Oil-droplet anchors accelerate the gelation of regenerated silk fibroin-based emulsion gels.

The oil fraction will affect the aggregation behavior and structural strength of emulsion gels. In this study, the effect of the camellia oil (CO) fraction on the properties of emulsion gels stabilized by regenerated silk fibroin (RSF) was studied. The results showed that CO was essential for gel formation, with oil droplets incorporated into the RSF matrix as anchors to achieve rapid gelation of RSF. The gel hardness significantly increased from 20.03 to 53.35 g as the fraction of CO increased from 5 % to 25 %. The oxidation stability of the emulsion gels was also improved, and the peroxide value (POV) decreased from 2419.3 to 839.9 µmol/kg. As the oil fraction rose from 5 % to 25 %, the percentage of released free fatty acids decreased from 73.24 % to 59.49 % due to forming a more compact gel structure. In addition, the rheological results revealed that all emulsion gels had a shear-thinning behavior and good temperature stability in the range of 5 to 90 °C. This study provided a theoretical basis for preparing RSF-based emulsion gels, helps in the recycling of silk protein resources, and promotes the development of emulsion gel applications in the food industry.

The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased NF-κB signaling and significant upregulation of BIRC3, a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion: TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Fabrication, characterization, and oxidation resistance of gelatin/egg white protein cryogel-templated oleogels through apple polyphenol crosslinking.

Cryogel-templated oleogels (CTO) were fabricated via a facile polyphenol crosslinking strategy, where apple polyphenol was utilized to crosslink the gelatin/egg white protein conjugates without forming hydrogels. After freeze-drying, cryogel templates were obtained and used to construct CTO by oil absorption. Apple polyphenol crosslinking improved the emulsion-related properties with appearance changes on samples, and infrared spectroscopy further confirmed the interactions between proteins and apple polyphenol. The crosslinked cryogels presented porous microstructures (porosity of over 96 %), enhanced thermal/mechanical stabilities, and could absorb a high content of oil (14.41 g/g) with a considerable oil holding capacity (90.98 %). Apple polyphenol crosslinking also influenced the rheological performances of CTO, where the highly crosslinked samples owned the best thixotropic recovery of 85.88 %. Moreover, after the rapid oxidation of oleogels, the generation of oxidation products was effectively inhibited by crosslinking (POV: 0.48 nmol/g, and TBARS: 0.53 mg/L). The polyphenol crosslinking strategy successfully involved egg white protein and gelatin to fabricate CTO with desired physical/chemical properties. Apple polyphenol acted as both a crosslinker and an antioxidant, which provided a good reference for fabricating pure protein-based CTO.

Development and Application of IoT Monitoring Systems for Typical Large Amusement Facilities.

The advent of internet of things (IoT) technology has ushered in a new dawn for the digital realm, offering innovative avenues for real-time surveillance and assessment of the operational conditions of intricate mechanical systems. Nowadays, mechanical system monitoring technologies are extensively utilized in various sectors, such as rotating and reciprocating machinery, expansive bridges, and intricate aircraft. Nevertheless, in comparison to standard mechanical frameworks, large amusement facilities, which constitute the primary manned electromechanical installations in amusement parks and scenic locales, showcase a myriad of structural designs and multiple failure patterns. The predominant method for fault diagnosis still relies on offline manual evaluations and intermittent testing of vital elements. This practice heavily depends on the inspectors' expertise and proficiency for effective detection. Moreover, periodic inspections cannot provide immediate feedback on the safety status of crucial components, they lack preemptive warnings for potential malfunctions, and fail to elevate safety measures during equipment operation. Hence, developing an equipment monitoring system grounded in IoT technology and sensor networks is paramount, especially considering the structural nuances and risk profiles of large amusement facilities. This study aims to develop customized operational status monitoring sensors and an IoT platform for large roller coasters, encompassing the design and fabrication of sensors and IoT platforms and data acquisition and processing. The ultimate objective is to enable timely warnings when monitoring signals deviate from normal ranges or violate relevant standards, thereby facilitating the prompt identification of potential safety hazards and equipment faults.

Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial.

BACKGROUND: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. METHODS: This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600). FINDINGS: Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed. INTERPRETATION: This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients. FUNDING: Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Clinical characteristics and survival of esophageal cancer patients: annual report of the surgical treatment in Shanghai Chest Hospital, 2017.

Background: Esophageal cancer remains a significant burden of lethal cancers worldwide, particularly in China. This is an annual report of Shanghai Chest Hospital (SCH) on surgical treatment for esophageal cancer patients in 2017. Methods: All patients who received surgical treatment for esophageal cancer at SCH in 2017 were given a detailed summary of clinical information based on the database of SCH. Kaplan-Meier method was used to present their survival, subgroup analyses, and multivariate Cox regression analysis were used to estimate the potential risk factors for prognosis. Results: In 2017, a total of 663 patients received surgical treatment (628 esophagectomies and 35 endoscopic resections) for esophageal cancer at SCH. Of the patients who underwent esophagectomy, 292 patients received perioperative treatment, majority of which was postoperative treatment (47.9%). Only 69 (10.4%) patients received preoperative treatment. Minimally invasive techniques were used in 444 (70.7%) patients and robotic-assisted esophagectomies were used in 130 (20.7%) patients. Complete resection (R0) was achieved in 90.3% of esophagectomy patients. The 5-year overall survival (OS) rate after esophagectomy was 52.5%. Conclusions: The 5-year OS of patients with esophageal cancer can reach 52.5% after surgical treatment in 2017 at SCH. The exact beneficiaries of neoadjuvant therapy are still unclear in the 2017 cohort.

Deciphering the molecular mechanism of long non-coding RNA HIF1A-AS1 regulating pancreatic cancer cells.

Background: HIF1A-AS1, an antisense transcript of HIF1α gene, is a 652-bp LncRNA that is globally expressed in multiple tissues of animals. Recent evidence indicated that HIF1A-AS1 was involved in tumorigenesis of several types of cancer. However, the role of lncRNA in PC has not been reported, and the molecular mechanism remains elusive. Results: In order to investigate the role of HIF1A-AS1 in PC, it was overexpressed in some PC cell lines (PANC-1, PATU8988 and SW1990), and a series of experiments including cell viability detection, flow cytometry, transwell migration, clone formation and wound healing were performed. Functionally, the results indicated that overexpression of HIF1A-AS1 could greatly inhibit proliferation and migration and promote apoptosis of PC cells. Moreover, the isobaric tags for relative and absolute quantification (iTRAQ) quantitative proteomics analysis was implemented to explore the underlying mechanism and the results indicated that OE of HIF1A-AS1 globally affected the expression levels of multiple proteins associated with metabolism of cancer. At last, the network analysis revealed that most of these differentially expressed proteins (DEPs) were integrated and severed essential roles in regulatory function. In view of this, we guessed HIF1A-AS1 overexpression induced the dysfunction of metabolism and disordered proteins' translation, which may account for its excellent tumour suppressor effect. Conclusions: HIF1A-AS1 altered the cell function of PC cell lines via affecting the expression of numerous proteins. In summary, HIF1A-AS1 may exhibit a potential therapeutic effect on PC, and our study provided useful information in this filed.

Fabrication, characterization, and in vitro digestion of gelatin/gluten oleogels from thermally crosslinked electrospun short fiber aerogel templates.

In this work, the electrospun short fiber-based oleogels (ESFO) were formed by thermal crosslinking. Gelatin and gluten nanofibers were obtained via electrospinning, then homogenized and transformed into short fiber dispersions. Through freeze-drying, electrospun short fiber-based aerogel (ESF-A) templates were obtained for oil adsorption. All ESF-A exhibited the micromorphology of loose fibrous pore structure and prominent changes of characteristic peaks in the thermal and infrared analyses. Moreover, the highly crosslinked templates owned excellent hydrophobicity and mechanical performances (elastic modulus: 0.25 kPa, yield strength: 14.56 kPa, compressive strength: 52.54 kPa, and the final compression recovery: 91.27%). Meanwhile, the oil adsorption/oil holding capacity could reach 76.56 g/g and 80.04%, respectively. Through thermal crosslinking, ESF-O presented good and controllable rheological/in vitro digestion properties, which were further confirmed by PCA analysis. According to different application conditions, ESF-O properties could be adjusted by different degrees of fiber addition or thermal crosslinking.

O1/W/O2 double emulsion gels based on nanoemulsions and Pickering particles for co-encapsulating quercetin and cyanidin: A functional fat substitute.

An O1/W/O2 double emulsion gel, as a functional fat substitute and based on nanoemulsions and hydrophobic Pickering particles, is prepared by two-step emulsification to co-encapsulate hydrophilic cyanidin and hydrophobic quercetin. Nanoemulsions loading quercetin are fabricated by Tween-80 and combining high-speed and high-pressure emulsification. Phytosterol nanoparticles stabilize the W-O2 interface of the secondary emulsion to load cyanidin in the W phase. The concentration of Tween-80 is optimized as 0.3% by the droplet size and viscosity of nanoemulsions. The structural stability of double emulsion gels will be weakened along with the increase of nanoemulsions, showing lower modulus and encapsulation efficiency (EE) and bigger droplets. In double emulsion gels, the EE of quercetin and cyanidin reaches 93% and 85.6%, respectively. Analysis of molecular interaction indicates that Tween-80 would decrease the in-situ hydrophobicity of phytosterol nanoparticles by hydrogen bonding adsorption, thereby weakening the emulsification. The pH-chromic 3D printing of double emulsion gels is designed according to the pH sensitivity of cyanidin. Texture profile analysis is performed to test the textural properties of 3D-printed objects. The simulated digestion is conducted on double emulsion gels. The double emulsion gel with fewer nanoemulsions is beneficial for protecting quercetin and improving the delivery due to the higher structural stability, while that with more nanoemulsions is conducive to the digestion of cyanidin and camellia oil due to weakened semi-solid properties. This double emulsion gel further simulates fat tissues by co-encapsulating hydrophilic and hydrophobic substances, promoting the application of fat substitutes in the food industry.

Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma.

BACKGROUND: Current approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors. OBJECTIVE: To validate a noninvasive urine-based RNA test for accurate UTUC diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Urine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ2, and Student t test were used. RESULTS AND LIMITATIONS: The eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population. CONCLUSIONS: Our results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery. PATIENT SUMMARY: In this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.

Development and validation of a 23-gene expression signature for molecular subtyping of medulloblastoma in a long-term Chinese cohort.

PURPOSE: Medulloblastoma is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. Recent transcriptional studies have shown that medulloblastomas comprise at least four molecular subgroups, each with distinct demographics, genetics, and clinical outcomes. Medulloblastoma subtyping has become critical for subgroup-specific therapies. The use of gene expression assays to determine the molecular subgroup of clinical specimens is a long-awaited application of molecular biology for this pediatric cancer. METHODS: In the current study, we established a medulloblastoma transcriptome database of 460 samples retrieved from three published datasets (GSE21140, GSE37382, and GSE37418). With this database, we identified a 23-gene signature that is significantly associated with the medulloblastoma subgroups and achieved a classification accuracy of 95.2%. RESULTS: The 23-gene signature was further validated in a long-term cohort of 142 Chinese medulloblastoma patients. The 23-gene signature classified 21 patients as WNT (15%), 41 as SHH (29%), 16 as Group 3 (11%), and 64 as Group 4 (45%). For patients of WNT, SHH, Group 3, and Group 4, 5-year overall-survival rate reached 80%, 62%, 27%, and 47%, respectively (p < 0.0001), meanwhile 5-year progression-free survival reached 80%, 52%, 27%, and 45%, respectively (p < 0.0001). Besides, SHH/TP53-mutant tumors were associated with worse prognosis compared with SHH/TP53 wild-type tumors and other subgroups. We demonstrated that subgroup assignments by the 23-gene signature and Northcott's NanoString assay were highly comparable with a concordance rate of 96.4%. CONCLUSIONS: In conclusion, we present a novel gene signature that is capable of accurately and reliably assigning FFPE medulloblastoma samples to their molecular subgroup, which may serve as an auxiliary tool for medulloblastoma subtyping in the clinic. Future incorporation of this gene signature into prospective clinical trials is warranted to further evaluate its clinical.

Development of Multifunctional Detection Robot for Roller Coaster Track.

Recent advances in roller coasters accelerate the creation of complex tracks to provide stimulation and excitement for humans. As the main load-bearing component, tracks are prone to damage such as loose connecting bolts, paint peeling, corroded sleeper welds, corroded butt welds, reduced track wall thickness and surface cracks under complex environments and long-term alternating loads. However, inspection of the roller coaster tracks, especially the high-altitude rolling tracks, is a crucial problem that traditional manual detection methods have difficulty solving. In addition, traditional inspection is labor-intensive, time-consuming, and provides only discrete information. Here, a concept of the multifunctional detection robot with a mechanical structure, electrical control system, camera, electromagnetic ultrasonic probes and an array of eddy current probes for detecting large roller coaster tracks is reported. By optimizing the design layout, integrating multiple systems and completing machine testing, the multifunctional roller coaster track detection robot exhibits outstanding performance in track appearance, thickness and crack detection. This study provides great potential for intelligent detection in amusement equipment, railcar, train and so on.

GANT-61 induces cell cycle resting and autophagy by down-regulating RNAP III signal pathway and tRNA-Gly-CCC synthesis to combate chondrosarcoma.

Chondrosarcoma is ineffective for conventional radiotherapy and chemotherapy with a poor prognosis. Hedgehog (Hh) signal pathway plays a crucial role in tumor growth and progression, which is constitutive activated in chondrosarcoma. GLI transcription factors as targets for new drugs or interference technology for the treatment of chondrosarcoma are of great significance. In this study, we indicated that the Hedgehog-GLI1 signal pathway is activated in chondrosarcoma, which further enhances the RNAP III signal pathway to mediate endogenous tRNA fragments synthesis. Downstream oncology functions of endogenous tRNA fragments, such as "cell cycle" and "death receptor binding", are involved in malignant chondrosarcoma. The GANT-61, as an inhibitor of GLI1, could inhibit chondrosarcoma tumor growth effectively by inhibiting the RNAP III signal pathway and tRNA-Gly-CCC synthesis in vivo. Induced G2/M cell cycle resting, apoptosis, and autophagy were the main mechanisms for the inhibitory effect of GANT-61 on chondrosarcoma, which correspond with the above-described downstream oncology functions of endogenous tRNA fragments. We also identified the molecular mechanism by which GANT-61-induced autophagy is involved in ULK1 expression and MAPK signaling pathway. Thus, GANT-61 will be an ideal and promising strategy for combating chondrosarcoma.

Identifying the O3 chemical regime inferred from the weekly pattern of atmospheric O3, CO, NOx, and PM10: Five-year observations at a center urban site in Shanghai, China.

Ozone pollution is still considered a severe environmental problem in China despite the fact that great efforts have been devoted to monitoring and alleviating its impact by the Chinese government including the establishment of numerous observational networks. One of the issues most relevant to the design of emission reduction policies is to distinguish the O3 chemical regime. Here a method of quantifying the fraction of the radical loss versus NOx chemistry was applied to identify the O3 chemical regime inferred from the weekly pattern of atmospheric O3, CO, NOx, and PM10, which were monitored by Ministry of Ecology and Environment of China (MEEC). During spring and autumn, O3 and the total odd oxygen (Ox, Ox = O3 + NO2) weekend afternoon concentrations are both higher than the weekday values during 2015-2019 except in 2016, while CO and NOx weekend morning concentrations were generally both smaller than weekday values except 2017. Results from the calculated values of fraction of the radical loss by NOx chemistry relative to total radical loss (Ln/Q) suggested a volatile organic compound (VOC)-limited regime at this site in the spring of 2015-2019, as expected from the decreasing trend in NOx concentration and essentially constant CO after 2017. With respect to autumn, a shift from a transition regime during 2015-2017 to a VOC-limited regime in 2018 was found, which rapidly took place to a NOx-limited regime in 2019. No significant differences were detected in the Ln/Q values under different assumptions on photolysis frequencies both in spring and autumn mostly from 2015 to 2019, giving the same conclusion of determining the O3 sensitivity regime. This study develops a new method in determining the O3 sensitivity regime in the typical season in China and provides insight into efficient O3 control strategies in different seasons.

Aggressive systemic mastocytosis of colon and lymph node: A case report.

RATIONALE: Mastocytosis is a group of rare neoplastic diseases characterized by monoclonal proliferation of mast cells in the skin or other tissues and organs, including cutaneous mastocytosis and systemic mastocytosis (SM). Mastocytosis can also occur in the gastrointestinal tract, mostly manifested as increased mast cells dispersed in various layers of the intestinal wall; a few may present as polypoid nodules, but rarely as soft tissue mass formation. Pulmonary fungal infections mostly occur in patients with low immune function and have not been reported in the literature as the initial manifestation in patients with mastocytosis. In this case report, we present the enhanced computed tomography (CT), fluorodeoxyglucose (FDG) positron emission tomography/CT, and colonoscopy findings of a pathologically confirmed patient with aggressive SM of the colon and lymph nodes and extensive fungal infection of both lungs. PATIENT CONCERNS: A 55-year-old female patient visited our hospital because of repeated cough for more than half a month. Laboratory tests revealed a significantly high CA125 serum level. Chest CT showed multiple plaques and patchy high-density shadows in both lungs, and a small amount of ascites was observed in the lower-level image. Abdominal CT revealed a soft tissue mass with an ill-defined boundary in the lower ascending colon. Whole-body positron emission tomography/CT images showed multiple nodular and patchy density-increasing lesions with significantly increased FDG uptake in both lungs. The wall of the ascending colon in the lower segment was significantly thickened with soft tissue mass formation, and retroperitoneal lymph node enlargement was accompanied by increased uptake of FDG. Colonoscopy revealed a soft tissue mass at the base of the cecum. DIAGNOSIS: Colonoscopic biopsy was performed and the specimen was diagnosed with mastocytosis. At the same time, a puncture biopsy was also performed on the patient's lung lesions, and pulmonary cryptococcosis was considered a pathological diagnosis. INTERVENTIONS: The patient was in remission after repeated treatment with imatinib and prednisone for 8 months. OUTCOMES: In the ninth month, the patient suddenly died of a cerebral hemorrhage. LESSONS: Gastrointestinal involvement due to aggressive SM presents with nonspecific symptoms and different endoscopic and radiologic findings. This is the first report of a single patient with colon SM, retroperitoneal lymph node SM, and extensive fungal infection in both lungs.

Salvage Esophagectomy After Definitive Chemoradiotherapy for Squamous Cell Esophageal Cancer: A Propensity Score Matching Study in a High-Volume Center.

BACKGROUND: Salvage esophagectomy, indicated for some patients with locally recurrent/persistent disease after definitive chemoradiotherapy (dCRT), reportedly has high postoperative complications. This study aims to compare the safety and efficacy of dCRT followed by salvage esophagectomy (DCRE) with planned esophagectomy after neoadjuvant chemoradiotherapy (NCRE) in esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed all locally advanced ESCC patients treated with DCRE or NCRE at Shanghai Chest Hospital from 2018 to 2021. Propensity score matching (PSM) was used to balance baseline differences. DCRE is defined as esophagectomy for recurrent/persistent disease after dCRT. RESULTS: A total of 302 patients (41 for DCRE and 261 for NCRE) were included. The median interval of chemoradiotherapy-to-surgery was 47d in NCRE, 43d and 440d in DCRE of persistent disease (n = 24) and recurrence (n = 17), respectively. DCRE was observed with advanced ypT stage (63% vs 38%), poorer differentiation (32% vs 15%) and more lymphovascular invasion (29% vs 11%) compared with NCRE (all p < 0.05). The above factors were comparable between the two groups after PSM (all p > 0.05). There were no significant differences before and after PSM in postoperative complications over Clavien-Dindo grade III (e.g., respiratory failure and anastomotic leak), 30/90-day postoperative mortality, and survival. CONCLUSION: Through a standardized surgical procedure in a high-volume center, DCRE exhibited comparable postoperative complications and prognosis with NCRE.

PES1 reduces CD8+ T cell infiltration and immunotherapy sensitivity via interrupting ILF3-IL15 complex in esophageal squamous cell carcinoma.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has brought survival benefits to patients with specific cancer types, most of cancer patients remain refractory to the ICB therapy, which is largely attributed to the immunosuppressive tumor microenvironment. Thereby, it is urgent to profile key molecules and signal pathways responsible for modification of tumor microenvironment. METHODS: Multiple databases of esophageal squamous cell carcinoma (ESCC) were integratively analyzed to screen candidate genes responsible for infiltration of CD8+ T cells. Expression of pescadillo ribosomal biogenesis factor 1 (PES1) in clinical ESCC samples was examined by qRT-PCR, western blotting, and immunohistochemistry. The mechanisms of PES1 were investigated via RNA sequencing and mass spectrometry followed by immunoprecipitation and proximity ligation assay. The clinical and therapeutic significance of PES1 in ESCC was comprehensively investigated using ESCC cells and mouse model. RESULTS: PES1 was significantly upregulated and correlated with poor prognosis in ESCC patients. PES1 knockdown decreased ESCC cell growth in vitro and in vivo and enhanced the efficacy of ICB therapy in mouse model, which was established through subcutaneous inoculation with ESCC cells. Analyses on RNA sequencing and mass spectrometry suggested that PES1 expression was negatively correlated with IL15 and ILF3 was one of the PES1-associated proteins. It has been known that ILF3 interacts with and stabilizes IL15 mRNA to increase IL15 protein level. Our data further indicated that PES1 interfered with the interaction between ILF3 and IL15 mRNA and impaired ILF3-mediated stabilization of IL15 mRNA, which eventually reduced the protein level of IL15. Interestingly, the inhibitory effect of ICB therapy boosted by PES1 knockdown dramatically antagonized by knockdown of IL15, which suppressed the tumor-infiltrated CD8+ T cells in ESCC. Finally, we confirmed the relationships among PES1, IL15, and CD8+ T cell infiltration in 10 locally advanced ESCC patients receiving ICB neoadjuvant therapy and demonstrated that ICB therapy would be more effective in those with low expression of PES1. CONCLUSIONS: Altogether, our findings herein provided novel insights on biological function and clinical significance of PES1 and suggested that high expression of PES1 could suppress ILF3-IL15 axis-mediated immunosurveillance and promote resistance to ICB through restraining tumor-infiltrated CD8+ T cells.

Abnormal signal pathways and tumor heterogeneity in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed. METHODS: We analyzed integrated single-cell transcriptomes, bulk RNA-seq, and microarray data from Gene Expression Omnibus (GEO) datasets. We also used Weighted Gene Co-expression Network Analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), along with Simple ClinVar and Enrichr web servers. RESULTS: The findings of integrated single-cell analysis showed that OS arises from imperfect osteogenesis during development. Novel abnormalities comprised deficient TGFß and P53 signal pathways, and cell cycle pathway activation, and a potentially new driver mutation in the interferon induced transmembrane protein 5 (IFITM5) that might function as a pathogenic factor in OS. Osteosarcoma is characterized by oncocyte heterogeneity, especially in immunogenic and adipocyte-like subtypes that respectively promote and hamper OS treatment. Etoposide is a promising chemotherapeutic that provides palliation by affecting the subtype of OS and correcting the abnormal pathways. CONCLUSION: Various abnormal signal pathways play indispensable roles in OS development. We explored the heterogeneity and underlying mechanisms of OS and generated findings that will assist with OS assessment and selecting optimal therapies.

Effect of the timing of iliac vein stent implantation on catheter-directed thrombolysis in acute lower extremity deep venous thrombosis patients with severe iliac vein stenosis: a retrospective study.

OBJECTIVE: To investigate the effect of the timing of iliac vein stent implantation on catheter-directed thrombolysis (CDT) in acute lower extremity deep venous thrombosis (DVT) patients with severe iliac vein stenosis. METHODS: The clinical data of 66 patients with acute lower extremity DVT complicated with severe iliac vein stenosis from May 2017 to May 2020 were retrospectively analyzed. Patients were divided into two groups by timing of iliac vein stent implantation: group A (iliac vein stent implantation before CDT treatment) for 34 and group B (iliac vein stent implantation after CDT treatment) for 32. The detumescence rate of affected limb, the thrombus clearance rate, the thrombolytic efficiency, the complication rate, the hospitalization cost, the stent patency rate within 1 year, and the scores (venous clinical severity score, Villalta, and chronic venous insufficiency questionnaire (CIVIQ) score) at 1 year postoperatively were compared between the two groups. RESULTS: The thrombolytic efficiency of group A was higher than that of group B, while the incidence of complications and hospitalization expenses in group A were lower than those in group B. There was no statistical significance in the detumescence rate of affected limb, the thrombus clearance rate, the stent patency rate within 1 year, and the scores (VCSS, Villalta, and CIVIQ score) at 1 year postoperatively between the two groups. CONCLUSIONS: For acute lower extremity DVT patients with severe iliac vein stenosis, iliac vein stent implantation before CDT treatment can improve the thrombolytic efficiency, and reduce the incidence of complications and hospitalization costs.