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Background: Neoadjuvant immunochemotherapy (nICT) has emerged as a popular treatment approach for advanced gastric cancer (AGC) in clinical practice worldwide. However, the response of AGC patients to nICT displays significant heterogeneity, and no existing radiomic model utilizes baseline computed tomography to predict treatment outcomes., Aim: To establish a radiomic model to predict the response of AGC patients to nICT., Methods: Patients with AGC who received nICT ( n = 60) were randomly assigned to a training cohort ( n = 42) or a test cohort ( n = 18). Various machine learning models were developed using selected radiomic features and clinical risk factors to predict the response of AGC patients to nICT. An individual radiomic nomogram was established based on the chosen radiomic signature and clinical signature. The performance of all the models was assessed through receiver operating characteristic curve analysis, decision curve analysis (DCA) and the Hosmer-Lemeshow goodness-of-fit test., Results: The radiomic nomogram could accurately predict the response of AGC patients to nICT. In the test cohort, the area under curve was 0.893, with a 95% confidence interval of 0.803-0.991. DCA indicated that the clinical application of the radiomic nomogram yielded greater net benefit than alternative models., Conclusion: A nomogram combining a radiomic signature and a clinical signature was designed to predict the efficacy of nICT in patients with AGC. This tool can assist clinicians in treatment-related decision-making., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase ( MTHFR ) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI] 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis., (Copyright © 2023 Copyright: © The Author(s)(2023).)

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality., Competing Interests: None

Background: The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival., Methods: Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study., Results: The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8 + T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1., Conclusions: The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Unplanned excision (UPE) of soft tissue sarcoma (STS) is often chosen in the early phase by general physicians without any radiological evaluation., Purpose: The present study aimed to evaluate the impact of UPE on the clinical outcomes of patients with STS of the trunk and extremity., Materials and Methods: Patients with STS of the trunk and extremity who underwent R0 resection between 1998 and 2016 were included and divided into the UPE and planned excision (PE) groups. Propensity score matching (PSM) was used to control the selection bias. The endpoints were disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS)., Results: In total, 458 patients (277 males, 181 females; median age: 43 years) were included: 329 (71.8%) in the PE group and 129 (28.2%) in the UPE group. The follow-up time ranged from 7.1 to 313.78 months, with a median of 112.18 months. UPE patients were more likely to have a smaller or superficial lesion and were more frequently administered adjuvant therapy. After PSM, compared with the PE group, the UPE group had a longer LRFS (P=0.015), but there was no difference between the two groups regarding DSS and MFS. Residual disease was observed in 77.5% of the re-resected specimens in the UPE group and was a risk factor for DSS (P = 0.046) and MFS (P = 0.029) but was not associated with local recurrence (LR) (P=0.475) or LRFS (P=0.334). Moreover, we found no difference in DSS, LRFS or MFS according to the interval from UPE to definitive resection., Conclusion: STS treated with UPE had distinct characteristics. Patients who undergo UPE followed by an additional wide R0 resection have similar oncological survival compared to patients who undergo an initial PE, although the high incidence of residual tumor in the UPE group leads to an unfavorable clinical course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liang, Guo, Xu, Hong, Qiu, Zhou and Zhang.)

Objective: To observe the expression of cyclin-dependent kinase 5 (Cdk5), p35, tau protein and the activity of Cdk5 in rat hippocampus during pentylenetetrazole (PTZ) kindling process and their correlation with mossy fiber sprouting (MFS) so as to investigate the role of Cdk5/p35 in epileptogenesis., Methods: A total of 240 healthy male SD rats were divided randomly into normal controls and pentylenetetrazole (PTZ) treatment groups. The epileptic models were established by injection of PTZ intraperitoneally. At Day 3, Weeks 1, 2, 4 & 6 after a daily injection of PTZ, Timm staining was scored in the CA3 region and dentate gyrus. At the same time, the mRNA and protein of Cdk5 and p35, total tau protein and its phosphorylation at ser202 and Cdk5 activity were analyzed in the hilus and stratum granulosum of dentate gyrus and the CA1, CA3 regions of hippocampus. The methods of in situ hybridization, immunohistochemistry, Western blot and immuno-precipitation and liquid scintillation counter were employed respectively., Results: Prominent MFS was observed in area CA3 rather than the inner molecular layer in PTZ-treated rats. And the degree of MFS progressed with the development of behavioral kindled seizures. The expressions of Cdk5/p35 mRNA and protein, tau protein and its phosphorylation at Ser202 significantly increased from Day 3 to Week 4 in the PTZ treatment group. It was in accordance with the progression of MFS in area CA3., Conclusion: Cdk5/p35 and its substrate tau protein may be involved in MFS. Understanding the molecular mechanisms of MFS may lead to therapeutic interventions for limiting epileptogenesis.

Aim: The aim of this study was to determine the correlations among hippocampal damage, spontaneous recurrent seizures (SRS), and mossy fiber sprouting (MFS) using pentylenetetrazole (PTZ) kindling model., Methods: Chronic epileptic model was established by administration of PTZ. Behaviour and EEG seizure activity were recorded. Rats' hippocampus were analyzed with haematoxylin and eosin (H&E) stain for histological lesions and evaluated for MFS with Timm stain., Results: Prominent MFS was observed in area CA3 rather than the inner molecular layer in PTZ treated rats and the degree of MFS progressed with the development of behavioral kindled seizures. MFS preceded the occurrence of spontaneous seizures. No obvious neuronal necrosis and loss were observed in different regions of the hippocampus during kindling progression., Conclusion: MFS is not the outcome of SRS. Severe hippocampal damage is not required in the development of MFS and SRS.

Infiltrating spinal epidural angiolipoma is an uncommon benign tumor composed of mature adipose elements admixed with abnormal blood vessel, which tends to invade the surrounding soft tissue and may potentially be mistaken for an aggressive tumor. In this report, we present the MR imaging findings of a pathologically proved infiltrating spinal epidural angiolipoma that appeared largely hypointense on T1-weighted images and enhanced strongly with IV injection of contrast medium, features that suggested a malignant tumor.