ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

ObjectiveTo study the mechanism of compound Xishu granules （CXG） in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model， Fufang Banmao （0.21 g·kg^-1）， low-dose （1.87 g·kg^-1） CXG， medium-dose （3.74 g·kg^-1） CXG， and high-dose （7.49 g·kg^-1） CXG groups. Mice were administrated with drinking water or CXG for 28 days， and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 （CCK-8） was used to examine the survival rate of Huh7 cells treated with different concentrations （0， 31.25， 62.5， 125， 250， 500， 1 000 mg·L^-1） of CXG for 24 h and 48 h. CA-AM， DCFH-DA， and C11-BODIPY^581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion （Fe²⁺）， reactive oxygen species （ROS）， and lipid peroxide （LPO）， respectively. The colorimetric method was employed to measure the levels of glutathione （GSH） and superoxide dismutase （SOD）. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， and ferritin heavy chain 1 （FTH1）， respectively. ResultsIn the animal experiment， compared with the model group， the drug treatment groups showed reductions in the tumor volume from day 12 （P<0.01）. After treatment， the Fufang Banmao and low-， medium-， and high-dose CXG groups had lower tumor volume， relative tumor volume， and tumor weight than the model group （P<0.05）， with tumor inhibition rates of 48.99%， 79.93%， 91.38%， and 97.36%， respectively. Moreover， the CXG groups had lower tumor volume and relative tumor volume （P<0.05 in all the three dose groups） and lower tumor weight （P<0.05 in medium-dose and high-dose groups） than the Fufang Banmao group. Compared with the model group， the drug treatment groups showed reduced number of tumor cells， necrotic foci with karyopyknosis， nuclear fragmentation， and nucleolysis， and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment， compared with the blank group， CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h （P<0.05）. Compared with the blank group， the RSL3 group and the low-， medium-， and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY^581/591， which indicated elevations in the levels of Fe²⁺ （P<0.01）， ROS （P<0.05）， and LPO （P<0.01）， respectively. Compared with the blank group， the RSL3 and low-， medium-， and high-dose CXG groups showed lowered levels of GSH and SOD （P<0.05）. In addition， the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 （P<0.05）， and the low- and high-dose CXG groups presented up-regulated expression of TFR1 （P<0.05）. ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe²⁺and LPO levels.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Objective:To explore the predictive value of admission serum homocysteine levels and quantitative electroencephalogram (qEEG) indicators for adverse outcomes in patients with cerebral hemorrhage.Methods:A retrospective study was conducted on 89 patients, who were collected as the study objects with hemorrhagic stroke treated in the neurology intensive care unit at Kailuan General Hospital from January 2017 to December 2022. Patients were categorized into two groups based on modified Rankin Scale (mRS) scores at discharge: a good prognosis group (mRS≤2) and a poor prognosis group (mRS 3-6). Clinical data and qEEG monitoring of various brain regions were collected. The impact factors of hemorrhagic prognosis were analyzed using multifactorial logistic regression. ROC curve analysis was performed to assess the predictive value of qEEG and admission homocysteine levels for adverse outcomes in hemorrhagic stroke patients.Results:(1) The age of the poor prognosis group was higher than that of the good prognosis group((66.51+13.64) to (60.53+11.69), t=2.15, P=0.034) and admission serum homocysteine levels were significantly higher in the poor prognosis group than in the good prognosis group (17.28(15.52,24.72)mmol/L to 14.50(10.28,16.00)mmol/L, Z=4.14, P<0.001). (2) In the poor prognosis group, power values of δ brain waves in leads Fp1-2, F4, C4, P4, F8, and T4 were higher than those in the good prognosis group (87.99(41.57,196.69) to 50.67(26.64,54.75), Z=2.76, P=0.006); (79.17(40.71,200.00) to 45.06(20.22,61.00), Z=2.10, P=0.036); (72.64(34.97,219.78) to 34.42(19.81,63.4), Z=2.03, P=0.043); (65.06(33.36,177.45) to 28.12(15.88,63.36), Z=2.08, P=0.038); (52.92(25.64,187.91) to 23.61(11.67,43.26), Z=2.21, P=0.027); (66.67(32.56,180.76) to 36.31(17.2,53.78), Z=2.46, P=0.014); (57.30(25.24,127.04) to 29.57(11.91,41.89), Z=2.26, P=0.024). Power values of θ brain waves in leads Fp1-2, F3, F4, C3, C4, P3-4, O1, F7-8, and T3-4 were higher in the poor prognosis group(77.45(47.63,138.72)比35.88(20.92,44.81), Z=3.50, P<0.001); (77.05(35.16,120.22) to 38.74(19.86,58.09), Z=2.27, P=0.023); (85.24(52.53,147.90) to 35.42(14.7,52.59), Z=2.61, P=0.009); (75.81(37.90,124.97) to 36.85(17.92,55.43), Z=2.30, P=0.021); (72.00(43.92,123.54) to 28.37(14.02,51.9), Z=2.22, P=0.027); (67.08(32.01,104.05) to 31.32(17.98,45.28), Z=2.10, P=0.035); (55.33(32.29,94.30) to 25.64(11.87,34.01), Z=2.24, P=0.025); (48.84(20.64,96.28) to 19.85(9.83,28.58), Z=2.30, P=0.022);(48.46(25.06,81.78) to 23.95(8.80,29.16), Z=2.51, P=0.012); (64.46(39.38,112.44) to 26.85(15.74,39.58), Z=2.80, P=0.005); (65.68(31.78,102.00) to 31.09(15.98,46.96), Z=2.38, P=0.017); (45.26(28.34,73.14) to 21.45(10.57,36.59), Z=2.04, P=0.042); (43.50(22.58,78.67) to 25.45(11.91,32.26), Z=2.22, P=0.027). Power values of slow-wave index in leads Fp1-2, F3-4, C3-4, P4, F7-8, and T4, as well as the overall brain average, were higher in the poor prognosis group (6.64(2.98,10.42) to 3.65(2.31,4.30), Z=2.65, P=0.01); (6.53(3.96,11.65) to 3.53(2.56,4.51), Z=2.30, P=0.022); (7.38(4.62,13.12) to 3.83(1.70,4.71), Z=2.38, P=0.017); (5.88(4.02,12.15) to 3.18(2.21,4.46), Z=2.29, P=0.022); (6.13(3.83,11.22) to 2.97(1.53,4.58), Z=2.01, P=0.044); (6.07(3.53,9.39) to 2.74(2.00,3.81), Z=2.40, P=0.016);(4.11(2.51,9.23) to 2.18(1.37,2.82), Z=2.25, P=0.024); (5.71(3.81,10.44) to 3.22(1.86,4.04), Z=2.28, P=0.023); (6.00(3.65,10.37) to 3.04(2.00,4.00), Z=2.39, P=0.017); (4.08(2.56,8.33) to 2.08(1.60,3.14), Z=2.50, P=0.013), with significant statistical differences noted (5.45(3.31,10.08) to 3.17(2.02,4.88), Z=3.62, P=0.005). (3) Logistic regression results showed that admission homocysteine levels ( OR 1.311,95% CI 1.008-1.705, P=0.044), admission NIHSS scores ( OR 1.588,95% CI 1.074-2.349, P=0.020), and overall brain average slow-wave index were influencing factors for poor prognosis in cerebral hemorrhage ( OR 8.596,95% CI 1.088-67.889, P=0.041). (4) ROC curve analysis revealed that the AUC for predicting adverse outcomes in cerebral hemorrhage was 0.768 (95% CI (0.665, 0.872)) for admission homocysteine levels, 0.743 (95% CI (0.634, 0.852)) for the overall brain average slow-wave index, and 0.896 (95% CI (0.827, 0.965)) for admission NIHSS. The cutoff values were 15.67, 3.62, and 8.5, respectively. Sensitivity was 77.8%, 71.1%, and 68.9%, and specificity was 59.4%, 68.7%, and 100%, respectively. The Youden indices were 0.372, 0.398, and 0.689. Conclusion:In the acute phase of cerebral hemorrhage, electroencephalographic physiological changes manifest shows an increase in the δ, θ, and slow-wave index throughout the entire brain. Higher admission homocysteine levels suggest a worse prognosis in patients with cerebral hemorrhage. Admission homocysteine levels and overall brain average slow-wave index have certain predictive value for adverse outcomes in acute cerebral hemorrhage.

Objective To investigate the effects of modified Yupingfeng Powder medicated serum on the inflammatory response of rat lung epithelial type Ⅱ cells RLE-6TN;To explore the mechanism based on nuclear factor(NF)-κB signaling pathway.Methods The inflammatory reaction of RLE-6TN cells was induced by lipopolysaccharide,and the cells were divided into control group,model group,dexamethasone medicated serum group,and 5%,10%and 20%TCM serum group,and the cell model was intervened with different serum.After 24 hours,the content of lactate dehydrogenase(LDH)in cell supernatant was detected by kit,and the content of reactive oxygen species(ROS)in cells were detected by fluorescence staining,Hoechst/PI double staining was used to observe cell apoptosis,and ELISA was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β contents in cell supernatant,RT-qPCR was used to detect Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and NF-κB inhibitory protein α(IκBα)mRNA expression,Western blot was used to detect protein expressions of TLR4,MyD88,NF-κBp65 and IκBα.Results Compared with the control group,the contents of LDH,TNF-α,IL-6,IL-1β in RLE-6TN cell supernatant and ROS content in cells of model group significantly increased(P<0.01),the cell apoptosis rate significantly increased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly increased(P<0.01),the expression of IκBα mRNA significantly decreased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly increased(P<0.01).Compared with the model group,the content of LDH,TNF-α,IL-6,IL-1 in RLE-6TN cell supernatant and ROS content in cells significant decreased in the 20%TCM serum group and dexamethasone medicated serum group(P<0.01),the cell apoptosis rate significantly decreased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly decreased(P<0.05,P<0.01),the expression of IκBα mRNA significantly increased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly decreased(P<0.05,P<0.01).Conclusion Modified Yupingfeng Powder medicated serum can reduce RLE-6TN cells inflammatory reaction,and its mechanism may be related to the regulation of NF-κB signaling pathway.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To analyze and summarize the clinical, genotypic and pathological characteristics of children with PAX2 gene mutation in China, and to provide information for the monitoring, treatment and prognosis of the disease. Methods:It was a case series analysis study. The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2022 were collected, and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing. The clinical, pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed, Medline, China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center. Results:Among the 13 children with PAX2 gene mutation, there were 9 males and 4 females, 12 patients with abnormal urine tests, 7 patients with small kidney volume by imaging examination, and 5 patients with renal cysts. The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases, renal coloboma syndrome in 1 case, and hematuria or proteinuria in 3 cases. Five patients underwent renal biopsies, showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case, focal segmental glomerulosclerosis in 1 case, thin basement membrane lesion in 1 case, and IgA nephropathy in 2 cases. The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A, c.213-8C>G, c.63C>A and c.449C>T. There were 2 cases of 76dupG (p.V26Gfs*28) mutant. A total of 51 Chinese children with PAX2 gene mutation were found in the literature search. There were 32 males and 19 females, 8 cases with small kidney volume and 12 cases with renal cysts. The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases, renal coloboma syndrome in 17 cases, and hematuria or proteinuria in 6 cases. Seven patients underwent renal biopsies, including 2 cases with focal segmental glomerulosclerosis, 1 case with minimal lesion, 1 case with mesangial proliferative glomerulonephritis, 1 case with IgA nephropathy, 1 case with membranous nephropathy and a case with focal proliferative sclerosing purpura nephritis combined with glomerular hypertrophy. Thirty-four cases were de novo mutations, and 12 mutations were from the father or mother. The father or mother of 5 children had no clinical manifestations, with normal renal function. There were 11 cases of 76dupG (p.V26Gfs*28) mutant. Conclusions:The clinical phenotypes and genotypes of PAX2 gene variation in Chinese children are diverse. The most common clinical phenotype of PAX2 gene variation is congenital anomalies of kidney and urinary tract. c.76dupG (p.V26Gfs*28) is the most common of PAX2 gene variant.