A total of 153 patients with rectal cancer were retrospectively analyzed. Clinicopathological and MRI data mainly including tumor border configuration (TBC) on MRI, MRI-detected extramural vascular invasion (MEMVI), tumor length, tumor growth pattern, maximal extramural depth, pathology-proven lymph node metastasis (PLN) and pathology-proven extramural vascular invasion (PEMVI) were analyzed. The correlation of MRI factors with PEMVI and PLN was analyzed by univariate and multivariate logistic regression analyses. The nomograms were established based on multivariate logistic regression analysis and were confirmed by Bootstrap self-sampling. The receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to evaluate the diagnostic efficiency. RESULTS: Fifty cases of PEMVI and 48 cases of PLN were found. Forty cases of PEMVI and 34 cases of PLN in 62 cases of iTBC were also found. iTBC, MEMVI and maximal extramural depth were significantly associated with PEMVI and PLN (P < 0.05). iTBC (odds ratio = 3.84 and 3.02) and MEMVI (odds ratio = 7.27 and 3.22) were independent risk factors for PEMVI and PLN. The C-indices of the two nomograms for predicting PEMVI and PLN were 0.863 and 0.752, respectively. The calibration curves and ROC curves of the two nomograms showed that the correlation between the predicted and the actual incidence of PEMVI and PLN was good. The AUCs of iTBC for predicting PEMVI and PLN were 0.793 (95% CI: 0.714-0.872) and 0.721 (95% CI: 0.632-0.810), respectively. The DeLong test showed that the predictive efficiency of the nomogram in predicting PEMVI was better than that of iTBC (P = 0.0009) and MEMVI (P = 0.0095). CONCLUSION: iTBC and MEMVI are risk factors for PEMVI and pelvic lymph node metastasis. The nomograms based on iTBC show a good performance in predicting PEMVI and pelvic lymph node metastasis, possessing a certain clinical reference value. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Beijing Friendship Hospital, and individual consent was waived for this retrospective analysis.

[Effectiveness analysis of posterolateral approach lumbar interbody fusion assisted by one-hole split endoscope for L4, 5 degenerative lumbar spondylolisthesis].

Objective: To compare the effectiveness of posterolateral approach lumbar interbody fusion assisted by one-hole split endoscope (OSE) and traditional posterior lumbar interbody fusion (PLIF) in the treatment of L4, 5 degenerative lumbar spondylolisthesis (DLS). Methods: The clinical data of 58 patients with DLS who met the selection criteria admitted between February 2020 and March 2022 were retrospectively analyzed, of which 26 were treated with OSE-assisted posterolateral approach lumbar interbody fusion (OSE group) and 32 were treated with PLIF (PLIF group). There was no significant difference between the two groups in terms of gender, age, body mass index, Meyerding grade, lower limb symptom side, decompression side, stenosis type, and preoperative low back pain visual analogue scale (VAS) score, leg pain VAS score, Oswestry disability index (ODI), and the height of the anterior and posterior margins of the intervertebral space (P>0.05). The operation time, intraoperative blood loss, postoperative hospital stay, and complications were compared between the two groups. The low back pain and leg pain VAS scores and ODI before operation, at 1 month, 6 months after operation, and last follow-up, the height of anterior and posterior margins of the intervertebral space before operation, at 6 months after operation, and last follow-up, the modified MacNab criteria at last follow-up after operation were used to evaluate the effectiveness; and the Bridwell method at last follow-up was used to evaluate the interbody fusion. Results: Both groups successfully completed the operation. Compared with the PLIF group, the OSE group showed a decrease in intraoperative blood loss and postoperative hospital stay, but an increase in operation time, with significant differences (P<0.05). In the OSE group, no complication such as nerve root injury and thecal sac tear occurred; in the PLIF group, there were 1 case of thecal sac tear and 1 case of epidural hematoma, which were cured after conservative management. Both groups of patients were followed up 13-20 months with an average of 15.5 months. There was no complication such as loosening, sinking, or displacement of the fusion cage. The low back pain and leg pain VAS scores, ODI, and the height of anterior and posterior margins of the intervertebral space at each time point after operation in both groups were significantly improved when compared with those before operation (P<0.05). Except for the VAS score of lower back pain in the OSE group being significantly better than that in the PLIF group at 1 month after operation (P<0.05), there was no significant difference in all indicators between the two groups at all other time points (P>0.05). At last follow-up, both groups achieved bone fusion, and there was no significant difference in Bridwell interbody fusion and modified MacNab standard evaluation between the two groups (P>0.05). Conclusion: OSE-assisted posterolateral approach lumbar interbody fusion for L4, 5 DLS, although the operation time is relatively long, but the postoperative hospitalization stay is short, the complications are few, the operation is safe and effective, and the early effectiveness is satisfactory.

Identification of cuproptosis-related subtypes, cuproptosis-related gene prognostic index in hepatocellular carcinoma.

Cuproptosis is a novel form of cell death, correlated with the tricarboxylic acid (TCA) cycle. However, the metabolic features and the benefit of immune checkpoint inhibitor (ICI) therapy based on cuproptosis have not yet been elucidated in Hepatocellular carcinoma (HCC). First, we identified and validated three cuproptosis subtypes based on 10 cuproptosis-related genes (CRGs) in HCC patients. We explored the correlation between three cuproptosis subtypes and metabolism-related pathways. Besides, a comprehensive immune analysis of three cuproptosis subtypes was performed. Then, we calculated the cuproptosis-related gene prognostic index (CRGPI) score for predicting prognosis and validated its predictive capability by Decision curve analysis (DCA). We as well explored the benefit of ICI therapy of different CRGPI subgroups in two anti-PD1/PD-L1 therapy cohorts (IMvigor210 cohort and GSE176307). Finally, we performed the ridge regression algorithm to calculate the IC50 value for drug sensitivity and Gene set enrichment analysis (GSEA) analysis to explore the potential mechanism. We found that cluster A presented a higher expression of FDX1 and was correlated with metabolism, glycolysis, and TCA cycle pathways, compared with the other two clusters. HCC patients with high CRGPI scores had a worse OS probability, and we further found that the CRGPI-high group had high expression of PD1/PDL1, TMB, and better response (PR/CR) to immunotherapy in the IMvigor210 cohort and GSE176307. These findings highlight the importance of CRGPI serving as a potential biomarker for both prognostic and immunotherapy for HCC patients. Generally, our results provide novel insights about cuproptosis into immune therapeutic strategies.

A randomized trial comparing the clinical efficacy and safety of a novel steerable percutaneous kyphoplasty with traditional PKP in osteoporotic vertebral fractures.

BACKGROUND: Percutaneous kyphoplasty (PKP) is a highly practical technology to treat osteoporotic vertebral compression fractures (OVCFs). However, the operation time and radiation exposure remain problematic. This study explored the differences in surgical effects and safety between a novel steerable percutaneous kyphoplasty (S-PKP) and traditional PKP in order to achieve better clinical outcomes for OVCF patients. It is also exploring whether the new technology could reduce the radiation exposure. METHODS: This study recruited 72 patients (between March 2019 and January 2020) with OVCFs (single vertebra). The patients were semi-randomly divided these patients into two groups according to ID numbers: a S-PKP group (33 cases) and a PKP group (39 cases). We evaluated the clinical efficacy using the kyphotic Cobb angle, Oswestry disability index (ODI), visual analogue scale (VAS) score, injected cement volume, operation time, intraoperative radiation times, bone cement leakage, and postoperative complications. Patients were followed up once preoperatively, and at 1 day, 6 months, and 1 year postoperatively. RESULTS: There were no cases of cement leakage or postoperative complications. There were no significant differences in gender, age, Bone mineral density T-score (BMD T) value, Cobb angle between the two groups (P>0.05). Intraoperative bone cement injection was approximately 5.25±1.37 and 5.32±1.29 mL in the PKP and S-PKP groups respectively. The postoperative VAS score and ODI of the two groups at 1 day, 6 months, and 1 year were markedly lower than before (P<0.05). There was a considerable improvement in the Cobb angle postoperatively (P<0.05). However, as the follow-up time extended, the Cobb Angle increased. The operation time and X-ray exposure times of patients in the PKP group were notably higher than those in the S-PKP group. The operation time was 51.59±9.14 min in the PKP group and 30.76±4.82 min in the S-PKP group. The frequency of intraoperative radiation was 105.9±31.93 times in the PKP group and 47.42±11.88 times in the S-PKP group. CONCLUSIONS: Early results showed that S-PKP is a safe and efficient method for the treatment of OVCFs. S-PKP can reduce the operation time and radiation exposure. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046727.

A novel full endoscopic annular repair technique combined with autologous conditioned plasma intradiscal injection: a new safe serial therapeutic model for the treatment of lumbar disc herniation.

BACKGROUND: Recurrent intervertebral disc herniation and an exacerbated degenerative process have been identified as the most important factors contributing to persistent pain and disability after surgical discectomy. Defects in the annulus fibrosus remain a surgical challenge, as the preference for minimally invasive surgical approaches for lumbar microdiscectomy, surgical access, and the specifics of anatomy limit the types of devices that permit annulus fibrosus repair. Furthermore, the intervertebral disc is a relatively avascular structure, and surgical procedures can accelerate the degenerative disc process. This study aimed to evaluate the clinical safety and efficacy of a novel microdiscectomy annular repair technique combined with an autologous conditioned plasma (ACP) intradiscal injection for the treatment of lumbar disc herniation (LDH). METHODS: From July 2017 to December 2018 this study recruited 75 patients with LDH (single segment) and randomly divided these patients into the following three groups: group A, full endoscopic discectomy; group B: full endoscopic discectomy and annular repair; group C, full endoscopic discectomy annular repair and ACP intradiscal injection. The pre- and postoperative neurological function and pain status were evaluated by the visual analog scale (VAS) score and the Oswestry disability index (ODI). Patients were followed up once preoperatively, and at 1, 3, and 6 months postoperatively. RESULTS: The procedure was successfully performed in all cases. No cases required conversion to an open procedure. The preoperative symptoms were alleviated significantly after surgery. The VAS scores for lower back and lower limb pain and ODI score were significantly difference at 1 month, 3 months, 6 months post operation compared to pre-operation scores (P<0.05). For VAS scores of the lower back, the difference between group A and group C was statistically significant (A>C), as was the difference between group B and group C (B>C). CONCLUSIONS: Early results showed that the use of the novel full endoscopic annular repair technique and ACP intradiscal injection serial therapeutic model are beneficial for short term outcomes and demonstrates a reduction in symptomatic disc reherniation with low postoperative complication rates. This new serial therapeutic model may significantly improve the symptoms of postoperative lower back pain.

Two FERONIA-Like Receptor Kinases Regulate Apple Fruit Ripening by Modulating Ethylene Production.

Ethylene has long been known to be a critical signal controlling the ripening of climacteric fruits; however, the signaling mechanism underlying ethylene production during fruit development is unknown. Here, we report that two FERONIA-like receptor kinases (FERLs) regulate fruit ripening by modulating ethylene production in the climacteric fruit, apple (Malus×domestica). Bioinformatic analysis indicated that the apple genome contains 14 members of the FER family (MdFERL1-17), of these 17 FERLs, MdFERL6 was expressed at the highest level in fruit. Heterologous expression of MdFERL6 or MdFERL1, the apple homolog of Arabidopsis FER, in another climacteric fruit, tomato (Solanum lycopersicum) fruit delayed ripening and suppressed ethylene production. Overexpression and antisense expression of MdFERL6 in apple fruit calli inhibited and promoted ethylene production, respectively. Additionally, virus-induced gene silencing (VIGS) of SlFERL1, the tomato homolog of FER, promoted tomato fruit ripening and ethylene production. Both MdFERL6 and MdFERL1 physically interacted with MdSAMS (S-adenosylmethionine synthase), a key enzyme in the ethylene biosynthesis pathway. MdFERL6 was expressed at high levels during early fruit development, but dramatically declined when fruit ripening commenced, implying that MdFERL6 might limit ethylene production prior to fruit development and the ethylene production burst during fruit ripening. These results indicate that FERLs regulate apple and tomato fruit ripening, shedding light on the molecular mechanisms underlying ripening in climacteric fruit.

A FERONIA-Like Receptor Kinase Regulates Strawberry (Fragaria × ananassa) Fruit Ripening and Quality Formation.

Ripening of fleshy fruits is controlled by a series of intricate signaling processes. Here, we report a FERONIA/FER-like receptor kinase, FaMRLK47, that regulates both strawberry (Fragaria × ananassa) fruit ripening and quality formation. Overexpression and RNAi-mediated downregulation of FaMRLK47 delayed and accelerated fruit ripening, respectively. We showed that FaMRLK47 physically interacts with FaABI1, a negative regulator of abscisic acid (ABA) signaling, and demonstrated that FaMRLK47 regulates fruit ripening by modulating ABA signaling, a major pathway governing strawberry fruit ripening. In accordance with these findings, overexpression and RNAi-mediated downregulation of FaMRLK47 caused a decrease and increase, respectively, in the ABA-induced expression of a series of ripening-related genes. Additionally, overexpression and RNAi-mediated downregulation of FaMRLK47 resulted in an increase and decrease in sucrose content, respectively, as compared with control fruits, and respectively promoted and inhibited the expression of genes in the sucrose biosynthesis pathway (FaSS and FaSPS). Collectively, this study demonstrates that FaMRLK47 is an important regulator of strawberry fruit ripening and quality formation, and sheds light on the signaling mechanisms underlying strawberry fruit development and ripening.

High expression of Beclin-1 predicts favorable prognosis for patients with colorectal cancer.

PURPOSE: Beclin-1 is an autophagy gene. It promotes the formation of the autophagic vesicle as well as plays an essential role in guarding the cells against chromosomal instability. Overexpression of Beclin-1 has been reported to predict a favorable survival in various cancers. However, little is known about its prognostic significance in colorectal cancer. METHODS AND MATERIALS: A total of three hundred and sixty-three (363) colorectal tissues from colorectal cancer (CRC) patients were collected. Tissue micro-arrays and immunohistochemistry were used to investigate the expression and prognostic significance of Beclin-1 in CRC. The associations among Beclin-1 expression, clinicopathological parameters and prognosis were evaluated. RESULTS: Beclin-1 had a higher expression in CRC tissues than in normal tissues. A high expression of Beclin-1 was positively correlated with gender (P=0.027), histological grade (P=0.003), pM status (P=0.003) and clinical stage (P=0.024). Patients with a high Beclin-1 expression, when compared to those with a lower expression had both a better overall survival (OS, P=0.006) and disease-free survival (DFS, P=0.008). In the pT3 subgroup, Beclin-1 was also found to be a good prognostic indicator (P<0.05). Multivariate analysis showed a high expression of Beclin-1 was indeed a positive independent prognostic factor of OS and DFS for CRC patients (P<0.05). CONCLUSION: Our results demonstrated that a high expression of Beclin-1 correlated with a better overall survival and disease-free survival, thus serving as a favorable independent prognostic marker in CRC.

Expression of A disintegrin and metalloprotease 8 is associated with cell growth and poor survival in colorectal cancer.

BACKGROUND: A disintegrin and metalloprotease 8 (ADAM8) has been reported to be associated with various malignancies. However, no studies have examined ADAM8 association in colorectal cancer (CRC). The aim of this study was to investigate the expression and function of ADAM8 in CRC. METHODS: Expression level of ADAM8 in CRC was evaluated by quantitative RT-PCR, western blot and immunohistochemical staining analysis. The role of ADAM8 in colorectal carcinogenesis was evaluated by in vitro assays. The correlations between ADAM8 status and clinicopathological features including survival were analyzed. RESULTS: ADAM8 was highly expressed in CRC tissues compared with adjacent normal tissues. Knockdown of ADAM8 in two CRC cell lines resulted in reduced cellular growth and proliferation, and increased apoptosis. Immunohistochemistry analysis showed no significant correlations of ADAM8 protein expression with clinicopathologic features. Survival analysis indicated that patients with ADAM8-positive tumors had worse 5-year overall survival (OS, p = 0.037) and 5-year disease free survival (DFS, p = 0.014) compared with those with ADAM8-negative tumors. Multivariate analysis indicated ADAM8 expression was an independent prognostic factor for both OS and DFS (both p< 0.001). Subgroup analysis showed that 5-year OS of colon cancer, T3-T4 stage and N0 stage was worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05). The 5-year DFS in colon cancer, T3-T4 stage, N0 stage, TNM stage II, adenocarcinoma, moderate differentiation and male patient subgroups was also worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05). CONCLUSIONS: Our results show that ADAM8 is overexpressed in CRC, promotes cell growth and correlates with worse OS and DFS, and thus could serve as a biomarker for individual CRC patient therapy.