PEM is a major influence on the quality of life and survival of patients with CRF. PEM is an independent correlate affecting the prognosis of CRF. The pathogenesis of PEM is multifaceted, and its occurrence and pathophysiologic changes have been extensively studied in recent years. 1, loss of appetite Anorexia and loss of appetite are the most common clinical symptoms in patients with CRF. It can be caused by psychobiological reasons or reactions to acute and chronic infections, uremic toxins, etc., but the exact mechanism of its occurrence is still unclear. It has been found that there may be a link between changes in neuropeptide hormones that regulate appetite and loss of appetite in CRF malnutrition. The hypothalamic arcuate nucleus (ARC) is a key part of the central regulator of appetite and energy balance of the body, and the “Appetite Regulation Network” (ARN) within the ARC can comprehensively regulate appetite through the signaling effect of various appetite regulators. Neuropeptide Y (NPY): Appetite promoter α-melanocyte stimulating hormone (MSH): Appetite suppressor Other regulators: Galanin (GAL), melanin-concentrating hormone, orexigenic peptide (OX) and so on. Leptin receptor (OB-R) was found on NPY-ergic neurons, GAL, melanin-concentrating hormone, OX-ergic neurons, and α-MSH and NPY-expressing neurons in ARC Leptin was found to be closely related to feeding behavior and energy metabolism CRF is often accompanied by hyper-Leptinemia. Leptin levels in the blood correlate negatively with protein intake, with serum ALB and TF, and with proteolytic rate, suggesting that hyper-Leptinemia may be an important factor contributing to CRF-PEM. Biological effects of Leptin: Binding to hypothalamic Leptin long type receptor (OB-Rb) causes decreased appetite and energy expenditure by inhibiting neuropeptide secretion in the arcuate nucleus of the hypothalamus. The JAK2-STAT3 pathway is the major pathway for Leptin receptor signaling. Leptin binding to OB-Rb acts on the JAK2/STAT3 pathway, activates STAT3, and translocates and localizes to the nucleus, where it interacts with DNA elements in the promoter region of specific genes or other transcription factors or accessory proteins to regulate the transcription of target genes, resulting in a decrease in appetite. Initiating the JAK2-STAT3 pathway, leptin initiates the negative feedback inhibitory loop of the pathway-Suppressor of cytokine signaling 3 (SOCS3) and protein inhibitor of activated STAT 3 (PIAS3) . Leptin stimulates the expression of SOCS3 and PIAS3 in tissues such as the center SOCS3 inhibits the JAK/STAT signaling pathway after OB-R by the following mechanisms: ① Inhibiting phosphorylation activation of JAK2 ② Blocking activation of the transcription factor STAT ③ SOCSbox/elonginBC-mediated inhibition PIAS is another factor that negatively feeds back on JAK-STAT activity and is another important protein in the negative feedback regulation of JAK-STAT activity. It can bind to tyrosine-phosphorylated STATs and inhibit STAT-mediated signaling by blocking the DNA-binding activity of STATs. Its mechanism is: ① with the dimerization of STATs binding, masking the DNA binding region of STATs ② with the STATs monomer binding to impede its dimerization and achieve 2, protein anabolism decreased, increased catabolism (1) metabolic acidosis: metabolic acidosis is one of the main complications of chronic renal insufficiency patients . The rate of muscle protein degradation increases – requiring the participation of glucocorticoids; the oxidation of branched-chain amino acids (BACC) increases – activation of branched-chain amino acid dehydrogenase; some studies have confirmed that the ubiquitin-proteasome pathway (UPP) pathway in skeletal muscle is involved in the acidosis-promoted protein catabolism and muscle atrophy. (2) Microinflammatory state Decreased immune function, reduced glomerular filtration rate, toxin retention and oxidative stress, fluid overload, and permeability bioincompatibility. Inhibition of hepatic albumin synthesis and inhibition of muscle protein synthesis via NF-κB Activation of the UPP system Increased catabolism in skeletal muscle . Suppression of appetite and alteration of feeding behavior promote PEM . (3) Endocrine dysfunction CRF can lead to abnormal production and clearance of hormones in the kidney, and its intraplasma transport, extrarenal metabolism, and feedback apoptosis are also altered. Insulin resistance; increased blood levels of insulin and glucagon; secondary hyperparathyroidism; lack of growth hormone and insulin-like growth factor (IGF) and decreased biological activity, etc. Insulin resistance: insulin must bind to the insulin receptor tyrosine kinase in order to function; CRF toxin can interfere with the action of insulin, so that peripheral tissues produce insulin resistance; therefore, it is believed that insulin resistance causes impaired protein synthesis and increased catabolism in the skeletal muscle, which is one of the causes of protein malnutrition in patients with CRF. Hyperglucagonemia: This hormone promotes amino acid transport into hepatocytes, provides raw materials for gluconeogenesis and inhibits protein synthesis, and is mainly degraded in the kidneys.In CRF, the half-life of glucagon is prolonged, resulting in hyperglucagonemia, which is involved in the inhibition of protein synthesis. (iii) Abnormalities in the growth hormone/insulin-like growth factor-1 axis: The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis promotes tissue growth and protein synthesis, and also reduces protein catabolism. In CRF there is reduced expression of GH receptors in target organs, reduced binding capacity to GH, and GH resistance, leading to increased catabolism. Increased circulating levels of insulin-like growth factor binding protein can (IGFBP) in patients with CRF, which binds to IGF-1 leading to decreased levels of free IGF-1, also greatly reducing the biological activity of IGF-1. (4) Disorders of mineral metabolism and elevated parathyroid hormone: Abnormalities in calcium and phosphorus metabolism, causing an increase in PTH; Increased levels of serum PTH and its N-terminal fragment may affect protein synthesis, amino acid transport, and abnormalities in glucose metabolism, thus becoming one of the causes of PEM in patients . (4) Mechanism study of protein catabolism and metabolism: ① ubiquitin proteasome pathway ② apoptotic protease-3 pathway ③ insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B signaling pathway ④ loss of nutrients in dialysis ① ubiquitin proteasome pathway (UUP): ubiquitin proteasome pathway (UUP) is an important system for regulating protein degradation and function. The UUP consists of ubiquitin, ubiquitin-activating enzyme E1, ubiquitin transferase E2s, ubiquitin ligases E3s and 26s proteasome. The process of protein degradation by this pathway requires two steps: 1. ubiquitin binds to the substrate protein through a series of catalytic steps by E1, E2 and E3 enzymes, and the ubiquitin chain binds to the substrate protein to form the ubiquitinated target protein. 2. The ubiquitin-protein coupling is recognized and degraded by the proteasome, and ubiquitin is released for recycling. Ubiquitin proteasome protein degradation pathway ② apoptotic protease-3 (caspase-3) pathway: uremia environment activates cellular caspase-3, prompting the cleavage of the actin-protomyosin complex into actin monomers, so that the complex structure of the muscle is cleaved into smaller fragments, and the latter then degraded through the UPP pathway into peptides and amino acids. The factors involved in the activation of caspase-3 have not been fully elucidated. Recently, angiotensin II (Ang II) has been found to down-regulate protein kinase B and activate skeletal muscle caspase-3 expression, leading to muscle protein hydrolysis and apoptosis. Insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B (IRS-1/PI3-K/Akt) signaling pathway : The IRS-1/PI3-K/Akt system plays an important role in promoting protein synthesis and inhibiting protein catabolism under the joint action of insulin and IGF-1. The roles of insulin, IGF-1 and IRS-1/PI3-K/Akt signaling pathway, in CRF protein metabolism need to be further explored. ④ Loss of nutrients in dialysis: Once dialysis treatment is initiated, the incidence of PEM increases significantly. Large amounts of nutrients such as amino acids, glucose and water-soluble vitamins are lost from the dialysate, and the enhanced catabolism induced by dialysis, the inadequacy of dialysis, and the adverse effects of dialysis all exacerbate the nutritional damage in CRF patients. Western medicine treatment Traditional Chinese medicine treatment 1.Western medicine treatment: ① low protein diet + α keto acid Reduce azotemia, improve metabolic acidosis Supplementation of amino acid deficiency, improve protein metabolism Reduce insulin resistance, improve glucose metabolism Increase lipase lipase activity, improve lipid metabolism Decrease blood phosphorus, increase blood calcium, alleviate secondary hyperthyroidism Reduce protein urinary excretion, delay the progress of CKD Non-diabetic Nephropathy Protein Intake Program Before Dialysis Pre-dialysis diabetic nephropathy protein intake program Conventional dialysis protein intake program ② Nutritional support including enteral nutrition and parenteral nutrition. ③ Correct lipid metabolism disorders ④ Supplement vitamins and inorganic salts to maintain water and electrolyte balance ⑤ Correct metabolic acidosis Theoretically, it should be able to improve the nutritional status, and clinical studies have found that the effect is not obvious. ⑥ Anti-inflammatory drugs There is no definite and effective method. (7) Hormones Recombinant human growth hormone (rhGH) has been used to treat growth retardation in children with chronic renal failure, but the efficacy, dosage, and safety in adult patients are uncertain. (8) Carnitine The clinical value of its application must be further explored, and is currently recommended only for carnitine deficiency and poor response to conventional treatment of patients. 2. Chinese medicine treatment: Chinese medicine to improve the nutritional status of patients has certain advantages, and the clinical also achieved good results. Spleen and kidney treatment, tonifying the spleen and stomach, qi deficiency and blood stasis, identification of symptoms and treatment (1) Treatment from the spleen and kidney theory, tonifying qi and blood with the aid of resolving turbidities. Apply herbs that tonify the kidneys and strengthen the spleen (Astragalus, Radix Codonopsis, Salviae Miltiorrhizae, Epimedium, Polygonum multiflorum, Fructus Lycii, Rhizoma Atractylodis Macrocephalae, Rhizoma Dioscoreae). Apply methods of tonifying the Kidneys and strengthening the Spleen, resolving blood stasis and dispelling turbidity (Cordyceps Sinensis, American ginseng, Astragalus, Cornu Cervi Pantotrichum, Atractylodes Macrocephalae, Fenghuang, Rheum Palmatum, Rhizoma Ligustici Chuanxiong and Licorice). (2) Starting from the spleen and stomach, strengthening the spleen and nourishing the stomach, and draining turbidity from the internal organs. For example, Xu’s treatment of anorexia in patients with abdominal dialysis with ginseng astragali gastric nourishing soup improves the nutritional status of patients; Xie’s treatment of malnutrition in patients with hemodialysis by regulating the spleen and stomach improves the patients’ insufficient storage of fats and proteins. (3) Deficiency of qi and blood stasis: Yang’s view is that “deficiency of qi and blood stasis” is the main cause of microinflammatory disease in patients with chronic renal failure and hemodialysis. Yang believed that “qi deficiency and blood stasis” is the basic etiology of microinflammatory state and malnutrition in chronic renal failure patients on hemodialysis, and the treatment was “benefiting qi and activating blood circulation”, and the results showed that it improved microinflammatory and malnutrition state significantly. (4) Diagnosis and treatment: Xu’s treatment was based on Zhang Qi’s “Eight Methods of Preserving Yuan and Reducing Turbidity”: (1) Dampness and turbidity trapped in the spleen – Pinggui Huo Tang; (2) Dampness-heat and turbid toxin in the middle obstruction – Huo Turbid Drink; (3) Heat toxin and stasis of blood – Jiawei Xueyi Xieyue Tang; (4) Dampness and heat with deficiency of yin and heat in the lungs and stomach – Jiawei Ganluo Drink; (5) Dampness-heat in the middle Jiao – Zhongmanyuan Fenxia Drink; (6) Deficiency of qi and blood of the spleen and kidneys – Gui Shao Liu Jun Zi Tang. (6) deficiency of qi and blood in the spleen and kidneys–Gui Shao Liu Jun Zi Tang; (7) deficiency of the spleen and kidneys, internal obstruction of dampness and toxins–Spleen, Kidney and Turbid Drainage Tang; (8) deficiency of yin and yang in the spleen and kidneys–Spleen, Kidney and Double Complementary Formula We believe that the pathogenesis of chronic renal failure malnutrition belongs to the Chinese medicine of the spleen and kidneys, qi and blood deficiency, and dampness and turbidity obstruction. One of the most critical is the spleen. The spleen is responsible for transporting and transforming water, grain, essence and micro-organisms, and generating qi and blood. If the spleen and qi fail, the transport and transformation are weak, and the qi and blood cannot be transformed and generated, then qi and blood will be deficient. The treatment should benefit qi, nourish blood and eliminate turbidity, and the formula is Ginseng Nourishing Rong Tang plus subtractions, which has been proved to be effective in improving the malnutrition state of chronic renal failure and improving the survival rate in both clinical and animal studies.