Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

Objective To observe resting-state functional connectivity(rs-FC)changes of mirror neuron system(MNS)brain regions in male nicotine addicts,and to explore their correlations with the degree of addiction.Methods Twenty-five male nicotine addicts(addiction group)and 27 healthy males(control group)were prospectively recruited,and resting-statefunctional MR scanning was performed.The general information and rs-FC values were compared between groups,and correlations of rs-FC values with Fagerstr?m test for nicotine dependence(FTND)and heaviness of smoking index(HSI)scale scores in addiction group were analyzed.Results No significant difference of age nor education level was found between groups(both P＞0.05).Compared to control group,rs-FC values between left inferior frontal gyrus(IFG.L)and right middle temporal gyrus(MTG.R)as well as right middle occipital gyrus(MOG.R)increased(GRF corrected,voxel-level P＜0.005,cluster-level P＜0.05),while between right fusiform gyrus(FFG.R)and right dorsal cingulate gyrus(DCG.R),right supplementary motor area(SMA.R),left medial superior frontal gyrus(SFGmed.L)and left supplementary motor area(SMA.L)decreased(GRF corrected,voxel-level P＜0.005,cluster-level P＜0.05).In addiction group,rs-FC value between IFG.L and MTG.R was negatively correlated with HSI scale score(r=-0.457,P=0.022),while that between IFG.L and MOG.R was negatively correlated with HSI scale and FTND scores(r=-0.440,-0.458,P=0.028,0.021).Conclusion There were specific changes of rs-FC patterns of MNS brain regions in male nicotine addicts,which were correlated with the degree of addiction.

Objective To observe resting-state functional connectivity(rs-FC)changes of mirror neuron system(MNS)brain regions in male nicotine addicts,and to explore their correlations with the degree of addiction.Methods Twenty-five male nicotine addicts(addiction group)and 27 healthy males(control group)were prospectively recruited,and resting-statefunctional MR scanning was performed.The general information and rs-FC values were compared between groups,and correlations of rs-FC values with Fagerstr?m test for nicotine dependence(FTND)and heaviness of smoking index(HSI)scale scores in addiction group were analyzed.Results No significant difference of age nor education level was found between groups(both P＞0.05).Compared to control group,rs-FC values between left inferior frontal gyrus(IFG.L)and right middle temporal gyrus(MTG.R)as well as right middle occipital gyrus(MOG.R)increased(GRF corrected,voxel-level P＜0.005,cluster-level P＜0.05),while between right fusiform gyrus(FFG.R)and right dorsal cingulate gyrus(DCG.R),right supplementary motor area(SMA.R),left medial superior frontal gyrus(SFGmed.L)and left supplementary motor area(SMA.L)decreased(GRF corrected,voxel-level P＜0.005,cluster-level P＜0.05).In addiction group,rs-FC value between IFG.L and MTG.R was negatively correlated with HSI scale score(r=-0.457,P=0.022),while that between IFG.L and MOG.R was negatively correlated with HSI scale and FTND scores(r=-0.440,-0.458,P=0.028,0.021).Conclusion There were specific changes of rs-FC patterns of MNS brain regions in male nicotine addicts,which were correlated with the degree of addiction.

Objective To investigate the effects of different culture conditions(RPMI-1640,DMEM and DMEM/F12 medium)on the passage of MPM cells isolated from the tissues of Malignant pleural mesothelioma(MPM),and to study the effects of CDKN2B on the proliferation,invasion and apoptosis of MPM cells.Methods MPM cells were isolated from MPM tissues and cultured in RPMI-1640,DMEM and DMEM/F12 medium,respectively.Cell proliferation was examined by CCK-8,and the nuclei and chromosomes were observed by Wright-Giemsa staining.Fluorescence intensities of Calretinin,CD141,CK5,EMA and WT-1 were conducted by immunofluorescence assay.The mRNA and protein expression of CDKN2B were detected by RT-qPCR and Western blot,respectively.Transwell was used to detect cell invasion and flow cytometry was used to detect cell apoptosis.Results The established MPM cells showed good viability when passaged to the 10th generation in RPMI-1640,DMEM and DMEM/F12 cultures,and the MPM markers Calretinin,CD141,CK5,EMA and WT-1 were all expressed in the cells.The viability of MPM cells in RPMI-1640 culture medium was relatively stable.CDKN2B was downregulated in MPM cells(P<0.05),and overexpression of CDKN2B significantly suppressed the proliferation(P<0.05),invasion(P<0.05)and epithelial interstitial transformation of MPM cells(P<0.01),and promoted the apoptosis(P<0.01).Conclusion The established MPM cells were stably passaged in RPMI-1640 culture medium,and CDKN2B may be a potential target for the diagnosis and treatment of MPM.

ObjectiveTo observe the effect of natural moxibustion at "Feishu （BL 13）" on immune balance of T helper cell 17 （Th17） / regulatory T cell （Treg） in healthy rats. MethodsForty-eight rats were randomly divided into 10 rats in the sham moxibustion group and 38 rats in natural moxibustion group. The rats in the sham moxibustion group applied blank acupoint stickers to bilateral "Feishu （BL 13）"， and the rats in natural moxibustion group applied acupoint stickers filled with Compound Banmao Ointment （复方斑蝥膏） to bilateral "Feishu （BL 13）" for a period of 8 h. Thirty rats in natural moxibustion group were successfully blistered after 8 h， and then were randomly divided into 1-day， 3-day and 7-day groups with 10 rats in each group. The general condition of rats was recorded during the experiment； different time groups of natural moxibustion were sampled at the corresponding time， and HE staining was used to observe the pathological changes of the skin in the area of application； flow cytometry was used to detect the subpopulations of Th17 and Treg in peripheral blood， and the value of Th17/Treg was calculated； and ELISA was used to detect the serum interleukin 17A （IL-17A） and interleukin 6 （IL-6）， interleukin 10 （IL-10） levels. ResultsCompared with sham moxibustion group， blisters can be seen in the application area of rats in 1-day natural moxibustion group， and the rats often scratched the skin of the moxibustion area， which showed loose stratum corneum， thickening of the stratum spinosum and stratum granulosum， absence of cells in the basal layer， inflammatory cell infiltration， and elevation of Treg in peripheral blood， and serum IL-17A， IL-6； in 3-day natural moxibustion group， the moxibustion area of the rats was scabbed and partially detached， with the most obvious dermatopathological changes， and elevated peripheral blood Th17 and Treg， and serum IL-17A， IL-6， IL-10； in 7-day natural moxibustion group， skin damage and pathological changes in the area of moxibustion were basically restored； Th17/Treg values were reduced in 1-， 3- and 7-day moxibustion groups after blistering （P＜0.05 or P＜0.01）. Compared with the 1-day moxibustion group， peripheral blood Th17， Treg， and serum IL-17A elevated in the 3-day moxibustion group； peripheral blood Treg， serum IL-17A， and IL-6 decreased， and Th17/Treg values elevated in the 7-day moxibustion group （P＜0.05 or P＜0.01）. Compared with the 3-day moxibustion group， the 7-day moxibustion group had lower peripheral blood Th17 and Treg， serum IL-17A， IL-6， and IL-10， and higher Th17/Treg values （P＜0.05 or P＜0.01）. ConclusionNatural moxibustion at "Feishu （BL 13）" can shift the Th17/Treg balance towards Treg of healthy rats， which will gradually lead to immune homeostasis， and regulate the relevant inflammatory factors in the serum to prevent inflammation from occurring and developing.

Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation.Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used,and data processing was performed using the Seurat package,with integrated data to remove batch effects.Cell subpopulations were annotated based on known markers.Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package,and inferred based on the expression of cell surface receptors and ligands.Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors.Finally,differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting.Results A total of 7 different cell subpopulations were found in mouse islets,with β-cells being the most abundant.Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest.Gene set enrichment analysis showed that after treatment with inflammatory factors,the immune response was positively enriched in β-cells,while peptide hormone metabolism,bile acid metabolism,and ion homeostasis were downregulated.The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1(EGR1),nuclear factor-κB inhibitor α(NFKBIA),and activating transcription factor 3(ATF3).Among them,NFKBIA and ATF3 were upregulated,while EGR1 was downregulated.The expression of EGR1 protein was downregulated after 24 h,48 h,and 72 h of cold ischemia.Conclusions EGR1 is a transcription factor closely related to islet cold ischemia,and future research should focus on the specific mechanisms of EGR1 and its downstream target genes,in order to provide more effective strategies for clinical treatment of islet transplantation.

Objective To identify and analyze the bioinformatics and expression patterns of the F-box-LRR(FBXL)gene family of Salvia miltiorrhiza based on genomic data,and provide a foundation for further elucidating its gene functions.Methods The SmFBXL gene was identified from the Salvia miltiorrhiza genomic database.Its gene structure features,promoter cis-acting elements,physicochemical properties of encoded proteins,evolutionary relationships,and tissue expression were analyzed by bioinformatics methods and online tools.Results A total of 104 SmFBXL genes were identified from the Salvia miltiorrhiza genome,unevenly distributed on 8 chromosomes,with upstream promoters containing cis-acting elements related to plant stress resistance,growth and development,and hormone response.A phylogenetic tree of the FBXL family members of Salvia miltiorrhiza,Arabidopsis thaliana,and Glycine max was constructed,dividing the 104 SmFBXL genes into 7 subfamilies.Through homologous evolution analysis,it was speculated that SmFBXL36 might be involved in defense against pathogen invasion,SmFBXL86 and SmFBXL79 might play important roles in regulating lateral root growth in Salvia miltiorrhiza,and SmFBXL11 and SmFBXL40 might regulate hypocotyl growth.Transcriptome data showed differential expression of SmFBXL genes in different tissues of Salvia miltiorrhiza,with 13 SmFBXL genes showing higher expression levels in roots and leaves,serving as candidate genes for further research on the SmFBXL gene family.Conclusion The research results provided a reference for further elucidating the regulatory mechanisms of SmFBXL genes in stress response and secondary metabolite biosynthesis in Salvia miltiorrhiza.

Background::Given the established genetic linkage between triggering receptors expressed on myeloid cells 2 (TREM2) and Alzheimer’s disease (AD), an expanding research body has delved into the intricate role of TREM2 within the AD context. However, a conflicting landscape of outcomes has emerged from both in vivo and in vitro investigations. This study aimed to elucidate the multifaceted nuances and gain a clearer comprehension of the role of TREM2. Methods::PubMed database was searched spanning from its inception to January 2022. The search criteria took the form of ( "Alzheimer’s disease" OR "AD" ) AND ( "transgenic mice model" OR "transgenic mouse model" ) AND ( "Triggering receptor expressed on myeloid cells" OR "TREM2" ). Inclusion criteria consisted of the following: (1) publication of original studies in English; (2) utilization of transgenic mouse models for AD research; and (3) reports addressing the subject of TREM2.Results::A total of 43 eligible articles were identified. Our analysis addresses four pivotal queries concerning the interrelation of TREM2 with microglial function, Aβ accumulation, tau pathology, and inflammatory processes. However, the diverse inquiries posed yielded inconsistent responses. Nevertheless, the inconsistent roles of TREM2 within these AD mouse models potentially hinge upon factors such as age, sex, brain region, model type, and detection methodologies.Conclusions::This review substantiates the evolving understanding of TREM2’s disease progression-dependent impacts. Furthermore, it reviews the interplay between TREM2 and its effects across diverse tissues and temporal stages.

Humans ; Liposarcoma/surgery* ; Retroperitoneal Neoplasms/surgery* ; Neoplasm Recurrence, Local/surgery*

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.