Exploration into the Mechanism of Yiyi Baijiang Decoction Attenuating Chronic Pelvic Inflammation Based on Network Pharmacology and Experimental Verification.

Patients with chronic pelvic inflammation (CPI) experience irregular menstrual, ectopic pregnancy, and infertility. Yiyi Baijiang Decoction attenuates CPI in patients with uncovered mechanisms. CPI therapeutic targets intersected with those of Yiyi Baijiang Decoction, followed by importing into STRING to obtain protein-target interaction. "Drug-component-disease-target" interaction was constructed by Cytoscape. mRNA and protein levels were detected by real-time quantitative PCR (RT-qPCR) and western blot. Yiyi Baijiang Decoction contained 199 active ingredients. There were 1071 drug targets for Yiyi Baijiang Decoction and 1622 therapeutic targets for CPI. The GO functional enrichment analysis revealed 3445 biological processes, and the KEGG pathway enrichment analysis screened 67 signal pathways. Decreased ALB, increased protein kinase B (AKT1), interleukin (IL)-6, vascular endothelial growth factor A (VEGFA), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K/AKT)-extracellular-regulated protein kinases (ERK)1/2 activation in CPI mice were abolished by Yiyi Baijiang Decoction. Yiyi Baijiang Decoction attenuates CPI by inactivating PI3K/AKT and ERK1/2 and regulating ALB, VEGFA, AKT1, and IL-6.

Exploring 3D Human Action Recognition Using STACOG on Multi-View Depth Motion Maps Sequences.

This paper proposes an action recognition framework for depth map sequences using the 3D Space-Time Auto-Correlation of Gradients (STACOG) algorithm. First, each depth map sequence is split into two sets of sub-sequences of two different frame lengths individually. Second, a number of Depth Motion Maps (DMMs) sequences from every set are generated and are fed into STACOG to find an auto-correlation feature vector. For two distinct sets of sub-sequences, two auto-correlation feature vectors are obtained and applied gradually to L2-regularized Collaborative Representation Classifier (L2-CRC) for computing a pair of sets of residual values. Next, the Logarithmic Opinion Pool (LOGP) rule is used to combine the two different outcomes of L2-CRC and to allocate an action label of the depth map sequence. Finally, our proposed framework is evaluated on three benchmark datasets named MSR-action 3D dataset, DHA dataset, and UTD-MHAD dataset. We compare the experimental results of our proposed framework with state-of-the-art approaches to prove the effectiveness of the proposed framework. The computational efficiency of the framework is also analyzed for all the datasets to check whether it is suitable for real-time operation or not.

Action of nitromezuril against Eimeria tenella with clinically anticoccidial indices and histopathology.

Nitromezuril is a novel triazine compound for preventing coccidiosis in broiler chickens. A single treatment of chickens inoculated with Eimeria tenella during the endogenous phase were used to evaluate the developmental stages of action of nitromezuril by clinically anticoccidial indices and histopathology. Results showed that a single dose of nitromezuril at 5 mg/kg b.w. during 56 to 80 h post-inoculation can most effectively prevent weight loss and reduce both oocyst shedding and caecal lesions. The anticoccidial index reached the level of middle efficacy. Histological examinations indicated that administration of nitromezuril during 44 to 104 h after infection significantly reduced the merozoite population and the pathological damage to the caecum. Nitromezuril treatment could disturb the process of schizonts division into schizoites and produce abnormal schizonts. Overall, nitromezuril may exert its effects during the entire endogenous stage of the parasites but the schizogony stages were intrinsically more vulnerable. Nitromezuril is a potential novel anticoccidial agent suitable for further development.

Ultrastructural effects of acetamizuril on endogenous phases of Eimeria tenella.

To explore the primary stage or site of action of acetamizuril (AZL), a novel triazine anticoccidial compound, the ultrastructural development of Eimeria tenella at different endogenous stages was studied in experimentally infected chickens treated with a single oral dose of 15 mg/kg AZL. As a result of drug action, the differentiations of second-generation schizonts and microgamonts were largely inhibited and merozoites became irregular in shape. Meanwhile, the outer membrane blistering and perinuclear space enlargement were obvious in the second-generation schizonts and microgamonts, which were never observed in the classic triazine anticoccidiosis drug diclazuril-treated E. tenella. The chromatin aggregation, anachromasis, and marginalization were visible in merozoites and microgamonts. Furthermore, the abnormal evagination of microgametes finally resulted in the degeneration of microgamonts and the failure of subsequent fertilization. The most marked micromorphological alteration occurring in the macrogamonts was the WFB2. Even if the fertilization occurred, the formation of oocyst wall became malformed and the zygote proceeded to the obvious degeneration. In addition, mitochondria swelling and cytoplasm vacuolization were discerned in respective intracellular stages, while endoplasmic reticulum and Golgi body swelling was less seen. These alterations may be the causes leading to the final death of E. tenella and also provide some information for further exploring the mechanism of action of AZL at the molecular level.

Multi-scale hyperspectral imaging of cervical neoplasia.

PURPOSE: This preliminary study aimed at investigating the feasibility and effective of multi-scale hyperspectral imaging in detecting cervical neoplasia at both tissue and cellular levels. METHODS: In this paper, we describe a noninvasive diagnosis method with a hyperspectral imager for detection and location of cervical intraepithelial neoplasia (CIN) at multiple scales. At the macroscopic level, the hyperspectral imager was applied to capture the reflectance images of the entire cervix in vivo at a series of wavelengths. At the microscopic level, the hyperspectral imager was coupled with a microscope to collect the transmittance images of the pathological slide. The collected image data were calibrated. A wide-gap second derivative analysis was applied to differentiate CIN from other types of tissue. RESULTS: At both macroscopic and microscopic levels, hyperspectral imaging analysis results were consistent with those of histopathological analysis, indicating the technical feasibility of multi-scale hyperspectral imaging for cervical neoplasia detection with accuracy and efficacy. CONCLUSION: We propose a multi-scale hyperspectral imaging method for noninvasive detection of cervical neoplasia. Comparison of the imaging results with those of gold standard histologic measurements demonstrates that the hyperspectral diagnostic imaging system can distinguish CIN at both tissue and cellular levels.

Safety evaluation of a triazine compound nitromezuril by assessing bacterial reverse mutation, sperm abnormalities, micronucleus and chromosomal aberration.

Nitromezuril (NZL) is a novel triazine compound that exhibits remarkable anticoccidial activity. However, mutagenicity and genotoxicity of NZL have not been evaluated to date. This study evaluated the potential risks of NZL by testing for bacterial reverse mutation (Ames), mouse sperm abnormality (SA), bone marrow micronucleus (MN) and chromosomal aberration (CA). Mice were orally administered with NZL at 385, 192 and 96 mg/kg, corresponding to 0.5 ×, 0.25 × and 0.125 × the LD50 of NZL, respectively. No significant increases in SA and CA were found in mice treated with NZL for 5d and 3d, respectively (P>0.05). NZL at 96-385 mg/kg did not have significant influence on micronucleated polychromatic erythrocyte counts (P>0.05). These results suggest that NZL is not genotoxic. However, Ames test results were positive both with and without the S9 system for Salmonella typhimurium TA98 and TA100, suggesting that NZL may be mutagenic. The mutagenic effects of NZL were different in in vitro and in vivo assays. Further studies should be conducted to confirm the safety of using and developing NZL as a novel anticoccidial drug.

Effects of Low Molecular Weight Yeast ß-Glucan on Antioxidant and Immunological Activities in Mice.

To evaluate the antioxidant and immune effects of low molecular yeast ß-glucan on mice, three sulfated glucans from Saccharomyces cerevisiae (sGSCs) with different molecular weight (MW) and degrees of sulfation (DS) were prepared. The structures of the sGSCs were analyzed through high performance liquid chromatography-gel permeation chromatography (HPLC-GPC) and Fourier transform infrared spectroscopy (FTIR). sGSC1, sGSC2, and sGSC3 had MW of 12.9, 16.5 and 19.2 kDa, respectively, and DS of 0.16, 0.24 and 0.27, respectively. In vitro and in vivo experiments were conducted to evaluate the antioxidant and immunological activities of the sGSCs. In vitro experiment, the reactive oxygen species (ROS) scavenging activities were determined. In vivo experiment, 50 male BALB/c mice were divided into five groups. The sGSC1, sGSC2 and sGSC3 treatment groups received the corresponding sGSCs at 50 mg/kg/day each. The GSC (glucans from Saccharomyces cerevisiae) treatment group received 50 mg/kg/day GSC. The normal control group received equal volume of physiological saline solution. All treatments were administered intragastrically for 14 day. Results showed that sGSC1, sGSC2 and sGSC3 can scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH), superoxide, and hydroxyl radicals in vitro. The strength of the radical scavenging effects of the sGSCs was in the order of sGSC1 > sGSC2 > sGSC3. Oral administration of sGSC1 significantly improved serum catalase (CAT) and glutathione peroxidase (GSH-Px) activities and decreased malondialdehyde (MDA) level in mice. sGSC1 significantly improved the spleen and thymus indexes and the lymphocyte proliferation, effectively enhanced the percentage of CD4⁺ T cells, decreased the percentage of CD8⁺ T cells, and elevated the CD4⁺/CD8⁺ ratio. sGSC1 significantly promoted the secretion of IL-2 and IFN-γ. These results indicate that sGSC1 with low MW and DS has better antioxidant and immunological activities than the other sGSCs, and sGSC1 could be used as a new antioxidant and immune-enhancing agent.

Identification of in vitro metabolites of a new anticoccidial drug nitromezuril using HepG2 cells, rat S9 and primary hepatocytes by liquid chromatography/tandem mass spectrometry.

RATIONALE: Nitromezuril is a novel triazine compound possessing remarkable anticoccidial activity that could have possible future use in the prevention of coccidiosis; however, its metabolic characteristics have still not been revealed. METHODS: In the present study, the in vitro metabolism of nitromezuril in HepG2 cells, rat S9 and primary hepatocytes was investigated using high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. The structures of metabolites and their product ions were easily and reliably characterized based on the accurate MS(2) spectra and known structure of nitromezuril. RESULTS: As expected, three metabolites (M1-M3) were detected in a HepG2 cells system, one metabolite was respectively detected and identified as M1 in rat S9 and M2 in rat primary hepatocytes. M1 and M2 were confirmed respectively based on comparing their retention times, full scan, product ion scan with available authentic standards and M3 was tentatively identified as hydroxyl compound of M2. CONCLUSIONS: Pathways of nitromezuril were reported for the first time and no obvious species difference was shown. The proposed metabolic pathways of nitromezuril can be expected to play a key role in pharmacodynamics and food safety evaluations.

Identification of oxidative stress and responsive genes of HepG2 cells exposed to quinocetone, and compared with its metabolites.

Quinocetone, a new quinoxaline 1,4-dioxide derivative used in food-producing animals in China, exerts genotoxic effects on HepG2 cells. It triggers significant cytotoxicity and genotoxicity in vitro, but the detailed mechanism by which quinocetone induces adverse biological effects is not yet known. We analyzed the mechanisms behind quinocetone intoxication by investigating oxidative stress based on non-enzymatic and enzymatic antioxidant activities, and by identifying differentially regulated genes of HepG2 cells exposed to quinocetone using polymerase chain reaction (PCR)-based suppression subtractive hybridization to illustrate the toxicity mechanism of quinocetone. Meanwhile, the characteristics of oxidative stress and differentially regulated genes induced by quinocetone metabolites, 1,4-bisdesoxyquinocetone and 3-methylquinoxaline-2-carboxylic acid, were investigated too. Results showed that quinocetone damaged the antioxidant defense abilities of HepG2 cells by reducing the activities of endogenous antioxidant enzymes, lowering glutathione concentration, and elevating malondialdehyde level. We identified 160 quinocetone-responsive genes that were associated with cell proliferation, glucose metabolism, oxidative stress, and apoptosis, such as NAD(P)H dehydrogenase, quinone 1; and prolyl 4-hydroxylase, beta polypeptide. The expressions of some differentially regulated genes were confirmed by real-time reverse transcription-polymerase chain reaction. However, quinocetone metabolites showed little effects on HepG2 cells. These results showed that reactive oxygen species were the key mediators of quinocetone cytotoxicity in HepG2 cells and that c-MYC-dependent activation of the mitochondrial apoptotic pathway may be associated with quinocetone-induced toxicity.

Elucidating doxycycline biotransformation mechanism by Chryseobacterium sp. WX1: Multi-omics insights.

Doxycycline (DOX) represents a second-generation tetracycline antibiotic that persists as a challenging-to-degrade contaminant in environmental compartments. Despite its ubiquity, scant literature exists on bacteria proficient in DOX degradation. This study marked a substantial advancement in this field by isolating Chryseobacterium sp. WX1 from an activated sludge enrichment culture, showcasing its unprecedented ability to completely degrade 50 mg/L of DOX within 44 h. Throughout the degradation process, seven biotransformation products were identified, revealing a complex pathway that began with the hydroxylation of DOX, followed by a series of transformations. Employing an integrated multi-omics approach alongside in vitro heterologous expression assays, our study distinctly identified the tetX gene as a critical facilitator of DOX hydroxylation. Proteomic analyses further pinpointed the enzymes postulated to mediate the downstream modifications of DOX hydroxylation derivatives. The elucidated degradation pathway encompassed several key biological processes, such as the microbial transmembrane transport of DOX and its intermediates, the orchestration of enzyme synthesis for transformation, energy metabolism, and other gene-regulated biological directives. This study provides the first insight into the adaptive biotransformation strategies of Chryseobacterium under DOX-induced stress, highlighting the potential applications of this strain to augment DOX removal in wastewater treatment systems containing high concentrations of DOX.

An Integrated Multi-omics prediction model for stroke recurrence based on Lnet transformer layer and dynamic weighting mechanism.

BACKGROUND AND OBJECTIVE: Stroke is a disease with high mortality and disability. Importantly, the fatality rate demonstrates a significant increase among patients afflicted by recurrent strokes compared to those experiencing their initial stroke episode. Currently, the existing research encounters three primary challenges. The first is the lack of a reliable, multi-omics image dataset related to stroke recurrence. The second is how to establish a high-performance feature extraction model and eliminate noise from continuous magnetic resonance imaging (MRI) data. The third is how to integration multi-omics data and dynamically weighted for different omics data. METHODS: We systematically compiled MRI and conventional detection data from a cohort comprising 737 stroke patients and established PSTSZC, a multi-omics dataset for predicting stroke recurrence. We introduced the first-ever Integrated Multi-omics Prediction Model for Stroke Recurrence, MPSR, which is based on ResNet, Lnet-transformer, LSTM and dynamically weighted DNN. The MPSR model comprises two principal modules, the Feature Extraction Module, and the Integrated Multi-Omics Prediction Module. In the Feature Extraction module, we proposed a novel Lnet regularization layer, which effectively addresses noise issues in MRI data. In the Integrated Multi-omics Prediction Module, we propose a dynamic weighted mechanism based on evaluators, which mitigates the noise impact brought about by low-performance omics. RESULTS: We compared seven single-omics models and six state-of-the-art multi-omics stroke recurrence models. The experimental results demonstrate that the MPSR model exhibited superior performance. The accuracy, AUROC, specificity, and sensitivity of the MPSR model can reach 0.96, 0.97, 1, and 0.94, respectively, which is higher than the results of contrast model. CONCLUSION: MPSR is the first available high-performance multi-omics prediction model for stroke recurrence. We assert that the MPSR model holds the potential to function as a valuable tool in assisting clinicians in accurately diagnosing individuals with a predisposition to stroke recurrence.

[Effect of Water Components on Aggregation and Sedimentation of Polystyrene Nanoplastics].

The aggregation and sedimentation of micro/nano-plastics significantly affect their migration and distribution in the environment. This study investigated the effects of Na+ and natural organic matter （NOM） on the aggregation and sedimentation of polystyrene nano-plastics （PS-NPs） in the aqueous phase. Six types of water， such as seawater， lake water， and domestic sewage， were used to evaluate the above effects and other potential influencing factors. The results indicated that Na+ could facilitate the sedimentation of PS-NPs when it was less than 80 mmol·L-1， whereas it could promote the aggregation and suspension of PS-NPs when the concentration was greater than 80 mmol·L-1. NOM molecules affected the aggregation and sedimentation of PS-NPs by changing the ζ potential and relative density of particles via forming a multilayer adsorption structure with Na+ on the particle surface. It was observed that NOM greater than 10 mg·L-1 enhanced the dispersion and suspension of PS-NPs， which might have been attributed to the decrease in relative density of the particles as a large amount of NOM was absorbed onto the surface. Compared with synthetic waters， environmental waters enhanced the aggregation of PS-NPs， which may have been related to the amino acid， protein， and other organic macro-molecules in the water.

Nuclear translocation and accumulation of glyceraldehyde-3-phosphate dehydrogenase involved in diclazuril-induced apoptosis in Eimeria tenella (E. tenella).

In mammalian cells, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) has recently been shown to be implicated in numerous apoptotic paradigms, especially in neuronal apoptosis, and has been demonstrated to play a vital role in some neurodegenerative disorders. However, this phenomenon has not been reported in protists. In the present study, we report for the first time that such a mechanism is involved in diclazuril-induced apoptosis in Eimeria tenella (E. tenella). We found that upon treatment of parasites with diclazuril, the expression levels of GAPDH transcript and protein were significantly increased in second-generation merozoites. Then, we examined the subcellular localization of GAPDH by fluorescence microscopy and Western blot analysis. The results show that a considerable amount of GAPDH protein appeared in the nucleus within diclazuril-treated second-generation merozoites; in contrast, the control group had very low levels of GAPDH in the nucleus. The glycolytic activity of GAPDH was kinetically analyzed in different subcellular fractions. A substantial decrease (48.5%) in glycolytic activity of GAPDH in the nucleus was displayed. Moreover, the activities of caspases-3, -9, and -8 were measured in cell extracts using specific caspase substrates. The data show significant increases in caspase-3 and caspase-9 activities in the diclazuril-treated group.

Analysis of clinical and laboratory characteristics in 42 patients with thrombotic thrombocytopenic purpura from a single center in China.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by microvascular platelet deposition and thrombus formation with resulting microangiopathic hemolytic anemia. Deficiency of the von Willebrand factor cleavage protease, also known as ADAMTS 13, has been implicated as an important etiological factor in TTP. Little studies were obtained on Chinese patients with TTP until now. Our aim was to analyze the clinical features, outcome and laboratory characteristics of Chinese TTP patients, and determine whether plasma ADAMTS 13 activity is decreased in TTP and its diagnostic value for TTP. Forty-two TTP patients (29 females; 13 males) admitted to our hospital from 1998 to 2010 were analyzed. There were 34 patients (81%) with the triad of TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; 7 (16.7%) had the classical pentad of TTP. Major etiologic factors were acquired autoimmunological abnormalities (31%); no familial TTP was identified in this series. The schistocytes of peripheral blood smears were present in all cases with a mean frequency of 4.6% (range from 0.3% to 13.4%). Plasma ADAMTS 13 activity was determined in 22 patients with the FRET-vWF86 assay. Only 4 idiopathic TTP patients (18.2%) had severe ADAMTS 13 deficiency (activity<10%); 9 (40.9%) had moderate decrease of ADAMTS 13 activity (activity: 10-40%); another 9 (40.91%) had normal ADAMTS 13 activity (>40%). T lymphocyte subpopulation was measured in 23 TTP patients with FACS Calibur; 14 of the 23 (60.9%) had significantly decreased CD4 cells count and CD4/CD8 ratio, suggesting cellular immune dysfunction may be involved in the pathogenesis of TTP. In the studies, plasmapheresis is the main therapeutic method. 26 of 31 patients (83.9%) accepting plasmapheresis achieved complete remission; those patients who only underwent plasma infusion had low remission rate (18.2%) and high mortality (9/11; 81.8%). Four patients with packed RBC infusion manifested transient exacerbation of neurologic or psychiatric symptoms. In conclusion, the diagnosis of TTP in China is still based on clinical features including evidence of microangiopathic hemolysis. Severe ADAMTS 13 activity deficiency might be a valuable indicator for idiopathic TTP diagnosis. Further studies are needed to determine the real value of ADAMTS 13 activity for TTP diagnosis and whether T lymphocytes subset dysregulation plays important role in TTP pathogenesis.

Intractable hyponatremia secondary to syndrome of inappropriate antidiuresis complicated with empty sella: A case report.

RATIONALE: Hyponatremia is a common electrolyte disorder in elderly critically ill patients, and it may be associated with poor outcomes, higher morbidity, and mortality. Syndrome of inappropriate antidiuresis (SIAD) is one of the main causes of hyponatremia, with an insidious onset that is highly misdiagnosed. Primary empty sella lesions are specific, mostly asymptomatic, and easily overlooked. SIAD combined with empty sella is much rarer in clinic, this article focuses on the diagnosis and management of an elderly patient with intractable hyponatremia secondary to syndrome of inappropriate antidiuresis complicated with empty sella. PATIENT CONCERNS: An 85-year-old male patient with severe pneumonia presented with progressive and intractable hyponatremia. DIAGNOSES: The patient had clinical signs of persistent hyponatremia, low plasma osmolality, elevated urinary sodium excretion, and hyponatremia that worsened with increased intravenous rehydration and was effective with appropriate fluid restriction. The diagnosis of SIAD combined with empty sella was made in combination with the findings of the pituitary and its target gland function. INTERVENTIONS: Numerous screenings were performed to clarify the cause of hyponatremia. His overall condition was poor due to recurrent episodes of hospital-acquired pneumonia. We treated with ventilation support, circulatory support, nutritional support, anti-infection, and continuous correction of electrolyte imbalance. OUTCOMES: His hyponatremia gradually improved through aggressive infection control, appropriate fluid restriction (intake controlled at 1500-2000mL/d), continuous electrolyte correction, supplementation with hypertonic salt solution, and potassium replacement therapy. LESSONS: Electrolyte disorders, especially hyponatremia, are very common in critically ill patients, but the etiology of hyponatremia is challenging to diagnose and treat, and timely attention and proper diagnosis of SIAD and individualized treatment are the significance of this article.

Surrounding-aware representation prediction in Birds-Eye-View using transformers.

Birds-Eye-View (BEV) maps provide an accurate representation of sensory cues present in the surroundings, including dynamic and static elements. Generating a semantic representation of BEV maps can be a challenging task since it relies on object detection and image segmentation. Recent studies have developed Convolutional Neural networks (CNNs) to tackle the underlying challenge. However, current CNN-based models encounter a bottleneck in perceiving subtle nuances of information due to their limited capacity, which constrains the efficiency and accuracy of representation prediction, especially for multi-scale and multi-class elements. To address this issue, we propose novel neural networks for BEV semantic representation prediction that are built upon Transformers without convolution layers in a significantly different way from existing pure CNNs and hybrid architectures that merge CNNs and Transformers. Given a sequence of image frames as input, the proposed neural networks can directly output the BEV maps with per-class probabilities in end-to-end forecasting. The core innovations of the current study contain (1) a new pixel generation method powered by Transformers, (2) a novel algorithm for image-to-BEV transformation, and (3) a novel network for image feature extraction using attention mechanisms. We evaluate the proposed Models performance on two challenging benchmarks, the NuScenes dataset and the Argoverse 3D dataset, and compare it with state-of-the-art methods. Results show that the proposed model outperforms CNNs, achieving a relative improvement of 2.4 and 5.2% on the NuScenes and Argoverse 3D datasets, respectively.

An ultrasonographic study of gouty arthritis: Synovitis and its relationship to clinical symptoms: A retrospective analysis.

Background and Aims: Joint pain is the main symptom of acute attacks in patients with gout, which if not managed properly, can develop into chronic gout. The aim of this study was to investigate the correlation between ultrasound (US) features of gouty arthritis (GA) and its clinical manifestations to provide a basis for diagnosing and evaluating the disease. Methods: We retrospectively analyzed 182 sites in 139 patients with GA diagnosed by the Rheumatology and Immunology Department. Degree of pain was evaluated using the visual analog scale (VAS). Patients with GA were divided into active and inactive arthritis groups. Statistical differences between the two groups and the correlation between US features and clinical manifestations of the affected joints in patients with GA were analyzed. Results: The groups had statistical significance in joint effusion, power Doppler ultrasonography (PDS), double contour sign, and bone erosion (p = 0.02, 0.001, 0.04, 0.04, respectively). Correlation analysis in this study showed that joint effusion and PDS were positively correlated with degree of pain (r s = 0.275, 0.269; p < 0.001, <0.001, respectively). Additionally, PDS was positively correlated with synovitis, joint effusion, bone erosion, and aggregates (r s = 0.271, 0.281, 0.222, 0.281; p < 0.001, <0.001, 0.003, <0.001, respectively). Conclusions: Pathological US features, such as joint effusion, synovitis, PDS and bone erosion were more likely to be detected in GA with clinical signs and symptoms. PDS was positively correlated with joint effusion and synovitis, pain was closely related to PDS and joint effusion, which suggested that the clinical symptoms of GA were related to inflammation, reflecting the patient's condition to some extent. Therefore, musculoskeletal US is a useful clinical tool for managing patients with GA and can provide a reliable reference for diagnosing and treating GA.

Case report: Targeting the PD-1 receptor and genetic mutations validated in primary histiocytic sarcoma with hemophagocytic lymphohistiocytosis.

Histiocytic sarcoma (HS) is a rare hematological malignancy with limited treatment options, and it is also prone to complications such as hemophagocytic lymphohistiocytosis (HLH) in the later stages of the disease, leading to difficulties in treatment and poor prognosis. It highlights the importance of developing novel therapeutic agents. Herein, we present a case of a 45-year-old male patient who was diagnosed with PD-L1-positive HS with HLH. The patient was admitted to our hospital with recurrent high fever, multiple skin rashes with pruritus throughout the body and enlarged lymph nodes. Subsequently, pathological biopsy of the lymph nodes revealed high expression of CD163, CD68, S100, Lys and CD34 in the tumor cells and no expression of CD1a and CD207, confirming this rare clinical diagnosis. Concerning the low remission rate by conventional treatment in this disease, the patient was administered with sintilimab (an anti-programmed cell death 1 [anti-PD-1] monoclonal antibody) at 200 mg/d combined with a first-line chemotherapy regimen for one cycle. Further exploration of pathological biopsy by using next-generation gene sequencing led to the use of targeted therapy of chidamide. After one cycle of combination therapy (chidamide+sintilimab, abbreviated as CS), the patient achieved a favorable response. The patient showed remarkable improvement in the general symptoms and laboratory examination results (e.g., elevated indicators of inflammation); even the clinical benefits was not persistent, he survived one more month after his cessation of treatment by himself due to economic difficulty. Our case suggests that PD-1 inhibitor coupled with targeted therapy might constitute a potential therapeutic option for primary HS with HLH.

Exploring the Mechanism of Curcumin on Retinoblastoma Based on Network Pharmacology and Molecular Docking.

Background: Curcumin shows great effects of inhibiting tumor cell proliferation, inducing apoptosis, inhibiting tumor metastasis, and inhibiting angiogenesis on a variety of tumors. However, the biological activity and possible mechanisms of curcumin in the treatment of retinoblastoma have not been fully elucidated. This study explored the potential therapeutic targets and pharmacological mechanisms of curcumin against retinoblastoma based on network pharmacology and molecular docking. Methods: The genes corresponding to curcumin targets were screened from the HERB, PharmMapper, and SwissTargetPrediction databases. Protein-protein interaction (PPI) networks were constructed for the intersecting targets in the STRING database. Cytoscape 3.7.0 was used for network topology analysis and screening of important targets. R 4.1.0 software was used for Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of intersection targets. The molecular structures of curcumin and core target proteins were obtained from PubChem and PDB databases, and the two were preprocessed and molecularly docked using AutoDockTools and PyMOL software. Results: Through network data mining, we obtained 504 curcumin targets and 966 retinoblastoma disease targets, and 44 potential targets for curcumin treatment of retinoblastoma were obtained by mapping. Three core targets were obtained from network topology analysis. 462 biological processes, 21 cellular compositions, and 34 molecular functions were obtained by GO enrichment analysis. KEGG pathway analysis revealed 94 signaling pathways, mainly involving chemical carcinogenesis-receptor activation, chemical carcinogenesis-reactive oxygen species, viral carcinogenesis, Th17 cell differentiation, etc. The molecular docking results indicated that the binding energy of curcumin to the core targets was less than 0 kJ mol-1, among which the binding energy of RB1 and CDKN2A to curcumin was less than -5 kJ mol-1 with significant binding activity. Conclusion: Based on molecular docking technology and network pharmacology, we initially revealed that curcumin exerts its therapeutic effects on retinoblastoma with multitarget, multipathway, and multibiological functions, providing a theoretical basis for subsequent studies.

Shifts in structure and function of bacterial community in river and fish pond sediments after a phenol spill.

Phenol is widely used in industrial processes and has microbial toxicity. However, the effects of a phenol spill on the microbial community are not clear. The present study explored the changes of bacterial communities in river and fish pond sediments after a phenol spill. The bacterial richness and diversity in river sediments were lower on day 30 (36 days after the spill) than on day 0, while they increased in fish pond sediments. The structures and functions of bacterial communities in both river and fish pond sediments were changed, and a more dramatical variation was detected in fish pond sediments. In river sediments, Proteobacteria, Chloroflexi, Acidobacteria, Bacteroidetes, and Nitrospirae were the major bacterial phyla, and Chloroflexi was enriched. In fish pond sediments, genera Brevibacillus dominated bacterial communities initially, and bacterial composition showed a dramatic change on day 30. Most predicted metabolism functions, as well as genetic information processing functions of translation, replication, and repair, were enhanced in both river and fish pond sediments, while they showed an opposite change trend for xenobiotic degradation function. This work could strengthen our understanding of the effects of phenol spills on sediment bacterial communities in both lotic and lentic ecosystems.