Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation.

STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Different extramedullary disease shown in chemokine receptor 4 targeted PET/CT with [68Ga]Ga-pentixafor in patients with Waldenström macroglobulinemia and smoldering disease.

INTRODUCTION: It is important to distinguish Waldenström macroglobulinemia from smoldering Waldenström macroglobulinemia (sWM), because only patients with Waldenström macroglobulinemia require treatment, however the distinction can be clinically complex. The aim of this study is to investigate whether [68Ga]Ga-pentixafor PET/CT shows different characteristics in sWM and Waldenström macroglobulinemia patients and therefore can help to differentiate Waldenström macroglobulinemia and sWM. RESULTS: Thirty-seven patients with newly diagnosed Waldenström macroglobulinemia and 11 sWM patients were analyzed [35 men and 13 women; 64.3 ±â€…10.7 (range, 29-87) years old]. The SUVmax of bone marrow disease, lymph nodes, and other extramedullary diseases on [68Ga]Ga-pentixafor were significantly higher than those on 2-[18F]FDG PET/CT (P < 0.05). On [68Ga]Ga-pentixafor PET/CT, patients with Waldenström macroglobulinemia had more lymph node regions involved, significantly higher incidence of involvement in more than three lymph node regions, larger nodal disease, and higher incidence of other extramedullary disease when compared with sWM patients (P < 0.05). Waldenström macroglobulinemia patients showed significantly higher total lesions uptake, total lesion volume, and SUVmax of extramedullary disease than sWM patients did (P < 0.05). None of the visual or semiquantitative indexes in 2-[18F]FDG PET/CT showed significant difference between Waldenström macroglobulinemia and sWM patients. CONCLUSION: [68Ga]Ga-pentixafor PET/CT had better diagnostic performance than 2-[18F]FDG PET/CT in Waldenström macroglobulinemia. Patients with Waldenström macroglobulinemia presented with more extensive extramedullary disease shown in [68Ga]Ga-pentixafor PET/CT than sWM patients did.

TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway.

OBJECTIVE: Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage. Notably, the knockout of transient receptor potential channel 6 (TRPC6) has shown promise in alleviating renal fibrosis. However, the regulatory impact of TRPC6 on renal fibrosis remains unclear. METHODS: In vivo, TRPC6 knockout (TRPC6-/-) mice and age-matched 129 SvEv (WT) mice underwent unilateral renal ischemia-reperfusion (uIR) injury surgery on the left renal pedicle or sham operation. Kidneys and serum were collected on days 7, 14, 21, and 28 after euthanasia. In vitro, primary tubular epithelial cells (PTECs) were isolated from TRPC6-/- and WT mice, followed by treatment with transforming growth factor ß1 (TGFß1) for 72 h. The anti-fibrotic effect of TRPC6-/- and the underlying mechanisms were assessed through hematoxylin-eosin staining, Masson staining, immunostaining, qRT-PCR, and Western blotting. RESULTS: Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFß1. TRPC6-/- alleviated renal fibrosis by reducing the expression of fibrotic markers (Col-1, α-SMA, and vimentin), as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro. Additionally, we found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3ß) signaling pathway, a pivotal player in renal fibrosis, was down-regulated following TRPC6 deletion. CONCLUSION: These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3ß pathway. Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

A novel model incorporating quantitative contrast-enhanced ultrasound into PI-RADSv2-based nomogram detecting clinically significant prostate cancer.

The diagnostic accuracy of clinically significant prostate cancer (csPCa) of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) is limited by subjectivity in result interpretation and the false positive results from certain similar anatomic structures. We aimed to establish a new model combining quantitative contrast-enhanced ultrasound, PI-RADSv2, clinical parameters to optimize the PI-RADSv2-based model. The analysis was conducted based on a data set of 151 patients from 2019 to 2022, multiple regression analysis showed that prostate specific antigen density, age, PI-RADSv2, quantitative parameters (rush time, wash-out area under the curve) were independent predictors. Based on these predictors, we established a new predictive model, the AUCs of the model were 0.910 and 0.879 in training and validation cohort, which were higher than those of PI-RADSv2-based model (0.865 and 0.821 in training and validation cohort). Net Reclassification Index analysis indicated that the new predictive model improved the classification of patients. Decision curve analysis showed that in most risk probabilities, the new predictive model improved the clinical utility of PI-RADSv2-based model. Generally, this new predictive model showed that quantitative parameters from contrast enhanced ultrasound could help to improve the diagnostic performance of PI-RADSv2 based model in detecting csPCa.

Optimizing Triage: Assessing Shock Index, Pediatric Age-Adjusted as an Adjunct to Improve Emergency Severity Index Mistriage.

OBJECTIVE: We investigated the diagnostic value of shock index, pediatric age-adjusted (SIPA) in predicting Emergency Severity Index level 3 patients' outcomes. Secondary objectives included exploring the impact of fever and participant variables on SIPA's predictive ability. METHODS: A retrospective chart review identified children aged 1 to 15 years triaged as a level 3 in the emergency department between January 2018 and December 2021. Shock index, pediatric age-adjusted thresholds based on age, 1 to 6 years (>1.2), 7 to 12 years (>1.0), and 13 to 17 years (>0.9), were used. We assessed elevated SIPA and SIPA corrected for fever to evaluate associations with outcomes and interventions. RESULTS: Our findings, involving 192 patients, revealed that elevated SIPA demonstrated enhanced discrimination relative to nonelevated SIPA. Patients with elevated SIPA had more average interventions: 1.14 versus 0.74, P < 0.016; average interventions using SIPA corrected for fever: 1.14 versus 0.77, P < 0.006; average interventions controlling for race and sex: 1.15 versus 0.71, P < 0.001; hospital admission: 64.4% versus 42.9%, P = 0.004; hospital length of stay (LOS): 3.06 days (SE, 0.42) versus 1.46 days (SE, 0.23); hospital LOS using SIPA corrected for fever: 2.75 days (SE, 0.44) versus 1.72 days (SE, 0.24); ventilatory support: 16.44% versus 3.36%, P < 0.002; fluid bolus: 28.77% versus 14.29%, P < 0.015; intravenous medications (antibiotics, antiepileptics, immune globulin, albumin): 45.21% versus 30.25%, P < 0.036. There was no difference between other interventions, pediatric intensive care admission, and LOS between the 2 groups. Importantly, SIPA was unaffected by fever, race, or sex. CONCLUSIONS: Shock index, pediatric age-adjusted identifies level 3 Emergency Severity Index pediatric patients more likely to require hospital admission, longer LOS, and a lifesaving intervention especially ventilatory support, intravenous fluids, or specific intravenous medications. Shock index, pediatric age-adjusted's predictive ability remained unaffected by fever, race, or sex, making it a valuable tool in preventing mistriage and justifying inclusion in the Emergency Severity Index danger zone vitals criteria for up-triage.

Structural basis for raccoon dog receptor recognition by SARS-CoV-2.

Since the COVID-19 outbreak, raccoon dogs have been suggested as a potential intermediary in transmitting SARS-CoV-2 to humans. To understand their role in the COVID-19 pandemic and the species barrier for SARS-CoV-2 transmission to humans, we analyzed how their ACE2 protein interacts with SARS-CoV-2 spike protein. Biochemical data showed that raccoon dog ACE2 is an effective receptor for SARS-CoV-2 spike protein, though not as effective as human ACE2. Structural comparisons highlighted differences in the virus-binding residues of raccoon dog ACE2 compared to human ACE2 (L24Q, Y34H, E38D, T82M, R353K), explaining their varied effectiveness as receptors for SARS-CoV-2. These variations contribute to the species barrier that exists between raccoon dogs and humans regarding SARS-CoV-2 transmission. Identifying these barriers can help assess the susceptibility of other mammals to SARS-CoV-2. Our research underscores the potential of raccoon dogs as SARS-CoV-2 carriers and identifies molecular barriers that affect the virus's ability to jump between species.

Establishment of Transgene-Free Porcine Induced Pluripotent Stem Cells.

Although protocols to generate authentic transgene-free mouse and human induced pluripotent stem cells (iPSCs) are now well established, standard methods for reprogramming porcine somatic cells still suffer from low efficiency and transgene retention. The Basic Protocol describes reprogramming procedures to establish transgene-free porcine iPSCs (PiPSCs) from porcine fibroblasts. This method uses episomal plasmids encoding POU5F1, SOX2, NANOG, KLF4, SV40LT, c-MYC, LIN28A, and microRNA-302/367, combined with an optimized medium, to establish PiPSC lines. Support protocols describe the establishment and characterization of clonal PiPSC lines, as well as the preparation of feeder cells and EBNA1 mRNA. This optimized, step-by-step approach tailored to this species enables the efficient derivation of PiPSCs in ∼4 weeks. The establishment of transgene-free PiPSCs provides a new and valuable model for studies of larger mammalian species' development, disease, and regenerative biology. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Reprogramming of porcine fibroblasts with episomal plasmids Support Protocol 1: Preparation of mouse embryonic fibroblasts for feeder layer Support Protocol 2: Preparation of in vitro-transcribed EBNA1 mRNA Support Protocol 3: Establishment of clonal porcine induced pluripotent stem cell (PiPSC) lines Support Protocol 4: PiPSC characterization: Genomic DNA PCR and RT-PCR Support Protocol 5: PiPSC characterization: Immunostaining.

An association study of m6A methylation with major depressive disorder.

OBJECTIVE: To find the relationship between N6-methyladenosine (m6A) genes and Major Depressive Disorder (MDD). METHODS: Differential expression of m6A associated genes between normal and MDD samples was initially identified. Subsequent analysis was conducted on the functions of these genes and the pathways they may affect. A diagnostic model was constructed using the expression matrix of these differential genes, and visualized using a nomogram. Simultaneously, an unsupervised classification method was employed to classify all patients based on the expression of these m6A associated genes. Following this, common differential genes among different clusters were computed. By analyzing the functions of the common differential expressed genes among clusters, the role of m6A-related genes in the pathogenesis of MDD patients was elucidated. RESULTS: Differential expression was observed in ELAVL1 and YTHDC2 between the MDD group and the control group. ELAVL1 was associated with comorbid anxiety in MDD patients. A linear regression model based on these two genes could accurately predict whether patients in the GSE98793 dataset had MDD and could provide a net benefit for clinical decision-making. Based on the expression matrix of ELAVL1 and YTHDC2, MDD patients were classified into three clusters. Among these clusters, there were 937 common differential genes. Enrichment analysis was also performed on these genes. The ssGSEA method was applied to predict the content of 23 immune cells in the GSE98793 dataset samples. The relationship between these immune cells and ELAVL1, YTHDC2, and different clusters was analyzed. CONCLUSION: Among all the m6A genes, ELAVL1 and YTHDC2 are closely associated with MDD, ELAVL1 is related to comorbid anxiety in MDD. ELAVL1 and YTHDC2 have opposite associations with immune cells in MDD.

A nomogram based on neuron-specific enolase and substantia nigra hyperechogenicity for identifying cognitive impairment in Parkinson's disease.

Background: One in four individuals with Parkinson's disease (PD) experience cognitive impairment (CI). However, few practical models integrating clinical and neuroimaging biomarkers have been developed to address CI in PD. This study aimed to evaluate the correlation between circulating neuron-specific enolase (NSE) levels, substantia nigra hyperechogenicity (SNH), and cognitive function in PD and to develop a nomogram based on clinical and neuroimaging biomarkers for predicting CI in patients with PD. Methods: A total of 385 patients with PD who underwent transcranial sonography (TCS) from January 2021 to December 2022 at Beijing Tiantan Hospital, Capital Medical University, were recruited as the training cohort. For validation, 165 patients with PD treated from January 2023 to December 2023 were enrolled. Data for SNH, plasma NSE, and other clinical measures were collected, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Logistic regression analysis was employed to select potential risk factors and establish a nomogram. The receiver operating characteristic curve and calibration curve were generated to evaluate the performance of the nomogram. Results: Patients with PD exhibiting CI displayed advanced age, elevated Unified PD Rating Scale-III (UPDRS-III) score, an increased percentage of SNH, higher levels of plasma NSE and homocysteine (Hcy), a larger SNH area, and lower education levels compared to PD patients without CI. Gender [odds ratio (OR) =0.561, 95% confidence interval (CI): 0.330-0.954, P=0.03], age (OR =1.039; 95% CI: 1.011-1.066; P=0.005), education level (OR =0.892; 95% CI: 0.842-0.954; P<0.001), UPDRS-III scores (OR =1.026; 95% CI: 1.009-1.043; P=0.003), plasma NSE concentration (OR =1.562; 95% CI: 1.374-1.776; P<0.001), and SNH (OR =0.545; 95% CI: 0.330-0.902; P=0.02) were independent predictors of CI in patients with PD. A nomogram developed using these six factors yielded a moderate discrimination performance with an area under the curve (AUC) of 0.823 (95% CI 0.781-0.864; P<0.001). The calibration curve demonstrated acceptable agreement between predicted outcomes and actual values. Validation further confirmed the reliability of the nomogram, with an AUC of 0.864 (95% CI: 0.805-0.922; P<0.001). Conclusions: The level of NSE in plasma and the SNH assessed by TCS are associated with CI in patients with PD. The proposed nomogram has the potential to facilitate the detection of cognitive decline in individuals with PD.

Enzyme-Driven LC-HRMS Approach for Specific Recognition of 12α-Hydroxy Bile Acids.

The synthesis of 12α-hydroxylated bile acids (12HBAs) and non-12α-hydroxylated bile acids (non-12HBAs) occurs via classical and alternative pathways, respectively. The composition of these BAs is a crucial index for pathophysiologic assessment. However, accurately differentiating 12HBAs and non-12HBAs is highly challenging due to the limited standard substances. Here, we innovatively introduce 12α-hydroxysteroid dehydrogenase (12α-HSDH) as an enzymatic probe synthesized by heterologous expression in Escherichia coli, which can specifically and efficiently convert 12HBAs in vitro under mild conditions. Coupled to the conversion rate determined by liquid chromatography-high resolution mass spectrometry (LC-HRMS), this enzymatic probe allows for the straightforward distinguishing of 210 12HBAs and 312 non-12HBAs from complex biological matrices, resulting in a BAs profile with a well-defined hydroxyl feature at the C12 site. Notably, this enzyme-driven LC-HRMS approach can be extended to any molecule with explicit knowledge of enzymatic transformation. We demonstrate the practicality of this BAs profile in terms of both revealing cross-species BAs heterogeneity and monitoring the alterations of 12HBAs and non-12HBAs under asthma disease. We envisage that this work will provide a novel pattern to recognize the shift of BA metabolism from classical to alternative synthesis pathways in different pathophysiological states, thereby offering valuable insights into the management of related diseases.

MyoD1 promotes the transcription of BIK and plays an apoptosis-promoting role in the development of gastric cancer.

Myogenic differentiation (MyoD) 1, which is known as a pivotal transcription factor during myogenesis, has been proven dysregulated in several cancers. However, litter is known about the precise role and downstream genes of MyoD1 in gastric cancer (GC) cells. Here, we report that MyoD1 is lowly expressed in primary GC tissues and cells. In our experiments, overexpression of MyoD1 inhibited cell proliferation. Downstream genes of MyoD1 regulation were investigated using RNA-Seq. As a result, 138 up-regulated genes and 20 down-regulated genes and 27 up-regulated lncRNAs and 20 down-regulated lncRNAs were identified in MyoD1 overexpressed MKN-45 cells, which participated in epithelial cell signaling in Helicobacter pylori infection, glycosaminoglycan biosynthesis (keratan sulfate), notch signaling pathway, and others. Among these genes, BIK was directly regulated by MyoD1 in GC cells and inhibited cancer cell proliferation. The BIK knockdown rescued the effects of MyoD1 overexpression on GC cells. In conclusion, MyoD1 inhibited cell proliferation via 158 genes and 47 lncRNAs downstream directly or indirectly that participated in multiple signaling pathways in GC, and among these, MyoD1 promotes BIK transcription by binding to its promoter, then promotes BIK-Bcl2-caspase 3 axis and regulates GC cell apoptosis.

Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1.

BACKGROUND: While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure. METHODS: FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1. RESULTS: Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival. CONCLUSIONS: Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.

Online continual decoding of streaming EEG signal with a balanced and informative memory buffer.

Electroencephalography (EEG) based Brain Computer Interface (BCI) systems play a significant role in facilitating how individuals with neurological impairments effectively interact with their environment. In real world applications of BCI system for clinical assistance and rehabilitation training, the EEG classifier often needs to learn on sequentially arriving subjects in an online manner. As patterns of EEG signals can be significantly different for different subjects, the EEG classifier can easily erase knowledge of learnt subjects after learning on later ones as it performs decoding in online streaming scenario, namely catastrophic forgetting. In this work, we tackle this problem with a memory-based approach, which considers the following conditions: (1) subjects arrive sequentially in an online manner, with no large scale dataset available for joint training beforehand, (2) data volume from the different subjects could be imbalanced, (3) decoding difficulty of the sequential streaming signal vary, (4) continual classification for a long time is required. This online sequential EEG decoding problem is more challenging than classic cross subject EEG decoding as there is no large-scale training data from the different subjects available beforehand. The proposed model keeps a small balanced memory buffer during sequential learning, with memory data dynamically selected based on joint consideration of data volume and informativeness. Furthermore, for the more general scenarios where subject identity is unknown to the EEG decoder, aka. subject agnostic scenario, we propose a kernel based subject shift detection method that identifies underlying subject changes on the fly in a computationally efficient manner. We develop challenging benchmarks of streaming EEG data from sequentially arriving subjects with both balanced and imbalanced data volumes, and performed extensive experiments with a detailed ablation study on the proposed model. The results show the effectiveness of our proposed approach, enabling the decoder to maintain performance on all previously seen subjects over a long period of sequential decoding. The model demonstrates the potential for real-world applications.

Preperitoneal pelvic balloon tamponade-an effective intervention to control pelvic injury hemorrhage in a swine model.

Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model. Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration. Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group. Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury.

Review on the biological activities of Codonopsis Radix Tonic.

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis Radix, commonly known as Dangshen in Chinese, is frequently used to treat deficiencies of spleen and lung Qi, gastrointestinal discomfort, fatigue, asthmatic breathing, sallow complexion, lack of strength, shortness of breath, deficiencies of both Qi and blood, as well as impairments to both Qi and body fluids in suboptimal health status. AIM OF THE REVIEW: This review systematically expounds on the modern pharmacological studies related to the use of Codonopsis Radix in invigorating Qi and nourishing the body in recent years. The aim is to provide theoretical research and reference for the in-depth and systematic exploration and development of the applications of Codonopsis Radix in the fields of food and medicine. MATERIALS AND METHODS: This study employs "Codonopsis Radix," "Codonopsis," and "Dangshen" as keywords to gather pertinent information on Codonopsis Radix medicine through electronic searches of classical literature and databases such as PubMed, Elsevier, Google Scholar, Wiley, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Baidu Scholar. RESULTS: From previous studies, activities such as immune system modulation, gastrointestinal motility regulation, cardiac function revitalization, lung function improvement, blood circulation enhancement, aging process deceleration, learning and memory augmentation, fatigue resistance enhancement, and liver and kidney damage protection of Codonopsis Radix have been reported. Recognized as an important medicine and food homologous traditional Chinese herbal remedy for supplementing deficiencies, its mode of action is multi-elemental, multi-systemic, multi-organ, multi-mechanistic, and multi-targeted. Furthermore, the benefits of its tonic surpass its therapeutic value, establishing it as an extraordinary preventive and therapeutic medicine. CONCLUSIONS: With its long history of traditional applications and the revelations of contemporary pharmacological research, Codonopsis Radix exhibits great potential as both a therapeutic agent and dietary supplement for further research in medicine, nutrition, and healthcare.

Clinical Effects of Ultrasound-Guided Acupotomy in Knee Osteoarthritis Treatment.

The protocol presented here demonstrates the operation method of ultrasound-guided acupotomy for knee osteoarthritis (KOA), including patient recruitment, preoperative preparation, manual operation, and postoperative care. The purpose of this protocol is to relieve pain and improve knee function in patients with KOA. A total of 60 patients with KOA admitted between June 2022 and June 2023 were treated with ultrasound-guided acupotomy. Pathological changes and knee function scores were compared before and after the treatment. After 1 week of treatment, the synovial thickness of the suprapatellar bursae was significantly lesser than before treatment (p < 0.05), the Hospital for Special Surgery Knee Score (HSS) was significantly higher than before treatment (p < 0.05), the Visual analogue scale (VAS) was significantly lower than those of the control group (p < 0.05) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were significantly lower than those of the control group (p < 0.05). Therefore, ultrasound-guided acupotomy for the treatment of KOA can reduce synovial thickness, relieve pain, improve knee joint function, and have a remarkable curative effect.

Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease.

BACKGROUND: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell-like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis. METHODS: We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis. RESULTS: SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell-like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant KrasG12D in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. CONCLUSIONS: Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.

Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis.

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Psychometric properties and factor structure of the traditional Chinese version of the Community Integration Questionnaire-Revised in traumatic brain injury survivors.

This study aimed to translate and validate the traditional Chinese version of the Community Integration Questionnaire-Revised (TC-CIQ-R) in patients with traumatic brain injury (TBI). We included participants aged ≥20 years and diagnosed as having TBI for ≥6 months from neurosurgical clinics. The 18-item TC-CIQ-R, Participation Measure - 3 Domains, 4 Dimensions (PM-3D4D), Extended Glasgow Outcome Scale (GOSE), and Taiwanese Quality of Life After Brain Injury (TQOLIBRI) were completed. The sample included 180 TBI survivors (54% male, mean age 47 years) of whom 87% sustained a mild TBI. Exploratory factor analysis extracted four factors - home integration, social integration, productivity, and electronic social networking - which explained 63.03% of the variation, after discarding the tenth item with a factor loading of 0.25. For criterion-related validity, the TC-CIQ-R was significantly correlated with the PM-3D4D; convergent validity was exhibited by demonstrating the associations between the TC-CIQ-R and TQOLIBRI. Known-group validity testing revealed significant differences in the subdomain and total scores of the TC-CIQ-R between participants with a mean GOSE score of ≤6 and >7 (all P  < 0.001). The TC-CIQ-R exhibited acceptable Cronbach's α values (0.68-0.88). We suggest the 17-item TC-CIQ-R as a valid tool for rehabilitation professionals, useful for both clinical practice and research in assessing community integration levels following TBI.

[Role of NLRP3 inflammasome in heart failure and traditional Chinese medicine intervention: a review].

Heart failure is characterized by high incidence and mortality rates, and the search for effective treatment strategies for heart failure and the improvement of clinical outcomes have always been important research directions. Imbalanced inflammation has been proven to be one of the critical pathological factors in heart failure, positively correlated with adverse events such as impaired cardiac function and myocardial fibrosis. In recent years, studies have confirmed that the activation of the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome plays a common regulatory role in the inflammation imbalance induced by various factors in heart failure. Moreover, certain traditional Chinese medicine(TCM) and active components can significantly inhibit the activation of the NLRP3 inflammasome, thereby improving heart failure. This article first overviewed the basic information about the NLRP3 inflammasome, summarized the regulatory mechanisms of the NLRP3 inflammasome in heart failure induced by various factors, introduced recent research progress on TCM and active components that inhibited the NLRP3 inflammasome to improve heart failure, aiming to provide references for innovative drug research in the field of integrated Chinese and western medicine for the prevention and treatment of heart failure.