ObjectiveTo explore the protective effect and mechanism of Gegen Qianliantang （GQT） on intestinal mucosal barrier function in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） model mice. MethodsA UC model was established in C57BL/6 mice using a 2.5% DSS solution. Mice were randomly divided into five groups （n=8 per group）： blank group， model group， mesalazine sustained-release granule group （0.52 g·kg^-1）， high-dose GQT group （2.23 g·kg^-1）， and low-dose GQT group （1.12 g·kg^-1）. Fecal characteristics and body weight changes were observed before and after treatment. The body weight loss and disease activity index （DAI） of UC mice were calculated to evaluate symptom severity. Hematoxylin-eosin （HE） staining and Alizarin blue-periodic acid-Schiff （AB-PAS） staining were used to detect histological changes in colon tissue. Immunohistochemistry was used to detect the expression of zonula occludens-1 （ZO-1） and mucin 2 （MUC2）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pro-inflammatory cytokines interferon-γ （IFN-γ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-17A， and anti-inflammatory cytokine IL-10. Flow cytometry was used to detect the activation of helper T lymphocyte subsets （Th1， Th17）， regulatory T cells （Treg）， and regulatory B cells （Breg） in spleen and colon tissues. Western blot was used to detect the expression levels of T-bet， forkhead box protein P3（FoxP3）， nuclear transcription factor（NF）-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， signal transducer and activator of transcription 3（STAT3）， and phosphorylated STAT3 （p-STAT3）. ResultsCompared with the model group， both high- and low-dose GQT groups significantly improved the body weight loss and DAI scores （P<0.05）， alleviated colonic inflammation， and showed optimal efficacy in the high-dose group. AB-PAS staining showed that compared with the model group， both the high- and low-dose GQT groups significantly increased goblet cell proliferation and mucin secretion， indicating improved mucosal barrier function. GQT upregulated the expression of ZO-1 and MUC2 in colon tissue （P<0.05）， suppressed IFN-γ， IL-6， and TNF-α secretion （P<0.05）， elevated IL-10 secretion （P<0.05）， but had no significant effect on IL-17A. At the same time， high- and low-dose GQT intervention increased the activation of CD4⁺ FoxP3⁺ Treg cells （P<0.05） and suppressed activation of CD4⁺ IFN-γ⁺ Th1 cells （P<0.05）. Western blot showed that GQT downregulated T-bet， NF-κB p65， and STAT3 protein expression （P<0.05）， upregulated FoxP3 （P<0.05）， and also reduced phosphorylation levels of p-NF-κB p65 and p-STAT3 （P<0.05）. ConclusionGQT can upregulate the activation of CD4⁺ FoxP3⁺ Treg cells， reduce the activation of CD4⁺ IFN-γ⁺ Th1 cells， inhibit the secretion of IFN-γ， IL-6， and TNF-α， and increase the secretion of IL-10. It enhances the expression of MUC2 and ZO-1 in colon tissue， thereby alleviating inflammatory damage to the intestinal mucosa and restoring mucosal barrier integrity. These effects may be related to its regulation of NF-κB p65 and STAT3 signaling pathways， ultimately regulating the activation of transcription factors T-bet and FoxP3.

Cochlear spiral ganglion neurons (SGNs) are bipolar ganglion cells and are the first neurons in the auditory transduction pathway. They transmit complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus for sound processing. Injury to SGNs causes largely irreversible hearing impairment because these neurons are highly differentiated cells and cannot regenerate, making treatment of sensorineural hearing loss (SNHL) arising from SGN injury difficult. When exposed to ototoxic drugs or damaging levels of noise or when there is loss of neurotrophic factors (NTFs), aging, and presence of other factors, SGNs can be irreversibly damaged, resulting in SNHL. It has been found that NTFs and stem cells can induce regeneration among dead spiral ganglion cells. In this paper, we summarized the present knowledge regarding injury, protection, and regeneration of SGNs.

Objective To analyze the predictive value of serum micro RNA(miR)-411-5p and micro RNA(miR)-485-5p levels in preeclampsia(PE)pregnant women combined with ultrasound blood flow indicators for perinatal outcomes.Methods A total of 88 pregnant women with PE who were enrolled in the obstetric card and underwent cesarean section in Beijing Nuclear Industry Hospital from January 2020 to December 2021 were selected as the study subjects(PE group).In addition,90 normal pregnant women who delivered by cesarean section due to other reasons in the same period were regarded as the control group.The differences of pulsitility index(PI)and resistance index(RI)were compared between the two groups.The serum levels of miR-411-5p and miR-485-5p were measured and compared between the two groups by real time fluorescent quantitative PCR(qRT-PCR).According to the different perinatal outcomes of PE patients,they were grouped into good outcome group and poor outcome group.The differences of PI,RI,miR-411-5p and miR-485-5p between the two groups were compared.The predictive effect of PI,RI,miR-411-5p,miR-485-5p and combined detection on the adverse perinatal outcome of PE patients was analyzed by the receiver operating characteristic(ROC)curve method.Results The RI(0.79±0.08)and PI values(1.82±0.08)of pregnant women in the PE group were higher than those in the control group(0.66±0.06,1.38±0.15),the serum levels of miR-411-5p(0.32±0.09)and miR-485-5p(0.26±0.03)were lower than those in the control group(1.01±0.08,1.02±0.09),and the differences were statistically significant(t=12.283,24.339,54.091,75.231,all P＜0.001).The RI(0.83±0.08)and PI(1.86±0.09)values of PE patients in the poor outcome group were higher than those in the good outcome group(0.70±0.07,1.71±0.07),the serum levels of miR-411-5p(0.27±0.02)and miR-485-5p(0.24±0.02)were lower than those in the good outcome group(0.45±0.04,0.31±0.04),and the differences were statistically significant(t=11.545,12.428,37.840,14.716,all P＜0.001).The areas under the curve of ultrasound blood flow index RI and PI to predict the adverse perinatal outcome of PE patients were 0.838(sensitivity was 90.8％,specificity was 65.2％),and 0.758(sensitivity was 50.8％,specificity was 91.3％),respectively.The areas under the curve of serum miR-411-5p and miR-485-5p in predicting adverse perinatal outcome of PE patients were 0.830(sensitivity was 90.8％,specificity was 73.9％),and 0.769(sensitivity was 95.4％,specificity was 61.9％),respectively.The area under the curve of the four combined tests to predict the adverse perinatal outcome of PE patients was 0.976(sensitivity was 98.5％,specificity was 91.3％).Conclusion The levels of miR-411-5p and miR-485-5p in serum of PE pregnant women were decreased,and the combination of miR-411-5p and miR-485-5p and ultrasound blood flow indicators PI and RI may predict the perinatal fetal outcome of PE pregnant women.

Porcine deltacoronavirus(PDCoV),a newly discovered virus in recent years,can cause severe diarrhea,vomiting,dehydration and even death in piglets.S protein is an important structur-al protein of PDCoV,which determines the host or tissue tropism of the virus,and is an important target for the development of PDCoV vaccines and detection methods.In order to prepare mono-clonal antibody(MAb)against the S protein of PDCoV,the recombinant plasmid of S protein was constructed based on the extracellular domain sequence of S protein of PDCoV epidemic strain in China and transformed into DH10Bac competent cells.The recombinant bacmid was identified by blue-white spot screening and PCR.BALB/c mice were immunized with S protein,and the spleen cells of immunized mice were fused with myeloma cells.The positive hybridoma cells that secreted stable antibodies were screened by indirect ELISA and subcloning.Five hybridoma cell superna-tants(MAb)specifically recognizing S protein(2E5,4D5,5D10,2F7 and 5A9)were identified by Western blot and immunofluorescence assay(IFA).Subsequently,the neutralization test showed that three of the monoclonal antibodies(2E5,4D5 and 5D10)could neutralize the virus to varying degrees.The S protein was successfully expressed and 5 monoclonal antibodies that can stably se-crete and specifically bind to PDCoV and S protein were prepared,which laid an important founda-tion for further research on the structure and function of S protein,the development of detection methods for PDCoV infection,and the prevention or treatment of PDCoV infection.

Objective To investigate the current status of health behavioral decision-making in ischemic stroke patients and analyze its influencing factors.Methods Totally 250 ischemic stroke patients were selected from 2 hospitals in Zhengzhou and Anyang from February to May 2023.A general information questionnaire,Behavioral Decision-Making Scale for Stroke Patients,Recurrence Risk Perception Scale for Patients with Stroke,and Stroke Self-Efficacy Questionnaire were used to conduct the questionnaire survey.Results The Behavioral Decision-Making Scale for Stroke Patients score of 229 ischemic stroke patients was(117.83±7.15)scores.The results of multiple linear regression analysis showed that occupational status,glycemic compliance,primary caregiver,current symptoms,stroke self-efficacy,and recurrence risk perception were the influencing factors of health behavioral decision making in ischemic stroke patients(P＜0.05).Conclusion The health behavioral decision making of ischemic stroke patients is at an upper-middle level.Individualized interventions can be carried out for patients with different characteristics to promote the patients'ability to behavior decision making and the formation of preventive behaviors.

ObjectiveThis study aims to investigate the effect of modified Baitouwengtang （MBTWD） on tumor growth and the number of tumor-associated macrophages （TAMs） in tumor tissue of MC38 cell tumor-bearing mice with colorectal cancer and explores whether MBTWD mediates the remodeling of TAM phenotype to play an immunologically antitumor effect. MethodFirstly， The C57BL/6 mouse tumor model grafted subcutaneously was established， and then model mice were classified into a model group， positive control group（3 mg·kg^-1）， and MBTWD groups with high and low dosages（23.43、46.86 g·kg^-1）， with 10 mice in each group. In addition， 10 healthy mice were set as the blank group， and the changes in body weight， tumor volume， and survival status of mice in each group were observed. Tumor tissue， spleen， and peripheral blood were collected to calculate the tumor volume change， tumor inhibition rate， and spleen mass. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of tumor tissue， and an immunofluorescence assay was used to detect the expression levels of CD4， CD8， and CD206 in tumor tissues of tumor-bearing mice. The secretion levels of transforming growth factor （TGF）-β， interleukin （IL）-6， and chemokine （C-C Motif） ligand 2 （CCL2） in peripheral serum were measured by using enzyme-linked immunosorbent assay （ELISA）. Secondly， a co-culture model induced by IL-4 in vitro of MC38 cells and murine monocytic macrophage RAW264.7 cells was established. Cell proliferation and activity assay （CCK-8） was used to detect the inhibitory effect of MBTWD containing serum on cell proliferation. A transwell experiment was used to detect the effect of IL-4-induced M2 macrophages on the invasion of MC38 cells. Flow cytometry was used to detect the expression of CD86 on the membrane of M2 macrophages induced by IL-4 with MBTWD containing serum. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the effect of MBTWD containing serum on the mRNA expression levels of M1 macrophage-related polarization factors CD86， nitric oxide synthase （iNOS）， and IL-12， as well as M2 macrophage-related polarization factors CD206， CD163， and IL-10 after co-cultivation. Finally， the protein expression levels of colony-stimulating factor 1 receptor （CSF1R）， stimulator of interferon genes （STING）， and TANK binding kinase 1 （TBK1） in tumor tissues of tumor-bearing mice were detected by Western blot. ResultIn vivo experimental results show that compared with the model group， the MBTWD can significantly inhibit the tumor growth of tumor-bearing mice. Immunofluorescence experiments show that the MBTWD can increase the number of CD8⁺ T cell infiltration in tumor tissue of tumor-bearing mice， reduce the number of CD206⁺ TAMs infiltration， and down-regulate the secretion levels of cytokines IL-6， TGF-β， and CCL2 in peripheral blood of tumor-bearing mice. The results of in vitro experiments show that the MBTWD containing serum has no obvious inhibitory effect on cell proliferation， but the cell supernatant after co-cultivation with RAW264.7 cells can inhibit the proliferation activity of MC38 cells， and the invasion ability of MC38 cells is enhanced by IL-4-induced M2 macrophages. However， this effect can be inhibited in a concentration-dependent manner by the MBTWD containing serum. At the same time， the results of Real-time PCR show that the MBTWD containing serum can up-regulate the mRNA expression levels of M1 macrophage-related polarization factors CD86， iNOS， and IL-12 and down-regulate those of M2 macrophage-related polarization factors CD206， CD163， and IL-10. Flow cytometry results also confirm that the MBTWD containing serum can increase the number of repolarized CD86⁺ M1 macrophages， indicating that MBTWD can induce M2 macrophages to repolarized M1 macrophages to play an anti-tumor growth role. Finally， Western blot results show that MBTWD can down-regulate the expression of CSF1R protein and up-regulate that of STING and TBK1 proteins in tumor tissue of tumor-bearing mice. ConclusionMBTWD can down-regulate the infiltration number of CD206⁺ TAMs and increase the infiltration of CD8⁺ T cells， thereby playing an immunologically antitumor effect on the growth inhibition of colorectal cancer， which may be related to regulating CSF1R signaling and then activating STING/TBK1 signaling pathway to induce phenotypic remodeling of TAMs.

Pancreatic cancer is a major threat to population health, and there is an urgent need for the novel diagnostic and therapeutic patterns to improve the prognosis. Artificial intelligence (AI) has efficient computing and intelligent analysis capabilities, which brings a new opportunity for the upgrade of the diagnostic and therapeutic patterns of pancreatic cancer. This article reviews the recent progress of AI technology in early screening, diagnosis, treatment and prognosis prediction of pancreatic cancer, then describes the main difficulty and challenges of current AI research in pancreatic cancer, and proposes the future development directions from data quality and algorithm interpretation, etc. The aim is to provide new research ideas for the fusion of AI technology and pancreatic cancer, then promote the development and application of new pancreatic cancer diagnostic and therapeutic models, and ultimately improve the prognosis of patients.

Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival. Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers. However, the study and knowledge on drug resistance to CDK9 inhibitors are very limited. In this study, we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152. Through genomic sequencing, we identified in the kinase domain of CDK9 a mutation L156F, which is also a coding SNP in the CDK9 gene. By knocking in L156F into cancer cells using CRISPR/Cas9, we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors, not only ATP competitive inhibitor but also PROTAC degrader. Mechanistically, CDK9 L156F disrupts the binding with inhibitors due to steric hindrance, further, the mutation affects the thermal stability and catalytic activity of CDK9 protein. To overcome the drug resistance mediated by the CDK9-L156F mutation, we discovered a compound, IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant. Together, we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.

Objective:To evaluate the ability of vascular endothelial growth factor receptor 2(VEGFR2)/integrin α vβ 3 dual-targeted microubble (MBD) to target angiogenesis of renal cell carcinoma (RCC) in vivo. Methods:Non-targeted microbubble (MBN) USphere LA was employed as a template to prepare single- and dual-targeted microbubbles which could bind VEGFR2 and/or integrin α vβ 3 (MBV and MBI) by the biotin-avidin bridging method. A total of 40 RCC nude mice models were established by subcutaneously injecting 786-O cells.Twenty of the models were all injected with MBN, MBV, MBI and MBD in a random order, and the other 20 models were registered for antibody blocking assays. The results of ultrasound images were used for quantitative analyses, and the following quantitative parameters were obtained: intensity increment (a 1), peak halving speed (a 2), curve rising slope (a 3), perfusion time (t 0), time to peak (TTP), peak intensity (PI), mean transit time (MTT) and area under the curve (AUC) for the first three minutes, peak intensity at 10 s before (P 1) and after (P 2) ultrasound destruction, and the differences of tissue enhancement (dTE) between P 1 and P 2 (dTE=P 1-P 2). All the quantitative parameters of four contrast agents and the antibody blocking assays were compared.Besides, the immunohistochemical assays were performed to evaluate the expression of CD31, VEGFR2 and integrin α vβ 3 in tumor tissues. Results:The differences of parameters of a 1, a 3, t 0, TTP, PI and P 2 among four different microbubbles had no statistical significances (all P>0.05), and all parameters between the two single-targeted contrast agents were not statistically different (all P>0.05). The parameters of AUC, MTT, P 1 and dTE all showed a trend that dual-targeted bubbles > single-targeted bubbles > non-targeted bubbles (all P<0.05). On the contrary, the trend of dual-targeted bubbles < single-targeted bubbles < non-targeted bubbles (all P<0.05) was observed for a 2. In the antibody blocking experiment, a 2 was faster after the antibody injection ( P<0.001), while AUC, MTT, P 1 and dTE were all lower than those before the antibody injection ( P<0.001), and the other parameters were not statistically different before and after the antibody injection (all P>0.05). Immunohistochemical analyses confirmed the high expression of CD31, VEGFR2 and integrin β 3 in tumor tissues. Conclusions:The VEGFR2 and integrin α vβ 3 dual-targeted microbubble has a good potential to target the angiogenesis of human RCC in vivo.

Objective: To detect varicella-zoster virus ( VZV ) antibody levels among children aged 1 to 12 years in Lu'an City, Anhui Province, so as to provide insights into perfection of the varicella immunization strategy. Methods: Children aged 1 to 12 years were recruited from Lu'an City using the stratified random sampling method from July 2018 to February 2019, and subjects' demographics were collected using questionnaires. The inoculation of varicella vaccines was retrieved through the Anhui Immunization Information Management System or review of preventive immunization certificates, and the serum VZV IgG antibody was detected using enzyme-linked immunosorbent assay ( ELISA ). The seroprevalence and geometric mean concentration of the VZV-IgG antibody were estimated, and the changes of serum the VZV-IgG antibody levels were analyzed at different time intervals following varicella vaccination. Results: Totally 734 children were surveyed, with a mean age of ( 6.94±2.95 ) years, and the subjects included 412 boys ( 56.13% ) and 322 girls ( 43.87% ). There were 514 children ( 70.03% ) with a history of varicella vaccination, including 501 children ( 68.26% ) with one dose of varicella vaccine and 13 children ( 1.77% ) with two doses. There were 297 children ( 40.46% ) positive for VZV-IgG antibody, with seroprevalence of 40.46%, and the GMC of VZV-IgG antibody was 74.97 ( 95%CI: 65.55-85.75 ) mIU/mL. The seroprevalence of the VZV-IgG antibody were 34.55%, 42.91%, and 46.15% among the unvaccinated children and children receiving one dose and two doses of varicella vaccine, with the GMCs of 53.04, 86.31 and 114.46 mIU/mL, respectively. The mean time interval between inoculation of the last dose of varicella vaccine and blood sample collection was ( 5.21±2.79 ) years, and the lowest seroprevalene (31.48%) and GMC of the VZV-IgG antibody (49.96 mIU/mL) were found 4 years after inoculation of varicella vaccine. Conclusions The serum VZV-IgG antibody level is low among children aged 1 to 12 years in Lu'an City, and the seroprevalence of the VZV-IgG antibody is affected by age and doses of varicella vaccine. A 2-dose schedule of varicella vaccine is recommended for children.