ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

Objective To investigate the rules of medication and combinations of anti-tumor formulas containing marine Chinese medicinals. Methods The anti-tumor formulas containing marine Chinese medicinal were collected from Marine Chinese Medicinal and Effective formulas, Dictionary of Chinese Marine Medicinals, Marine Chinese Materia Medica, and databases including CNKI. A database was established for data mining by using V2. 5 software of TCM inheritance support system (TCMISS). Results There were totally 251 anti-tumor formulas containing marine Chinese medicinals involved 417 Chinese medicinal including 36 marine Chinese medicinals. The nature of medicinals in these formulas were mainly cold, neutral and warm, flavors of them were mainly bitterness, pungency, sweetness and saltiness,and they mainly entered into meridians of liver,lung,stomach,spleen and heart. The analysis of association rules showed that core combination was Muli (Oyster Shell, Concha Ostreae)-Haizao (Seaweed, Sargassum)-Kunbu (Kelp, Thallus Laminariae), which was commonly combined with medicinals with effects of clearing heart,tonifying,resolving phlegm,dissipating binds,activating blood and resolving stasis in clinical practice. Entropy clustering analysis showed that there were 12 combinations with core medicinals,and they were Haizao-Haigeqiao(Clam Shell,Goncha Meretricis seu Cyclinae)-Kunbu, Zaojiaoci (Chinese Honeylocust Spine, Spina Gleditsiae)-Chuanshanjia (Pangolin Scales,Squama Manitis)-Jiangcan (Batryticated Silkworm, Bombyx Batryticatus), Muxiang (Common Aucklandia Root,Radix Aucklandiae)-Walengzi (Ark Shell, Concha Arcae)-Puhuang (Cattail Pollen, Pollen Typhae), Chansu (Toad Venom, Venenum Bufonis)-Xionghuang (Realgar, Realgar)-Zhenzhu (Pearl,Pernulo),Huangbai(Amur Cork-Tree,Cortex Phellodendri)-Yunaoshi(Fish Otolith,Asteriscus Pseudosciaenae)-Bingpian (Bomeol, Bomeolum Syntheticum), Haima (Sea Horse, Hippocampus)-Qingpi (Green Tangerine Peel, Pericarpium Citri Reticulatae Viride)-Qianniuzi (Pharbitis Seed, Semen Pharbitidis), Haizao-Kunbu-Gancao (Liquorice Root, Radix Glycyrrhizae), Wangbuliuxing (Vaccaria Seed,Semen Vaccariae)-Chuanshanjia-Muli, Fengfang (Hornet Nest, Nidus Vespae)-Walengzi-Qianxie (Scorpion,Scorpio),Shexiang (Musk,Moschus)-Xuejie (Dragon's Blood,Risina Draconis)-Zhenzhu, Huangbai (Amur Cork-Tree, Cortex Phellodendri)-Ruxiang (Frankincense, Olibanum)-Bingpian, and Qingpi-Wulingzhi (Trogopterus Dung, Faeces Trogopterorum)-Dafupi (Shell of Arecanut, Pericarpium Arecae). There were 6 new combinations, and they were Haizao-Haigeqiao-Kunbu-Gancao, Zaojiaoci-Chuanshanjia-Jiangcan-Wangbuliuxing-Muli, Muxiang-Walengzi-Puhuang-Fengfang-Qianxie, Chansu-Xionghuang-Zhenzhu-Shexiang-Xuejie, Huangbai-Yunaoshi-Bingpian-Ruxiang, and Haima-Qingpi-Qianniuzi-Wulingzhi-Dafupi. The high-frequency tumor diseases, totally 47, treated with anti-tumor for-mulas containing marine Chinese medicinals,were successively thyroid tumor,lung cancer,liver cancer, uterine fibroids, nasopharyngeal carcinoma, esophageal cancer, gastric cancer and mammary cancer. Conclusion There are rules to follow in treatment of tumors with marine Chinese medicinal. The different therapeutic effects can be achieved by different medicinal combinations,which has a very important value in guiding clinical medication and new medicinal development.