CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors.

Claudin18.2 has been recently recognized as a potential therapeutic target for gastric/gastroesophageal junction or pancreatic cancer. Here, we develop a Claudin18.2-directed antibody-drug conjugate (ADC), CMG901, with a potent microtubule-targeting agent MMAE (monomethyl auristatin E) and evaluate its preclinical profiles. In vitro studies show that CMG901 binds specifically to Claudin18.2 on the cell surface and kills tumor cells through direct cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and bystander killing activity. In vivo pharmacological studies show significant antitumor activity in patient-derived xenograft (PDX) models. Toxicity studies show that the major adverse effects related to CMG901 are reversible hematopoietic changes attributed to MMAE. The highest non-severely toxic dose (HNSTD) is 6 mg/kg in cynomolgus monkeys and 10 mg/kg in rats once every 3 weeks. CMG901's favorable preclinical profile supports its entry into the human clinical study. CMG901 is currently under phase 3 investigation in patients with advanced gastric/gastroesophageal junction adenocarcinoma expressing Claudin18.2 (NCT06346392).

Sustainable design and synthesis of high-performance lignin-based sunscreen ingredients.

The active ingredients most commonly employed in sunscreens are compounds containing one or two aromatic rings. Lignin is the most abundant renewable aromatic polymer that has the potential to yield low molecular weight aromatic chemicals when strategically depolymerized. Here, the UV absorbance of a series of monomeric and dimeric lignin model compounds (LMCs) were studied. Specifically, vanillin and ferulic acid demonstrated good absorption in the UVB (280-320 nm) range, while the 5-5 dimer showed efficient absorption in the UVA (320-400 nm) range. Based on this, vanillin, ferulic acid and 5-5 dimer were mixed in pairs and dispersed in the oily isoeugenol to prepare LMC hybrid dispersions. Subsequently, demethylated lignin (DL) was synthesized and used to encapsulate the LMC hybrid dispersions via ultrasonic cavitation to prepare DL-based nano-capsules (DLNCs). The DLNCs were used as the only active ingredient in sunscreens, whose sun protection factor (SPF) value could be up to 55 with a dosage of 10 wt%. Due to anti-photolysis property of DL, the SPF value of DLNCs-based sunscreens increased initially and maintained >8 h under UV irradiation. Additionally, the prepared DLNCs exhibited excellent anti-permeability, antioxidant capacity and biocompatibility, making them a potential substitute for conventional petroleum-based sunscreen agents.

Comparison of intravascular ultrasound-guided with optical coherence tomography-guided percutaneous coronary intervention for left main distal bifurcation lesions: Rationale and design of the ISOLEDS trial.

BACKGROUND: Percutaneous coronary intervention (PCI) can provide benefits for anatomically suitable left main coronary artery (LMCA) lesions. When compared to traditional coronary angiography (CAG) -guided PCI, the use of intravascular ultrasound (IVUS) guidance has shown significant long-term prognostic improvements in LMCA PCI. Optical coherence tomography (OCT) offers a higher axial resolution than IVUS. However, there is currently a lack of relevant randomized controlled trials investigating the use of OCT specifically for left main distal bifurcation lesions. METHODS: The ISOLEDS trial is an ongoing multicenter study that aims to compare IVUS-guided PCI with OCT-guided PCI for patients with true LMCA distal bifurcation lesions. This prospective, randomized, controlled, non-inferiority trial will enroll a total of 664 patients with visually-defined Medina 1,1,1 or 0,1,1 classification of left main distal bifurcation lesions. The patients will be randomly assigned in a 1:1 ratio to either IVUS-guided or OCT-guided PCI. The primary endpoint is to assess the occurrence of target lesion failure (TLF) within 12 months after the procedure. After undergoing PCI, patients are required to visit the hospital for a 12-month clinical follow-up. During this clinical assessment, CAG can be performed to evaluate the status of target lesions. DISCUSSION: The ISOLEDS trial represents the first attempt to compare two distinct intracoronary imaging techniques for guiding PCI in patients with true LMCA distal bifurcation lesions. By evaluating and comparing the outcomes of these two imaging techniques, the trial results will aid operators in selection of the most effective approach for guiding PCI in these patients.

The influence of knee position during static calibration trials on evaluation of knee loading during gait in individual with medial knee osteoarthritis.

Quantitative three-dimensional gait analysis has been used to evaluate the loading at the knee (i.e. external knee adduction moment, EKAM) during level ground walking in individuals with knee osteoarthritis (OA). The magnitude of EKAM can be influenced by some factors, such as knee marker position and foot placement angles in static calibration trials, which may lead to inaccurate functional assessments and intervention planning. This study aimed to clarify the effects of knee position during static calibration trials on the evaluation of knee loading during gait in individuals with medial knee OA. Seventeen individuals with medial knee OA completed three different static standing trials; (1) knee flexed at 0 degrees, (2) knee flexed at 15 degrees, and (3) knee flexed at 30 degrees before walking at their self-selected speed. A sixteen-camera three-dimensional VICON gait analysis system with four AMTI force platforms was used to collect the EKAM, knee adduction angular impulse (KAAI), knee joint center (KJC), and other knee kinematic and kinetic variables during gait. A repeated measures ANOVA was used to investigate the differences between conditions. The 1st peak of EKAM, the 1st peak EKAM arm, KAAI, and knee extension moment were significantly increased at the 15-degree and 30-degree conditions in comparison with the 0-degree condition (P < 0.05). Additionally, the knee flexion moment and knee external rotation moment were significantly reduced at the 15-degree and 30-degree conditions in comparison with the 0-degree condition (P < 0.05). All biomechanical variables were influenced by the localization of the KJC during static calibration trials. The changes in knee position during static trials significantly affected the 1st peak EKAM, KAAI, and other knee kinematics and kinetics variables during gait. Therefore, future studies should consider keeping the participants' knees in a consistent position during static trials between visits, as the variations in knee position could mask or exaggerate the differences between groups and interventions.

Patency and factors related to patency after percutaneous transluminal angioplasty for inflow arterial stenosis in native arteriovenous fistula dysfunction: a single-center retrospective study.

Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan-Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan-Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P < 0.05), but the groups had similar secondary patency. Cox proportional hazard analysis indicated that none of the analyzed clinical and biochemical indexes had clinically meaningful effects on primary patency, assisted primary patency, or secondary patency in either group. The patency and safety after PTA for inflow arterial stenosis were satisfactory, and none of the examined risk factors had a major clinical impact on patency. We recommend PTA as treatment for inflow stenosis of an AVF.

Reduction of prolonged excitatory neuron swelling after spinal cord injury improves locomotor recovery in mice.

Spinal cord injury (SCI) results in acute damage and triggers secondary injury responses with sustained neuronal loss and dysfunction. However, the underlying mechanisms for these delayed neuronal pathologies are not entirely understood. SCI results in the swelling of spinal neurons, but the contribution of cell swelling to neuronal loss and functional deficits after SCI has not been systematically characterized. In this study, we devised a three-dimensional image analysis pipeline to evaluate spinal neurons, examining their types, quantities, volumes, and spatial distribution in a double-lateral hemisection SCI mouse model. We found that both excitatory and inhibitory neurons swell and are lost, albeit with distinct temporal patterns. Inhibitory neurons demonstrated marked swelling and decline in number on day 2 after SCI, which resolved by day 14. In contrast, excitatory neurons maintained persistent swelling and continued cell loss for at least 35 days after SCI in mice. Excitatory neurons exhibited sustained expression of the Na+-K+-Cl- cotransporter 1 (NKCC1), whereas inhibitory neurons down-regulated the protein by day 14 after SCI. Treatment with a Food and Drug Administration-approved NKCC1 inhibitor, bumetanide, mitigated swelling of excitatory neurons and reduced their loss in the secondary injury phase after SCI. The administration of bumetanide after SCI in mouse improved locomotor recovery, with functional benefits persisting for at least 4 weeks after treatment cessation. This study advances our understanding of SCI-related pathology and introduces bumetanide as a potential treatment to mitigate sustained neuronal swelling and enhance recovery after SCI.

Emergence and transmission of the high-risk ST78 clone of OXA-48-producing Enterobacter hormaechei in a single hospital in Taiwan.

Carbapenem-resistant Enterobacter cloacae complex is a significant global healthcare threat, particularly carbapenemase-producing Enterobacter hormaechei (CPEH). From January 2017 to January 2021, twenty-two CPEH isolates from a regional teaching hospital in central Taiwan were identified with the carriage of carbapenemase genes blaKPC-2, blaIMP-8, and predominantly blaOXA-48. Over 80% of these CPEH strains clustered into the high-risk ST78 lineage, carrying a blaOXA-48 IncL plasmid (pOXA48-CREH), nearly identical to the endemic plasmid pOXA48-KP in ST11 Klebsiella pneumoniae. This OXA-48-producing ST78 lineage disseminated clonally from 2018 to 2021 and transferred pOXA48-CREH to ST66 and ST90 E. hormaechei. An IMP-8-producing ST78 strain harbouring a blaIMP-8-carrying pIncHI2 plasmid appeared in 2018, and by late 2020, a KPC-2-producing ST78 strain was identified after acquiring a novel blaKPC-2-carrying IncFII plasmid. These findings suggest that the high-risk ST78 lineage of E. hormaechei has emerged as the primary driver behind the transmission of CPEH. ST78 has not only acquired various carbapenemase-gene-carrying plasmids but has also facilitated the transfer of pOXA48-CREH to other lineages. Continuous genomic surveillance and targeted interventions are urgently needed to control the spread of emerging CPEH clones in hospital settings.

Base-Promoted Ring Expansion Reaction of 4-Quinolones To Access Benzazepinones.

4-Quinolone derivatives undergo an unexpected ring expansion reaction with α-halo esters/phosphonates/sulfones in the presence of a base, such as NaH, to produce novel benzazepinones. Under these mild and transition-metal-free conditions, most substrates gave moderate to excellent yields. The reaction could be applied in gram-scale synthesis of drug-like molecules that greatly accelerated our structure-activity relationship studies. A plausible mechanism was proposed.

A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer.

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease's prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin's ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin's application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies.

Plants' molecular behavior to heavy metals: from criticality to toxicity.

The contamination of soil and water with high levels of heavy metals (HMs) has emerged as a significant obstacle to agricultural productivity and overall crop quality. Certain HMs, although serving as essential micronutrients, are required in smaller quantities for plant growth. However, when present in higher concentrations, they become very toxic. Several studies have shown that to balance out the harmful effects of HMs, complex systems are needed at the molecular, physiological, biochemical, cellular, tissue, and whole plant levels. This could lead to more crops being grown. Our review focused on HMs' resources, occurrences, and agricultural implications. This review will also look at how plants react to HMs and how they affect seed performance as well as the benefits that HMs provide for plants. Furthermore, the review examines HMs' transport genes in plants and their molecular, biochemical, and metabolic responses to HMs. We have also examined the obstacles and potential for HMs in plants and their management strategies.

Association of overall survival benefit of radiotherapy with progression-free survival after chemotherapy for diffuse large B-cell lymphoma: A systematic review and meta-analysis.

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639-0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882-0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60-80%, >40-60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51-0.97) to 0.48 (95% CI, 0.36-0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

Substrate-directed regioselective alkene functionalizations of (E)-ß,γ-unsaturated carboxylic acids.

A carboxylate-directed regioselective Heck-type alkenylation and alkenylative lactonization of (E)-ß,γ-unsaturated carboxylic acids by simply substrate control is reported. (E)- and (Z)-alkenyl bromides reacted to give energetically more favorable palladacyles, allowing access to fully stereocontrolled conjugated 1,3-dienes and alkenyled γ-lactones. Mechanistic studies suggest that excellent regioselectivity may be strongly influenced by the steric factors of reactants involved in the palladacycle intermediates.

[Investigation on cognition for insomnia and preference for acupuncture in breast cancer survivors: a in-depth interview study].

OBJECTIVE: To understand the cognition for insomnia and preference for acupuncture in breast cancer survivors based on the in-depth interview. METHODS: Thirty breast cancer survivors with insomnia symptoms were collected for in-depth interview. The interview questions included three aspects, i.e. sleep expectation, cognition for insomnia (discomfort caused by insomnia, and underlying inducing factors of insomnia) and the preference for acupuncture (treatment methods used in the past, the reasons for not choosing acupuncture, and the tendency of acupuncture treatment). Using Colaizzi content analysis method, the data was analyzed. RESULTS: Regarding sleep expectation, most breast cancer survivors with insomnia symptoms were able to maintain normal activity in daytime. Insomnia symptoms often led to fatigue, and the inducing factors of insomnia referred to the treatment with endocrine therapy, anticipatory anxiety and inadequate sleep hygiene. All of the patients had received pharmacotherapy. The use proportion of non-pharmacological therapies was relatively low, and acupuncture was not chosen due to "not familiar with" and "fear of pain". Concerning to the preference for acupuncture, patients preferred the therapeutic methods of acupuncture with mild pain sensation and gentle stimulation; and the treatment should be more acceptable if delivered 2 or 3 times a week. CONCLUSION: Breast cancer survivors have the expectations for sleep, and are willing to receive the treatment with medication for their sleep disorders. Because of lack of the knowledge for acupuncture effect on insomnia and fear of strong needling sensation, a part of patients are unwilling to be treated with acupuncture therapy, but they are expected to receive the treatment with acupuncture while feeling more comfortable.

Comparison of Superselective Renal Artery Embolization versus Retroperitoneal Laparoscopic Partial Nephrectomy in Ruptured Hemorrhagic Renal Angiomyolipoma: A Single-Center Study.

PURPOSE: To analyze the clinical efficacy of superselective renal artery embolization and retroperitoneal laparoscopic partial nephrectomy for the treatment of ruptured hemorrhagic renal angiomyolipoma and to provide a reference for the selection of treatment methods for ruptured hemorrhagic renal angiomyolipoma. METHODS: A retrospective analysis was conducted on the clinical data of 24 patients who were diagnosed with ruptured hemorrhagic renal angiomyolipoma at the Second Hospital of Tianjin Medical University between January 2019 and December 2021. Among them, 10 patients were treated with superselective arterial embolization (SAE), and 14 patients were treated with retroperitoneal laparoscopic part nephrectomy (RLPN). The differences between the two treatment methods in terms of hospital stay, hospital costs, anesthesia method, operation time, intraoperative blood loss, postoperative bed rest time, antibiotic dosage, postoperative complication rate, tumor diameter changes, creatinine value changes, hemoglobin value changes, tumor recurrence rate, and reoperation rate were compared. RESULTS: All patients completed the treatment and were discharged. There were no significant differences in length of hospital stay, hospital costs, creatinine change values, or postoperative complication rates between the two groups (p > 0.05). However, there were statistically significant differences (p < 0.05) in surgical time (85.50 ± 19.94 min vs. 141.07 ± 76.33 min), intraoperative blood loss (21.50 ± 14.72 mL vs. 153.57 ± 97.00 mL), postoperative bed rest time (22.7 ± 1.56 h vs. 41.21 ± 3.57 h), preoperative hemoglobin levels (94.7 ± 23.62 g/L vs. 113.79 ± 17.83 g/L), and hemoglobin changes (-6.60 ± 10.36 g/L vs. -15.21 ± 8.79 g/L) between the two groups. Both groups of patients had an average follow-up period of 22 months, and patients in the SAE group had a mean reduction of 3.33 cm in tumor diameter within the follow-up period compared with the pre-embolization period (p < 0.05). None of the patients in the SAE group experienced rebleeding, and there was no tumor recurrence in either group. CONCLUSION: SAE and RLPN are effective treatments for ruptured renal angiomyolipoma with good outcomes. Furthermore, compared to RLPN, SAE offers advantages such as simplicity of operation, minimal trauma, shorter surgical time, minimal impact on hemoglobin levels, shorter bed rest time, faster postoperative recovery, and maximal preservation of renal units.

Increase in short-term and long-term stress-associated mental illness after Jiji earthquake in Taiwan: A twenty-year longitudinal population-based cohort study (1999-2019).

BACKGROUND: Earthquakes have caused profound physical and mental health impacts in human history. The Jiji earthquake, which had a magnitude of 7.6 on the Richter scale, occurred on 21 September 1999 in Taiwan. A close follow-up on the mental health status of affected adults after major natural disasters to construct the short-term and long-term risk and prevalence of stress-associated mental illnesses has not been performed by using the nationwide health databases. METHODS: This population-based cohort study included 468,804 adults affected by Jiji earthquake spanning from 2000 to 2019 who were matched at a 1:4 ratio with unaffected individuals based on age and sex (n = 1,875,216). Employing a subdistribution hazard regression analysis, we assessed the incidence of sleep, anxiety, and depressive disorders after Jiji earthquake. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS: Affected adults experienced an increased incidence of short-term (approximately twice) stress-associated psychiatric disorders. The risk of the post-traumatic stress disorder (PTSD) is significantly higher in the affected adults (40-64 years: aSHR: 92.0; ≥65 years: aSHR: 96.7, p < 0.0001). Middle-aged (aged 40-64 years) male adults presented with significantly more short-term (< one year) and long-term (up to 20 years) stress-related mental illnesses, i.e., insomnia, anxiety, and depressive disorders, than individuals in the control group. CONCLUSIONS: An earthquake has significant short and long-term effects on sleep quality, anxiety, and depressive disorders in affected adults. Optimal short and long-term close monitoring is needed to deploy medical resources and socioeconomic support to relieve mental stress burdens.

Evaluation of carotid artery elasticity and its influencing factors in non-obese PCOS patients using a technique for quantitative vascular elasticity measurement.

Objectives: To evaluate the intima-media thickness (IMT) and elasticity of the carotid artery in non-obese polycystic ovary syndrome (PCOS) patients using a quantitative technique for vascular elasticity measurement and to explore the influencing factors. Methods: Sixty non-obese patients without metabolic and cardiovascular diseases who were diagnosed with PCOS in the Women and Children's Hospital of Chongqing Medical University from January to December 2022 were prospectively selected (case group), and 60 healthy volunteers matched for body mass index were included as the control group. Body weight, height, heart rate, blood pressure, and waist-to-hip ratio were recorded. Fasting blood samples were drawn from the elbow vein to measure hormone levels including total testosterone (TT), sex hormone-binding globulin (SHBG), fasting plasma glucose (FPG), fasting insulin (FINS), lipids, and homocysteine (Hcy). The insulin resistance index (HOMA-IR) and free androgen index (FAI) were calculated. Ultrasound elastography was used to measure the IMT and elastic function parameters of the right carotid artery, including vessel diameter, wall displacement, stiffness coefficient, and pulse wave velocity. Differences in various parameters between the two groups were analyzed, and correlations between the carotid stiffness coefficient and other serological indicators were assessed using Spearman correlation analysis. Results: No significant differences in age, body mass index, heart rate, systolic blood pressure, and diastolic blood pressure were observed between the two groups (all P>0.05), while the waist-to-hip ratio (WHR) was higher in the case group than in the control group (P<0.05).The hormone level serological indicators TT and FAI were higher in the case group than in the control group, and SHBG was lower in the case group than in the control group (all P<0.05). The metabolism-related serum indicators LDL-C, HDL-C, FPG, triglycerides, and total cholesterol levels were not statistically different between the two groups (all P>0.05), and serum FINS, HOMA-IR, and Hcy levels were significantly higher in the case group than in the control group (all P<0.05).No significant difference in carotid artery diameter was observed between the case group and control group (P>0.05). The carotid artery displacement in the case group was significantly smaller than that in the control group (P<0.05), and carotid IMT, hardness coefficient, and pulse wave propagation velocity were greater in the case group than in the control group (all P<0.05). The carotid elastic stiffness coefficient was positively correlated with WHR, TT, SHBG, FAI, FINS, HOMA-IR and Hcy to varying extents and negatively correlated with SHBG. Conclusion: In non-obese PCOS patients with no metabolic or cardiovascular disease, the carotid stiffness coefficient was increased and correlated with indicators of hyperandrogenism, insulin resistance, and hyperhomocysteinemia.

Bioactive Macromolecule-mediated Biogenic FeONPs Attenuate Inflammation in Atherosclerotic Rat by Activating PI3K/Akt/eNOS Pathway.

INTRODUCTION: Atherosclerosis refers to the thickening and hardening of artery walls. In our latest experiment, we utilized environmentally friendly techniques to produce multifunctional iron oxide nanoparticles (FeONPs) aimed at reducing inflammation in rats with atherosclerosis. METHOD: The formulation was synthesized using curcumin (as the potent bioactive molecule) and was characterized. We assessed the in vitro antioxidant capability of the formulation against DPPH free radicals. Additionally, we quantified the mRNA levels of eNOS, PI3K, and AKT using Real Time-Polymerase Chain Reaction (RT-PCR). We tested the therapeutic impact of the bioactive formulation on a Triton X-100-induced atherosclerosis mouse model. RESULTS: The crystallinity and magnetic behavior confirmed the magnetic properties of the FeONPs. The DPPH assay exhibited the dose-dependent radical scavenging characteristics of FeONPs. In the animal experiments, significant upregulation of the studied genes was noticed in treated groups 2 and 3 compared to treated group 1. Moreover, the expression of PI3K/eNOS/Akt was greater in treated group 3 than in treated group 2. These results indicate a dose-dependent elevation in target gene expression. CONCLUSION: Nevertheless, the variation in gene expression between the negative control and the untreated control was not statistically significant (p > 0.05) across all genes.

Traditional Chinese medicine interventions based on meridian theory for pain relief in patients with primary dysmenorrhea: a systematic review and network meta-analysis.

Objective: To determine the comparative effects and safety of traditional Chinese medicine (TCM) interventions based on meridian theory for pain relief in patients with primary dysmenorrhea (PD). Methods: This is a systematic review with network meta-analysis. Randomized controlled trials (RCTs) comparing meridian-based TCM interventions with waitlist, placebo, western medicine, and conventional therapies for PD pain. A SUCRA was used to estimate the probability ranking for the effects of interventions. Results: 57 RCTs involving 3,903 participants and 15interventions were included. Thirty-two RCTs were rated as low risk of bias. A network diagram was drawn with 105 pairs of comparisons. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = -1.51, 95%CI (-2.91, -0.12)/SMD = -2.31, 95%CI (-4.61, -0.02)], warm needling [SMD = -1.43, 95%CI (-2.68, -0.18)/SMD = -2.23, 95%CI (-4.43, -0.03)], moxibustion [SMD = -1.21, 95%CI (-1.85, -0.57)/SMD = -2.10, 95%CI (-3.95, -0.07)], and acupuncture [SMD = -1.09, 95%CI (-1.62, -0.55)/SMD = -1.89, 95%CI (-3.67, -0.11)]. No adverse events were detected. Conclusion: For PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. More high-quality clinical trials are needed to provide more robust evidence of this network. Systematic review registration: PROSPERO CRD42022373312.

Sphingosine kinase 1 aggravates liver fibrosis by mediating macrophage recruitment and polarization.

BACKGROUND & AIMS: Sphingosine kinase 1 (SphK1) has distinct roles in the activation of Kupffer cells (KCs) and hepatic stellate cells (HSCs) in liver fibrosis. Here, we aim to investigate the roles of SphK1 on hepatic macrophage recruitment and polarization in liver fibrosis. METHODS: Liver fibrosis was induced by carbon tetrachloride (CCl4) in wild-type and SphK1-/- mice to study the recruitment and polarization of macrophages. The effects of SphK1 originated from macrophages or other liver cell types on liver fibrosis were further strengthened by bone marrow transplantation (BMT). The direct effects of SphK1 on macrophage polarization were also investigated in vitro. Expression analysis of SphK1 and macrophage polarization index was conducted with human liver samples. RESULTS: SphK1 deletion attenuated the recruitment of hepatic macrophages along with reduced M1 and M2 polarization in mice induced by CCl4. SphK1 deficiency in endogenous liver cells attenuated macrophage recruitment via CCL2. Macrophage SphK1 activated the ASK1-JNK1/2-p38 signaling pathway to promote M1 polarization. Furthermore, macrophage SphK1 downregulated small ubiquitin-like modifier (SUMO) specific peptidase1 (SENP1) to decrease de-SUMOylation of Kruppel-like factor 4 (KLF4) to promote M2 polarization. Finally, we confirmed that SphK1 expression was elevated and positively correlated with macrophage M1 and M2 polarization in human fibrosis livers. CONCLUSIONS: Our findings demonstrated that SphK1 aggravated liver fibrosis by promoting macrophage recruitment and M1/M2 polarization. SphK1 in macrophages is a potential therapeutic target for the treatment of liver fibrosis.

The feasibility of a novel method to remove circumferentially ruptured balloons during ultrasound-guided percutaneous transluminal angioplasty for arteriovenous dialysis access.

OBJECTIVE: Angioplasty balloon rupture is a rare complication during percutaneous transluminal angioplasty (PTA). Conventional approach to retrieve circumferentially ruptured balloons is open surgery. This study examined the feasibility of a novel approach which can remove ruptured balloon during PTA in vascular access. METHODS: This retrospective study analyzed 35 patients of a total 6465 patients that underwent ultrasound-guided PTA with a circumferential balloon rupture from February 2016 and August 2023. The patients underwent surgery (Group I, n = 13) or the novel method (Group II, n = 22) for balloon retrieval. Kaplan-Meier curve was used to assess the primary patency rates of the two groups. RESULT: The total incidence of circumferential balloon rupture was 0.5% in our center. Balloon retrieval was successful in both groups with no complications except one case had an infection in the surgical wound. Kaplan-Meier curve analysis showed that the post-intervention primary patency rates of the two methods were not significantly different (p > 0.05). There was a significant difference between pre-operation and post-operation brachial arterial flow (p < 0.001). CONCLUSION: The feasibility of the novel technique for retrieval of circumferential ruptured balloons during ultrasound-guided PTA is validated. The technique enables less invasive retrieval and continuation of PTA.