Dentatorubral-pallidoluysian atrophy: a case report and review of literature.

BACKGROUND: Dentatorubral-pallidoluysian atrophy is a rare autosomal dominant neurodegenerative disease. It is a rare disease in the world. Therefore, sharing clinical encounters of this case can deepen global awareness and understanding of the disease. CASE PRESENTATION: The patient was a 34-year-old male of Han nationality who was unmarried. The patient was admitted owing to weakness of the left lower limb with walking instability for 2 months and aggravation for 1 month. There was no dizziness, headache, numbness of limbs, convulsions, nausea, vomiting, abdominal pain, ataxia, nausea, vomiting, or abdominal pain. No nausea, vomiting, diarrhea, abdominal distension, tinnitus, hearing loss, fever, cough, expectoration. Personal history: worked in Cambodia 5 years ago, worked in Dubai 3 years ago, engaged in computer work, smoking or drinking habits. The patient was unmarried. Family history: the mother had symptoms similar to walking unsteadily (undiagnosed). Positive signs include a wide-base gait with a rotatory nystagmus that jumps upward in both eyes. Bilateral finger-nose instability test was quasi-positive, rapid alternating test was negative, and eye closure tolerance test was positive. Tendon reflexes were active in both upper limbs and hyperreflexia in both lower limbs. Stability of the heel, knee, and tibia. Genetic testing showed that the number of repeats in the dentatorubral-pallidoluysian atrophy ATN1 gene was 18 and 62, and the (CAG)n repeat sequence in the ATN1 gene was abnormal, with a repeat number of 62, and the patient was a pathogenic variant. The patient was diagnosed with dentatorubral-pallidoluysian atrophy. Dentatorubral-pallidoluysian atrophy remains a progressive neurodegenerative disease with no effective treatment. At present, the proband is taking 5 mg of buspirone three times a day, which has been reported to improve the symptoms. The patient was followed up for 6 months after taking buspirone, and there was no significant improvement in the temporary symptoms. At present, there are few cases of dentatorubral-pallidoluysian atrophy, and the characteristics of nystagmus in this disease have not been proposed in the past. This case reported the unusual presentation of nystagmus. CONCLUSION: Dentatorubral-pallidoluygur atrophy is a rare neurodegenerative disease with autosomal dominant inheritance. To the best of our knowledge, our present case report is the first case report of dentatorubral-pallidoluygur atrophy with specific nystagmus. We describe the special eye shake and its positive signs to increase dentatorubral-pallidoluysian atrophy clinical positive signs.

Corticosteroid-dependent immune checkpoint inhibitor-induced enterocolitis treated with vedolizumab: a case report.

Background: Immune checkpoint inhibitors (ICIs) have greatly improved the survival in several cancers. Immune-related adverse events (irAEs) are common in patients on ICI therapy, as inhibition of cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death protein 1 (PD-1) leads to non-selective activation of the immune system. ICI-induced enterocolitis is highly prevalent and corticosteroid administration is the first-line treatment. Selective immunosuppressive therapy was employed for steroid-refractory patients. The monoclonal antibody vedolizumab exhibits gut-specific immunosuppressive effects by targeting the α4ß7 integrin. Case Description: We report a case of corticosteroid-dependent camrelizumab-induced enterocolitis in a 58-year-old man with hepatocellular carcinoma (HCC) who was treated with vedolizumab. The patient's diarrhea resolved following the administration of two doses of vedolizumab (300 mg), and he was able to stop using corticosteroids. He later underwent surgery and HCC treatment, including appropriate management of ICI-induced enterocolitis, and achieved a complete pathological response. Conclusions: This report illustrates the valuable role of vedolizumab in treating ICI-induced enterocolitis that is refractory to corticosteroid treatment.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC). AIM: To investigate the feasibility and efficacy of programmed cell death 1 (PD-1) inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC. METHODS: Eligible patients had LAPC, an Eastern cooperative oncology group performance status of 0 or 1, adequate organ and marrow functions, and no prior anticancer therapy. In the observation group, participants received intravenous sintilimab 200 mg once every 3 wk, and received concurrent chemoradiotherapy (concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-1 40 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression, death, or unacceptable toxicity). In the control group, participants only received concurrent chemoradiotherapy. From April 2020 to November 2021, 64 participants were finally enrolled with 34 in the observation group and 30 in the control group. RESULTS: Thirty-four patients completed the scheduled course of chemoradiotherapy, while 32 (94.1%) received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group. Thirty patients completed the scheduled course of chemoradiotherapy in the control group. Based on the Response Evaluation Criteria in Solid Tumors guidelines, the analysis of the observation group revealed that a partial response was observed in 11 patients (32.4%), stable disease was evident in 19 patients (55.9%), and 4 patients (11.8%) experienced progressive disease; a partial response was observed in 6 (20.0%) patients, stable disease in 18 (60%), and progressive disease in 6 (20%) in the control group. The major toxic effects were leukopenia and nausea. The incidence of severe adverse events (AEs) (grade 3 or 4) was 26.5% (9/34) in the observation group and 23.3% (7/30) in the control group. There were no treatment-related deaths. The observation group demonstrated a significantly longer median overall survival (22.1 mo compared to 15.8 mo) (P < 0.05) and progression-free survival (12.2 mo vs 10.1 mo) (P < 0.05) in comparison to the control group. The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group (P > 0.05). CONCLUSION: Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients, and warrants further investigation.

New species, new records and common species of Pluteussect.Celluloderma from northern China.

Wood-rotting fungi are organisms that can decompose wood substrates and extract nutrients from them to support their growth. They play a crucial role in the material cycle of forest ecosystems. The genus Pluteus plays a significant role in wood decomposition. In this study, the morphology and molecular systematics of the sect. Celluloderma of the genus Pluteus were carried out. Pluteusbrunneodiscus was identified as a new species, along with the discovery of two new records, P.cystidiosus and P.chrysophlebius, and a common species, P.romellii. Pluteusbrunneodiscus is characterized by the brown center of the pileus that transitions to white towards the margins, with the surface cracking to form irregular granules. It is typically found in Populus forests growing on decomposing twigs or wood chips. Line drawings, color photographs, and phylogenetic analyses of related species within the genus Pluteus accompany the descriptions of these four species. The analyses are based on ITS + TEF1-α sequence data. Finally, a key for the twenty species within the sect. Celluloderma of the genus Pluteus, which has been documented in China, is provided.

Identification and validation of mitophagy-related signatures as a novel prognostic model for colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. Mitophagy is associated with tumorigenesis and development of malignancy. However, the specific role of mitophagy has yet not been systematically explored in CRC. Methods: The RNA-sequencing dataset of CRC from The Cancer Genome Atlas (TCGA) and microarray data of gene expression profiles of CRC from Gene Expression Omnibus (GEO) were downloaded. Mitophagy-related gene sets were obtained from the Pathway Unification database. The package "limma" was used for differential gene expression analysis. Kaplan-Meier (KM) survival analyses were utilized to evaluate the prognostic value of the mitophagy regulators. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the infiltrating immune cells and the activity of immune response. The ConsensusClusterPlus algorithm was used to determine mitophagy-related subtypes. Principal component analysis (PCA) was used to create composite measurement of mitophagy scores. The R packages "survminer" and "ReGlot" were used to plot the nomogram and calibration curves. Results: Integrated analysis of the GEO and TCGA databases revealed some common differentially expressed genes (DEGs) in CRC. MFN2, UBB, PINK1, and PRKN were significantly downregulated in CRC samples as compared to normal samples, and other genes were significantly upregulated in CRC samples. KM survival analyses showed that high expression of ATG12 and MAP1LC3B predicted a poor prognosis, whereas high expression of TOMM22 and TOMM40 predicted a better prognosis. Mitophagy showed significant correlation with immune-related pathways in CRC samples. We identified 2 distinct CRC subtypes with different mitophagy accumulation, of which subtype B had better prognosis and immune activity. The mitophagy score may be employed as a new and efficient clinical predictor in conjunction with other clinical indicators to predict the prognosis of CRC patients. Conclusions: We systematically investigated the CRC heterogeneity with reference to mitophagy based on bioinformatics analyses, and the findings of this study might provide some guidance for future research into potential biomarkers for diagnosis and prognosis prediction of CRC patients.

Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

BACKGROUND: As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. METHODS: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. RESULTS: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12-74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92-1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. CONCLUSION: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

Anatomical studies and early results on endoscopic transoral medial pterygomandibular fold approach to salvage retropharyngeal lymphadenectomy in nasopharyngeal carcinoma.

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.

Human Adipose Tissue Lysate-Based Hydrogel for Lasting Immunomodulation to Effectively Improve Spinal Cord Injury Repair.

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.

Long non-coding RNA SNHG17 may function as a competitive endogenous RNA in diffuse large B-cell lymphoma progression by sponging miR-34a-5p.

We investigated the functional mechanism of long non-coding small nucleolar host gene 17 (SNHG17) in diffuse large B-cell lymphoma (DLBCL). lncRNAs related to the prognosis of patients with DLBCL were screened to analyze long non-coding small nucleolar host gene 17 (SNHG17) expression in DLBCL and normal tissues, and a nomogram established for predicting DLBCL prognosis. SNHG17 expression in B-cell lymphoma cells was detected using qPCR. The effects of SNHG17 with/without doxorubicin on the proliferation and apoptosis of DoHH2 and Daudi were detected. The effects of combined SNHG17 and doxorubicin were analyzed. The regulatory function of SNHG17 in DLBCL was investigated using a mouse tumor xenotransplantation model. RNA sequencing was used to analyze the signaling pathways involved in SNHG17 knockdown in B-cell lymphoma cell lines. The target relationships among SNHG17, microRNA, and downstream mRNA biomolecules were detected. A higher SNHG17 level predicted a lower survival rate. SNHG17 was highly expressed in DLBCL patient tissues and cell lines. We established a prognostic model containing SNHG17 expression, which could effectively predict the overall survival rate of DLBCL patients. SNHG17 knockdown inhibited the proliferation and induced the apoptosis of B-cell lymphoma cells, and the combination of SNHG17 and doxorubicin had a synergistic effect. SNHG17, miR-34a-5p, and ZESTE gene enhancer homolog 2 (EZH2) had common hypothetical binding sites, and the luciferase reporter assay verified that miR-34a-5p was the direct target of SNHG17, and EZH2 was the direct target of miR-34a-5p. The carcinogenic function of SNHG17 in the proliferation and apoptosis of DLBCL cells was partially reversed by a miR-34a-5p inhibitor. SNHG17 increases EZH2 levels by inhibiting miR-34a-5p. Our findings indicate SNHG17 as critical for promoting DLBCL progression by regulating the EZH2 signaling pathway and sponging miR-34a-5p. These findings provide a new prognostic marker and therapeutic target for the prognosis and treatment of DLBCL.

Long-term organic carbon preservation enhanced by iron and manganese.

The balance between degradation and preservation of sedimentary organic carbon (OC) is important for global carbon and oxygen cycles1. The relative importance of different mechanisms and environmental conditions contributing to marine sedimentary OC preservation, however, remains unclear2-8. Simple organic molecules can be geopolymerized into recalcitrant forms by means of the Maillard reaction5, although reaction kinetics at marine sedimentary temperatures are thought to be slow9,10. More recent work in terrestrial systems suggests that the reaction can be catalysed by manganese minerals11-13, but the potential for the promotion of geopolymerized OC formation at marine sedimentary temperatures is uncertain. Here we present incubation experiments and find that iron and manganese ions and minerals abiotically catalyse the Maillard reaction by up to two orders of magnitude at temperatures relevant to continental margins where most preservation occurs4. Furthermore, the chemical signature of the reaction products closely resembles dissolved and total OC found in continental margin sediments globally. With the aid of a pore-water model14, we estimate that iron- and manganese-catalysed transformation of simple organic molecules into complex macromolecules might generate on the order of approximately 4.1 Tg C yr-1 for preservation in marine sediments. In the context of perhaps only about 63 Tg C yr-1 variation in sedimentary organic preservation over the past 300 million years6, we propose that variable iron and manganese inputs to the ocean could exert a substantial but hitherto unexplored impact on global OC preservation over geological time.

Case report: A longitudinal study of an unusual rapidly progressive dementia case.

It is daunting to determine the etiology of rapidly progressive dementia (RPD), which includes metabolic, neoplastic, infectious, autoimmune, neurodegenerative and other conditions. Herein, we illustrate an unusual case of a patient primarily exhibiting RPD, overlapping sleep dysfunction, psychosis and abnormal movement, which was finally defined as anti-IgLON5 disease, a novel and rare autoimmune encephalopathy. Furthermore, we longitudinally described his cognitive and psychological performance in detail, and determined that early initiation of immunotherapy in this patient did not result in a good outcome. These data highlight anti-IgLON5 disease as a possible differential diagnosis in patients with RPD.

Robust Acute Pancreatitis Identification and Diagnosis: RAPIDx.

The occurrence of acute pancreatitis (AP) is increasing significantly worldwide. However, current diagnostic methods of AP do not provide a clear clinical stratification of severity, and the prediction of complications in AP is still limited. Here, we present a robust AP identification and diagnosis (RAPIDx) method by the proteomic fingerprinting of intact nanoscale extracellular vesicles (EVs) from clinical samples. By tracking analysis of circulating biological nanoparticles released by cells (i.e., EVs) via bottom-up proteomics, we obtain close phenotype connections between EVs, cell types, and multiple tissues based on their specific proteomes and identify the serum amyloid A (SAA) proteins on EVs as potential biomarkers that are differentially expressed from AP patients significantly. We accomplish the quantitative analysis of EVs fingerprints using MALDI-TOF MS and find the SAA proteins (SAA1-1, desR-SAA1-2, SAA2, SAA1-2) with areas under the curve (AUCs) from 0.92 to 0.97, which allows us to detect AP within 30 min. We further realize that SAA1-1 and SAA2, combined with two protein peaks (5290.19, 14032.33 m/z), can achieve an AUC of 0.83 for classifying the severity of AP. The RAPIDx platform will facilitate timely diagnosis and treatment of AP before severity development and persistent organ failure and promote precision diagnostics and the early diagnosis of pancreatic cancer.

A new species and new records species of Pluteus from Xinjiang Uygur Autonomous Region, China.

Xinjiang Uyghur Autonomous Region in China embraces a unique geographical and ecological environment, and the macrofungi represent a rich resource. However, few studies on the genus Pluteus have been reported from Xinjiang. In 2021, the macrofungal resources in Xinjiang were surveyed, and 10 specimens belonging to the genus Pluteus were collected. Based on the morphological study and molecular analysis, three species were recognized, P. aletaiensis, P. brunneidiscus, and P. hongoi. Pluteus aletaiensis is proposed as a new species. It is characterized by its bright yellow lamellae and stipe, brittle texture, subfusiform to vesicular pleurocystidia, with short pedicels to broadly lageniform to obtuse at apices, a hymeniderm pileipellis, containing dark brown intracellular pigment, and it grows on the ground. Pluteus brunneidiscus, a new record to China, is characterized by uneven, smooth, grayish brown to brown pileus, with an entire margin, and pointed or flatter apices intermediate cystidia, without apical hooks. Pluteus hongoi, a new record to Xinjiang Uyghur Autonomous Region, China, is characterized by the apical hook's structure (commonly bifid) of pleurocystidia. The nuclear internal transcribed spacer (nrITS) and translation elongation factor 1-alpha (TEF1-a) region were used for the molecular analysis. Phylogenetic trees were constructed using both the maximum likelihood analysis (ML) and Bayesian inference (BI). Detailed descriptions of the three species are presented herein. Finally, a key to the list of eight species of the genus Pluteus knew from Xinjiang is provided.

Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in adults. Tumour microenvironment is closely related to tumour prognosis and immune checkpoint blocking therapy (ICBT). This study aimed to investigate the immunological and prognostic characteristics of the tumour microenvironment (TME), as well as the regulatory mechanisms. Methods: Gene expression profiles and clinical data of patients with DLBCL were obtained from GEO database. ESTIMATE, CIBERSORT, and ssGSEA analyses were used to explore microenvironment characteristics and regulatory mechanism of the immune subtypes, which were identified by consistent clustering. The differences in enriched pathways were showed by GSEA. Hub genes associated with CD8+ T cells, which were identified by WCGNA, were exhibited biological functions through GO and KEGG. Immune-related gene scores (IRGSs) based on hub genes were used to evaluate the prediction of immune subtypes and ICBT, and retrospective analysis was used for validation. Finally, prognostic genes were screened to construct risk models. Results: Consensus clustering divided patients with DLBCL into two subtypes with significant heterogeneities in prognosis and immune microenvironment. Low immune infiltration was associated with poor prognosis. Subtype C1 with high immune infiltration was enriched in multiple immune pathways. We observed that two common mutated genes (B2M and EZH2) in DLBCL were closely related to MHC-I and microenvironment. Our further analysis manifested that MYD88L265P may be the main cause of TLR signalling pathway activation in subtype C1. Hub genes (SH2D1A, CD8A, GBP2, ITK, CD3D, RORA, IL1R2, CD28, CD247, CD3G, PRKCQ, CXCR6, and CD3E) in relation with CD8+ T cells were used to establish IRGS, which was proved an accurate predictor of immune subtypes, and patients in high-IRGS group were more likely to benefit from ICBT. Retrospective analysis showed that absolute lymphocyte count (ALC) was higher in the group that responded to the PD-1 inhibitor. Finally, the risk model was constructed based on two genes (CD3G and CD3D), and the low-risk group showed better prognosis. Conclusion: DLBCL immune classifications with highly heterogeneity are a powerful predictor of prognosis and ICBT. The IRGS is proved to be a reliable tool to distinguish immune subtypes as a substitute for gene expression profile.

Nickel-Catalyzed Three-Component Cross-Electrophile Coupling of 1,3-Dienes with Aldehydes and Aryl Bromides.

We herein report a Ni-catalyzed three-component cross-electrophile coupling of 1,3-dienes with aldehydes and aryl bromides using manganese metal as the reducing agent. This efficient protocol accomplishes dicarbofunctionalization of 1,3-dienes to synthesize diverse structural 1,4-disubstituted homoallylic alcohols by forming two new C-C bonds in one time. Mechanistic study suggests that an allyl-nickel(I) species is involved in the catalytic cycle.

BDNF expression in GISTs predicts poor prognosis when associated with PD-L1 positive tumor-infiltrating lymphocytes.

Substantial evidence indicates that brain-derived neurotrophic factor (BDNF) plays an important role in tumorigenesis, in addition to its primary role in neuronal activity. Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal neoplasms of the gastrointestinal tract, contain multiple types of tumor-infiltrating lymphocytes (TILs) that express relevant immune checkpoint proteins. However, no data have been reported on the role of BDNF in GISTs. This study aimed to investigate the expression pattern and prognostic value of BDNF in GIST patients with different degrees of risk, as well as the relationship between BDNF expression and immune checkpoints. Immunohistochemistry (IHC) demonstrated that higher BDNF expression was more likely to be present in high-risk patients and suggested a poor prognosis. A similar phenomenon was demonstrated in plasma. Even more interesting was that a positive correlation was present between BDNF and PD-L1+ expression on TILs. Moreover, high BDNF expression levels in combination with a high PD-L1+ TIL count predict extremely poor survival. The combination of BDNF expression and TIL PD-L1+ expression as a single biomarker was a powerful significant independent predictor of prognosis. Taken together, BDNF expression may serve as a significant prognostic factor, as the combination of BDNF expression and the PD-L1+ TIL subset led to superior prediction of GIST prognosis. Furthermore, our research coupled a neurotrophin with immunity, which provides novel evidence of neural and immune regulation in a clinical study of GIST.

Proteomic screening of potential N-glycoprotein biomarkers for colorectal cancer by TMT labeling combined with LC-MS/MS.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is part of the most widespread malignant tumors. At present, colonoscopy is a routine procedure in the diagnosis of CRC, but it is traumatic. Carcinoembryonic antigen, CA199, and CA242 are common serum markers for the diagnosis of CRC; however, they do not demonstrate satisfactory specificity and sensitivity for the diagnosis of CRC. Hence, Now it is necessary to screen many valuable serum biomarkers for CRC, proteomics methods have been used to investigate PTMs such as glycosylation of proteins with prominent roles in the occurrence and development of tumors. METHODS: This study screens altering glycosylated proteins of CRC tissues using LC-MS/MS quantitative glycoproteomics, and then these candidate biomarkers for CRC are further validated by serum glycoproteomics. RESULTS: The results of glycoproteomics in CRC tissues show that the abundance of 160 and 79 glycerogelatin proteins was obviously upregulated and downregulated compared with their adjacent tissues(P < 0.05). Bioinformatics analysis suggests that these molecules are mainly involved in many biological processes, including skeletal system development, collagen fibril organization, and receptor-mediated endocytosis. Results of serum glycoproteomics show that the changing trends of 2 protein glycosylation were consistent with MS results of CRC tissues, including ICAM1and APMAP. Areas under the ROC curve (AUC) results confirm that ICAM1and APMAP as early immune diagnosis markers of CRC has excellent sensitivity and specificity. CONCLUSION: The ICAM1 and APMAP may serve as a potential tumor marker for CRC.

IL-11 mediates the Radioresistance of Cervical Cancer Cells via the PI3K/Akt Signaling Pathway.

Cervical cancer is one of the most common malignant tumors in the female reproductive system. Radioresistance remains a significant factor that limits the efficacy of radiotherapy for cervical cancer. Interleukin-11 (IL-11) has been reported to be upregulated in various types of human cancer and correlate with clinical stage and poor survival. However, the exact effects and mechanisms of IL-11 in the radioresistance of cervical cancer have not yet been defined. In this research, TCGA databases revealed that IL-11 expression was upregulated in cervical cancer tissues and was associated with clinical stages and poor prognosis in cervical cancer patients. We discovered that IL-11 concentration was significantly upregulated in radioresistant cervical cancer cells. Knocking down IL-11 in Hela cells could reduce clonogenic survival rate, decrease cell viability, induce G2/M phase block, and facilitate cell apoptosis. In contrast, Exogeneous IL-11 in C33A cells could upregulate clonogenic survival rate, increase cell viability, curb G2/M phase block, and cell apoptosis. Mechanistic investigations showed that radioresistance conferred by IL-11 was attributed to the activation of the PI3K/Akt signaling pathway. Altogether, our results demonstrate that IL-11 might be involved in radioresistance, and IL-11 may be a potent radiosensitization target for cervical cancer therapy.