This paper summarized professor LIU Guangzhen's experience in treating diabetes kidney disease （DKD） with kidney-draining method. Guided by kidney excess theory， it is believed that the basic pathogenesis of DKD is turbidity complicated by dampness stasis toxin damaging the kidneys. The treatment should primarily focus on draining the kidneys， and accordingly， a method of draining the kidneys， promoting circulation and clearing turbidity has been proposed， with self-made Shuangwu Juanzhuo Decoction （双五蠲浊汤） taken as the basic formula. Meanwhile， for the four compound syndromes which were turbidity pathogen complicated by dampness， turbidity pathogen complicated by dampness transforming into heat， turbidity toxin invading the brain， and turbidity pathogen complicated by stasis， medicinals that can drain dampness， cool blood， dissolve stasis and resolve toxins can be flexibly used based on Shuangwu Juanzhuo Decoction according to the syndromes， and Sanwu Juanzhuo Decoction （三五蠲浊汤）， Fufang Shelong Capsules （复方蛇龙胶囊） and other formulas were suggested for dispersing kidney pathogen， thereby promoting the recovery of the disease.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective: To investigate the effect of G protein-coupled receptor 108(GPR108) gene knockout on systemic inflammation in lipopolysaccharide(LPS)-induced sepsis mice. Methods: Male C57BL/6 mice and GPR108 gene knockout mice were randomly divided into 4 groups: WT group, WT-LPS group, KO group, KO-LPS group. The physiological characteristics of mice in different groups were observed, and the morphological changes of liver and lung tissues were observed. Macrophages were extracted from bone marrow and subjected to flow cytometry to detect their M1 polarization status. The expression levels of IL-6 in liver and lung tissues, macrophages, and serum were also measured. Results: KO-LPS group mice showed significant liver and lung tissue damage, with a significantly greater number of bone marrow-derived macrophages polarizing towards M1 in the KO-LPS group compared to the WT-LPS group. Additionally, at the tissue, cellular, and serum levels, the expression of IL-6 in the KO-LPS group mice was significantly higher than that in the WT-LPS group mice(P<0.05). Conclusion During the systemic inflammatory infection induced by LPS in mice, the lack of GPR108 exacerbates the systemic inflammatory response. GPR108 has an inhibitory effect on the inflammatory response in mice with LPS-induced sepsis.

Objective:To explore the role and mechanism of P311 in the differentiation of mouse skin fibroblasts (Fbs) into myofibroblasts.Methods:The study was an experimental research. Six 2-day-old male C57BL/6 mouse were used to extract skin Fbs by enzymatic hydrolysis method and routinely cultured. The 1 st to 3 rd passage cells were taken and divided into empty vector group transfected with empty adenovirus and P311 group transfected with P311 high expression adenovirus, and P311+myocardin-related transcription factor A (MRTF-A) small interfering RNA (siMRTF-A) group transfected with P311 high expression adenovirus and siMRTF-A according to the random number table. After 72 h of culture, the cell proliferation vitality of cells in 3 groups was detected by cell counting kit 8, the protein expressions of MRTF-A, α-smooth muscle actin (α-SMA), and serum response factor (SRF) in cells in 3 groups were detected by Western blotting, the collagen gel contraction assay was performed and the 72 h gel contraction rates in 3 groups were calculated. The sample numbers in the above experiments were all 3. The protein expressions of MRTF-A and SRF in cells, cytoplasm, and nucleus in cells in empty vector group and P311 group were detected by Western blotting, with sample number of 4. Results:After 72 h of culture, the cell proliferation vitality of cells in empty vector group, P311 group, and P311+siMRTF-A group was similar ( P>0.05). After 72 h of culture, compared with those in empty vector group, the protein expressions of MRTF-A, α-SMA, and SRF in cells in P311 group were significantly increased ( P<0.05), while the protein expressions of MRTF-A and SRF in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). Compared with those in P311 group, the protein expressions of MRTF-A, SRF, and α-SMA in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). The 72 h gel contraction rate showing cell contractility in P311 group was (84.8±6.2)%, which was significantly higher than (27.8±2.6)% in empty vector group and (24.7±3.2)% in P311+siMRTF-A group (with P values all <0.05). The 72 h gel contraction rates in empty vector group and P311+siMRTF-A group were similar ( P>0.05). After 72 hours of culture, the protein expressions of MRTF-A (with t values of 5.86 and 3.77, respectively, P<0.05) and SRF (with t values of 3.95 and 3.97, respectively, P<0.05) in cells and cytoplasm in P311 group were significantly higher than those in empty vector group, while the protein expressions of MRTF-A and SRF in the nucleus of cells were similar between the two groups ( P>0.05). Conclusions:P311 can promote the differentiation of fibroblasts into myofibroblasts through MRTF-A, and then participate in scar formation.

Objective:To investigate correlation between neutrophil lymphocyte ratio(NLR),IL-6 and lymphocyte subsets and prognosis of viral pneumonia complicated with acute respiratory distress syndrome(ARDS).Methods:A total of 98 patients with viral pneumonia complicated with ARDS admitted to Xinxiang Central Hospital/the Fourth Clinical College from May 2017 to June 2019 were selected,NLR,IL-6 and lymphocyte subsets expressions in patients with different severity were analyzed.Correlation between NLR,IL-6 and lymphocyte subsets levels in prognosis of viral pneumonia complicated with ARDS was analyzed by Pearson correlation.Logistc regression was used to analyze prognostic risk factors of viral pneumonia complicated with ARDS.Results:With aggravation of viral pneumonia complicated with ARDS,NLR and IL-6 levels were significantly increased(P<0.05),while CD3+T,CD4+T and CD19+T cells levels were significantly decreased(P<0.05).Pearson correlation analysis results showed that NLR and IL-6 were positively correlated with prognosis of viral pneumonia complicated with ARDS(P<0.05),while CD3+T,CD4+T,CD19+T and CD8+T cells were negatively correlated with prognosis of ARDS with viral pneumonia(P<0.05).Multivariate Logistic analysis showed that NLR,IL-6,CD3+T and CD19+T cells were risk factors for viral pneumonia complicated with ARDS(P<0.05).Conclusion:Serum NLR,IL-6,CD3+T and CD19+T cells are closely related to severity and prognosis of patients with viral pneumonia complicated with ARDS.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang （XXMT） combined with electroacupuncture （EA） collaboratively in alleviating cerebral ischemia/reperfusion （I/R） injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling， rats in the XXMT+EA groups were administered XXMT at low （15 g·kg^-1）， medium （30 g·kg^-1）， and high （60 g·kg^-1） doses， alongside daily 20-min EA treatment （stimulating acupoints GV14 and GV20）. Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score， TTC staining， and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 （NLRP3）， Gasdermin D （GSDMD）， cysteinyl aspartate specific proteinase-1 （Caspase-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the ischemic area of the cerebral cortex. ResultCompared with the sham group， the I/R group showed a significant increase in neurological deficit scores and infarct volume （P<0.01）， along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. In contrast， the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume （P<0.01）， and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway， thereby reducing neurological deficits， minimizing brain infarct size， and improving cortical neuronal damage.

Objective:To compare the efficacy between vonoprazan fumarate and rabeprazole for the treatment of artificial ulcers after endoscopic submucosal dissection (ESD).Methods:In this prospective randomized controlled study, patients who underwent ESD between December 2021 and August 2023 at Jiangsu Province Hospital were enrolled and randomly divided into two groups. Vonoprazan fumarate combined with rebamipide (vonoprazan group) or rabeprazole combined with rebamipide (rabeprazole group) were given respectively from the 4th day after ESD. After 8 weeks, the healing of the ulcers was compared.Results:Ninety-one patients were enrolled in the study, including 51 in the vonoprazan group and 40 in the rabeprazole group. The ulcer area reduction rate of the vonoprazan group was significantly higher than that of the rabeprazole group (92.86%±3.80% VS 90.04%±4.28%, t=3.281, P=0.001), but there was no significant difference in the healing rate [15.69% (8/51) VS 7.50% (3/40), χ2=1.414, P=0.234] or the adverse event occurrence ( P>0.05) between the two groups. Conclusion:Vonoprazan fumarate can achieve better ulcer treatment without increasing the risk of adverse events.

The diagnostic technology of acute stroke by microwave imaging has the advantages of being non-ionizing, fast, small, and low-cost. Therefore, this technology is expected to become an auxiliary or alternative means to CT and MRI technology. As the signal transmitting and receiving device of the microwave imaging system, the antenna has an important influence on the performance of the imaging system. At present, there are many antennas with different performances used in imaging systems, but there is a lack of clear evaluation criteria for them. In this paper, several typical antennas were introduced, their advantages and disadvantages from the perspective of bandwidth and near-field were analyzed, and the common requirements of imaging systems for antennas and the performance indicators of various types of imaging systems were summarized. Moreover, the development trend of antenna technology for microwave imaging was pointed out to provide a reference for the study of stroke microwave imaging technology.