LEF is a novel immunosuppressant with unique chemical structure and novel mechanism of action, which mainly acts by inhibiting the ab initio synthesis pathway of pyrimidines and tyrosine kinase activity, and has precise efficacy and good safety in a variety of autoimmune diseases and immune-mediated diseases, with broad clinical application prospects in rheumatic diseases, renal diseases, skin diseases and organ transplantation. The rheumatic diseases are introduced as follows. 1, rheumatoid arthritis (RA) RA is an indication for LEF. LEF generally takes effect 3-6 weeks after the drug is administered and reaches steady state at 12 weeks. the improvement of rest pain, grip strength and living ability in the LEF group is significantly better than that of methotrexate (MTX) at 6 weeks, and the improvement rate of rest pain, morning stiffness, daily living ability, doctor’s evaluation and rheumatoid factor is significantly higher than that of MTX group at 12 weeks. The total effective rate of LEF at 12 and 24 weeks was 86.9% and 92.3%, respectively. The literature on the efficacy of LEF in the treatment of RA has been very extensive at home and abroad. RA can lead to bone and joint destruction and disability, mainly because bone resorption increases significantly during the active period of the disease, while bone production is the same as normal people, so the overall result is that bone resorption is greater than bone production, leading to bone and joint destruction. The balance between bone resorption and bone production is re-established, effectively preventing bone and joint destruction. Controlled clinical trials in Europe and the United States have shown that the inhibitory effect of LEF on bone destruction for 6, 12 and 24 months is significantly better than that of MTX and salazosulfapyridine. The adverse effects of LEF for RA are mild, and serious adverse effects are rare. The main adverse reactions include: rash, gastrointestinal reactions, transient transaminase elevation and decrease in white blood cell count, reversible alopecia, etc. In domestic clinical trials, the incidence of adverse reactions and serious adverse reactions in the LEF group were significantly lower than those in the MTX group.The adverse reactions of LEF are generally reversible, but the use of the drug is not recommended for patients with severe liver impairment, alcoholism, or hepatitis. If the liver enzymes increase or the white blood cell count decreases during the course of the drug, the treatment principles are as follows: if the ALT increases within 2 times the normal value, continue to observe; if it increases 2-3 times, reduce the dose by half and continue to observe; if it continues to increase or remains 80-120 U/L, interrupt the treatment; if it is >3 times, stop the drug and observe. After stopping the medication and returning to normal, the patient can continue to take the medication, and at the same time strengthen the liver protection treatment and follow-up, most of the patients will not have ALT rise again. If the white blood cell count decreases during the drug administration, the treatment principles are as follows: if the white blood cell count is not lower than 3. 0×109/L, continue to take the drug for observation; (2. 0-3. 0)×109/L, reduce the dose by half for observation, continue the drug, most patients can return to normal, recheck the white blood cell is still lower than 3. 0×109/L, interrupt the treatment; white blood cell count decreases to less than 2. 0×109/L, interrupt the treatment. Adverse reactions to LEF generally occur within six months of administration, especially within three months, and no new adverse reactions have been found in 5-year follow-up data from abroad. Long-term use of MTX can lead to an increased incidence of malignant tumors such as lymphoma, but according to the animal experiments and clinical data available so far, no increased incidence of tumors due to LEF has been found. 2. Systemic lupus erythematosus (SLE) Remer et al [16] used LEF to treat 18 outpatients with SLE with a loading dose of 100 mg/d for 3 d. The dose was changed to a maintenance dose of 20 mg/d after 3 d. The observation period was 2-3 months. Baltimore [17] treated 20 patients with refractory lupus with active arthritic manifestations with LEF, 75% of whom had been taking prednisone ( The loading dose of LEF was 100 mg/d for 3 d; the maintenance dose was changed to 40 mg/d for 3 months. The results showed that 30% (6/20) of the patients achieved complete remission at 1 month of treatment, even after 3 months when the dosage of LEF was reduced to 20 mg/d. Moreover, the mean blood creatinine level of patients decreased significantly after treatment. A large number of overseas clinical observation studies have shown that patients who had been treated with various immunosuppressive drugs and had failed or relapsed, the original oral hormone dosage remained unchanged, and the hormone dosage was gradually reduced after a month of treatment with LEF, without using other immunosuppressive drugs. The 24-h urine protein decreased significantly at 2 months after treatment, and continued to improve at 3 months; plasma protein gradually returned to normal, with statistical significance at 3 months; anti-dsDNA decreased significantly at 1 month after treatment; C3 increased to normal at 2 months (P<0. 05), with a highly significant difference at 3 months (P<0. 01). 3, ankylosing spondylitis Ankylosing spondylitis (AS) is a common systemic rheumatic disease with chronic inflammation of the sacroiliac joints and spine as the main manifestation, there is no specific treatment, generally advocate the use of slow-acting drugs and non-steroidal anti-inflammatory analgesics, but a considerable number of patients are not ideal treatment. There are some clinical studies on the use of LEF in the treatment of this disease at home and abroad, but there is a lack of large samples and randomized, double-blind controlled studies. A recent report in China] used a combination of MTX and LEF for the treatment of AS, in which the usage of LEF was: 50mg/d for 3 d followed by 20mg/d for maintenance; MTX was 7.5-15mg/week (5mg/d of folic acid was added for those who exceeded 10mg/week). The results showed that the patients' pain level, number of involved joints, finger-ground distance and blood sedimentation indexes improved significantly after six months and one year of treatment. 4. Application to autoimmune skin diseases Clinical studies of LEF for psoriasis have been reported one after another, mainly focusing on psoriatic arthritis. One researcher used LEF at a loading dose of 100 mg/d for 3 d and a maintenance dose of 20 mg/d. The results showed that after 3 months of treatment, the number of painful joints, swollen joints, pain, C-reactive protein (CRP) and other indicators were significantly improved, and there were significant differences before and after treatment, and there were no significant changes in hematological examination and liver function. Therefore, the study concluded that LEF provides an effective and well-tolerated new treatment for psoriatic arthritis, and it also has a good therapeutic effect on psoriatic skin damage.