Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective:To investigate the epidemiological status of knee joint tuberculous arthritis in 52 patients and to identify risk factors for recurrence after treatment.Methods:A retrospective analysis was conducted involving 52 patients with knee joint tuberculous arthritis who received treatment at Shaanxi Provincial Tuberculosis Prevention and Control Hospital from January 2018 to June 2023. Patients concurrently diagnosed with knee joint tuberculous arthritis were identified from the hospital's records, and their clinical data were collected. Logistic regression analysis was performed to determine the risk factors associated with recurrence of knee joint tuberculous arthritis.Results:The incidence of knee joint tuberculous arthritis is higher in males than in females, with the most affected age group being 40-60 years old. The most common form of the disease is total knee joint tuberculosis. The positive rate of Mycobacterium tuberculosis culture is 100%, indicating high diagnostic value. Logistic regression analysis results show that the following are independent risk factors for recurrence of knee joint tuberculous arthritis: age > 45 years ( OR = 3.080, 95% CI: 1.445-6.564, P = 0.004), body mass index < 18.5 kg/m2 ( OR = 6.062, 95% CI: 1.621-22.671, P = 0.007), smoking ( OR = 2.649, 95% CI: 1.032-6.799, P = 0.043), diabetes ( OR = 3.629, 95% CI: 1.799-7.321, P = 0.007), duration of tuberculosis symptoms > 6 months ( OR = 5.507, 95% CI: 1.210-25.055, P = 0.027), non-compliance with anti-tuberculosis medication ( OR = 3.152, 95% CI: 1.149-8.649, P = 0.026), elevated erythrocyte sedimentation rate ( OR = 3.297, 95% CI: 1.223-8.889, P = 0.018), and elevated C-reactive protein ( OR = 2.519, 95% CI: 1.025-6.194, P = 0.044). Conclusions:Knee joint tuberculous arthritis is more prevalent in males, with the most affected age group being 40-60 years old. Clinically, a comprehensive diagnosis that includes clinical evaluation, imaging, and bacterial culture is necessary. Lesion excision surgery can result in a good prognosis. Independent risk factors for the recurrence of knee joint tuberculous arthritis include age > 45 years, body mass index < 18.5 kg/m2, smoking, diabetes, duration of tuberculosis symptoms > 6 months, non-compliance with anti-tuberculosis medication, elevated serum erythrocyte sedimentation rate, and elevated C-reactive protein.

Objective To investigate the changes of inflammatory factors in bronchoalveolar lavage fluid(BALF),lung tissue,and serum of a rat pneumonia model induced by inhalation of lipopolysaccharides(LPS).Methods Three days after modeling by LPS 4 mg/mL inhalation,15 min/d,was conducted while monitoring the particle size distribution and aerosol concentration of LPS,the degree of inflammation in lung tissues of rats in each group was observed via HE staining,and neutrophils in BALF were counted by microscope.The contents of interferon gamma(IFN-γ),interleukin-1 beta(IL-1 β),IL-4,IL-5,IL-6,IL-10,IL-13,tumor necrosis factor alpha(TNF-α),and KC/GRO in lung tissue,serum,and BALF were detected by Meso Scale Discovery.Results The lung histopathology of model rats displayed focal and diffuse alveolar epithelial necrosis with shedding and the aggregation and infiltration of inflammatory cells.The particle size distribution of atomized LPS was as follows,Dv(10)=0.6974μm,Dv(50)=3.387 μm,Dv(90)=8.836 μm.The aerosol concentration of LPS was 4.08 g/m3,and the calculated inhalation dose for rats was 47.10 mg/kg.The neutrophil count(P＜0.01)and contents of IL-1β,IL-6,and TNF-α(P＜0.05,P＜0.001,P＜0.001)in the BALF,and the contents of IL-1β,IL-6,and KC/GRO in lung tissue(P＜0.01,P＜0.05,P＜0.01),of model rats were significantly increased.No biologically significant changes were observed in inflammatory factor levels in the serum.Conclusions In the acute pneumonia model induced by inhalation of LPS,significant changes in inflammatory factors such as IL-1β,IL-6,KC/GRO,and TNF-α were observed in both lung tissue and bronchoalveolar lavage fluid(BALF),while no notable changes in these inflammatory factors were detected in serum.This indicates that the inflammation responses are primarily localized in the lungs.

Objective To evaluate the application of rabbit liver cancer model in teaching interventional medicine for graduate students.Methods A total of 10 first-year master graduate students majoring in Radiological Imaging(Interventional Medicine).who were studying at Zhengzhou University of China,were enrolled in this study.The rabbit liver cancer model was used as the experimental teaching materials.The teaching contents included the establishment of rabbit liver cancer model,the interventional operation of rabbit liver cancer,the method of scientific research and teaching,the evaluation of the teaching effect,and the survey of student satisfaction.Results Under the guidance of teaching tutor,the success rate of VX2 rabbit liver cancer modeling performed by the 10 master graduate students majoring in interventional medicine was 100％,and the mean operational quality assessment score was(11.5±2.0)points.During the operation of interventional surgery,the success rate of femoral artery puncture was also 100％,and the mean score for each interventional operation was(11.8±2.3)points.The students'experimental designs were evaluated by the expert group,the results were as follows:2 cases were rated as excellent,7 cases were rated as good,and one case was rated as moderate.The degree of students'satisfaction with experimental teaching method was high,the specific scores of each item are as follows:the understanding of the rabbit liver cancer model was(4.80±0.40)points,the command of interventional technology was(4.60±0.49)points,and the quality and practicability of teaching materials was(4.90±0.30)points.Conclusion This teaching method of using rabbit liver cancer model experiment can improve the animal experiment ability,interventional operation ability and scientific research innovation ability of graduate students.Animal model teaching method is an innovation of teaching mode for graduate students majoring in interventional medicine.

Varicocele-induced infertility(VCI)is a common andrological disease in clinical practice.Oxidative stress represents the primary mechanism through which varicocele causes male infertility.Traditional Chinese medicine(TCM)treatment,characterized by its multi-target,multi-component,multi-system,and multi-pathway actions,has achieved favorable outcomes in the field of VCI treatment.This paper summarizes the underlying oxidative stress mechanism of VCI and the relevant signaling pathways involved.By reviewing the current research status on how monomers,active fractions,compound formulas,and related preparations of TCM can intervene in oxidative stress through the regulation of these signaling pathways to improve VCI,it is found that the nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway,the mitogen-activated protein kinase(MAPK)signaling pathway,and the hypoxia-inducible factor-1α(HIF-1α)signaling pathway are closely related to the development of VCI.TCM monomers and active fractions(flavonoids from Cuscutae Semen,polysaccharides from Astragali Radix,curcumin,ginsenoside Rg1,hyperin and echinacoside),as well as compound formulas and related preparations of TCM(modified Dahuang zhechong granules,Shengjing huoxue formula,modified Tianxiong san,Tongjingling,Bushen huoxue formula,Mailuoshutong pill,Zishen yutai pill,Danhong tongjing formula)can alleviate oxidative stress,reduce lipid peroxidation damage,improve mitochondrial dysfunction,decrease sperm DNA fragmentation,and inhibit apoptosis by activating the Nrf2 signaling pathways and inhibiting the MAPK and HIF-1α signaling pathways,thereby improving reproductive function.

Objective To investigate the changes of inflammatory factors in bronchoalveolar lavage fluid(BALF),lung tissue,and serum of a rat pneumonia model induced by inhalation of lipopolysaccharides(LPS).Methods Three days after modeling by LPS 4 mg/mL inhalation,15 min/d,was conducted while monitoring the particle size distribution and aerosol concentration of LPS,the degree of inflammation in lung tissues of rats in each group was observed via HE staining,and neutrophils in BALF were counted by microscope.The contents of interferon gamma(IFN-γ),interleukin-1 beta(IL-1 β),IL-4,IL-5,IL-6,IL-10,IL-13,tumor necrosis factor alpha(TNF-α),and KC/GRO in lung tissue,serum,and BALF were detected by Meso Scale Discovery.Results The lung histopathology of model rats displayed focal and diffuse alveolar epithelial necrosis with shedding and the aggregation and infiltration of inflammatory cells.The particle size distribution of atomized LPS was as follows,Dv(10)=0.6974μm,Dv(50)=3.387 μm,Dv(90)=8.836 μm.The aerosol concentration of LPS was 4.08 g/m3,and the calculated inhalation dose for rats was 47.10 mg/kg.The neutrophil count(P＜0.01)and contents of IL-1β,IL-6,and TNF-α(P＜0.05,P＜0.001,P＜0.001)in the BALF,and the contents of IL-1β,IL-6,and KC/GRO in lung tissue(P＜0.01,P＜0.05,P＜0.01),of model rats were significantly increased.No biologically significant changes were observed in inflammatory factor levels in the serum.Conclusions In the acute pneumonia model induced by inhalation of LPS,significant changes in inflammatory factors such as IL-1β,IL-6,KC/GRO,and TNF-α were observed in both lung tissue and bronchoalveolar lavage fluid(BALF),while no notable changes in these inflammatory factors were detected in serum.This indicates that the inflammation responses are primarily localized in the lungs.

Objective:To investigate the epidemiological status of knee joint tuberculous arthritis in 52 patients and to identify risk factors for recurrence after treatment.Methods:A retrospective analysis was conducted involving 52 patients with knee joint tuberculous arthritis who received treatment at Shaanxi Provincial Tuberculosis Prevention and Control Hospital from January 2018 to June 2023. Patients concurrently diagnosed with knee joint tuberculous arthritis were identified from the hospital's records, and their clinical data were collected. Logistic regression analysis was performed to determine the risk factors associated with recurrence of knee joint tuberculous arthritis.Results:The incidence of knee joint tuberculous arthritis is higher in males than in females, with the most affected age group being 40-60 years old. The most common form of the disease is total knee joint tuberculosis. The positive rate of Mycobacterium tuberculosis culture is 100%, indicating high diagnostic value. Logistic regression analysis results show that the following are independent risk factors for recurrence of knee joint tuberculous arthritis: age > 45 years ( OR = 3.080, 95% CI: 1.445-6.564, P = 0.004), body mass index < 18.5 kg/m2 ( OR = 6.062, 95% CI: 1.621-22.671, P = 0.007), smoking ( OR = 2.649, 95% CI: 1.032-6.799, P = 0.043), diabetes ( OR = 3.629, 95% CI: 1.799-7.321, P = 0.007), duration of tuberculosis symptoms > 6 months ( OR = 5.507, 95% CI: 1.210-25.055, P = 0.027), non-compliance with anti-tuberculosis medication ( OR = 3.152, 95% CI: 1.149-8.649, P = 0.026), elevated erythrocyte sedimentation rate ( OR = 3.297, 95% CI: 1.223-8.889, P = 0.018), and elevated C-reactive protein ( OR = 2.519, 95% CI: 1.025-6.194, P = 0.044). Conclusions:Knee joint tuberculous arthritis is more prevalent in males, with the most affected age group being 40-60 years old. Clinically, a comprehensive diagnosis that includes clinical evaluation, imaging, and bacterial culture is necessary. Lesion excision surgery can result in a good prognosis. Independent risk factors for the recurrence of knee joint tuberculous arthritis include age > 45 years, body mass index < 18.5 kg/m2, smoking, diabetes, duration of tuberculosis symptoms > 6 months, non-compliance with anti-tuberculosis medication, elevated serum erythrocyte sedimentation rate, and elevated C-reactive protein.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

ObjectiveTo predict the potential nephrotoxic components in traditional Chinese medicine health food products based on the Traditional Chinese Medicine Toxicity Alert System and Basic Toxicology Database （TCMTAS-BTD）， screen and validate the predicted components by cell and animal experiments， and decipher the mechanism of nephrotoxicity by network pharmacology. MethodTCMTAS-BTD was utilized to predict the toxicity of 3 540 compounds found in the catalogue of traditional Chinese health food ingredients. In the cell experiment， the top 5 compounds with high toxicity probability were screened by measurement of cell proliferation and viability （CCK-8） and high-content screening. ICR mice were randomized into a control group， a low-dose （2.91 mg·kg^-1·d^-1） ecliptasaponin A， and a high-dose （29.1 mg·kg^-1·d^-1） ecliptasaponin A group， with 10 mice in each group， and treated continuously for 28 days. During the experiment， the general conditions of the rats were observed， and the kidney index was calculated. The levels of serum creatinine （SCr） and blood urea nitrogen （BUN） in the serum as well as the content of malondialdehyde （MDA） and superoxide dismutase （SOD） in the renal tissue were measured. The pathological changes of the kidney were observed. Network pharmacology was employed to predict the potential pathways of nephrotoxicity. Finally， the pathway-associated proteins were validated by Western blot. ResultThe top 5 compounds with high probability of nephrotoxicity were ecliptasaponin A， chrysophanol， rutaecarpine， tanshinoneⅠ， and geniposidic acid. In the cell experiment， CCK-8 results showed that 10 μmol·L^-1 ecliptasaponin A， 60 μmol·L^-1 chrysophanol， 40 μmol·L^-1 rutaecarpine， and 20 μmol·L^-1 tanshinone I altered the viability of HK-2 cells. High-content analysis showed that 10 μmol·L^-1 ecliptasaponin A， chrysophanol， rutaecarpine， and tanshinone Ⅰ reduced the cell number （P<0.05， P<0.01）. The animal experiment showed that the mice in the high-dose ecliptasaponin A group presented slow movement， slow weight gain （P<0.01）， increased kidney index （P<0.01）， elevated SCr， BUN， and MDA levels （P<0.01）， and lowered SOD level （P<0.01）. Mild histopathological changes were observed in the high-dose ecliptasaponin A group. The network pharmacology results showed that the key targets of nephrotoxicity induced by ecliptasaponin A were mainly enriched in the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， prostatic cancer and lipid and atherosclerosis pathways. Western blot results verified that high dose of ecliptasaponin A raised the phosphorylation levels of PI3K and Akt （P<0.01）. ConclusionOn day 28 of administration， 29.1 mg·kg^-1 ecliptasaponin A was found to induce renal injury in rats. The mechanism may be related with the PI3K/Akt signaling pathway， which implied that excessive and prolonged usage of Ecliptae Herba may increase the incidence of adverse drug reactions.

ObjectiveTo study the effect of Tanreqing injection （TRQ） on the pulmonary flora in the rat model of chronic obstructive pulmonary disease （COPD）. MethodWistar rats were randomized into control， model， and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ （2 g·kg^-1）. At the end of the experiment， after blood collection from the abdominal aorta of the rats， the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected， and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal， and those of the model group showed neutrophil infiltration， telangiectasia， lung hemorrhage and emphysema in individual cases， and thickening of collagen fibers in the trachea. Compared with the model group， the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group， the model group showcased increased alveolar space （P<0.01）， which was reduced in the TRQ group （P<0.05）. Compared with the control group， the model group showed increased wall thickness （P<0.01）， and the increase was attenuated in the TRQ group （P<0.01）. TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level， the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas， compared with the control group. After treatment with TRQ， the relative abundance of g_Stenotrophomonas increased， and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group， and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD， which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.