Comparative efficacy and safety between endoscopic submucosal dissection, surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) and surgical resection are the standard of care for cT1N0M0 esophageal cancer (EC), whereas definitive chemoradiotherapy (d-CRT) is a treatment option. Nevertheless, the comparative efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC remain unclear. AIM: To compare the efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC. METHODS: We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th, 2022. We analyzed demographic, medical recorded, histopathologic characteristics, imaging and endoscopic, and follow-up data. The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments. Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors. RESULTS: We retrospectively analyzed patients who underwent ESD (n = 99) or surgery (n = 220) or d-CRT (n = 16) at the Sun Yat-sen University Cancer Center from 2017 to 2019. The median follow-up time for the ESD group, the surgery group, and the d-CRT group was 42.0 mo (95%CI: 35.0-60.2), 45.0 mo (95%CI: 34.0-61.75) and 32.5 mo (95%CI: 28.3-40.0), respectively. After adjusting for background factors using IPTW, the highest 3-year overall survival (OS) rate and 3-year recurrence-free survival (RFS) rate were observed in the ESD group (3-year OS: 99.7% and 94.7% and 79.1%; and 3-year RFS: 98.3%, 87.4% and 79.1%, in the ESD, surgical, and d-CRT groups, respectively). There was no difference of severe complications occurring between the three groups (P ≥ 0.05). Multivariate analysis showed that treatment method, histology and depth of infiltration were independently associated with OS and RFS. CONCLUSION: For cT1N0M0 EC, ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery, with a similar rate of severe complications occurring.

Effects of lakeshore landcover types and environmental factors on microplastic distribution in lakes on the Inner Mongolia Plateau, China.

Microplastic pollution in freshwater environments has received increasing attention. However, limited research on the occurrence and distribution of microplastics in plateau lakes. This study investigated the microplastic characteristics and influencing factors in lakes with different land cover types on the Inner Mongolia Plateau. Results showed that microplastic abundance ranged from 0.5 to 12.6 items/L in water and 50-325 items/kg in sediments. Microplastics in water were predominantly polypropylene (50.5%), fragments (40.5%), and 50-200 µm (66.7%). High-density (27.9%), fibrous (69.3%), and large-sized microplastics (47.7%) were retained primarily in lake sediments. The highest microplastic abundance in water was found in cropland lakes and grassland lakes, while that in sediments was in descending order of desert lakes > cropland lakes > grassland lakes > forest-grassland lakes. Differences among lake types suggest that agriculture, tourism, and atmospheric transport may be critical microplastic sources. Microplastic distribution was positively correlated with farmland and artificial surface coverage, showing that land cover types related to human activities could exacerbate microplastic pollution in lakes. Redundancy analysis showed that ammonia nitrogen and pH were the key physicochemical factors affecting microplastic distribution in lakes, indicating the potential sources of microplastics in lakes and the uniqueness of microplastic occurrence characteristics in desert saline-alkaline lakes, respectively.

Targeted drug delivery systems for matrix metalloproteinase-responsive anoparticles in tumor cells: A review.

Nanodrug delivery systems based on tumor microenvironment responses have shown excellent performance in tumor-targeted therapy, given their unique targeting and drug-release characteristics. Matrix metalloproteinases (MMPs) have been widely explored owing to their high specificity and expression in various tumor microenvironments. The design of an enzyme-sensitive nanodelivery system using MMPs as targeted receptors could markedly improve the performance of drug targeting. The current review focuses on the development and application of MMP-responsive drug carriers, and summarizes the classification of single- and multi-target nanocarriers based on their MMP responsiveness. The potential applications and challenges of this nanodrug delivery system are discussed to provide a reference for designing high-performance nanodrug delivery systems.

Synergistic effects of multidrug/material combination deliver system for anti-mutidrug-resistant tumor.

Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.

A novel complementary pathway of cordycepin biosynthesis in Cordyceps militaris.

We determined whether there exists a complementary pathway of cordycepin biosynthesis in wild-type Cordyceps militaris, high-cordycepin-producing strain C. militaris GYS60, and low-cordycepin-producing strain C. militaris GYS80. Differentially expressed genes were identified from the transcriptomes of the three strains. Compared with C. militaris, in GYS60 and GYS80, we identified 145 and 470 upregulated and 96 and 594 downregulated genes. Compared with GYS80, in GYS60, we identified 306 upregulated and 207 downregulated genes. Gene Ontology analysis revealed that upregulated genes were mostly involved in detoxification, antioxidant, and molecular transducer in GYS60. By Clusters of Orthologous Groups of Proteins and Kyoto Encyclopedia of Genes and Genomes analyses, eight genes were significantly upregulated: five genes related to purine metabolism, one to ATP production, one to secondary metabolite transport, and one to RNA degradation. In GYS60, cordycepin was significantly increased by upregulation of ATP production, which promoted 3',5'-cyclic AMP production. Cyclic AMP accelerated 3'-AMP accumulation, and cordycepin continued to be synthesized and exported. We verified the novel complementary pathway by adding the precursor adenosine and analyzing the expression of four key genes involved in the main pathway of cordycepin biosynthesis. Adenosine addition increased cordycepin production by 51.2% and 10.1%, respectively, in C. militaris and GYS60. Four genes in the main pathway in GYS60 were not upregulated.

Next-Generation Sequencing Analysis of 3 Uterine Adenosarcomas with Heterogeneously Differentiated Genomic Mutations.

Uterine adenosarcoma (UA) is an uncommon mixed tumor containing a benign to at most mildly atypical epithelial component and a sarcoma-like stroma, usually a low-grade, stromal component, with rare heterogeneous elements. Currently, tumor etiology is largely unknown. To better understand the gene mutations in UA, next-generation sequencing (NGS) technology analysis was performed. This study showed that two low-grade UAs with heterologous components had ATRX gene frameshift mutation, and one patient had a MED12 missense mutation. Copy number amplification genes were mainly observed on chromosome 12q13-15. In this study, PIK3/AKT/PTEN pathway mutations were found to be common in adenosarcoma. In addition, a rare BCORL1-PRR14L fusion mutation was also identified. These findings provide a basis for future research into these molecular changes in tumorigenesis and targeted therapy.

The oncogenic miR-429 promotes triple-negative breast cancer progression by degrading DLC1.

Lines of evidence have demonstrated that the oncogenic miRNAs are pivotal to the progression of breast cancer. In this study, we investigated the biological traits of microRNA-429 (miR-429) in triple-negative breast cancer (TNBC) and the underlying molecular mechanism. We found that miR-429 was notably overexpressed in TNBC, and promoted TNBC cell proliferation, migration, and invasion by degrading the tumor suppressor DLC1. In conclusion, our findings reveal the mechanism of tumorigenic miR-429 in TNBC, which paves the way for target therapies translation in clinical settings.

Influence mechanisms of different stalks on iron species type of magnetic biochar prepared from Fe2O3.

The current selection of biomass feedstock for magnetic biochar (MBC) catalysts is highly blind. Consequently, this study delves into understanding how the types of biomass influence the iron species present in MBC catalysts. The process involved the creation of MBC through simulated impregnation-pyrolysis, utilizing six types of stalks and Fe2O3. The type of iron species significantly impacted magnetic properties and likely influenced catalytic properties of MBC. MBC's iron species type was shaped by the reduction effects of the diverse stalks on Fe2O3. During the pyrolysis, discrepancies were observed in the release of reducing gases and direct reduction for the different stalks. These differences in reduction behavior directly accounted for the distinct reduction effects. To delve deeper, the reduction behavior and effect of the main components of the stalk (hemicellulose, cellulose, and lignin) on Fe2O3 were analyzed, highlighting lignin as the most effective. Nonetheless, the absolute values of Pearson's r between lignin content in the stalk and reduction behavior/effect ranged only from 0.078 to 0.421. In contrast, the values for K, Ca, and Si content in the stalks and their influence on reduction behavior and MBC's reduction/metallization degree ranged from 0.410 to 0.910. The catalytic impacts of K and Ca were confirmed through their incorporation into cotton and reed stalks. The disparities in K, Ca, and Si content among the six stalks appeared to be the primary driver behind the diverse iron species in MBC. This work provides a scientific basis for the rational selection of biomass feedstock for MBC catalysts.

Study of Salidroside and Its Inflammation Targeting Emulsion Gel for Wound Repair.

Salidroside has been widely used in anti-tumor, cardiovascular, and cerebrovascular protection. However, there are few reports of its use for wound repair. Herein, salidroside inflammation-targeted emulsion gel and non-targeted emulsion gel were developed for wound repair. The inflammation-targeted emulsion gels showed an overall trend of better transdermal penetration and lower potential than non-targeted emulsion gels (-58.7 mV and -1.6 mV, respectively). The apparent improvement of the trauma surface was significant in each administration group. There was a significant difference in the rate of wound healing of the rats between each administration group and the model group at days 7 and 14. Pathological tissue sections showed that inflammatory cells in the epidermis, dermis, and basal layer were significantly reduced, and the granulation tissue was proliferated in the inflammation-targeted emulsion gel group and the non-targeted emulsion gel group. Regarding the expressions of EGF and bFGF, the expressions of bFGF and EGF in the tissues of the inflammation-targeted group at days 7, 14, or 21 were significantly higher than that of the non-targeted emulsion gel group and the model group, both of which were statistically significant compared with the model group (p < 0.05). These results demonstrated that salidroside has the potential as an alternative drug for wound repair.

Klebsiella pneumoniae outer membrane vesicles induce strong IL-8 expression via NF-κB activation in normal pulmonary bronchial cells.

BACKGROUND: Outer membrane vesicles (OMVs) derived from bacteria are known to play a crucial role in the interactions between bacteria and their environment, as well as bacteria-bacteria and bacteria-host interactions.Specifically, OMVs derived from Klebsiella pneumoniae have been implicated in contributing to the pathogenesis of this bacterium.Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a global pathogen of great concern due to its heightened virulence compared to classical K. pneumoniae (cKp), and its ability to cause community-acquired infections, even in healthy individuals.The objective of this study was to investigate potential differences between hvKp-derived OMVs and cKp-derived OMVs in their interactions with microorganisms and host cells. METHODS: Four strains of K. pneumoniae were used to produce OMVs: hvKp strain NTUH-K2044 (K1, ST23), hvKp clinical strain AP8555, and two cKP clinical strains C19 and C250. To examine the morphology and size of the bacterial OMVs, transmission electron microscopy (TEM) was utilized. Additionally, dynamic light scattering (DLS) was used to analyze the size characterization of the OMVs.The normal pulmonary bronchial cell line HBE was exposed to OMVs derived from hvKp and cKP. Interleukin 8 (IL-8) messenger RNA (mRNA) expression was assessed using reverse transcription-polymerase chain reaction (RT-PCR), while IL-8 secretion was analyzed using enzyme-linked immunosorbent assay (ELISA).Furthermore, the activation of nuclear factor kappa B (NF-κB) was evaluated using both Western blotting and confocal microscopy. RESULTS: After purification, OMVs appeared as electron-dense particles with a uniform spherical morphology when observed through TEM.DLS analysis indicated that hvKp-derived OMVs from K2044 and AP8555 measured an average size of 116.87 ± 4.95 nm and 96.23 ± 2.16 nm, respectively, while cKP-derived OMVs from C19 and C250 measured an average size of 297.67 ± 26.3 nm and 325 ± 6.06 nm, respectively. The average diameter of hvKp-derived OMVs was smaller than that of cKP-derived OMVs.A total vesicular protein amount of 47.35 mg, 41.90 mg, 16.44 mg, and 12.65 mg was generated by hvKp-K2044, hvKp-AP8555, cKP-C19, and cKP-C250, respectively, obtained from 750 mL of culture supernatant. Both hvKp-derived OMVs and cKP-derived OMVs induced similar expression levels of IL-8 mRNA and protein. However, IL-8 expression was reduced when cells were exposed to BAY11-7028, an inhibitor of the NF-κB pathway.Western blotting and confocal microscopy revealed increased phosphorylation of p65 in cells exposed to OMVs. CONCLUSIONS: Klebsiella pneumoniae produces outer membrane vesicles (OMVs) that play a key role in microorganism-host interactions. HvKp, a hypervirulent strain of K. pneumoniae, generates more OMVs than cKP.The average size of OMVs derived from hvKp is smaller than that of cKP-derived OMVs.Despite these differences, both hvKp-derived and cKP-derived OMVs induce a similar level of expression of IL-8 mRNA and protein.OMVs secreted by K. pneumoniae stimulate the secretion of interleukin 8 by activating the nuclear factor NF-κB.

TBX5 Variants are Associated with Susceptibility to and the Incidence of Liver Cirrhosis and Hepatocellular Carcinoma in the Chinese Population: A Multicenter and Follow-Up Study.

Purpose: Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are progressions affected by genetic predispositions, and persistent hepatitis B virus infection also demonstrates genetic susceptibility. All HBV-related outcomes have been compared in parallel to identify risk polymorphism in HBV progression. Methods: The multiple-stage association study filtered and validated the risk SNPs for HBV progression and explored their association with persistent infection, with a total of 8906 subjects in China from three sites. Cox proportional hazards models and Kaplan-Meier Log rank tests were used to determine the time to the progressive event in relation to the risk SNPs. Results: Rs3825214 in TBX5 replicated a specific association with LC and HCC in 4 progression cohorts and was not related to persistent infection, naivety to HBV infection and natural clearance in 3 persistent cohorts. In combined samples, rs3825214 was associated with an increased risk of LC (P<0.001; OR = 1.98) and HCC (P<0.001; OR = 1.68). The results of bioinformatics analysis indicated that rs3825214 genotypes change RNA structure and intron excision ratio. In the follow-up of 571 hospital-based persistent HBV infection patients, ninety-three (16.29%) developed LC, and seventy-four (12.96%) progressed to HCC at a median follow-up of 5.1 years. Rs3825214 was associated with HCC and LC events in Cox proportional hazards models (P<0.001). Conclusion: We identified and confirmed that genetic variants in TBX5 are significantly associated with susceptibility to and the incidence of LC and HCC.

Enhancing effects of 60Co irradiation on the extraction and activities of phenolic components in edible Citri Sarcodactylis Fructus.

In this study, the impact of 60Co-γ ray irradiation treatment on the content of active chemicals and their functions in Citri Sarcodactylis Fructus (CSF) was assessed. Scanning electron microscopy, Fourier transform infrared spectroscopy, and γ-ray diffraction revealed physical structure changes in CSF powder. According to the findings, the content of total flavonoids in the ethanol extract of CSF increased by 9.5%-21.62%, 7-hydroxycoumarin, hesperidin, 5,7-dimethoxycoumarin, and 5-methoxypsoralen increased by 5.31%-51.8%, 10.07%-99.81%, 6.6%-62.29%, and 3.03%-300%, respectively, when the irradiation dosage was raised, and the antibacterial, anti-inflammatory, antioxidant, and anticancer properties were all raised considerably. These results imply that the principal components and activity changes are proportional to the irradiation dosage. At present, the findings of this study serve as a reference for the use of irradiation technology in assisting extraction and enhancing the effects of functional foods.

Postoperative recurrence of mixed extragonadal germ cell tumor in the right shoulder: a case report.

BACKGROUND: Extragonadal germ cell tumours (EGGCTs) originated in Shoulder are extremely rare, with 1 case described in the literature. We report a case of a patient with a primary Right Shoulder mixed EGGCT. CASE PRESENTATION: A 36-year-old male patient was hospitalized for 6 months due to progressive right shoulder swelling accompanied by pain. Subsequently, the right shoulder tumor was removed entirely. Gross pathological examination showed that the size of the tumor mass was about 14 × 10 × 6 cm.Mutations were observed in ENPEP (4q25), ZCCHC11, RREB1 (6p24.3), CKAP4 (12q23.3), and other genes were detected by whole exome sequencing. Histology revealed a mixed EGGCT of the Right Shoulder with immature teratoma and yolk sac tumour. The patient went through 6 cycles of chemotherapy. After 7 months of follow-up, the patient is recurrence. CONCLUSION: The primary MEGCT of the shoulder is an extremely rare condition. However, the recurrence and metastasis rates are high. Therefore, further research is necessary to determine this rare disease's genetic and clinical characteristics to develop an effective treatment plan.

Primary central nervous system CD20-negative diffuse large B-cell lymphoma: a case report.

BACKGROUND: CD20-negative diffuse large B-cell lymphoma is a very rare and heterogeneous invasive cancer characterized by chemical resistance and poor prognosis. Primary CD20-negative diffuse large B-cell lymphoma of the central nervous system is even rarer, presenting great challenges in pathological diagnosis and clinical treatment. CASE PRESENTATION: We report a case of primary CD20-negative diffuse large B-cell lymphoma of the CNS in a 54-year-old woman admitted to the hospital with a headache lasting more than 10 days. CT and MRI scans showed right temporal lobe lymphoma. Microscopically, large infiltrating lymphoid cells that induced brain tissue damage were observed. Immunohistochemistry showed that the tumor cells were CD79a+, PAX-5+, MUM1+, and CD20-. The patient was diagnosed with lymphoma and transferred to an oncology hospital for chemotherapy. However, because the disease progressed rapidly, the patient died only after two rounds of chemotherapy. CONCLUSIONS: To the best of our knowledge, this is one of the first reported cases of unclassifiable CD20-negative diffuse large B-cell lymphoma located in the CNS. This case report aims to deepen the understanding of clinicopathological features of this type of lymphoma and expand the scope of this disease.

Epidermal stem cells participate in the repair of scalds via Nanog and Myc regulation.

Epidermal stem cells (EpSCs) with high expression of regulatory factor Nanog can promote wound healing. The aim of the present study was to investigate the effectiveness and mechanism of epidermal stem cells (EpSCs) in healing scalds and the underlying molecular mechanism. Mouse EpSCs were isolated from skin tissues and cultured in vitro. First, the proliferative ability of EpSCs was determined via the upregulation and downregulation of Nanog expression levels in EpSCs using the MTS­assay. Second, a wound healing assay of the EpSCs with different Nanog expression levels was performed to investigate cell migratory capacities. Third, the protein expression levels of various proteins in EpSCs with Nanog overexpression or knockdown, were determined. Finally, the transfected EpSCs were applied to the rat scald model to observe their effect on scald healing. Subsequently, wound scores, re­epithelialization and capillary density were determined histologically. The results demonstrated that Nanog overexpression enhanced the proliferative ability of EpSCs via cellular (c)­Myc. Moreover, the LV­Nanog group of EpSCs with increased Nanog expression levels exhibited improved healing abilities in the wound healing test than control group. Using western blotting, it was demonstrated that EpSCs that were transfected with a Nanog­overexpression vector expressed high Nanog protein expression levels, whereas small interfering RNA­Nanog­transfected EpSCs exhibited low Nanog protein expression levels. Furthermore, c­Myc expression was synchronized with Nanog expression. It was also revealed that as the expression levels of c­Myc increased, p53 expression levels also increased. In the rat scald model, Nanog­overexpressing EpSCs enhanced wound closure and re­epithelialization. The EpSCs with Nanog knockdown exhibited the opposite effects. The present study therefore indicated that Nanog may have a positive effect on scald healing in rats, which supports its use in EpSC­based treatments against scalds. Furthermore, it was suggested that c­Myc potentially serves a key role in this process and that this process avoids cancerization by relying on the supervision of p53.

Study of preoperative diagnostic modalities in Chinese patients with superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic ultrasonography (EUS) and magnifying endoscopy (ME) reliably determine indications for endoscopic resection in patients with superficial esophageal squamous cell carcinoma (SESCC). ME is widely accepted for predicting the invasion depth of superficial esophageal cancer with satisfying accuracy. However, the addition of EUS is controversial. AIM: To evaluate the diagnostic efficiency of ME vs EUS for invasion depth prediction and investigate the influencing factors in patients with SESCC to determine the best diagnostic model in China. METHODS: We retrospectively analyzed patients with suspected SESCC who completed both ME and EUS and then underwent endoscopic or surgical resection at Sun Yat-Sen University Cancer Center between January 2018 and December 2021. We evaluated and compared the diagnostic efficiency of EUS and ME according to histological results, and investigated the influencing factors. RESULTS: We included 152 lesions from 144 patients in this study. The diagnostic accuracies of ME and EUS in differentiating invasion depth were not significantly different (73.0% and 66.4%, P = 0.24); both demonstrated moderate consistency with the pathological results (ME: kappa = 0.58, 95% confidence interval [CI]: 0.48-0.68, P < 0.01; EUS: kappa = 0.46, 95%CI: 0.34-0.57, P < 0.01). ME was significantly more accurate in the diagnosis of high-grade intraepithelial (HGIN) or carcinoma in situ (odds ratio [OR] = 3.62, 95%CI: 1.43-9.16, P = 0.007) subgroups. Using a miniature probe rather than conventional EUS can improve the accuracy of lesion depth determination (82.3% vs 49.3%, P < 0.01). Less than a quarter of circumferential occupation and application of a miniature probe were independent risk factors for the accuracy of tumor invasion depth as assessed by EUS (< 1/4 circumferential occupation: OR = 3.07, 95%CI: 1.04-9.10; application of a miniature probe: OR = 5.28, 95%CI: 2.41-11.59, P < 0.01). Of the 41 lesions (41/152, 27.0%) that were misdiagnosed by ME, 24 were corrected by EUS (24/41, 58.5%). CONCLUSION: Preoperative diagnosis of SESCC should be conducted endoscopically using white light and magnification. In China, EUS can be added after obtaining patient consent. Use of a high-frequency miniature probe or miniature probe combined with conventional EUS is preferable.

Multimodal Emotion Recognition in Response to Oil Paintings.

Most previous affective studies use facial expression pictures, music or movie clips as emotional stimuli, which are either too simplified without contexts or too dynamic for emotion annotations. In this work, we evaluate the effectiveness of oil paintings as stimuli. We develop an emotion stimuli dataset with 114 oil paintings selected from subject ratings to evoke three emotional states (i.e., negative, neutral and positive), and acquire both EEG and eye tracking data from 20 subjects while watching the oil paintings. Furthermore, we propose a novel affective model for multimodal emotion recognition by 1) extracting informative features of EEG signals from both the time domain and the frequency domain, 2) exploring topological information embedded in EEG channels with graph neural networks (GNNs), and 3) combining EEG and eye tracking data with a deep autoencoder neural network. From the exper-iments, our model obtains an averaged classification accuracy of 94.72 % ± 1.47 %, which demonstrates the feasibility of using oil paintings as emotion elicitation material.

Surveillance of Russell body inflammation of the digestive tract: a case report and review of literature.

INTRODUCTION: Russell body inflammation of the digestive tract (RBIDT) is a rare chronic inflammation of the digestive tract mucosa that commonly presents as Russell body gastritis (RBG). This disease is usually associated with Helicobacter pylori (HP) infection. However, it can also occur in individuals without HP infection and with specific immune profiles, as seen in HIV and hepatitis C infections. The aetiology and pathogenesis of this disease remain controversial. Given the rarity of the disease and the diversity of the immunophenotypes, there is a high probability of misdiagnosis. CASE PRESENTATION: A male patient with RBG and HP infection was included in this study. The case of RBG with an unusual morphology of Mott cells that mimics stamped ring cells.Endoscopy performed during the follow-up revealed regression of the lesion 1 week after anti-HP treatment. CONCLUSIONS: A case of RBG with a high likelihood of misdiagnosis of signet ring cell carcinoma (SRC) has been reported in this study along with a review of the relevant literature and an overview of RBIDT.

Enzyme-responsive nano-drug delivery system for combined antitumor therapy.

Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.

PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis.

BACKGROUND: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). METHODS: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1ß and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1ß in FLS by WB. RESULT: When PLCL1 was silenced, the level of IL-6, IL-1ß and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1ß and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. CONCLUSION: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.