ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Objective To establish in vitro the small intestinal organoid culture system and to investigate the effect of lipopolysaccharide(LPS)on the growth of small intestinal organoids and the secretion of inflammatory factors.Methods In vitro,the small intestinal crypt cell mass of C57BL/6 mice was aseptically isolated,collected and embedded in organoid matrix.Under the support of complete medium,the small intestinal organoids with three-dimensional multi-leaf structure with small intestinal epithelioid structure were formed.The small intestinal organoids were subcultured after 5-7 d culture.On the third day after passage,the small intestinal organoids were randomly divided into different mass concentrations of LPS groups(0,150,175,200,225,250,275 and 300 mg/L).After 24 h and 48 h of LPS induction,morphological changes of small intestinal organoid growth and differentiation were observed.CCK-8 method was used to detect the effect of different time points and mass concentrations of LPS on the proliferative activity of small intestinal organoids after induction of inflammation.The effects of four different mass concentrations of LPS(0,175,200 and 225 mg/L)on expression levels of granulocyte-macrophage colony stimulating factor(GM-CSF),interleukin(IL)-1α,IL-6 and IL-10 in organoid culture supernatant at different times were detected by enzyme-linked immunosorbent assay(ELISA).Results The mouse small intestinal organoid culture system was preliminarily constructed.After different time and mass concentration of LPS induced inflammation of small intestinal organoids,it was observed by morphology that small intestinal organoids would have different degrees of expansion and apoptosis in lumen.The proliferation,differentiation and budding of damaged intestinal epithelial crypts or intestinal stem cells were also inhibited to varying degrees,indicating that the growth of small intestinal organoids would be limited to varying degrees after induced inflammation.The proliferation activity of small intestinal organoids decreased to varying degrees after 24 h and 48 h of LPS induction at 175-225 mg/L(P＜0.05),but the cell viability was still greater than 50%.The levels of IL-1α,IL-6 and GM-CSF partially increased after induction with 200 mg/L and 225 mg/L LPS for 24 h and 48 h(P＜0.05).The level of IL-10 decreased after induction with 200 mg/L LPS for 24 h and 48 h(P＜0.05).Conclusion In this study,a model of intestinal inflammatory injury in vitro induced by LPS with different mass concentrations and time points is preliminarily constructed,which provides a more reliable research platform for the mechanism research of intestinal diseases and the screening of effective drugs in the future.

Objective To investigate the effect and mechanism of microRNA-10b(miR-10b)on idiopathic short stature(ISS).Methods A total of 54 children with ISS and 54 healthy children were collected.The serum expression of miR-10b was detected by RT-qPCR,and the relationship between serum miR-10b expression and clinical data of children with ISS was analyzed.miR-10b inhibitor,si-TGFBR1 and their negative control transfection C28/I2 cells were used.CCK-8 experimental detection was used to detect C28/I2 cell proliferation.Western blot assay was used to detect gnome related transcription factor 2(RUNX2),collagen type X alpha 1 chain(COL10A1),transforming growth factor beta receptor 1(TGFBR1),SMAD3 and pSMAD3 protein expression.The target of miR-10b was screened in StarBase database,and the targeting relationship between miR-10b and TGFBR1 was verified by dual luciferase reporter gene assay.Results The serum expression of miR-10b was higher in the ISS group than that of the healthy control group,and the higher the miR-10b expression,the more obvious the decrease of child height,IGF-1 and alkaline phosphatase(P＜0.05).Compared with the NC group,the cell proliferation ability and RUNX2,COL10A1,TGFBR1,and pSMAD3 protein expression were up-regulated in the miR-10b inhibitor group(P＜0.05).StarBase database suggested that miR-10b had a binding site of TGFBR1,and dual luciferase reporter gene assay confirmed that TGFBR1 interacted with miR-10b(P＜0.05).Compared with the si-NC group,the expression of TGFBR1 was down-regulated and the cell proliferation ability was decreased in the si-TGFBR1 group(P＜0.05).Conclusion miR-10b inhibits chondrocyte proliferation and hypertrophy in idiopathic short stature by targeting TGFBR1/SMAD3 pathway.

Objective:To investigate the clinical phenotype and genetic characteristics of developmental epileptic encephalopathy 18 (DEE18) caused by SZT2 gene variants. Methods:Clinical data of 2 children with SZT2 related DEE18 who visited the Department of Pediatric Neurology, Linyi People′s Hospital in March 2020 and July 2023 were collected. The whole exome sequencing (WES) and Sanger sequencing were applied to verify the child and their parents. SWISS-MODEL software was used to perform protein 3D modeling for the selected SZT2 gene variants. Results:Both of the 2 cases showed severe global developmental delay, epileptic seizures, autism, megacephaly, facial deformity, hypotonia, corpus callosum malformation, persistent cavum septum pellucidum, and slow background activity and focal discharge in video electroencephalography. Case 1 was easy to startle and thin in stature; case 2 had immune deficiency and clustered seizures. WES results showed that case 1 carried a compound heterozygous variant of c.5811G>A (p.W1937X) (paternal) and c.9269delG (p.S3090Ifs *94) (maternal), while case 2 carried a compound heterozygous variant of c.6302A>C(p.H2101P) (paternal) and c.7584dupA (p.E2529Rfs *20) (maternal), the parents of both patients with normal clinical phenotypes. The 4 mutations mentioned above were novel variations that had not yet been reported domestically or internationally. According to the American College of Medical Genetics and Genomics variant classification criteria and guidelines, the p.S3090Ifs *94 variant was interpreted as pathogenic; p.W1937X variant was interpreted as pathogenic; p.E2529Rfs *20 variant was interpreted as likely pathogenic; p.H2101P variant was interpreted as uncertain significance. 3D modeling showed that the variant of p.H2101P resulted in a significant change in the hydrogen bond around the 2 101st amino acid encoded, leading to a decrease in protein stability. The other 3 variants led to early truncation of peptide chain and obvious changes in protein structure. Conclusions:DEE18 caused by SZT2 gene mutation is mainly an autosome recessive genetic disease, and its clinical manifestations include global developmental delay, epileptic seizures, autism, craniofacial malformation, hypotonia, epileptic discharge, corpus callosum malformation, persistent cavum septum pellucidum, shock, small and thin stature, and immune deficiency. Four novel variants related to the SZT2 gene may be the genetic etiology of DEE18 patients in this study.

Objective:To investigate the clinical phenotype and genetic characteristics of infantile epileptic spasm syndrome caused by BRWD3 gene mutation. Methods:Clinical data of a child with BRWD3 related infantile epileptic spasm syndrome who was admitted to Department of Pediatric Neurology of Linyi People′s Hospital on August 2, 2019 were collected and followed up, whole exome sequencing technology and Sanger sequencing were applied to verify the child and his parents, and the pathogenicity of mutation site was analyzed. The studies till June 2023 were searched with keywords of " BRWD3" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical phenotype and genetic characteristics of patients with BRWD3 related epilepsy were summarized. Results:The patient was a 4 years and 4 months old boy, with a clinical phenotype including severe global development delay, focal seizures (the onset age was 4 months), epileptic spasm (the onset age was 6 months), autism, megacephaly, high forehead as well as hypsarrhythmia. The whole exome sequencing results showed a de novo and frameshift variation c.4318_4319del(p.Q1441Efs*20)(NM_153252) in the BRWD3 gene, and the variation was interpreted as pathogenic (PVS1+PS2+PM2) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. A total of 7 English literature articles were retrieved reporting 16 cases of BRWD3 gene related epilepsy in children (including 1 case of infantile epileptic spasm syndrome), and there has been no report in China yet. Totally there were 17 cases of BRWD3 gene related epilepsy including this case. All the cases showed X chromosome dominant inheritance, of whom 15 cases showed minor variations, including 7 missense variations, 3 frameshift variations, 3 splicing variations, 2 nonsense variations, and the remaining 2 cases showed large segment deletions. A total of 15 different variants were found. The phenotypes of the 17 patients mainly included epileptic seizures (17/17), intellectual disability (10/17), motor development disorder (7/17), speech impairment (9/17), megacephaly (8/17), facial malformation (8/17), autism (4/17) and hypotonia (4/17). The common seizure types were found to be focal seizures, occasionally epileptic spasm seizures and tonic seizures. Conclusions:BRWD3 gene variation related epilepsy is an X chromosome dominant genetic disease with a wide clinical phenotype spectrum. BRWD3 gene mutation c.4318_4319del(p.Q1441Efs *20) could cause infantile epileptic spasm syndrome, manifested as severe global developmental delay, epileptic spasm, focal seizures, autism, craniofacial malformation and hypsarrhythmia. This research enriches BRWD3 gene mutation spectrum.

Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.

Background With the increasing aging population in China, there is a significant shortage of labor force. Delaying retirement age has become a potential method to alleviate this labor shortage. Objective To estimate the healthy working life expectancy (HWLE) of individuals aged 50 years old in China. Methods This study was based on data from four waves (2011—2018) of the China Health and Retirement Longitudinal Study (CHARLS). HWLE was estimated for the overall sample of individuals aged 50 years old and above and stratified by sex, educational attainment, marital status, occupation, Hukou type, and region by using continuous-time multistate modelling. Results A total of 50991 person-times aged ≥ 50 years and older were included in the study. The average total life expectancy of the Chinese population aged 50 years old was 29.72 years (95%CI: 29.28, 30.12 years), with a HWLE of 14.05 years (95%CI: 13.76, 14.33 years). The remaining years lived in the states of healthy but not working, not healthy but working, and not healthy and not working were 8.82 years (95%CI: 8.53, 9.15 years), 2.54 years (95%CI: 2.41, 2.68 years),and 4.30 years (95%CI: 4.08, 4.54 years), respectively. The HWLE (95%CI) of individuals in the baseline states of healthy and working, healthy but not working, not healthy but working, and not healthy and not working were 14.97 (14.69, 15.23), 10.86 (10.52, 11.22), 11.73 (11.31, 12.09), and 9.51 (9.09, 9.97) years, respectively. Additionally, women had a higher total life expectancy (95%CI) than men [31.84 (31.10, 32.54) years vs 27.98 (27.35, 28.50) years], but a lower HWLE than men [12.47 (12.12, 12.82) years vs 15.62 (15.23, 15.98) years]. There was no difference in total life expectancy between rural residents and urban residents [29.43 (28.88, 29.97) years vs 30.31 (29.47, 31.02) years], but rural residents had a higher HWLE than urban residents [15.74 (15.39, 16.10) years vs 11.38 (10.97, 11.73) years]. Residents in East China [14.66 (14.22, 15.06) years] and Central China [14.15 (13.86, 14.43) years] had a higher HWLE than residents in West China [13.61 (13.27, 13.98) years] and Northeast China [13.06 (12.51, 13.63) years]. Conclusion The HWLE of Chinese residents supports the policy of raising the retirement age. There are differences in HWLE levels between urban and rural areas, as well as across different regions. Providing more flexible employment opportunities for older adults can help mitigate the labor shortages caused by population aging.

[摘 要] 目的：探讨四个半LIM结构域2（FHL2）蛋白对胶质瘤细胞增殖的影响及其分子机制。方法：利用TCGA和CGGA数据库分析胶质瘤组织中FHL2 mRNA表达水平与患者预后的关系。通过WB法检测人胶质瘤组织标本及人胶质瘤细胞U87、T98G、U251、SNB19、GSC23、A172、LN229、G267和星形胶质细胞NHA中的FHL2蛋白表达水平。利用慢病毒载体构建稳定敲低FHL2的U87细胞和过表达FHL2的SNB19细胞，即U87-shGFP、U87-shFHL2-1#、U87-shFHL2-4#和SNB19-3flag、SNB19-3flag-FHL2组。通过CCK-8法、克隆形成实验检测敲低和过表达FHL2对细胞增殖的影响，免疫共沉淀（Co-IP）和液相色谱-串联质谱（LC/MS）法筛选FHL2在胶质瘤细胞中的相互作用蛋白，并用Co-IP和免疫荧光法验证它们的结合作用和共定位情况。使用酶标仪检测敲低和过表达FHL2细胞内乳酸产量和乳酸脱氢酶（LDH）活性的变化，WB法分析FHL2、LDHA及p-LDHA在正常脑组织和胶质瘤组织中的蛋白表达差异及其相互关系。在过表达 FHL2的SNB19细胞中使用LDHA的小分子抑制剂AT-101，通过CCK-8实验和酶标仪比色法验证FHL2在胶质瘤乳酸代谢中的作用，验证AT-101在胶质瘤中潜在的治疗效果。结果：Co-IP和LC/MS检测发现，FHL2与LDHA在胶质瘤细胞中存在相互作用。FHL2过表达可提高LDHA活性和乳酸生成（均P < 0.001），进而促进胶质瘤细胞增殖（P < 0.001）。相反，敲低FHL2会降低LDHA活性和乳酸产量（P < 0.001或P < 0.05）并抑制细胞增殖（P < 0.001）。AT101能抑制LDHA活性，并显著抑制FHL2促进胶质瘤细胞的增殖，同时恢复磷酸化LDHA（Y10）水平（P<0.01或P < 0.001）。结论：FHL2与LDHA蛋白相互作用，FHL2通过激活p-LDHA（Y10）的表达促进LDHA活性和乳酸产生，进而促进胶质瘤细胞的增殖，靶向这种相互作用可能成为治疗胶质瘤的潜在策略。

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.