1.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
2.Efficacy and Mechanism of Shuanghua Drink in Treating Primary Dysmenorrhea Based on COX-2/NF-κB Signaling Pathway
Yuncheng MA ; Yuanyuan SHI ; Zhen LIU ; Yuxi WANG ; Yuan TIAN ; Qian LI ; Xiaozhu WANG ; Cheng HE ; Wenhui XU ; Weiling WANG ; Jian GAO ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):72-80
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 F2α (PGF2α), prostaglandin E2 (PGE2), thromboxane B2 (TXB2), prostacyclin metabolite (6-keto-PGF1α), 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 PGF2α/PGE2, TXB2/6-keto-PGF1α, 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 PGF2α/PGE2 (P<0.01), TXB2/6-keto-PGF1α (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 PGF2α/PGE2, TXB2/6-keto-PGF1α, iNOS, and NO, elevated β-EP level, and inhibited COX-2/NF-κB signaling pathway.
3.Efficacy and Mechanism of Shuanghua Drink in Treating Primary Dysmenorrhea Based on COX-2/NF-κB Signaling Pathway
Yuncheng MA ; Yuanyuan SHI ; Zhen LIU ; Yuxi WANG ; Yuan TIAN ; Qian LI ; Xiaozhu WANG ; Cheng HE ; Wenhui XU ; Weiling WANG ; Jian GAO ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):72-80
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 F2α (PGF2α), prostaglandin E2 (PGE2), thromboxane B2 (TXB2), prostacyclin metabolite (6-keto-PGF1α), 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 PGF2α/PGE2, TXB2/6-keto-PGF1α, 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 PGF2α/PGE2 (P<0.01), TXB2/6-keto-PGF1α (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 PGF2α/PGE2, TXB2/6-keto-PGF1α, iNOS, and NO, elevated β-EP level, and inhibited COX-2/NF-κB signaling pathway.
4.Development of a new paradigm for precision diagnosis and treatment in traditional Chinese medicine
Jingnian NI ; Mingqing WEI ; Ting LI ; Jing SHI ; Wei XIAO ; Jing CHENG ; Bin CONG ; Boli ZHANG ; Jinzhou TIAN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):43-47
The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.
5.Compound Xishu Granules Inhibit Proliferation of Hepatocellular Carcinoma Cells by Regulating Ferroptosis
Yuan TIAN ; Yuxi WANG ; Zhen LIU ; Yuncheng MA ; Hongyu ZHU ; Xiaozhu WANG ; Qian LI ; Jian GAO ; Weiling WANG ; Wenhui XU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):37-45
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-BODIPY581/591 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-BODIPY581/591, 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.
6.Isolated anterior cerebral artery territory infarction: etiology, clinical features, and outcome
Guangsheng WANG ; Junjie BAO ; Ting HU ; Yuanyuan TIAN ; Li HUANG
International Journal of Cerebrovascular Diseases 2024;32(6):414-420
Objective:To investigate the etiology, clinical features and outcome of isolated anterior cerebral artery (ACA) territory infarction.Methods:Patients with isolated ACA territory infarction admitted to the Affiliated Shuyang Hospital of Xuzhou Medical University from April 2019 to December 2023 were retrospectively included. The demographic and clinical data were collected. The etiology subtypes of stroke were divided into large artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined etiology (SOE), and stroke of undetermined etiology (SUE). At 90 days after onset, the modified Rankin Scale was used to evaluate the outcome. 0~2 points were defined as good outcome, and >2 points were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent risk factors for poor outcomes. Results:A total of 67 patients with isolated ACA territory infarction were enrolled, including 31 males (46.27%), aged 67.20±12.59 years. There were 26 patients (38.81%) of LAA type, 10 (14.93%) of CE type, 7 (10.45%) of SVO type, 12 (17.91%) of SOE type, and 12 (17.91%) of SUE type. Fifty-two patients (77.61%) had good outcome, while 15 (22.39%) had poor outcome. There were significant differences in gender, diabetes, atrial fibrillation, antithrombin-Ⅲ activity, urinary incontinence, cognitive impairment, and the baseline National Institutes of Health Stroke Scale (NIHSS) score among different etiological subtypes (all P<0.05). Multivariate logistic regression analysis showed that previous stroke history (odds ratio 17.995, 95% confidence interval 1.276-253.852; P=0.032) and high baseline NIHSS score (odds ratio 2.094, 95% confidence interval 1.333-3.292; P=0.001) were the independent risk factors for poor outcome. Conclusions:The most common etiology of isolated ACA territory infarction is LAA, and most patients have good outcome. Previous stroke history and high baseline NIHSS score are the independent risk factors for poor outcome.
7.Improvement and mechanism of PF-04957325,an 8-type phosphodiesterase inhibitor,in cognitive impairment induced by okadaic acid in mice with Alzheimer's disease
Yu-Li LYU ; Tian-Yang GUO ; Nian-Zhuang QIU ; Han-Ting ZHANG ; Hao WANG
Chinese Pharmacological Bulletin 2024;40(9):1719-1726
Aim To investigate the effects of the phos-phodiesterase 8(PDE8)inhibitor PF-04957325 on learning and memory,anxiety and depression in Alzhe-imer's disease(AD)mice induced by Okadaic acid(OA),and to explore its mechanism.Methods Twenty-one 2-month-old male C57BL/6J mice were se-lected for the experiment and randomly divided into the control group,AD model group,and PDE8 inhibitor group(0.1 mg·kg-1).AD model was induced by bi-lateral hippocampal localization injection of OA(50 ng on each side)in the model and PDE8 inhibitor groups of mice.Two days after the injection of OA,PDE8 in-hibitor group was given 0.1 mg·kg-1 drug,while the AD model groups and control group were given with the same volume of vehicle for 21 consecutive days.On day 13 of inhibitor administration,behavioral tests re-lated to learning and memory abilities,anxiety and de-pressive behaviors were performed in mice.HE stai-ning was used to observe the morphology of neuronal cells in the DG,CA1,and CA3 regions of the hippo-campus of mice,and Western blot was used to detect the levels of phosphorylated Tau proteins at different sites within the hippocampus of mice as well as the ex-pression of proteins related to the PDE8/cAMP/CREB pathway.Results Compared with the control group,the Y-maze Spontaneous alternation,Recognition index of NOR and Latency of PAT were significantly shorter(P<0.01),and Entries times、Time in the target quadrant of MWM were reduced(P<0.05)in the AD model group,which showed a decrease in the ability of learning and memory,whereas the administration of PF-04957325 significantly improved the ability of learning and memory in the AD mice;mice in the AD model group showed a significant decrease in the num-ber of entries into the central area of the OFT and the time spent in the central area(P<0.05),and a sig-nificant increase in the Immobility time of TST(P<0.01),suggesting that the mice had anxiety and de-pression,and the administration of PF-04957325 did not improve the anxious behavior of the mice,but im-proved the depressed behavior to a certain extent;the hippocampus of the AD model group mice showed ker-nel solidification in the DG,CA1 and CA3 regions,and neurons were not neatly arranged,and the admin-istration of PF-04957325 could alleviate the damage of hippocampal nerve cells in mice.Compared with the control group,the phosphorylation levels of Tau protein Ser1 99,Ser396 and Ser202 sites in the hippocampus of mice in the AD model group were significantly in-creased(P<0.01),the expression of PDE8A and PDE8B proteins was significantly increased(P<0.01),and the expression of p-PKA/PKA and BDNF proteins was decreased(P<0.05),after administra-tion of PF-04957325,the phosphorylation levels of Tau protein Ser396 and Ser202 sites were significantly re-duced(P<0.01),PDE8A and PDE8B protein ex-pression was significantly decreased(P<0.01),and p-PKA/PKA,p-CREB/CREB and BDNF protein ex-pression was significantly increased(P<0.01).Con-clusion PDE8 inhibitor PF-04957325 can improve learning memory ability,reduce cognitive dysfunction,restore Tau protein function,and attenuate neuronal cell damage in the hippocampus of AD mice with amel-iorative effects.The mechanism of action may be relat-ed to the activation of PDE8/cAMP/CREB pathway and inhibition of Tau protein phosphorylation.
8.Risk factors of gastrointestinal bleeding after type A aortic dissection
Shi-Si LI ; Chun-Shui LIANG ; Tian-Bo LI ; Yun ZHU ; Han-Ting LIU ; Xing-Lu WANG ; Si ZHANG ; Rui-Yan MA
Journal of Regional Anatomy and Operative Surgery 2024;33(6):497-500
Objective To analyze the risk factors of gastrointestinal bleeding in patients with type A aortic dissection(TAAD)after Sun's operation.Methods The clinical data of 87 patients who underwent TAAD Sun's operation in our hospital from March 2021 to June 2022 were retrospectively analyzed.They were divided into the bleeding group and the non-bleeding group according to whether there was gastrointestinal bleeding after operation.The clinical data of patients in the two groups was compared and analyzed.The binary Logistic regression analysis was used to analyze the risk factors of gastrointestinal bleeding.The clinical predictor of postoperative gastrointestinal bleeding was analyzed by receiver operating characteristic(ROC)curve.Results In this study,there were 40 cases of postoperative gastrointestinal bleeding(the bleeding group)and 47 cases of non-bleeding(the non-bleeding group).Compared with the non-bleeding group,the bleeding group had a shorter onset time,a higher proportion of patients with hypertension history,a higher preoperative creatinine abnormality rate,more intraoperative blood loss,longer postoperative mechanical ventilation time,higher postoperative infection rate,and higher poor prognosis rate,with statistically significant differences(P<0.05).There was no statistically significant difference in the gender,age,gastrointestinal diseases history,smoking history,preoperative platelets,preoperative international normalized ratio(INR),preoperative alanine aminotransferase(ALT),preoperative aspartate aminotransferase(AST),preoperative γ-glutamyl transpeptidase(GGT),preoperative dissection involving abdominal aorta,operation time,intraoperative cardiopulmonary bypass time,intraoperative circulatory arrest time,intraoperative aortic occlusion time or intraoperative blood transfusion rate.Logistic regression analysis showed that hypertension history(OR=2.468,95%CI:0.862 to 7.067,P=0.037),preoperative creatinine>105 μmol/L(OR=3.970,95%CI:1.352 to 11.659,P=0.011),long postoperative mechanical ventilation time(OR=1.015,95%CI:0.094 to 1.018,P=0.041)and postoperative infection(OR=3.435,95%CI:0.991 to 11.900,P=0.012)were the independent risk factors for postoperative gastrointestinal bleeding in TAAD patients.ROC curve showed that the postoperative mechanical ventilation time exceeding 64 hours were the clinical predictor of postoperative gastrointestinal bleeding in TAAD patients.Conclusion The prognosis of TAAD patients with postoperative gastrointestinal bleeding after Sun's operation is poor.Hypertension history,preoperative acute renal insufficiency,long postoperative mechanical ventilation time and postoperative infection are closely related to postoperative gastrointestinal bleeding in TAAD patients after operation,which should be paid more attention to,and corresponding evaluation,early identification and early intervention should be made to improve the prognosis of patients.
9.The effect of learning input on core competencies of rural order-oriented medical students and the moderating role of professional commitment
Yuan XIE ; Hao LIU ; Ting-Hui LIAN ; Ya-Yan TIAN ; Jian-Tao LI
Chinese Journal of Health Policy 2024;17(5):57-63
Objective:To explore the influence of learning input and professional commitment on the core competence of rural order-oriented medical students,and to provide theoretical reference for improving the quality of the grassroots health workforce.Methods:520 rural order-oriented medical students from two medical colleges in S province were selected as research subjects.Stratified regression method was used to analyze the effect of learning input on the core competence of rural order-oriented medical students,and simple slope test was used to analyze the moderating effect of professional commitment on the aforementioned relationship.Results:The overall mean score of core competence of rural order-oriented medical students in S province was(3.39±0.549),learning input had a significant positive effect on the core competence of rural order-oriented medical students(β=0.358),and there was a moderating effect of professional commitment on the relationship between the two,which made the effect of learning input on core competence stronger(β=0.206).Conclusion:Improve the policy of training rural order-oriented medical students,strictly control the quality of admission,increase the construction and investment in grass-roots bases,emphasize students'vocational quality education,and enhance their core competencies.
10.Protective effect of wogonin on retinal ganglion cells in mice with glaucoma and its mechanism
Xiaoyu TIAN ; Ting LI ; Shengnan ZHANG ; Linli DAI
Recent Advances in Ophthalmology 2024;44(6):438-442
Objective To explore the protective effect of wogonin on retinal ganglion cells(RGC)in mice with glau-coma and its related mechanism.Methods Ten(10 eyes)C57BL/6J mice were included in the control group,and 40(40 eyes)DBA/2J mice were selected to prepare glaucoma models,which were divided into the model group,experiment 1,2 and 3 groups,with 10 mice per group.Mice in the control and model groups were given normal saline intragastrically,and mice in the experiment 1,2 and 3 groups were intragastrically given 50,100 and 150 mg·kg-1 wogonin,respectively.The right eyes were selected as experimental eyes.The intraocular pressure(IOP)of mice was compared among the five groups before and after 2,4 and 8 weeks of intragastric administration.The RGC number and retinal thickness of mice in each group were compared after hematoxylin-eosin staining.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and nitric oxide synthase(NOS)in the retinal tissues of mice were detected by colorimetry.The levels of inter-leukin(IL)-6,IL-1 β and tumor necrosis factor-α(TNF-α)in the retinal tissues of mice were detected by enzyme-linked im-munosorbent assay.The expression levels of nucleotide oligomerization domain-like receptor family 3(NLRP3),Caspase-1 and apoptosis-associated speck-like protein(ASC)in the retinal tissues of mice were detected by Western blot.Results Compared with the control group,IOP in the model group and the experiment 1,2 and 3 groups increased(all P<0.05)before intragastric administration.After 2,4 and 8 weeks of intragastric administration,IOP in the model group and the ex-periment 1,2 and 3 groups increased compared with the control group(all P<0.05);IOP in the experiment 1,2 and 3 groups decreased compared with the model group(all P<0.05);IOP in the experiment 2 and 3 groups decreased compared with the experiment 1 group(both P<0.05);IOP in the experiment 3 group decreased compared with the experiment 2 group(P<0.05).Compared with the control group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the model group and the experiment 1,2 and 3 groups decreased,while the expression levels of NOS,IL-6,IL-1 β,TNF-α,and NLRP3,Caspase-1 and ASC proteins increased,and the differences were statistically significant(all P<0.05).Compared with the model group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the experiment 1,2 and 3 groups increased,while the expression levels of NOS,IL-6,IL-1β,TNF-α,and NLRP3,Caspase-1 and ASC proteins decreased,and the differences were statistically significant(all P<0.05).Compared with the experiment 1 group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the experiment 2 and 3 groups increased,while the expression levels of NOS,IL-6,IL-1 β,TNF-α,and NLRP3,Caspase-1 and ASC proteins decreased(all P<0.05);compared with the experi-ment 2 group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the experiment 3 group increased,while the expression levels of NOS,IL-6,IL-1β,TNF-α,and NLRP3,Caspase-1 and ASC proteins decreased(all P<0.05).Conclusion Wogonin can improve the retinal thickness of mice with glaucoma and alleviate retinal oxidative damage and inflammatory reaction,which may be related to inhibiting the activation of NLRP3 inflammasomes.


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