Aim To investigate the effect of Shenqi Dihuang decoction(SQDH)on henoch-schonlein pur-pura nephritis(HSPN)rats by regulating AMPK/Sirt1/Nrf2 mediated ferroptosis and the possible mech-anism.Methods Thirty SD rats were randomly divid-ed into a control group(Control),HSPN group,SQDH low-dose group(SQDH-L,5.4 g·kg-1),SQDH high-dose group(SQDH-H,21.6 g·kg-1),and SQDH high-dose+AMPK inhibitor group(SQDH-H+CC,20 mg·kg-1),with six rats in each group.Except for the control group,all other groups of rats were injected intraperitoneally with ovalbumin and complete Freund's adjuvant to establish HSPN rat models.After the successful construction of the model,each group of rats was orally administered with the cor-responding dosage or physiological saline once a day for five weeks.HE staining was used to observe the his-topathological changes in renal tissues;immunohisto-chemistry(IHC)was employed to detect the deposition of IgA and IgG in renal tissues;serum biochemical pa-rameters of renal function and urinary protein levels were measured;commercial assay kits were utilized to determine oxidative stress markers and Fe2+levels in renal tissues;Western blot analysis was performed to assess ferroptosis-related proteins and the protein ex-pression of the AMPK/Sirt1/Nrf2 signaling pathway in renal tissues.Results Compared with the control group,the HSPN group showed significant pathological damage in kidney tissue,with significantly increased scores,increased deposition of IgA and IgG in kidney tissue,decreased serum total protein(TP)and albu-min(ALB),and average increases in serum creatinine(Cre),urea nitrogen(BUN),and urinary protein levels(P＜0.05).The levels of MDA,ROS,Fe2+,and ACSL4 protein expression in the kidney tissue sig-nificantly increased,while SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein ex-pression significantly decreased(P＜0.05).Com-pared with the HSPN group,the pathological damage to renal tissue was reduced,IgA and IgG deposition in renal tissue decreased,TP and ALB decreased,Cre,BUN,and urinary protein levels were all reduced(P＜0.05),and the levels of MDA,ROS,Fe2+,and ACSL4 protein expression in renal tissue were signifi-cantly reduced in each dose group of SQDH rats.SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein expression significantly increased(P＜0.05).Compared with the SQDH-H group,the AMPK inhibitor CC could inhibit the AMPK/Sirt1/Nrf2 signaling pathway induced ferroptosis and reverse the protective effect of SQDH on renal injury in HSPN rats.Conclusions SQDH can improve renal injury in HSPN rats,and its mechanism may be related to the activation of AMPK/Sirt1/Nrf2 signaling pathway to in-hibit ferroptosis.

Aim To investigate the effect of Shenqi Dihuang decoction(SQDH)on henoch-schonlein pur-pura nephritis(HSPN)rats by regulating AMPK/Sirt1/Nrf2 mediated ferroptosis and the possible mech-anism.Methods Thirty SD rats were randomly divid-ed into a control group(Control),HSPN group,SQDH low-dose group(SQDH-L,5.4 g·kg-1),SQDH high-dose group(SQDH-H,21.6 g·kg-1),and SQDH high-dose+AMPK inhibitor group(SQDH-H+CC,20 mg·kg-1),with six rats in each group.Except for the control group,all other groups of rats were injected intraperitoneally with ovalbumin and complete Freund's adjuvant to establish HSPN rat models.After the successful construction of the model,each group of rats was orally administered with the cor-responding dosage or physiological saline once a day for five weeks.HE staining was used to observe the his-topathological changes in renal tissues;immunohisto-chemistry(IHC)was employed to detect the deposition of IgA and IgG in renal tissues;serum biochemical pa-rameters of renal function and urinary protein levels were measured;commercial assay kits were utilized to determine oxidative stress markers and Fe2+levels in renal tissues;Western blot analysis was performed to assess ferroptosis-related proteins and the protein ex-pression of the AMPK/Sirt1/Nrf2 signaling pathway in renal tissues.Results Compared with the control group,the HSPN group showed significant pathological damage in kidney tissue,with significantly increased scores,increased deposition of IgA and IgG in kidney tissue,decreased serum total protein(TP)and albu-min(ALB),and average increases in serum creatinine(Cre),urea nitrogen(BUN),and urinary protein levels(P＜0.05).The levels of MDA,ROS,Fe2+,and ACSL4 protein expression in the kidney tissue sig-nificantly increased,while SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein ex-pression significantly decreased(P＜0.05).Com-pared with the HSPN group,the pathological damage to renal tissue was reduced,IgA and IgG deposition in renal tissue decreased,TP and ALB decreased,Cre,BUN,and urinary protein levels were all reduced(P＜0.05),and the levels of MDA,ROS,Fe2+,and ACSL4 protein expression in renal tissue were signifi-cantly reduced in each dose group of SQDH rats.SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein expression significantly increased(P＜0.05).Compared with the SQDH-H group,the AMPK inhibitor CC could inhibit the AMPK/Sirt1/Nrf2 signaling pathway induced ferroptosis and reverse the protective effect of SQDH on renal injury in HSPN rats.Conclusions SQDH can improve renal injury in HSPN rats,and its mechanism may be related to the activation of AMPK/Sirt1/Nrf2 signaling pathway to in-hibit ferroptosis.

Objective To observe the clinical efficacy and safety of lupatadine tablets combined with azelastine hydrochloride nasal spray in the treatment of allergic rhinitis patients.Methods Patients with allergic rhinitis were randomly divided into control group and treatment group.Both groups received general treatment.On this basis,the control group was given azelastine hydrochloride nasal spray 0.14 mg per nostril each time,bid;on the basis of control group,the treatment group received lupatadine tablets 10 mg each time,orally,qd.Two groups were treated for 4 weeks.The clinical efficacy,rhinoconjunctivitis related quality of life questionnaire(RQLQ),serum indexes[interleukin-6(IL-6),IL-1 β,tumor necrosis factor-α(TNF-α),immunoglobulin E(IgE)]and safety were compared between the two groups.Results Treatment group were enrolled 53 cases,4 cases dropped out,and 49 cases were finally included in the statistical analysis.Control group were enrolled 53 cases,4 cases dropped out,and 49 cases were finally included in the statistical analysis.After treatment,the total effective rates of the treatment and control groups were 95.92％(47 cases/49 cases)and 81.63％(40 cases/49 cases)with significant difference(P＜0.05).After treatment,the RQLQ scores of treatment and control groups were(49.57±6.97)and(58.18±7.78)points,IL-6 levels were(5.12±1.25)and(7.34±1.46)ng·L-1,IL-1 β levels were(12.25±5.64)and(20.05±6.32)pg·mL-1,TNF-α levels were(3.25±0.62)and(4.45±0.49)pg·mL-1,the IgE levels were(114.28±19.63)and(136.84±30.14)μg·L-1,respectively,the differences were statistically significant difference(all P＜0.05).The adverse drug reactions of two groups were dry mouth,fatigue,dizziness and drowsiness.The total incidences of adverse drug reactions in the treatment and control groups were 16.33％and 10.20％without significant difference(P＞0.05).Conclusion Lupatadine tablets combined with azostine hydrochloride nasal spray have a definitive clinical efficacy in the treatment of allergic rhinitis patients,which can effectively reduce the inflammatory reaction,reduce the IgE levels,improve the quality of life,without increasing the incidence of adverse drug reactions.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Astragalus membranaceus has the effect of tonifying Qi and solid surface， diuretic support poison， discharging pus and astringent sores to produce muscle. It is not only used for syndromes such as deficiency of lung and temper， deficiency of spleen and diarrhea， but also for stroke， chest obstruction and other diseases. Due to the complex chemical composition and diverse pharmacological effect of Astragalus membranaceus， and the main role in invigorating qi and activating blood circulation has not been clarified. Astragaloside Ⅳ is one of its main active ingredients. In recent years， more and more studies on Astragaloside Ⅳ have been conducted at home and abroad. It has been reported that it has the medicinal value of enhancing immune function， strengthening heart and lowerin blood glucose， diuresis， anti-aging and anti-fatigue， et al， and has extensive pharmacological activity. Among them， the role of cardiovascular and cerebrovascular diseases in particular has attracted increasing attention. Cardiovascular and cerebrovascular diseases are ischemic or hemorrhagic diseases occurring in the heart， brain and systemic tissues due to blood viscosity， atherosclerosis， hypertension， hyperlipidemia， etc.， including cardiovascular and cerebrovascular diseases. Such diseases are a serious threat to mankind and are the leading cause of death worldwide. At present， western medicine is the main treatment， with many adverse reactions and poor long-term prognosis. TCM believes that the imbalance of qi and blood is the basic pathogenesis of this kind of disease. Qi deficiency and blood stasis are more common.At present， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases in a number of studies， and achieved some results， but this review in recent years， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases play the pharmacological activity， in order to explore whether Astragaloside Ⅳ is the main role of astragalus qi to find a theoretical basis for material basis， but also for the innovation of traditional Chinese medicine drug research and development of theoretical basis and practical guidance.

When this paper was first published the following ethical statement was omitted in error: All animal experimental protocols were approved by the Animal Ethics Committee of Guangdong Provincial Engineering Technology Institute of Traditional Chinese Medicine (Guangzhou, Guangdong, China, Approval NO: 048483). Further, all methods were performed in accordance with the relevant guidelines and regulations. NIH mice were purchased from the Guangdong Medical Laboratory Animal Center (Guangzhou, Guangdong, China, Certificate NO.44007200031795). The authors would like to apologise for any inconvenience caused.

Objective To observe the protective effect of polypyrimidine bundle-binding proteinrelated splicing factor (PSF) over-expression on RPE cell injury induced by advanced glycation end products (AGEs).Methods The human RPE cells cultured in vitro were divided into three groups:normal control group (N group),blank control group (N + AGEs group),empty vector control group (Vec + AGEs group),and PSF high expression group (PSF + AGEs).group).RPE cells in N group were routinely cultured;RPE cells in N + AGEs group were only transfected but did not introduce any exogenous genes combined with AGEs induction;Vec +AGEs group and PSF + AGEs group were transfected with pcDNA The empty vector or pcDNA-PSF eukaryotic expression plasmid was introduced into RPE cells and induced by AGEs.Except the N group,the other 3 groups of cells were transfected accordingly,and were stimulated with 150 μg/ml AGEs for 72 h after 24 h.HE staining and Hoechst 33258 staining were used to observe the effect of high PSF expression on the morphological changes of RPE cells;ROS level detection was used to analyze the effect of PSF high expression on the ROS expression of RPE cells induced by AGEs;MTT colorimetric method was used to detect the high PSF expression Effects on the viability of RPE cells;Western blot was used to detect the effects of different time and dose of PSF on the expression of heme oxygenase 1 (HO-1).Results HE staining and Hoechst 33258 staining observation showed that the cells in group N were full in shape,the nucleus was round,the cytoplasm was rich,and the staining was uniform;the cells in N + AGEs group and Vec + AGEs group were reduced in size,the eosinophilic staining was enhanced,and the nucleus was densely densely stained.Pyrolysis and even fragmentation;the morphology of cells in the PSF + AGEs group was still full,the cytoplasm staining was more uniform,and the nucleus staining was uniform.The results of MTT colorimetry showed that high expression of PSF can effectively improve the viability of RPE cells,but this effect can be effectively antagonized by ZnPP,and the difference is statistically significant (F=33.26,P＜0.05).DCFH-DA test results showed that compared with the N + AGEs group and Vec + AGEs group,the ROS production in PSF + AGEs group decreased,the difference was statistically significant (F=1 1.94,P＜0.05).Western blot analysis showed that PSF protein upregulated HO-1 expression in a time-and dose-dependent manner.The relative expression level of HO-1 at 24,48,and 72 h after PSF protein was significantly higher than that at 0 h,and the difference was statistically significant (F=164.91,P＜0.05).The relative expression level of HO-1 under the action of 0.1,0.5,1.0,1.5,and 2.0 μg PSF protein was significantly higher than 0.0 μg,and the difference was statistically significant (F=104.82,P＜0.05).Conclusion PSF may inhibit the production of ROS by up-regulating the expression of HO-1,thus protecting the RPE cells induced by AGEs.

Objective To investigate the inhibitory effect oflentivirus-mediated polypyrimidine bundle binding protein-associated splicing factor (PSF) on retinal neovascularization (RNV) in mice model of oxygeninduced retinopathy (OIR).Methods One hundred and twelve 5-day-old C57BL/6J mice were randomly divided into normal control group,simple OIR model group,OIR model + lentivirus empty vector treatment group (Vec group) and OIR model + PSF lentivirus treatment group (PSF group),with 16,32,32 and 32 mice,respectively.When the mice were 7 days old,the mice in the normal control group were fed in a routine environment,and the mice in the OIR model group,Vec group and PSF group were established OIR model.The mice in the Vec group and PSF group were given an intravitreal injection of 1 μl of lentiviral vector and PSF lentivirus (titer 1 × 10~ TU/ml) at the age of 12 days.No injection was performed in the normal control group and simple OIR group.RNV was evaluated by counting the number of pre-retinal neovascular cells and analysis of non-perfusion area by immunofluorescent staining of the mouse retina.Real-time quantitative PCR was applied to detect the mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase1 (HO-1).Western blot analysis was applied to detect the protein expression ofNrf2,HO-1 and PSF.Results Of the normal control group,simple OIR model group,Vec group and PSF group,the number of pre-retinal neovascular cell nuclei were 0.00,14.36 ± 5.50,15.67 ± 4.96,8.13 ± 2.09,the non-perfusion area were 0.00％,(35.71 ± 2.81)％,(36.57 ± 4.53)％,(15.33 ± 4.75)％,respectively.The differences of the number of pre-retinal neovascular cell nuclei and non-perfusion area among 4 groups were significant (F=24.87,165.70;P＜0.05).Compared with the normal control group,there were more pre-retinal neovascular cell nucleis and larger nonperfusion area in the simple OIR model group and Vec group (P＜0.05).Compared with the simple OIR model group and Vec group,there were lower pre-retinal neovascular cell nucleis and smaller non-perfusion area in the PSF group (P＜0.05).Real-time quantitative PCR and Western blot showed that the mRNA expression of Nrf2,HO-1 (F=53.66,83.54) and protein expression ofNrf2,HO-1 and PSF (F=58.38,52.69,24.79) among 4 groups were significant (P＜0.05).The rnRNA expression ofNrf2,HO-1 and protein expression of Nrf2,HO-1 and PSF in the simple OIR model group and Vec group decreased significantly than those in the normal control group (P＜0.05).The mRNA expression ofNrf2,HO-1 and protein expression ofNrf2,HO-1 and PSF in the PSF group were increased significantly than those in the simple OIR model group and Vec group (P＜0.05).model group and Vec group (P＜0.05).Conclusion Intravitreal injection of lentivirus-mediated PSF inhibits RNV in mice model of OIR possibly through up-regulating the expression of Nrf2 and HO-1.

Acupuncture Points ; Acupuncture Therapy ; Depression/therapy* ; Humans ; Liver ; Qi ; Sleep Initiation and Maintenance Disorders/therapy* ; Treatment Outcome