Global bibliometric mapping of the research trends in artificial intelligence-based digital pathology for lung cancer over the past two decades.

Background and Objective: The rapid development of computer technology has led to a revolutionary transformation in artificial intelligence (AI)-assisted healthcare. The integration of whole-slide imaging technology with AI algorithms has facilitated the development of digital pathology for lung cancer (LC). However, there is a lack of comprehensive scientometric analysis in this field. Methods: A bibliometric analysis was conducted on 197 publications related to digital pathology in LC from 502 institutions across 39 countries, published in 97 academic journals in the Web of Science Core Collection between 2004 and 2023. Results: Our analysis has identified the United States and China as the primary research nations in the field of digital pathology in LC. However, it is important to note that the current research primarily consists of independent studies among countries, emphasizing the necessity of strengthening academic collaboration and data sharing between nations. The current focus and challenge of research related to digital pathology in LC lie in enhancing the accuracy of classification and prediction through improved deep learning algorithms. The integration of multi-omics studies presents a promising future research direction. Additionally, researchers are increasingly exploring the application of digital pathology in immunotherapy for LC patients. Conclusions: In conclusion, this study provides a comprehensive knowledge framework for digital pathology in LC, highlighting research trends, hotspots, and gaps in this field. It also provides a theoretical basis for the application of AI in clinical decision-making for LC patients.

RIPK4 promotes oxidative stress and ferroptotic death through the downregulation of ACSM1.

One of the most critical axes for cell fate determination is how cells respond to excessive reactive oxygen species (ROS)-oxidative stress. Extensive lipid peroxidation commits cells to death via a distinct cell death paradigm termed ferroptosis. However, the molecular mechanism regulating cellular fates to distinct ROS remains incompletely understood. Through siRNA against human receptor-interacting protein kinase (RIPK) family members, we found that RIPK4 is crucial for oxidative stress and ferroptotic death. Upon ROS induction, RIPK4 is rapidly activated, and the kinase activity of RIPK4 is indispensable to induce cell death. Specific ablation of RIPK4 in kidney proximal tubules protects mice from acute kidney injury induced by cisplatin and renal ischemia/reperfusion. RNA sequencing revealed the dramatically decreased expression of acyl-CoA synthetase medium-chain (ACSM) family members induced by cisplatin treatment which is compromised in RIPK4-deficient mice. Among these ACSM family members, suppression of ACSM1 strongly augments oxidative stress and ferroptotic cell death with induced expression of ACS long-chain family member 4, an important component for ferroptosis execution. Our lipidome analysis revealed that overexpression of ACSM1 leads to the accumulation of monounsaturated fatty acids, attenuation of polyunsaturated fatty acid (PUFAs) production, and thereby cellular resistance to ferroptosis. Hence, knockdown of ACSM1 resensitizes RIPK4 KO cells to oxidative stress and ferroptotic death. In conclusion, RIPK4 is a key player involved in oxidative stress and ferroptotic death, which is potentially important for a broad spectrum of human pathologies. The link between the RIPK4-ASCM1 axis to PUFAs and ferroptosis reveals a unique mechanism to oxidative stress-induced necrosis and ferroptosis.

The Causal Relationship Between Physical Activity and Skin Cancer Risk: An Univariable Mendelian Randomization Study.

Background: The existing observational research on the relationship between physical activity (PA) and skin cancer (SC) is contentious, which points to the intricate nature of their association and underscores the imperative for more nuanced research to untangle the causal dynamics at play. The aim of this article is to delve deeper into this complex relationship, seeking to clarify whether PA serves as a protective factor against SC, or contributes to its risk. Methods: We utilized data from the genome-wide association study (GWAS) of PA from GWAS Catalog (include self-reported moderate to vigorous PA (MVPA), self-reported vigorous PA (VPA), and accelerometer-based average-accelerated PA). The data of SC is from FinnGen. All of the participants are of European ancestry. We used two-sample Mendelian Randomization (TSMR) to analyze the causal relationship between PA and SC.The research was conducted using inverse variance weighted (IVW) method as the primary approach, and MR Egger regression as supplementary analytical method. To ensure the robustness of the results, Cochran's Q-test and MR pleiotropy residual sum and outlier (MR-PRESSO) global tests were used to measure sensitivity. Results: Our analysis indicated that average-accelerated PA was associated with an increased risk of SC (ORIVW = 0.94, 95% CI 0.93-0.96, P < 0.001). While neither MVPA (ORIVW = 0.99, 95% CI 0.67-1.47, P = 0.962) nor VPA (ORIVW = 0.80, 95% CI 0.29-2.18, P = 0.656) shows causal relationship on risk of SC. Conclusion: Our research suggests that PA is associated with a decrease in SC, provides a new perspective for future SC prevention. Our research findings bolster the hypothesis that increased levels of PA, characterized by average acceleration, are associated with a reduced risk of developing skin cancer. This has filled the gap of research on the causal relationship between PA and SC, and could pave the way for novel preventive strategies against skin cancer.

Myotubularin 2 interacts with SEC23A and negatively regulates autophagy at ER exit sites in Arabidopsis.

Starvation- or stress-induced phosphatidylinositol 3-phosphate (PtdIns3P/PI3P) production at the endoplasmic reticulum (ER) subdomains organizes phagophore assembly and autophagosome formation. Coat protein complex II (COPII) vesicles budding from ER exit site (ERES) also contribute to autophagosome formation. Whether any PtdIns3P phosphatase functions at ERES to inhibit macroautophagy/autophagy is unknown. Here we report Myotubularin 2 (MTM2) of Arabidopsis as a PtdIns3P phosphatase that localizes to ERES and negatively regulates autophagy. MTM2 binds PtdIns3P with its PH-GRAM domain in vitro and acts toward PtdIns3P in vivo. Transiently expressed MTM2 colocalizes with ATG14b, a subunit of the phosphatidylinositol 3-kinase (PtdIns3K) complex, and overexpression of MTM2 blocks autophagic flux and causes over-accumulation of ATG18a, ATG5, and ATG8a. The mtm2 mutant has higher levels of autophagy and is more tolerant to starvation, whereas MTM2 overexpression leads to reduced autophagy and sensitivity to starvation. The phenotypes of mtm2 are suppressed by ATG2 mutation, suggesting that MTM2 acts upstream of ATG2. Importantly, MTM2 does not affect the endosomal functions of PtdIns3P. Instead, MTM2 specifically colocalizes with COPII coat proteins and is cradled by the ERES-defining protein SEC16. MTM2 interacts with SEC23A with its phosphatase domain and inhibits COPII-mediated protein secretion. Finally, a role for MTM2 in salt stress response is uncovered. mtm2 resembles the halophyte Thellungiella salsuginea in its efficient vacuolar compartmentation of Na+, maintenance of chloroplast integrity, and timely regulation of autophagy-related genes. Our findings reveal a balance between PtdIns3P synthesis and turnover in autophagosome formation, and provide a new link between autophagy and COPII function.Abbreviations: ATG: autophagy related; BFA: brefeldin A; BiFC: bimolecular fluorescence complementation; CHX: cycloheximide; ConA: concanamycin A; COPII: coat protein complex II; ER: endoplasmic reticulum; ERES: ER exit site; MS: Murashige and Skoog; MTM: myotubularin; MVB: multivesicular body; PAS: phagophore assembly site; PI: phosphoinositide; TEM: transmission electron microscopy; WT: wild-type.

Concurrent performance and security enhancement of ultrahigh-order DSM signals via null subcarriers.

In this paper, we propose leveraging null subcarriers in discrete multi-tone modulation (DMT) to process the DMT signal in both time and frequency domains. Additionally, we employ discrete memory enhanced chaos (DMEC) to scramble the signal in the frequency domain, thereby achieving physical layer signal encryption while ensuring a more uniform power distribution in the time-domain waveform. In our experimental demonstration, we achieved high-security transmission of a DSM-based 65536-QAM signal at a data rate of 16.01 Gb/s over a 25 km single-mode fiber (SMF) in an intensity-modulation direct-detection (IMDD) system. Additionally, in the transmission experiments for 13684-QAM and 65536-QAM signals, the proposed method demonstrated a receiver sensitivity gain of over 0.5 dB compared to the traditional DSM-based ultrahigh-order transmission.

Developing a modified textbook outcome for elderly patients with gastric cancer: a multi-center study.

OBJECTIVE: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. METHODS: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. RESULTS: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. CONCLUSION: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

Amiodarone-Induced Anaphylaxis.

Background: Amiodarone-induced anaphylaxis is seldom reported. The mechanism of this anaphylaxis is unknown. Methods: A literature search was carried out with keywords "Amiodarone" and "Anaphylaxis" and "polysorbate 80" or "hypotension." A search using "amiodarone" in the FDA Adverse Event Reporting System (FAERS) from 1969 to 2024 was also conducted. Results: There are a total of 10 cases of amiodarone-induced anaphylaxis in the literature. Six patients were male. Ages ranged from 15 to 86 years old. Nine cases were triggered by intravenous injection (IV) and one by oral administration. Eight patients did not have previous exposure to amiodarone. The trigger times for IV amiodarone were immediate to 90 minutes. All nine cases of IV amiodarone resulted in hypotension (90%), with an immeasurable blood pressure (70%). Presentations included bronchospasm or a skin rash (60%), angioedema (40%), and unconsciousness (20%). Only one patient had a history of allergy to penicillin and sulfonamide. An amiodarone skin test was positive on one patient. Increased blood tryptase (4 cases), positive basophil activation test to amiodarone (2 cases), increased eosinophil count (1 case), and increased serum IgE (1 case) were reported. Amiodarone was terminated in 80% of the patients. Epinephrine, norepinephrine, antihistamine-1, or steroids were used to rescue patients. Four patients were intubated. All patients fully recovered. In the FAERS database, 89 cases of amiodarone-associated anaphylaxis were reported, resulting in 14 deaths. Conclusions: Solvent polysorbate 80, amiodarone, and iodide may contribute to amiodarone-induced anaphylaxis. Prompt treatment is the key to saving patients.

Sleep, movement, and dietary behaviours: the mediating role of affect.

BACKGROUND: Previous studies indicated a link between good sleep, optimal movement, and a healthy diet, but the underlying mechanisms are poorly understood. This diary study aimed to investigate the effects of sleep behaviour on movement and dietary behaviours as well as the mediating role of affect. METHOD: One hundred and twenty college students completed twice daily assessments of health behaviours and affect for 28 days. Multilevel structural equation modelling was used to examine the relationships between sleep, health behaviours, and the mediating role of affect. RESULTS: At the between-person level, sufficient sleep was associated with less overeating. At the within-person level, sleep duration predicted less sedentary behaviour, while sufficient sleep predicted higher water intake and more sedentary behaviour. Negative affect mediated the relationship between sleep quality/duration and exercise measures (events, duration), while positive affect mediated the relationships between sleep quality/duration and overeating, exercise measures, and sedentary behaviour. Positive affect mediated the relationships between sufficient sleep, exercise measures, and sedentary behaviour. CONCLUSION: Sleep can indirectly influence other health behaviours by decreasing negative affect or increasing positive affect. These findings emphasise the significance of sleep in promoting a healthy lifestyle and the role of affect, especially positive affect, in this process.

Insulin enhances acid-sensing ion channel currents in rat primary sensory neurons.

Insulin has been shown to modulate neuronal processes through insulin receptors. The ion channels located on neurons may be important targets for insulin/insulin receptor signaling. Both insulin receptors and acid-sensing ion channels (ASICs) are expressed in dorsal root ganglia (DRG) neurons. However, it is still unclear whether there is an interaction between them. Therefore, the purpose of this investigation was to determine the effects of insulin on the functional activity of ASICs. A 5 min application of insulin rapidly enhanced acid-evoked ASIC currents in rat DRG neurons in a concentration-dependent manner. Insulin shifted the concentration-response plot for ASIC currents upward, with an increase of 46.2 ± 7.6% in the maximal current response. The insulin-induced increase in ASIC currents was eliminated by the insulin receptor antagonist GSK1838705, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol-3 kinase antagonist wortmannin. Moreover, insulin increased the number of acid-triggered action potentials by activating insulin receptors. Finally, local administration of insulin exacerbated the spontaneous nociceptive behaviors induced by intraplantar acid injection and the mechanical hyperalgesia induced by intramuscular acid injections through peripheral insulin receptors. These results suggested that insulin/insulin receptor signaling enhanced the functional activity of ASICs via tyrosine kinase and phosphatidylinositol-3 kinase pathways. Our findings revealed that ASICs were targets in primary sensory neurons for insulin receptor signaling, which may underlie insulin modulation of pain.

Efficacy and safety of current therapies for difficult-to-treat rheumatoid arthritis: a systematic review and network meta-analysis.

BACKGROUND: Difficult-to-treat Rheumatoid arthritis (D2T RA) is primarily characterised by failure of at least two different mechanism of action biologic/targeted synthetic disease-modifying antirheumatic drug (DMARDs) with evidence of active/progressive disease. While a variety of drugs have been used in previous studies to treat D2T RA, there has been no systematic summary of these drugs. This study conducted a systematic review of randomized controlled trials aimed at analyzing the efficacy and safety of individual therapeutic agents for the treatment of D2T RA and recommending the optimal therapeutic dose. METHODS: The English databases were searched for studies on the treatment of D2T RA published between the date of the database's establishment and March, 2024. This study uses R 3.1.2 for data analysis, and the rjags package runs JAGS 3.4.0.20. The study fitted a stochastic effects Bayesian network meta-analysis for each outcome measure. RESULT: A total of 42 studies were included in this study. Compared with placebo, the improvement of Disease Activity Score of 28 Joints (DAS28) score is ranked from high to low as tocilizumab, baricitinib and opinercept. The improvement of American College of Rheumatology 50 response (ACR50) score in patients with drug use was ranked from good to poor as follows: olokizumab, tocilizumab, adalimumab, baricitinib, and upadacitinib, and 8 mg/4w tocilizumab demonstrated the best efficacy. Notably, rituximab is generally the safest drug. Janus kinase (JAK) inhibitors and T cell costimulation modulators are effective in D2T RA refractory to biologic DMARDs, while JAK inhibitors and interleukin-6 (IL-6) inhibitors show effectiveness in D2T RA refractory to csDMARDs. CONCLUSION: Tocilizumab and rituximab have better efficacy and safety in the treatment of D2T RA, and the 8 mg/4w dose of tocilizumab may be the first choice for achieving disease remission.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Role of TRPC6 in apoptosis of skeletal muscle ischemia/reperfusion injury.

BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI. METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice. RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R. CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.

What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.

BACKGROUND: Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on LCBM, problems have emerged, such as confusing research structures. AIM: To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation, clinical treatment, and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research. METHODS: We used tools, including R, VOSviewer and CiteSpace software, to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection. We also performed enrichment and protein-protein interaction analyses of gene expression datasets from LCBM cases worldwide. RESULTS: Research on LCBM has received extensive attention from scholars worldwide over the last 20 years. Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions. The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis. The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence. CONCLUSION: Novel therapies for LCBM face animal testing and drug resistance issues. Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.

Dynamic updated key distribution encryption scheme with the wireless rate of 102†Gb/s based on a syncretic W band-PON transmission system.

In this paper, a dynamic updated key distribution encryption scheme based on syncretic W band-passive optical network (PON) is proposed. The 102 Gb/s encrypted data rate using 64QAM is successfully transmitted over the 50 m wireless distance under 15% soft-decision forward error correction (SD-FEC) for a pre-FEC bit error rate (BER) threshold of 1.56 × 10-2. The scheme can realize an error-free public key transmission and public key updates up to 1014 times. In the encryption transmission system, there is a small deviation of the private key, and the received BER is more than 0.45. As far as we know, this is the first time to complete a dynamic key distribution based on a syncretic W band-PON system.

Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice.

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

Increased ONECUT2 induced by Helicobacter pylori promotes gastric cancer cell stemness via an AKT-related pathway.

Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/ß-catenin phosphorylation. AKT/ß-catenin phosphorylation facilitates ß-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and ß-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/ß-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.

Role of hydrogen sulfide in the male reproductive system.

As an important gas signaling molecule, hydrogen sulfide (H2S) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, H2S not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between H2S and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of H2S in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of H2S in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K+ channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on H2S. Therefore, understanding the role of H2S in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.

Drug-induced musical hallucination.

Musical hallucination is a rare perceptual phenomenon wherein individuals hear music in the absence of external auditory stimuli. This phenomenon occurs across diverse medical conditions and can be triggered by some drugs. The underlying mechanism of drug-induced hallucination is unknown. This study explores drug-induced musical hallucination through a literature review, aiming to investigate its pathophysiology and potential treatment modalities. A literature search was conducted until January 2024 using databases PubMed, WorldCat, Google Scholar, and DOAJ, with keywords "drugs induced musical hallucination" or "drugs" combined with "musical hallucination." The search yielded 24 articles which met inclusion criteria, encompassing 27 cases. The average patient age was 58.3 years, with 67.9% females. Prevalent conditions among cases included hearing impairments, psychiatric disorders, cancers, and neurodegenerative conditions. Common trigger drugs comprised antidepressants, opioids, anti-Parkinson drugs, ketamine, and voriconazole. Musical hallucination descriptions varied widely, and 6 patients reported concurrent visual hallucinations. The onset of symptoms ranged from 75 min to 240 days. Treatment strategies included termination of trigger drugs, dosage reduction, alteration of administration routes or formula, switching to similar drugs, or addition of antidepressants, sedatives, or atypical antipsychotic medications. Musical hallucinations completely disappeared in 24/27 (88.9%) patients but continued in 3/27 (11.1%) patients. The current study concludes that drug-induced musical hallucination may arise from altering neurotransmitter/receptor balance and intricate interactions between trigger drugs and underlying conditions.

Investigation in image quality and immediate patient safety using pre-dual-flow injection for low-contrast dose spectral pulmonary artery CT angiography.

Purpose: The patient safety of iodine contrast-enhanced pulmonary artery CT angiography (CTPA) is widely concerned. This study aimed to investigate the image quality and immediate patient safety of spectral CTPA using a lower-contrast dose pre-dual-flow injection method. Methods: This retrospective study included 120 patients with suspected pulmonary embolisms who received spectral CTPA between February and December 2022. Patients were divided into normal contrast injection (Group A, n=60) and pre-dual-flow group (Group B, n=60). CT values of pulmonary arteries (PAs) at different levels, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), arteriovenous separation performance, and beam hardening artifact (BHA) index of two sets of images were measured or calculated. The subjective image quality and immediate patient safety were also scored using the three-point method. Results: Group B had a contrast dose reduction by 42.5 % (60 vs. 34.5 mL). Radiation exposure dose was not statistically different between the two groups (P>0.05). CT values of different-level PAs on group B images were higher than those on group A images (P<0.05). Group B images had higher SNR and CNR, better arteriovenous separation between PA trunk and pulmonary vein, and lower BHA index on soft tissue and PA (all P<0.05). For subjective evaluation of image quality, group B had a better score in beam hardening artifact (P<0.05). For immediate patient safety, the score in comfortability was statistically higher in group B, with P<0.05. Conclusions: Comparing with the normal injection method, pre-dual-flow spectral CTPA with a lower contrast dose injected results in better image quality and shows potential in patient-safety promotion.