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

Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*

OBJECTIVE To formulate an expert consensus on the prevention and control of respiratory infectious diseases in railway stations and trains in China,and to standardize the prevention and control of respiratory infec-tious diseases in railway stations and trains scientifically.METHODS The government authorities organized multi-ple prevention and control experts from transportation,medical care and prevention fields to conduct in-depth re-search through methods such as meetings and on-site investigations,and combined with their practical experi-ence in this field to formulate this expert consensus.RESULTS In-depth studies were conducted on the prevention and control strategies,measures and emergency response system construction of respiratory infectious diseases in railway stations and trains,and this expert consensus was formed.CONCLUSION This expert consensus supple-ments improves the existing prevention and control system for respiratory infectious diseases in railway stations and trains,and provides an important reference basis for the prevention and control of respiratory infectious disea-ses in railway stations and trains.

OBJECTIVE To formulate an expert consensus on the prevention and control of respiratory infectious diseases in railway stations and trains in China,and to standardize the prevention and control of respiratory infec-tious diseases in railway stations and trains scientifically.METHODS The government authorities organized multi-ple prevention and control experts from transportation,medical care and prevention fields to conduct in-depth re-search through methods such as meetings and on-site investigations,and combined with their practical experi-ence in this field to formulate this expert consensus.RESULTS In-depth studies were conducted on the prevention and control strategies,measures and emergency response system construction of respiratory infectious diseases in railway stations and trains,and this expert consensus was formed.CONCLUSION This expert consensus supple-ments improves the existing prevention and control system for respiratory infectious diseases in railway stations and trains,and provides an important reference basis for the prevention and control of respiratory infectious disea-ses in railway stations and trains.

OBJECTIVE To investigate the effects of galangin(GLA)on autophagy and apoptosis of chondrocytes in knee osteoarthritis(KOA)rats by regulating the adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)/UNC-51-like kinase 1(ULK1)signaling pathway.METHODS KOA rat model was constructed and separated into model group,L-GLA,M-GLA,H-GLA groups[subcutaneous injection of 100,200,400 μg/kg GLA],GLA+Compound C group[subcutaneous injection of 400 μg/kg GLA+0.2 mg/kg AMPK inhibitor Compound C],with 10 rats in each group.Additionally,10 normally fed rats were selected as the sham operation group.After the last medication,the degree of knee joint swelling of rats in each group was detected;the pathology of knee joints in KOA rats was observed.The serum expressions of matrix metalloproteinase 13(MMP-13)and interleukin-1 β(IL-1 β)in KOA rats were detected;the autophagy of chondrocytes in KOA rats was observed;the chondrocyte apoptosis in KOA rats was detected;the phosphorylation of AMPK/mTOR/ULK1 pathway-related proteins in cartilage tissue of knee joint were detected in rats.RESULTS Compared with the sham operation group,the arrangement of articular chondrocytes in the model group was disordered,with nuclear pyknosis and severe fibrosis of the articular cartilage layer,accompanied by a large amount of inflammatory cell infiltration;the degree of joint swelling,the number of autophagic vacuoles and apoptosis rate of chondrocytes,serum levels of MMP-13 and IL-1β,and the phosphorylation of mTOR protein in cartilage tissue of knee joint were all increased significantly(P＜0.05),while the phosphorylation of AMPK and ULK1 protein were all decreased significantly in cartilage tissue of knee joint(P＜0.05).Compared with the model group,L-GLA,M-GLA,H-GLA groups showed significant improvement in joint cartilage injury and reduced infiltration of inflammatory cells in rats.The above quantitative indicators were significantly reversed in a dose-dependent manner,except the number of autophagic vacuoles increased significantly(P＜0.05).Compared with the H-GLA group,the GLA+Compound C group showed aggravated cartilage tissue of joint cartilage injury and inflammatory cell infiltration in rats,and the above quantitative indicators were reversed significantly(P＜0.05).CONCLUSIONS GLA can promote autophagy and inhibit apoptosis of chondrocytes in KOA rats,the mechanism of which may be associated with activating AMPK/mTOR/ULK1 signaling pathway.

Objective To investigate the effects of narrow-band ultraviolet B (NB-UVB) therapy on the levels of plasmin and CC chemokine ligand 20 (CCL20) in peripheral blood of patients with psoriasis vulgaris.Methods A total of 60 patients with psoriasis vulgaris in progressive stage were treated with NB-UVB radiation thrice a week for 8 weeks.Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of plasmin and CCL20 in the peripheral blood of the patients before and after the treatment,as well as in the peripheral blood of 50 healthy controls.Results After the treatment,psoriasis area and severity index (PASI) scores in patients were significantly decreased compared with those before the treatment (2.54 ± 1.64 vs.10.26 ± 3.14,t =17.40,P ＜ 0.05),and the response rate was up to 87％ (52/60).Before the treatment,levels of plasmin and CCL20 were both significantly higher in the patient group than in the control group (plasmin:180.07 ± 40.62 μg/L vs.76.30 ± 26.92 μg/L,t =15.45,P ＜ 0.05;CCL20:422.41 ± 129.87 pg/L vs.205.33 ± 49.89 pg/L,t =11.15,P ＜ 0.05).After the treatment,levels of plasmin (148.22 ± 40.05 μg/L) and CCL20 (329.67 ± 100.73 pg/L) in patients were significantly decreased compared with those before the treatment (t =4.97,6.44,P ＜ 0.05),but still significantly higher than those in controls (t =10.82,7.95,P ＜ 0.05).Before the treatment,the level of plasmin was positively correlated with the level of CCL20 in peripheral blood of the patients (r =0.57,P ＜ 0.05),and the levels of plasmin and CCL20 were both positively correlated with the PASI score (r =0.49,0.62,respectively,both P ＜ 0.05).Conclusion NB-UVB radiation may exert a therapeutic effect on psoriasis vulgaris by reducing levels of plasmin and CCL20 in peripheral blood of patients.

Objective To evaluate the efficacy and adverse effect of valproic acid (VPA) in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome. Methods A total of 41 patients with intermediate (34) and high-risk (7) myelodysplastic syndrome were retrospectively analyzed. Among them, 19 patients received low dose chemotherapy regimen and 22 received low dose chemotherapy plus VPA.Low dose chemotherapy regimen included: homoharringtonine,1-2 mg·m-2·d-1 intravenously,14-28 d; clarubicin,5-7 mg·m-2·-1 intravenously,1-8 d,15-23 d;cytarabine 15 mg/m2 subcutaneously once every 12 h, 14-21 d; and subcutaneously use of granulocyte colony-stimulating factor 200 μg·m-2·d -1 when neutrophil deficiency.The outcome and adverse effect were recorded after the treatment. Results The overall response rate in the low dose chemotherapy regimen group was 47.4% (9/19), 6 patients (31.6%) achieved complete response (CR). The overall response rate in the VPA group was 77.2% (17/22), 9 patients (40.9%) achieved CR. The overall response rate of the low dose chemotherapy in combination with VPA group was significantly higher than that in the low dose chemotherapy group (P＜0.05) while no difference was found in CR rate. The adverse effect of the low dose chemotherapy in combination with VPA regimen was tolerated. Conclusion With acceptable adverse effect, the low dose chemotherapy in combination with VPA regimen is effective for the treatment of intermediate and high-risk myelodysplastic syndrome. Long-term outcome needs further investigation.

Objective: To find out the relation factors of hyperuricemia in cadres. Methods: The cadres who had health check on 2008 were analyzed. Results: The rate hyperuricemia in cadres of Zhuhai city was 35.42%. Conclusion: The rate of hyperuricemia in cadres is increasing by ages. It has the relations with sexual distinction, overweight or obesity, abnormal triglyceride and high purine-food.

BACKGROUND: Epidermal stem cells (ESCs) are of importance in the wound repair. Explaining the mechanism thatChinese herb speeds up the regeneration of injured skin from the angle of inducing stem cells deserves to be studied. OBJECTIVE: To observe the effect of Yuhong ointment on the proliferation and differentiation of ESCs during ratwound healing. DESIGN: A randomized controlled animal experiment. SETTING: Department of Pharmacology, Wangjing Hospital, China Academy of Chinese Medical Sciences. MATERIALS: This study was carried out in the Department of Pharmacology, Wangjing Hospital, China Academy ofChinese Medical Sciences between July and September 2006. Totally 114 healthy Wistar male adult rats, of cleangrade, weighing 180-210 g, were provided by the Laboratory Animal Center, Institute for Basic Theory of TraditionalChinese Medicine, China Academy of Chinese Medical Sciences were enrolled in this study. The processing ofanimals corresponded to the standard of Animal Ethics. Yuhong ointment was purchased from the PharmaceuticalCenter, Guanganmen Hospital, China Academy of Chinese Medical Sciences (Lot No. 20020110). Jingwanhong wasthe product of Tianjin Darentang Da'er Pharmcaceutical Co., Ltd (Lot No. Z12020440). METHODS: The 114 rats were completely randomly chosen and divided into 3 groups with 36 in each: Yuhongointment group, Jingwanhong group and model group, and the left 6 rats were involved as normal control group. Ratsin the normal control group were raised routinely, and no intervention was carried out. Immediately after beingmodeled, rats in the Yuhong ointment group were spread with Yuhong ointment, 0.1 g each wound, rats in theJingwanhong group were spread with Jingwanhong, 0.1 g each wound. Dressing change was daily carried out twice regularly until wound healing; The wounds of rats in the model group were untouched. MAIN OUTCOME MEASURES: On the 1st, 3rd, 5th, 7th, 14th and 21st days after modeling, wound healing time of rats in eachgroup was recorded, and integrinβ1 absorbance and transcription factor p63 positive cell amount were compared. RESULTS: Totally 114 rats were involved in the final analysis.① Wound healing time of rats in the Yuhong ointmentgroup and Jingwanhong group was significantly shorter than that in the model group, respectively (P ＜ 0.05). ② Integrinβ1 absorbance and transcription factor p63 positive cell amount of modeled rats in the Yuhong ointmentgroup, Jingwanhong group and model group were significantly higher than those in the normal control group, respectively (P ＜ 0.05); The above-mentioned two indexes in the Yuhong ointment group and Jingwanhong groupreached the peak on the 7th day, which was earlier than peak time in the model group, and peaked intensity of twoindexes was significantly higher than that in the model group, separately (P ＜ 0.05). CONCLUSION: Yuhong ointment can promote rat wound healing, which may be associated with Yuhong ointmentinducing the proliferation and differentiation of ESCS left in the wound edge.

Objective To observe the effect of Yuhonggao on proliferation and differentiation of epidermal stem cells and investigate the mechanism of promoting wound healing. Methods The whole layer skin defection rat was used and randomly divided into 3 groups:Yuhonggao group,Jingwanhong group,model group,with normal rats as control. The condition of skin wound surface and healing time were observed and recorded,and then draw the wound skin. The p63 and?1 integrin expression,the marker of epidermal stem cells,were measured and compared by immunohistochemistry staining. Results Average wound healing time hadn’t significant difference between the Yuhonggao group (13.5? 0.9)d and Jingwanhong group (12.6?0.9)d,which were better than model group (P