Correlation analysis between potential hepatotoxicity and ingredient content of polygoni multiflori caulis.

Polygoni Multiflori Caulis (PMC) is commonly used in clinical practice. While the adverse reactions of Polygoni Multiflori Radix (RPM) are well-known, the potential adverse reactions of PMC are often neglected. This article aims to clarify the relationship between hepatotoxic components in PMC and its various producing areas. This study provides a qualitative and quantitative analysis of PMC from various regions, which can serve as a basis for safe usage.

[Multi-objective Identification Method for Influencing Factors of Soil Heavy Metal Content Change].

Identifying the influencing factors of soil heavy metal content changes is the basis for reducing or preventing soil heavy metal pollution. Taking an agricultural experimental field in Changping District of Beijing as an example, the heavy metal content changes in As, Cr, Cu, Ni, Pb, and Zn from 2012 to 2022 were firstly analyzed. Secondly, the influencing factors of the heavy metal content changes were detected based on the geographical detector at the single-target and multi-target levels, respectively. Finally, comparative experiments with the correlation analysis method and existing studies were set up to evaluate the effectiveness of the identification method of influencing factors developed in this study. The results showed that human activity factors have exacerbated the changes in soil heavy metal content in the study area as follows： ① At the single-target level, the land use type was the main influencing factor on the changes in Cr, Cu, and Zn contents, and the annual deposition flux influenced the changes in As. The results of the interaction detection showed that there was an enhancement effect among the factors, and the interaction of the human activity factors dominated for the factor identification. ② The results of the multi-target level detection covered the results of the single-target level detection, which could identify more influencing factors. The land use type affected the changes in Cu, Zn, Cr, Ni, and As, and the changes in As and Zn were influenced by the annual deposition fluxes. ③ The multi-target identification method coupled with geographical detector and principal component analysis could effectively identify the influencing factors of soil heavy metal content changes, which was much more effective than the single soil heavy metal correlation method. The developed multi-target identification method for influencing factors of heavy metal content changes can provide technical support for the regional pollution monitoring and macro-management of soil heavy metals.

Three-dimensional inertial focusing based impedance cytometer enabling high-accuracy characterization of electrical properties of tumor cells.

The differences in the cross-sectional positions of cells in the detection area have a severe negative impact on achieving accurate characterization of the impedance spectra of cells. Herein, we proposed a three-dimensional (3D) inertial focusing based impedance cytometer integrating sheath fluid compression and inertial focusing for the high-accuracy electrical characterization and identification of tumor cells. First, we studied the effects of the particle initial position and the sheath fluid compression on particle focusing. Then, the relationship of the particle height and the signal-to-noise ratio (SNR) of the impedance signal was explored. The results showed that efficient single-line focusing of 7-20 µm particles close to the electrodes was achieved and impedance signals with a high SNR and a low coefficient of variation (CV) were obtained. Finally, the electrical properties of three types of tumor cells (A549, MDA-MB-231, and UM-UC-3 cells) were accurately characterized. Machine learning algorithms were implemented to accurately identify tumor cells based on the amplitude and phase opacities at multiple frequencies. Compared with traditional two-dimensional (2D) inertial focusing, the identification accuracy of A549, MDA-MB-231, and UM-UC-3 cells using our 3D inertial focusing increased by 57.5%, 36.4% and 36.6%, respectively. The impedance cytometer enables the detection of cells with a wide size range without causing clogging and obtains high SNR signals, improving applicability to different complex biological samples and cell identification accuracy.

Proteomic landscape of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Synergic effects and possible mechanism of emodin and stilbene glycosides on colorectal cancer.

BACKGROUND: Polygonum multiflorum (PM) is a core herb that enhances immunity. It can also detoxify, reduce swelling, and intercept malaria. Its main components, emodin (EMD) and 2,3,5,4'-Tetrahydroxy stilbene-2-O-ß-D-glucoside (stilbene glycoside, TSG), have good anti-cancer potential. PURPOSE: The study aims to investigate synergic effects of EMD and TSG on CRC and its possible mechanism. METHODS: Network pharmacology and bioinformatics were used to identify targets. HPLC was used to analyze the effective ingredients in PM and to determine the content of the main ingredients. HT-29 cells were used for in vitro experiments. Cell Counting Kit-8 (CCK8) and scratch test were used to detect the effects of various chemical components of PM on the proliferation and migration of HT-29 cells, and Western Bolt (WB) test was used to evaluate the effects of EMD and TSG on P53 pathway. In vivo experiments, the effects of EMD and TSG were evaluated by measuring tumor weight and tumor volume in CRC mice model and histological analysis were carried out with HE staining. The expressions of HSP90, P53, COX2, and ROS were detected by quantitative reverse transcription polymerase chain reaction (PCR), and IL-1ß, IL-4, IL-6, IL-10, TGF-ß and IFN-γ were detected by enzyme linked immunosorbent assay (ELISA). WB and Immunohistochemistry (IHC) were used to detect the expression of P53 related proteins. RESULTS: Network pharmacology showed PM closely related to colorectal cancer pathway and the core targets included STAT3 and P53; bioinformatics indicated P53 played an important role in the development and prognosis of CRC; chemical analysis showed identified and quantified gallic acid (GA), cis-TSG, trans-TSG, Emodin glucoside(EMDG), physcion glucoside (PHYG), EMD in PM; EMD induced apoptosis and TSG inhibited migration of HT-29 cells; EMD and TSG could coordinately shrink tumor size of CRC mice, elevate expressions of F4/80, decrease the content of IL-6 and TGF-ß, promote tumor oxidized and reduce expression of P53 and STAT3 in the tumor. CONCLUSIONS: In vitro experiments showed that TSG inhibited cancer cell migration and EMD induced apoptosis. EMD and TSG had synergic effects on CRC, whose possible mechanism might be to regulate the expression of cytokines and inhibit P53 pathway.

Liquid Biopsy Instrument for Ultra-Fast and Label-Free Detection of Circulating Tumor Cells.

Rapid diagnosis and real-time monitoring are of great important in the fight against cancer. However, most available diagnostic technologies are time-consuming and labor-intensive and are commonly invasive. Here, we describe CytoExam, an automatic liquid biopsy instrument designed based on inertial microfluidics and impedance cytometry, which uses a deep learning algorithm for the analysis of circulating tumor cells (CTCs). In silico and in vitro experiments demonstrated that CytoExam could achieve label-free detection of CTCs in the peripheral blood of cancer patients within 15 min. The clinical applicability of CytoExam was also verified using peripheral blood samples from 10 healthy donors and >50 patients with breast, colorectal, or lung cancer. Significant differences in the number of collected cells and predicted CTCs were observed between the 2 groups, with variations in the dielectric properties of the collected cells from cancer patients also being observed. The ultra-fast and minimally invasive features of CytoExam may pave the way for new paths for cancer diagnosis and scientific research.

Activation of glutamatergic neurons in the somatosensory cortex promotes remyelination in ischemic vascular dementia.

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

Multiparameter Mechanical Phenotyping for Accurate Cell Identification Using High-Throughput Microfluidic Deformability Cytometry.

Mechanical phenotyping has been widely employed for single-cell analysis over recent years. However, most previous works on characterizing the cellular mechanical properties measured only a single parameter from one image. In this paper, the quasi-real-time multiparameter analysis of cell mechanical properties was realized using high-throughput adjustable deformability cytometry. We first extracted 12 deformability parameters from the cell contours. Then, the machine learning for cell identification was performed to preliminarily verify the rationality of multiparameter mechanical phenotyping. The experiments on characterizing cells after cytoskeletal modification verified that multiple parameters extracted from the cell contours contributed to an identification accuracy of over 80%. Through continuous frame analysis of the cell deformation process, we found that temporal variation and an average level of parameters were correlated with cell type. To achieve quasi-real-time and high-precision multiplex-type cell detection, we constructed a back propagation (BP) neural network model to complete the fast identification of four cell lines. The multiparameter detection method based on time series achieved cell detection with an accuracy of over 90%. To solve the challenges of cell rarity and data lacking for clinical samples, based on the developed BP neural network model, the transfer learning method was used for the identification of three different clinical samples, and finally, a high identification accuracy of approximately 95% was achieved.

Epimedii Folium decoction ameliorates osteoporosis in mice through NLRP3/caspase-1/IL-1ß signalling pathway and gut-bone axis.

AIM OF THE STUDY: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis". MATERIAL AND METHODS: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation. RESULTS: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1ß signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM. CONCLUSIONS: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.

Increased risk of adverse gestational outcomes in pregnant women with primary Sjögren's syndrome.

OBJECTIVES: This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases. METHODS: A retrospective analysis was conducted on pregnant individuals with pSS, who received outpatient or inpatient care across multiple hospitals in Anhui Province, China, from January 2015 to December 2022. RESULTS: This study included 164 pregnant women with pSS and 328 control subjects, with no statistically significant difference in average age between the two groups. Analysis of pregnancy outcomes revealed that, compared with the control group, pregnant women in the pSS group were more likely to experience miscarriages, both spontaneous (12.80% vs 1.52%, p<0.001) and therapeutic (6.10% vs 0.91%, p<0.05). The proportion of placental abnormalities detected during prenatal ultrasound in women from the pSS group was higher (14.63% vs 6.40%, p<0.05). In the analysis of pregnancy outcomes for live-born neonates, a higher incidence of congenital heart abnormalities was observed in the pSS group (27.34% vs 12.03%, p<0.05). While there were no significant differences between the pSS pregnancies in terms of both normal and adverse pregnancy outcomes, a comparison of fetal survival and fetal loss in pSS pregnancies revealed a greater use of prophylactic anticoagulant therapy in the fetal survival group. Notably, the application of low molecular weight heparin (LMWH) emerged as an independent protective factor for fetal survival. CONCLUSIONS: Compared with non-autoimmune controls, pregnancy in women with pSS presents more challenges. Importantly, we observed that the use of LMWH as anticoagulant therapy is an independent protective measure for fetal survival.

Elasto-inertial particle focusing in sinusoidal microfluidic channels.

Dean flow existing in sinusoidal channels could enhance the throughput and efficiency for elasto-inertial particle focusing. However, the fundamental mechanisms of elasto-inertial focusing in sinusoidal channels are still unclear. This work employs four microfluidic devices with symmetric and asymmetric sinusoidal channels to explore the elasto-inertial focusing mechanisms over a wide range of flow rates. The effects of rheological property, flow rate, sinusoidal channel curvature, particle size, and asymmetric geometry on particle focusing performance are investigated. It is intriguing to find that the Dean flow makes a substantial contribution to the particle elasto-inertial focusing. The results illustrate that a better particle focusing performance and a faster focusing process are obtained in the sinusoidal channel with a small curvature radius due to stronger Dean flow. In addition, the particle focusing performance is also related to particle diameter and rheological properties, the larger particles show a better focusing performance than smaller particles, and the smaller flow rate is required for particles to achieve stable focusing at the outlet in the higher concentration of polyvinylpyrrolidone solutions. Our work offers an increased knowledge of the mechanisms of elasto-inertial focusing in sinusoidal channels. Ultimately, these results provide supportive guidelines into the design and development of sinusoidal elasto-inertial microfluidic devices for high-performance focusing.

Laparoscopic left hemihepatectomy using augmented reality navigation plus ICG fluorescence imaging for hepatolithiasis: a retrospective single-arm cohort study (with video).

BACKGROUND: Laparoscopic left hemihepatectomy (LLH) has been shown to be an effective and safe method for treating hepatolithiasis primarily affecting the left hemiliver. However, this procedure still presents challenges. Due to pathological changes in intrahepatic duct stones, safely dissecting the hilar vessels and determining precise resection boundaries remains difficult, even with fluorescent imaging. Our team proposed a new method of augmented reality navigation (ARN) combined with Indocyanine green (ICG) fluorescence imaging for LLH in hepatolithiasis cases. This study aimed to investigate the feasibility of this combined approach in the procedure. METHODS: Between May 2021 and September 2023, 16 patients with hepatolithiasis who underwent LLH were included. All patients underwent preoperative 3D evaluation and were then guided using ARN and ICG fluorescence imaging during the procedure. Perioperative and short-term postoperative outcomes were assessed to evaluate the safety and efficacy of the method. RESULTS: All 16 patients successfully underwent LLH. The mean operation time was 380.31 ± 92.17 min, with a mean estimated blood loss of 116.25 ± 64.49 ml. ARN successfully aided in guiding hilar vessel dissection in all patients. ICG fluorescence imaging successfully identified liver resection boundaries in 11 patients (68.8%). In the remaining 5 patients (31.3%) where fluorescence imaging failed, virtual liver segment projection (VLSP) successfully identified their resection boundaries. No major complications occurred in any patients. Immediate stone residual rate, stone recurrence rate, and stone extraction rate through the T-tube sinus tract were 12.5%, 6.3%, and 6.3%, respectively. CONCLUSION: The combination of ARN and ICG fluorescence imaging enhances the safety and precision of LLH for hepatolithiasis. Moreover, ARN may serve as a safe and effective tool for identifying precise resection boundaries in cases where ICG fluorescence imaging fails.

A pilot study of virtual liver segment projection technology in subsegment-oriented laparoscopic anatomical liver resection when indocyanine green staining fails (with video).

BACKGROUND: Precision surgery for liver tumors favors laparoscopic anatomical liver resection (LALR), involving the removal of specific liver segments or subsegments. Indocyanine green (ICG)-negative staining is a commonly used method for defining resection boundaries but may be prone to failure. The challenge arises when ICG staining fails, as it cannot be repeated during surgery. In this study, we employed the virtual liver segment projection (VLSP) technology as a salvage approach for precise boundary determination. Our aim was to assess the feasibility of the VLSP to be used for the determination of the boundaries of the liver resection in this situation. METHODS: Between January 2021 and June 2023, 12 consecutive patients undergoing subsegment-oriented LALR were included in this pilot series. The VLSP technology was utilized to define the resection boundaries at the time of ICG-negative staining failure. Routine surgical parameters and short-term outcomes were evaluated to assess the safety of VLSP in this procedure. In addition, its feasibility was assessed by analyzing the accuracy between the predicted resected liver volume (PRLV) and actual resected liver volume (ARLV). RESULTS: Of the 12 enrolled patients, the mean operation time was 444.58 ± 101.70 min (range 290-570 min), with a mean blood loss of 125.00 ± 96.53 ml (range 50-400 mL). One patient (8.3%) was converted to laparotomy for subsequent parenchymal transection, four (33.3%) received blood transfusions and four (33.3%) had postoperative complications. All patients received an R0 resection. The Pearson correlation coefficient (r) between PRLV and ARLV was 0.98 (R2 = 0.96, p < 0.05), and the relative error (RE) was 8.62 ± 6.66% in the 12 patients, indicating agreement. CONCLUSION: Failure of intraoperative ICG-negative staining during subsegment-oriented LALR is possible, and VLSP may be an alternative to define the resection boundaries in such cases.

High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics.

The carbohydrate antigen 19-9 (CA19-9) is commonly used as a representative biomarker for pancreatic cancer (PC); however, it lacks sensitivity and specificity for early-stage PC diagnosis. Furthermore, some patients with PC are negative for CA19-9 (<37 U/mL), which introduces additional limitations to their accurate diagnosis and treatment. Hence, improved methods to accurately detect PC stages in CA19-9-negative patients are warranted. In this study, tumor-proximal liquid biopsy and inertial microfluidics were coupled to enable high-throughput enrichment of portal venous circulating tumor cells (CTCs) and support the effective diagnosis of patients with early-stage PC. The proposed inertial microfluidic system was shown to provide size-based enrichment of CTCs using inertial focusing and Dean flow effects in slanted spiral channels. Notably, portal venous blood samples were found to have twice the yield of CTCs (21.4 cells per 5 mL) compared with peripheral blood (10.9 CTCs per 5 mL). A combination of peripheral and portal CTC data along with CA19-9 results showed to greatly improve the average accuracy of CA19-9-negative PC patients from 47.1% with regular CA19-9 tests up to 87.1%. Hence, portal venous CTC-based microfluidic biopsy can be used with high sensitivity and specificity for the diagnosis of early-stage PC, particularly in CA19-9-negative patients.

Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues. A four gene signature, including ALDH2, ALDH5A1, ALDH6A1, and ALDH8A1, robustly predicted prognosis and defined a high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration. Single-cell profiling revealed selective overexpression of tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated in high-risk HCC patients. We identified ALDH2 as a tumor suppressor in HCC, with three novel phosphorylation sites mediated by protein kinase C zeta that enhanced enzymatic activity. Mechanistically, ALDH2 suppressed Tregs differentiation by inhibiting ß-catenin/TGF-ß1 signaling in HCC. Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis that contributes to HCC pathogenesis and represents potential therapeutic targets for this aggressive malignancy.