KRT19 is regulated by miR-642a-5p and promotes pancreatic cancer progression through the Wnt/ß-catenin pathway.

Pancreatic cancer (PC) has a really poor prognosis, and we urgently need to delve deeper into its molecular mechanisms. In this study, we found that KRT19 expression was significantly increased in PC tissues and cell lines and it was linked to unfavorable outcomes for patients. Overexpression of KRT19 boosted the proliferation, migration, and invasion of PC cells. Additionally, miR-374b-5p targets KRT19, inhibiting the activation of the Wnt/ß-catenin pathway (WBC), which in turn suppresses epithelial-to-mesenchymal transition (EMT) and the progression of PC. Further experiments showed that under hypoxic conditions, HIF1α was positively correlated with KRT19, promoting its expression. The loss of miR-642a-5p and the upregulation of KRT19 induced by hypoxia can significantly favor PC progression. Plus, the increased expression of KRT19 might act as a predictive marker and potential target for PC treatment.

Long non-coding RNA MIR4435-2HG promotes pancreatic cancer progression by regulating ABHD17C through sponging miR-128-3p.

Background: The recently identified carcinogenic long non-coding RNA (lncRNA) MIR4435-2HG has been validated to contribute to the initiation and progression of several malignancies. Nonetheless, its specific mechanistic function in pancreatic cancer (PC) is yet to be determined. This study aims to investigate the expression and functional role of MIR4435-2HG in PC and to elucidate its potential mechanism. Methods: This study employed The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx)-Pancreas datasets for the analysis of MIR4435-2HG expression in PC and normal pancreatic tissues and its relations with prognosis in PC. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was employed for analyzing MIR4435-2HG, miR-128-3p, and ABHD17C expressions within cells and tissues. Cell proliferation and apoptosis were detected in vitro through Cell Counting Kit 8 (CCK-8) assay and flow cytometry while utilizing transwell and wound healing assays to assess cell migration and invasion. Predicting miR-128-3p binding sites with MIR4435-2HG or ABHD17C was conducted via the online tool starBase and validated through a dual-luciferase reporter (DLR), RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays. Herein, we deployed Western blot to assess protein expression levels. The in vivo role of MIR4435-2HG was studied using tumor xenografts. Results: MIR4435-2HG overexpression exhibited a correlation with poor prognosis in PC. Knocking down MIR4435-2HG significantly hindered the proliferative, invading, and migrating PC cell abilities, accompanied by apoptosis induction, counteracted via a miR-128-3p inhibitor. Moreover, MIR4435-2HG could directly bind to miR-128-3p. Additionally, miR-128-3p directly targeted ABHD17C. Furthermore, in vitro as well as in vivo experiment results elucidated that knocking down MIR4435-2HG hindered PC progression by suppressing ABHD17C expression via miR-128-3p upregulation. Conclusions: MIR4435-2HG can serve as a dependable target for PC diagnosis and treatment by modulating the miR-128-3p/ABHD17C axis to promote its progression.

A multitissue transcriptomic analysis reveals a potential mechanism whereby Brevibacillus laterosporus S62-9 promotes broiler growth.

Brevibacillus laterosporus S62-9 has been shown to improve broiler growth performance and immunity. In the present study, we aimed to evaluate the effects of B. laterosporus S62-9 on the immunity and lipid metabolism of broilers by means of transcriptomic analysis. A total of 160 1-day-old broilers were randomly allocated to a S62-9 group, the diet of which was supplemented with 106 CFU/g B. laterosporus S62-9 daily, and a control group, which was not. After 42 d of feeding, the broilers in the S62-9 group had higher body mass (7.2%) and feed conversion ratio (5.19%) than the control group. Supplementation with B. laterosporus S62-9 resulted in lower serum total cholesterol and low-density lipoprotein-cholesterol concentrations and higher high-density lipoprotein-cholesterol concentrations. An analysis of the fatty acid composition of the broiler's thigh muscles revealed that the proportions of the unsaturated fatty acids myristoleic acid (C14:1) and arachidonic acid (C20:1) were higher for birds in the S62-9 group. Transcriptomic analysis also showed an upregulation of immunity-related genes in the S62-9 group. Gene Ontology functional enrichment analysis showed that the mitogen-activated protein kinase pathway was enriched in the liver, the defense response was enriched in the duodenum, and immunoglobulin-related entries were enriched in the jejunum of the S62-9 group. Furthermore, the expression of key genes involved in unsaturated fatty acid synthesis (SCD, encoding stearoyl-CoA desaturase) and fatty acid metabolism (HACD2, encoding 3-hydroxyacyl-CoA dehydratase 2) was upregulated in the liver, and the expression of genes associated with fat biosynthesis and accumulation, such as PLIN1, encoding perilipin 1, and FABP4, encoding fatty acid binding protein 4, was upregulated in the ileum of the birds in the S62-9 group. In summary, supplementation with B. laterosporus S62-9 could improve immune defense and the fatty acid metabolism of broiler chickens, thereby enhancing their disease resistance and promoting growth and development.

Concomitant atypical knee gout and seronegative rheumatoid arthritis: A case report.

BACKGROUND: Gout and seronegative rheumatoid arthritis (SNRA) are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported. Limited information is available regarding the clinical management and prognosis of these combined diseases. CASE SUMMARY: A 57-year-old woman with a 20-year history of joint swelling, tenderness, and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA. The initial regimen of methotrexate, leflunomide, and celecoxib alleviated her symptoms, except for those associated with the knee. After symptom recurrence after medication cessation, her regimen was updated to include iguratimod, methotrexate, methylprednisolone, and folic acid, but her knee issues persisted. Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee, indicating coexistent SNRA and atypical knee gout. After postarthroscopic surgery to remove the synovium and urate crystals, and following a tailored regimen of methotrexate, leflunomide, celecoxib, benzbromarone, and allopurinol, her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year, indicating successful management of both conditions. CONCLUSION: This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

A dosimetric comparison of brachytherapy sources for endometrial cancer: an electronic brachytherapy and an iridium-192 source with multichannel cylinders and a three-dimensional technique.

BACKGROUND AND PURPOSE: Ir192 vaginal brachytherapy (IBT) is commonly used for patients with postoperative endometrial cancer (EC). We devised a novel multichannel vaginal applicator that could be equipped with an electronic brachytherapy (EBT) device. We aimed to explore the differences in physical parameters between the EBT and IBT. MATERIALS AND METHODS: This retrospective study included 20 EC patients who received adjuvant IBT from March 1, 2023, to May 1, 2023. Multichannel vaginal cylinders were used, and three-dimensional plans were generated. We designed an electronic multichannel vaginal applicator model and simulated a three-dimensional EBT plan. In order to ensure comparability, D90 of the CTV for the EBT plan was normalized to be equivalent to that of the IBT plan for the same patient. RESULTS: Twenty EBT plans were compared with 20 IBT plans. Results showed, the mean D90 value of clinical target volume (CTV) was 536.1 cGy for both treatment plans. For the mean dose of CTV, the EBT was significantly greater (738.3 vs. 684.3 cGy, p = 0.000). There was no significant difference in CTV coverage between the EBT and IBT plans. For high-dose areas (V200% and V150%), the EBTs were significantly greater. There were no significant differences in the maximum doses to the vaginal mucosa between the EBT and IBT, whether at the apex or in the middle segment. For the bladder and rectum, both the low-dose area and high-dose area were significantly lower in the EBT plans. For the conformity index, there was no significant difference between the EBT and IBT plans. For the dose homogeneity index, the EBT value was lower. CONCLUSION: In conclusion, under the premise of a three-dimensional brachytherapy plan, for patients receiving multichannel vaginal applicator brachytherapy, compared with IBT, EBT could reduce the dose to the surrounding organs at risk while maintaining the dose in the target area.

Label-Free Surface-Enhanced Raman Spectroscopy with Machine Learning for the Diagnosis of Thyroid Cancer by Using Fine-Needle Aspiration Liquid Samples.

The incidence of thyroid cancer is increasing worldwide. Fine-needle aspiration (FNA) cytology is widely applied with the use of extracted biological cell samples, but current FNA cytology is labor-intensive, time-consuming, and can lead to the risk of false-negative results. Surface-enhanced Raman spectroscopy (SERS) combined with machine learning algorithms holds promise for cancer diagnosis. In this study, we develop a label-free SERS liquid biopsy method with machine learning for the rapid and accurate diagnosis of thyroid cancer by using thyroid FNA washout fluids. These liquid supernatants are mixed with silver nanoparticle colloids, and dispersed in quartz capillary for SERS measurements to discriminate between healthy and malignant samples. We collect Raman spectra of 36 thyroid FNA samples (18 malignant and 18 benign) and compare four classification models: Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA), Random Forest (RF), Support Vector Machine (SVM), and Convolutional Neural Network (CNN). The results show that the CNN algorithm is the most precise, with a high accuracy of 88.1%, sensitivity of 87.8%, and the area under the receiver operating characteristic curve of 0.953. Our approach is simple, convenient, and cost-effective. This study indicates that label-free SERS liquid biopsy assisted by deep learning models holds great promise for the early detection and screening of thyroid cancer.

Evolution of quorum sensing process and their regulatory role on biochemical metabolism during the organic loading rate increase in dry anaerobic digestion.

The organic loading rate (OLR) is a critical parameter affecting the stability of dry anaerobic digestion (AD) of kitchen waste (KW), and significantly impacting the variations in physicochemical parameters and microbial communities. However, the evolution of quorum sensing (QS) and their role on anaerobic biochemical metabolism during the increase in OLR in dry AD remain unknown. Therefore, this study systematically elucidated the matter through multi-omics analysis based on a pilot-scale dry AD of KW. The results demonstrated that fluctuations in the OLR significantly influenced the microbial QS in dry AD. When the OLR ≤4.0 g·VS/L·d, the system operated stably, and methane production increased. The enrichment of Proteobacteria was crucial for sustaining high levels of functional genes associated with various types of QS, including acyl-homoserine lactones (AI-1), autoinducer-2 (AI-2), autoinducer-3 (AI-3), and gamma-aminobutyric acid (GABA). This enabled cooperative communication among microbes under low OLR. Furthermore, most genes associated with these QS processes positively affected hydrolysis, acidogenesis, and methanogenesis. When the OLR increased to 6.0 g·VS/L·d, the fatty acids and hydrogen partial pressure increased significantly. The autoinducing peptides (AIP)-type became the predominant QS and was positively correlated with fatty acids abundance. Syntrophaceticus and Syntrophomonas may promote syntrophic oxidation of acetate at high OLR through AIP-type QS. These findings provided new insights into the QS processes of microbes during dry AD of KW and a theoretical foundation for optimizing biochemical metabolic processes in dry AD through QS.

Deciphering the impact of organic loading rate and digestate recirculation on the occurrence patterns of antibiotics and antibiotic resistance genes in dry anaerobic digestion of kitchen waste.

Organic loading rate (OLR) is crucial for determining the stability of dry anaerobic digestion (AD). Digestate recirculation contributes to reactor stability and enhances methane production. Nevertheless, the understanding of how OLR and digestate recirculation affect the abundance and diversity of antibiotics and antibiotic resistance genes (ARGs), as well as the mechanisms involved in the dissemination of ARGs, remains limited. This study thoroughly investigated this critical issue through a long-term pilot-scale experiment. The metabolome analyses revealed the enrichment of various antibiotics, such as aminoglycoside, tetracycline, and macrolide, under low OLR conditions (OLR ≤ 4.0 g·VS/L·d) and the reactor instability. Antibiotics abundance decreased by approximately 19.66-31.69 % during high OLR operation (OLR ≥ 6.0 g·VS/L·d) with digestate recirculation. The metagenome analyses demonstrated that although low OLR promoted reactor stability, it facilitated the proliferation of antibiotic-resistant bacteria, such as Pseudomonas, and triggered functional profiles related to ATP generation, oxidative stress response, EPS secretion, and cell membrane permeability, thereby facilitating horizontal gene transfer (HGT) of ARGs. However, under stable operation at an OLR of 6.0 g·VS/L·d, there was a decrease in ARGs abundance but a notable increase in human pathogenic bacteria (HPB) and mobile genetic elements (MGEs). Subsequently, during reactor instability, the abundance of ARGs and HPB increased. Notably, during digestate recirculation at OLR levels of 6.0 and 7.0 g·VS/L·d, the process attenuated the risk of ARGs spread by reducing the diversity of ARGs hosts, minimizing interactions among ARGs hosts, ARGs, and MGEs, and weakening functional profiles associated with HGT of ARGs. Overall, digestate recirculation aids in reducing the abundance of antibiotics and ARGs under high OLR conditions. These findings provide advanced insights into how OLR and digestate recirculation affect the occurrence patterns of antibiotics and ARGs in dry AD.

The "Hypointense Focal Brain" on susceptibility-weighted imaging as a sign of venous congestion in cranial dural arteriovenous fistulas.

BACKGROUND: Cranial dural arteriovenous fistulas (dAVFs) are complex neurovascular malformations accounting for approximately 10%-15% of all intracranial arteriovenous malformations. The objective is to investigate the utility of susceptibility-weighted imaging (SWI) in identifying "hypointense focal brain" as an additional helpful sign of venous congestion in cranial dAVFs. MATERIALS AND METHODS: A retrospective review of patients diagnosed with cranial dAVFs between January 2015 and June 2023 was conducted, and SWI was used to identify the "hypointense focal brain" sign within the venous drainage region of the dAVF. The "hypointense focal brain" on SWI was identified as a low-intensity signal within the venous drainage region, indicative of venous congestion. The presence of this imaging sign was assessed by two neuroradiologists and signal intensity measurements were performed to support the presence of the sign. RESULTS: The study included six patients with cranial dAVFs exhibiting cortical venous retrograde drainage and the "hypointense focal brain" on SWI. Follow-up imaging post-treatment revealed resolution or improvement of the hypointense signal, confirming its association with venous congestion. Signal intensity measurements further supported the presence of this imaging sign in pre-treatment scans. CONCLUSION: The study's findings demonstrate the presence of a reversible "hypointense focal brain" sign on SWI in patients with cranial dAVFs and CVR, which can be useful as an additional imaging sign for venous congestion.

Clinical benefits of transarterial chemoembolization combined with tyrosine kinase and immune checkpoint inhibitors for unresectable hepatocellular carcinoma.

BACKGROUND: Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma (HCC). In recent years, several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). AIM: To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC. METHODS: All eligible cohort, non-randomized controlled, and randomized controlled trial studies from the PubMed, Web of Science, Embase, Cochrane Library, and MedLine databases up to March 20, 2024 were screened for the present meta-analysis. The study endpoints included complete response (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Stata 16/18 software was used for this meta-analysis, and a P value of <0.05 was considered statistically significant. RESULTS: A total of 29 studies with 1754 patients were included. Among the patients who received the TACE therapy with TKIs and ICIs, the tumor response results revealed a pooled CR, ORR, and DCR of 14% [95%CI (0.11-0.18)], 61% [95%CI (0.55-0.66)], and 85% [95%CI (0.83-0.87)], respectively. In terms of the survival outcomes, the pooled median PFS and OS were 10.25 months [95%CI (9.31-11.18)] and 20.47 months [95%CI (18.98-21.97)], respectively. The pooled prevalence of all-grade AEs during the triple treatment was 90% [95%CI (0.84-0.94)] and that of grade ≥ 3 AEs was 32% [95%CI (0.24-0.42)]. CONCLUSION: The combination therapy of TACE, TKIs, and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.

Arnicolide D Inhibits Proliferation and Induces Apoptosis of Osteosarcoma Cells through PI3K/Akt/mTOR Pathway.

BACKGROUND: Osteosarcoma is considered as the most prevalent form of primary malignant bone cancer, prompting a pressing need for novel therapeutic options. Arnicolide D, a sesquiterpene lactone derived from the traditional Chinese herbal medicine Centipeda minima (known as E Bu Shi Cao in Chinese), showed anticancer efficacy against several kinds of cancers. However, its effect on osteosarcoma remains unclear. OBJECTIVE: This study aimed to investigate the anticancer activity of arnicolide D and the underlying molecular mechanism of its action in osteosarcoma cells, MG63 and U2OS. METHODS: Cell viability and proliferation were evaluated through MTT assay and colony formation assay following 24 h and 48 h treatment with different concentrations of arnicolide D. Flow cytometry was employed to examine cell cycle progression and apoptosis after 24 h treatment of arnicolide D. Western blotting was performed to determine the expression of the PI3k, Akt and m-TOR and their phosphorylated forms. RESULTS: Our findings revealed that arnicolide D treatment resulted in a significant reduction in cell viability, the inhibition of proliferation, and the induction of apoptosis and cell cycle arrest in the G2/M phase. Furthermore, arnicolide D could inhibit the activation of PI3K/Akt/mTOR pathway in osteosarcoma cells. CONCLUSION: Based on our results, arnicolide D demonstrated significant anti-osteosarcoma activity and held the potential to be considered as a therapeutic candidate for osteosarcoma in the future.

Laparoscopic-assisted sclerotherapy in pediatric retroperitoneal lymphatic malformations.

Background: Retroperitoneal lymphatic malformations (LMs) are rare. Currently, the treatment of retroperitoneal LMs remains challenging. This study aimed to examine the safety and efficacy of laparoscopic-assisted sclerotherapy for retroperitoneal LMs in pediatric patients. Methods: We retrospectively reviewed patients treated with laparoscopic-assisted sclerotherapy for retroperitoneal LMs in a single tertiary medical center between July 2020 and February 2023. Doxycycline was prepared into a solution with a concentration of 10 mg/ml for use in sclerotherapy. Demographic data, clinical features, details of management, and outcomes were collected and analyzed. Results: A total of six patients, comprising three males and three females, were identified. The LMs were categorized into four macrocystic and two mixed-cystic types. The mean age and weight were 52.2 months (range, 11-108 months) and 20 kg (range, 12.5-27.5 kg), respectively. Three patients presented with abdominal pain or distension, while the other three patients were asymptomatic. All six patients underwent a total of eight sclerotherapy sessions. Two patients experienced intra-cystic hemorrhage and required a second sclerotherapy session. Only one patient presented with vomiting after sclerotherapy, which resolved spontaneously. Five patients met the complete response criteria, and one patient met the effective criteria. The mean reduction in lesion size was 92.3% (range, 69.9%-99.6%). No further complications or recurrence were recorded during follow-up. Conclusion: Laparoscopic-assisted sclerotherapy is a safe and effective approach for treating retroperitoneal LMs. This technique is applicable for both macrocystic and mixed-cystic retroperitoneal LMs.

Study on the mechanism of mitigating radiation damage by improving the hematopoietic system and intestinal barrier with Tenebrio molitor peptides.

Research on plant and animal peptides has garnered significant attention, but there is a lack of studies on the functional properties of Tenebrio molitor peptides, particularly in relation to their potential mitigating effect on radiation damage and the underlying mechanisms. This study aims to explore the protective effects of Tenebrio molitor peptides against radiation-induced damage. Mice were divided into five groups: normal, radiation model, and low-, medium-, and high-dose Tenebrio molitor peptide (TMP) groups (0.15 g per kg BW, 0.30 g per kg BW, and 0.60 g per kg BW). Various parameters such as blood cell counts, bone marrow DNA content, immune organ indices, serum levels of D-lactic acid, diamine oxidase (DAO), endotoxin (LPS), and inflammatory factors were assessed at 3 and 15 days post gamma irradiation. Additionally, the intestinal tissue morphology was examined through H&E staining, RT-qPCR experiments were conducted to analyze the expression of inflammatory factors in the intestine, and immunohistochemistry was utilized to evaluate the expression of tight junction proteins ZO-1 and Occludin in the intestine. The findings revealed that high-dose TMP significantly enhanced the hematopoietic system function in mice post radiation exposure, leading to increased spleen index, thymus index, blood cell counts, and bone marrow DNA production (p < 0.05). Moreover, TMP improved the intestinal barrier integrity and reduced the intestinal permeability. Mechanistic insights suggested that these peptides may safeguard intestinal barrier function by downregulating the gene expression of inflammatory factors TNF-α, IL-1ß, and IL-6, while upregulating the expression of tight junction proteins ZO-1 and Occludin (p < 0.05). Overall, supplementation with TMP mitigates radiation-induced intestinal damage by enhancing the hematopoietic system and the intestinal barrier, offering valuable insights for further investigations into the mechanisms underlying the protective effects of these peptides against ionizing radiation.

Immunologic insights in recurrent spontaneous abortion: Molecular mechanisms and therapeutic interventions.

Recurrent spontaneous abortion refers to the occurrence of two or more spontaneous abortions before or during the early stages of pregnancy. The immune system plays a crucial role in the maintenance of pregnancy and embryo implantation. Various immune cells, cytokines, and immune regulatory pathways are involved in the complex immune balance required for a stable pregnancy. Studies suggest that immune abnormalities may be associated with some recurrent spontaneous abortion cases, particularly those involving the dysregulation of immune cell function, autoimmune responses, and placental immunity. In terms of treatment, interventions targeting immune mechanisms are crucial. Various therapeutic approaches, including immunomodulatory drugs, immunoadsorption therapies, and immunocellular therapies, are continually being researched and developed. These approaches aim to restore the immune balance, enhance the success rate of pregnancies, and provide more effective treatment options for patients with recurrent spontaneous abortion.

When surface-enhanced Raman spectroscopy meets complex biofluids: A new representation strategy for reliable and comprehensive characterization.

BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) has gained increasing importance in molecular detection due to its high specificity and sensitivity. Complex biofluids (e.g., cell lysates and serums) typically contain large numbers of different bio-molecules with various concentrations, making it extremely challenging to be reliably and comprehensively characterized via conventional single SERS spectra due to uncontrollable electromagnetic hot spots and irregular molecular motions. The traditional approach of directly reading out the single SERS spectra or calculating the average of multiple spectra is less likely to take advantage of the full information of complex biofluid systems. RESULTS: Herein, we propose to construct a spectral set with unordered multiple SERS spectra as a novel representation strategy to characterize full molecular information of complex biofluids. This new SERS representation not only contains details from each single spectra but captures the temporal/spatial distribution characteristics. To address the ordering-independent property of traditional chemometric methods (e.g., the Euclidean distance and the Pearson correlation coefficient), we introduce Wasserstein distance (WD) to quantitatively and comprehensively assess the quality of spectral sets on biofluids. WD performs its superiority for the quantitative assessment of the spectral sets. Additionally, WD benefits from its independence of the ordering of spectra in a spectral set, which is undesirable for traditional chemometric methods. With experiments on cell lysates and human serums, we successfully achieve the verification for the reproducibility between parallel samples, the uniformity at different positions in the same sample, the repeatability from multiple tests at one location of the same sample, and the cardinality effect of the spectral set. SERS spectral sets also manage to distinguish different classes of human serums and achieve higher accuracy than the traditional prostate-specific antigen in prostate cancer classification. SIGNIFICANCE: The proposed SERS spectral set is a robust representation approach in accessing full information of biological samples compared to relying on a single or averaged spectra in terms of reproducibility, uniformity, repeatability, and cardinality effect. The application of WD further demonstrates the effectiveness and robustness of spectral sets in characterizing complex biofluid samples, which extends and consolidates the role of SERS.

THBru attenuates diabetic cardiomyopathy by inhibiting RAGE-dependent inflammation.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

Raman spectroscopy for esophageal tumor diagnosis and delineation using machine learning and the portable Raman spectrometer.

Esophageal cancer is one of the leading causes of cancer-related deaths worldwide. The identification of residual tumor tissues in the surgical margin of esophageal cancer is essential for the treatment and prognosis of cancer patients. But the current diagnostic methods, either pathological frozen section or paraffin section examination, are laborious, time-consuming, and inconvenient. Raman spectroscopy is a label-free and non-invasive analytical technique that provides molecular information with high specificity. Here, we report the use of a portable Raman system and machine learning algorithms to achieve accurate diagnosis of esophageal tumor tissue in surgically resected specimens. We tested five machine learning-based classification methods, including k-Nearest Neighbors, Adaptive Boosting, Random Forest, Principal Component Analysis-Linear Discriminant Analysis, and Support Vector Machine (SVM). Among them, SVM shows the highest accuracy (88.61 %) in classifying the esophageal tumor and normal tissues. The portable Raman system demonstrates robust measurements with an acceptable focal plane shift of up to 3 mm, which enables large-area Raman mapping on resected tissues. Based on this, we finally achieve successful Raman visualization of tumor boundaries on surgical margin specimens, and the Raman measurement time is less than 5 min. This work provides a robust, convenient, accurate, and cost-effective tool for the diagnosis of esophageal cancer tumors, advancing toward Raman-based clinical intraoperative applications.

Radiological insights into rheumatoid meningitis - a rare central nervous system manifestation of rheumatoid arthritis: a retrospective review of six cases.

BACKGROUND: The objective is to analyze and review the clinical, laboratory, and neuroimaging characteristics of rheumatoid meningitis (RM) in six patients with known rheumatoid arthritis (RA). METHODS: We performed a retrospective review of patients diagnosed with RM from August 2012 to June 2023. To identify the cases, we used medical term search engines and the hospital´s radiology case database. Clinical information and laboratory findings were gathered from the medical records. A neuroradiologist with five years of experience reviewed and analyzed the RM to determine the characteristics findings of RM. RESULTS: Six patients with RM are included. Seizures along with headaches were among the clinical signs that were documented. All the patients had high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (ACPA) in the peripheral blood. Biopsy in two cases confirmed typical rheumatoid nodules. Leptomeningeal enhancement was found bilaterally in all cases and was predominantly found in the frontoparietal region. "Mismatch DWI/FLAIR" was found in five patients. Bilateral subdural collections could be found in two patients. Brain PET scan revealed increased metabolism in two cases. CONCLUSION: Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA) with challenging clinical diagnosis due to non-specific symptoms. This study highlights the importance of MR in detecting characteristic neuroimaging patterns, including "mismatch DWI/FLAIR", to aid in early diagnosis. Increased awareness of this condition may facilitate timely intervention and improve prognosis. These results still need to be verified by large studies.

Effects of mind-regulating acupuncture on pain, negative emotion and sleep quality in patients with postherpetic neuralgia： a randomized controlled pilot trial. / è°ƒç¥žé’ˆæ³•å¯¹å¸¦çŠ¶ç–±ç–¹åŽé—ç¥žç»ç—›æ‚£è€ ç–¼ç—›ç¨‹åº¦ã€è´Ÿæ€§æƒ ç»ªå’Œç¡çœ è´¨é‡çš„å½±å“.

OBJECTIVES: To observe the effect of mind-regulating acupuncture on pain intensity, sleep quality, negative emotion in patients with postherpetic neuralgia (PHN), and evaluate the clinical effect of mind-regulating acupuncture combined with surrounding needling and heavy moxibustion at Ashi points (Extra) in treatment of PHN. METHODS: The patients with PHN were randomly divided into a control group (35 cases, 2 cases dropped out) and a comprehensive therapy group (35 cases). The patients in the control group were treated with surrounding needling and heavy moxibustion at Ashi points. In the comprehensive therapy group, the mind-regulating acupuncture therapy was delivered besides the treatment as the control group. The treatment was given once daily, one course of treatment was composed of 6 days and 2 courses were required in the 2 groups. Before and after treatment, the pain conditions were assessed using pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI), the negative emotions were assessed using Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD), and the sleep quality with Pittsburgh sleep quality index (PSQI). One week before and one week after treatment, the average sleep time was recorded. The therapeutic effect of 2 groups was evaluated. The effective cases of 2 groups were followed up in 2 months after treatment completion and the recurrence of neuralgia was recorded. RESULTS: There were no statistical differences in the above indicators between the 2 groups before treatment. After 2 courses of treatment, the scores of PRI, VAS, PPI, HAMA, HAMD and PSQI were reduced when compared with those before treatment in the patients of the 2 groups (P<0.05), and the average sleep time was increased (P<0.05). The scores of PRI, VAS, PPI, HAMA, HAMD and PSQI in the comprehensive therapy group, as well as the average sleep time were all improved when compared with those of the control group (P<0.05). The total effective rate in the comprehensive therapy group (34/35, 97.14%) was higher than that of the control group (27/33, 81.82%, P<0.05) and the recurrence rate was lower (ï¼»2/34, 5.88%ï¼½vsï¼»8/27, 29.63%ï¼½, P<0.05). CONCLUSIONS: The combination of mind-regulating acupuncture with surrounding needling and heavy moxibustion at Ashi acupoint can effectively relieve PHN. Compared with the traditional surrounding acupuncture in pain area combined with moxibustion at Ashi points, this comprehensive therapy is more effective for ameliorating pain intensity, improving sleep quality and reducing negative emotions. It is also effective for declining the recurrence.

Optimization of Dendritic Polypeptide Delivery System for Antisense Antibacterial Agents Targeting ftsZ.

There is an urgent requirement for a novel treatment strategy for drug-resistant Staphylococcus aureus (S. aureus) infection. Antisense antimicrobials are promising antimicrobials, and efficient drug delivery systems are necessary for the further development of antisense antimicrobials. To develop new antisense drugs and further improve delivery efficiency and safety, we designed and screened new antisense sequences and optimized dendritic polypeptide nanoparticles (DP-AD) discovered in previous studies. The N/P ratio is optimized from 8:1 to 6:1, and the positive charge number of the optimized DP-AD is studied comprehensively. The results show that the N/P ratio and positive charge number have no significant effect on the particle size distribution and transport efficiency of DP-AD. Reducing the N/P ratio can significantly reduce the cytotoxicity of DP-AD, but it does not affect its delivery efficiency and antibacterial activity. However, in drug-resistant strains, the antibacterial activity of DP-AD76:1 with 10 positive charges is higher than that of DP-AD86:1 with 8 positive charges. Our research discovered a novel ASOs targeting ftsZ and concluded that DP-AD76:1 with 10 positive charges was the optimal choice at the current stage, which provided a promising strategy for the treatment of drug-resistant S. aureus.