Objective To analyze the differences of free and esterified oxo-eicosatetraenoic acids (oxo-ETEs) in blood cells and plasma from arterial and venous blood in hemodialysis (HD) patients. Methods Arterial and venous blood samples from 12 patients with end-stage renal disease (ESRD) before and after HD treatment at Charité – Universitätsmedizin Berlin, Germany, from June to December 2020 were collected. The esterified and free oxo-ETEs derived from arachidonic acid in blood cells and plasma were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results Neither esterified nor free oxo-ETEs in blood cells displayed significant arteriovenous differences before and after HD. HD predominantly affected the metabolic levels of esterified and free oxo-ETEs in plasma. HD reduced the arteriovenous differences of esterified 12-oxo-ETE, free 15-oxo-ETE, and free 5-oxo-ETE in plasma, while raised the arteriovenous differences of esterified 15-oxo-ETE. Conclusions The oxo-ETEs in blood cells are relatively well-stabilized responding to HD treatment, whereas arteriovenous differences of free and esterified oxo-ETEs in plasma are present and active in response to HD treatment, potentially contributing to the cardiovascular disease.

ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

Objective To investigate the species of ticks in Suizhou City, Hubei Province, so as to provide insights into management of ticks and tick-borne diseases. Methods During the period between May 2023 and June 2024, livestock breeding farms and vegetation neighboring the place of residence of confirmed and suspected patients with tick-borne disease were selected as sampling points in rural areas from Yindian Township, Gaocheng Township, Wanhe Township, Wushan Township, Xiaolin Township, Xihe Township, Hedian Township and Beijiao Street in Suizhou City, Hubei Province, where confirmed and suspected cases with tick-borne diseases had been reported. The parasitic ticks on the body surface of free-range livestock were captured with tweezers in livestock breeding farms, and free ticks on the vegetation surface were captured with the flagging method. Morphological identification of tick samples was performed under a microscope, and the gender and developmental stage of ticks were determined. One engorged adult tick, 2 to 3 blood-feeding but non-engorged adult ticks, 10 to 15 unfed female ticks, 15 to 20 unfed male ticks, and 30 to 40 tick nymphs or larvae were assigned into a group, respectively. Genomic DNA was extracted from tick samples in each group, and mitochondrial 16S rRNA gene was amplified. Sequence analysis was performed with the DNASTAR software, and phylogenetic analysis was performed using the software MEGA 7.0. In addition, the phylogenetic tree was generated using the maximum likelihood method based on the Kimura 2 parameter model. Results A total of 2 438 ticks were captured from Suizhou City, Hubei Province during the period between May 2023 and June 2024, including 595 free ticks and 1 483 parasitic ticks. Three developmental stages of ticks were captured, including larvae, nymphs, and adults, and 75.18% (1 899/2 438) of captured ticks were adult, in which 79.04% (1 501/1 899) were female. Morphological and molecular biological assays identified one family, three genera and four species of captured ticks, including 2 425 Haemaphysalis longicornis ticks (99.47%) and one H. flava tick (0.04%) of the genus Haemaphysalis, 11 Rhipicephalus microplus ticks (0.45%) of the genus Rhipicephalus, and one Ixodes sinensis tick (0.04%) of the genus Ixodes in the family Ixodidae. Phylogenetic analysis revealed that the H. longicornis sequence (SZ49) in this study was clustered with sequences from Yunnan Province (GenBank accession number: MH024510.1), Hebei Province (GenBank accession number: MK450606.1) and Henan Province (GenBank accession number: MZ230645.1) into a clade, and the H. flava sequence (SZ19) in this study was clustered with sequences from Japan (GenBank accession number: MW064044.1), South Korea (GenBank accession number: ON629585.1), and Jiangsu Province (GenBank accession number: PP494741.1) and Hebei Province of China (GenBank accession number: MH520685.1) into a clade, while the R. microplus sequence (SZ8) in this study was clustered with the sequences from India (GenBank accession number: MK621328.1), and Henan Province (GenBank accession number: MT555307.1) and Guizhou Province of China (GenBank accession number: PP446801.1) into a clade. The sequence of I. sinensis (SZ23) in this study had 99.51% homology with that (GenBank accession number: OM368265.1) of ticks sampled from Wuhan City, Hubei Province. Conclusion There are four tick species of H. longicornis, H. flava, R. microplus and I. sinensis in Suizhou City, Hubei Province, and H. longicornis is the dominant species. H. flava is firstly recorded in Suizhou City.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Aim To evaluate the hypolipidemic effect of the total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) on hyperlipidemic golden hamsters and explore its regulatory effect on intestinal flora. Methods Sixty hamsters were randomly divided into a control group, a model group, a positive drug group, LRTPG-L group, LRTPG-M group, and LRTPG-H group. After the successful induction of the model by high-fat diet, the animals were continuously administered for four weeks, and their blood lipids and liver lipids were detected. The formed feces from the colorectal region of the hamsters in the control group, model group and LRTPG-H group were collected for 16S rDNA sequencing. Results LRTPG reduced serum TG, TC, LDL-C and liver TG, TC concentrations significantly in hyperlipidemic hamsters. The results of the intestinal microbiota sequencing showed that compared to the control group, LRTPG significantly decreased the relative abundance of the phylum Firmicutes and increased the relative abundance of the phylum Bacteroidetes and Verrucomicrobia (P < 0.01) at the phylum level. At the family level, LRTPG significantly increased the relative abundance of Christensenellaceae, Peptococcaceae, and Verrucomicrobiaceae (P < 0.05 or P < 0.01). At the genus level, LRTPG significantly increased the relative abundance of Oscillospira, Oscillibacter, Flavonifractor and Akkermansiaceae (P < 0.05 or P < 0.01). These changes in the flora were beneficial to the hypolipidemic effect of LRTPG. Conclusion LRTPG may exert its hypolipidemic effect by improving the intestinal flora disorder caused by a high-fat diet in golden hamsters.

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

Tricuspid regurgitation(TR)is a common heart valve disease.According to the pathogenesis,TR can be divided into primary(organic)and secondary(functional)regurgitation,of which functional TR accounts for more than 90%.Patients with severe TR have poor prognosis and poor drug treatment,and surgery(valvuloplasty)is the main treatment.At present,transcatheter edge-to-edge tricuspid valve repair(T-TEER)has become an essential program of transcatheter treatment for TR,providing minimally invasive treatment for TR patients who cannot undergo surgery or are at high risk of surgery.T-TEER reduces the degree of regurgitation by clamping leaflets,and is currently in the early stage of research and development exploration and clinical validation,mainly for functional TR.T-TEER devices have also made significant progress(TriClip,PASCAL),and Chinese-made novel-designed T-TEER devices are also undergoing clinical trials(DragonFly-TTM,SQ-Kyrin-TTM,NeoBlazarTM).This paper reviews the current applications and research progress of T-TEER.

To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6％(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4％in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

Purpose To investigate the predictive value of 18F-FDG PET/CT radiomic features before treatment for progression free survival(PFS)and overall survival(OS)in diffuse large B-cell lymphoma(DLBCL).Materials and Methods A total of 135 patients with pathologically proven DLBCL in Chinese PLA General Hospital from January 2016 to December 2018 and 18F-FDG PET/CT imaging prior to treatment were retrospectively collected.Patients were randomly divided into training set and test set using 8∶2,and then the training set was divided into training set and verification set using 8∶2 to construct the model.Semi-automatically delineated patients'lymphoma lesions as regions of interest and extracted the features.Univariate COX and least absolute shrinkage and selection operator regression were used to screen the features,and the non-zero radiomic features were obtained and the weight coefficients were used to calculate the Radscore value of each patient,and the predictive value of Radscore on PFS and OS was analyzed.Three models were established using traditional prognostic indicators(metabolic parameters and clinical factors),Radscore and combination.C-index,time-dependent area under the curve and decision curve were used to evaluate the model prediction efficiency.Finally,based on the optimal model,a column diagram was drawn,and the calibration curve was used to verify the efficiency of the column diagram.Results The combined model predicted PFS and OS at 3 and 5 years better than the traditional prognostic index model and Radscore model(Z=0.962 1-2.253 9,all P<0.05).Decision curve showed that the combined model achieved the greatest clinical net benefit.The calibration curve showed that the predicted values of the nomogram were in good agreement with the observed values.Conclusion Radscore is an independent prognostic factor for survival in DLBCL patients.The combined model has great application value in guiding the formulation of clinical individualized treatment plan.