ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

Objective:To investigate the effects of Xiaomudan Granules on PERK/eIF2α/ATF4 pathway and lipid metabolism in NAFLD mice.Methods:Totally 60 mice were divided into a normal group of 10 mice and a high-fat diet group of 50 mice. The high-fat diet group was given a high-fat diet to establish a NAFLD mouse model. The high-fat feed group was divided into model group, metformin group, and Xiaomudan Granules low-, medium-, and high-dosage groups according to the random number table method. Xiaomudan Granules low-, medium-, and high-dosage groups were orally administered with concentrated Xiaomudan Granules at dosages of 11.7, 23.4, and 46.8 g/kg, respectively. The metformin group was orally administered with metformin solution at a dose of 0.2 g/kg, while the normal group and model group were orally administered with distilled water of equal volume once a day for 8 consecutive weeks. The liver oil red O staining of mice was observed in each group. The protein expressions of p-PERK, p-eIF2α, ATF4, C/EBP homologous protein (CHOP), CCAAT enhancer binding protein alpha (C/EBPα), C/EBPβ, and steroid regulatory element binding protein 2 (SREBP2) were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of ATF4, CHOP, C/EBPα, C/EBPβ, and SREBP2.Results:The liver tissue structure and steatosis of mice were improved in Xiaomudan Granules groups. Compared with the model group, the expressions of p-PERK/PERK, ATF4, C/EBPα, C/EBPβ, and SREBP2 proteins decreased in Xiaomudan Granules groups and the metformin group ( P<0.01 or P<0.05). The expressions of p-eIF2α/eIF2α and CHOP proteins decreased in the Xiaomudan Granules medium- and high-dosage groups and the metformin group ( P<0.01); compared with the model group, the levels of ATF4, CHOP, C/EBPα, and C/EBPβ mRNA in Xiaomudan Granules groups and the metformin group decreased ( P<0.01), while the levels of SREBP2 mRNA in the Xiaomudan Granules medium- and high-dosage groups and the metformin group decreased ( P<0.01). Conclusion:Xiaomudan Granules may improve liver lipid metabolism and reduce liver fat deposition in NAFLD mice by regulating the PERK/eIF2α/ATF4 pathway.

Objective To investigate the effects of Jiawei Ditan Decoction on neurological function,pentraxin-3(PTX-3),and vascular endothelial growth factor(VEGF)in patients with post-ischemic stroke cognitive impairment(PSCI).Methods A total of 97 patients with PSCI who were admitted to Xuzhou Central Hospital from March 2022 to March 2024 were enrolled and randomly assigned to control group(n=48)or decoction group(n=49)using the envelope drawing method.The control group received conventional treatment,while the decoction group was additionally treated with Jiawei Ditan Decoction.Clinical efficacy,Traditional Chinese Medicine(TCM)syndrome scores,cognitive and functional assessments,laboratory markers,and oxidative stress levels were compared between the two groups.Results The total effective rate in the decoction group was significantly higher than that in the control group(P<0.05).At 3 and 6 months after treatment,TCM syndrome scores in the decoction group were lower than those in the control group(P<0.05).The scores of the Montreal cognitive assessment(MoCA),mini-mental state examination(MMSE),and Barthel index(BI)in the decoction group were higher than those in the control group at 3 months after treatment,while the National Institutes of Health stroke scale(NIHSS)score in the decoction group was lower than that in the control group(P<0.05).At 1 month after treatment,PTX-3 and hypersensitive C-reactive protein(hs-CRP)levels in the decoction group were lower than those in the control group,while VEGF,superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and nitric oxide(NO)levels in the decoction group were higher than those in the control group(P<0.05).Conclusion Jiawei Ditan Decoction exhibits significant effects on improving neurological function and modulating PTX-3 and VEGF levels in patients with PSCI.

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Objective To investigate the inhibitory effect of methionine-γ-lyase(METase) gene MEGL on glioblastoma(GBM) cells and its potential molecular mechanism,and to provide new ideas for the development of MEGL drugs.Methods MEGL expression system mediated by lentivirus was constructed and used to infect human GBM cell lines U87 and snb19,and the cells infected with empty virus were as the control.RT-qPCR and Western blot were used to detect the expression of MEGL gene and protein.The levels of methionine(Met) and its metabolites were detected by liquid chromatography tandem mass spectrometry(LC-MS/MS).The cell proliferation was measured by cell counting method.The changes of cell cycle were detected by flow cytometry,and the expression of cell cycle-related proteins(CDK2,CDK4 and p21) and mitogen-activated protein kinase(MAPK) signaling pathway proteins was determined by Western blot.Results Met levels in U87 and snb19cells stably expressing MEGL gene decreased significantly(t=10.996 and 15.733,respectively,each P <0.001).Furthermore,MEGL significantly suppressed the proliferation of U87(on the 3rd,4th and 5th day,t=14.698,9.746,and 12.263,respectively,each P<0.001) and snb19 cells(on the 3rd,4th and 5th day,t=8.480,6.939,and 13.258,respectively,each P <0.001),inducing a notable increase in the proportion of G0/G1 phase(t=7.997,P P<0.001).MGEL gene decreased the expression of cell cycle related proteins CDK2 and CDK4(t=8.471 and 3.369,P=0.0011 and 0.0281,respectively),while promoting the expression of p21(t=10.761,P <0.001).Moreover,it significantly inhibited the expression of proteins related to the MAPK signaling pathway,including p-p38,p-ERK1/2,and p-JNK(t=3.401,6.493,and9.413,P=0.027 2,0.002 9,and <0.001,respectively).Conclusion The MEGL gene can significantly reduce the intracellular Met levels in U87 and snb19 cells,while also inhibiting cell proliferation and cell cycle progression.This inhibitory effect may be achieved through MAPK signaling pathway.

ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

Objective To evaluate the impact of lens capsule diameter and capsular tension ring(CTR)fit on the ro-tational stability and visual function of Toric intraocular lenses(IOLs)in patients with high myopia cataract after surgery,and to explore the main influencing factors.Methods A prospective study included 100 eyes of patients with high myopia(axial length≥26 mm)who underwent phacoemulsification cataract extraction combined with Toric IOL implantation at the Cataract Department of Hebei Eye Hospital from September 2023 to March 2024.Based on the ratio of the capsule equivalent diameter measured by anterior segment OCT(CASIA2)to the standard diameter of CTR,the eyes were divided into the matched group(ratio of 0.8-1.2)and the unmatched group.Follow-up was conducted at 1 week,1 month,3 months,6 months,and 12 months postoperatively to observe the rotation angle of Toric IOL,residual astigmatism,uncor-rected visual acuity,and other indicators.Safety was assessed based on intraoperative and postoperative complications.Correlation analysis and multiple linear regression were used to explore the impact of capsule-CTR fit,corneal astigmatism,axial length,and other factors on Toric IOL rotation and postoperative refractive status.Results The mean IOL rotation angle at each postoperative time point in the matched group was significantly smaller than that in the unmatched group,with statistically significant differences between groups at different time points(all P＜0.05).The matched group showed better stability in IOL decentration distance and tilt angle.At 12 months postoperatively,the residual astigmatism in the matched group was(0.53±0.29)D,which was better than that in the unmatched group(0.71±0.34)D(P=0.08).The matched group also had more significant improvement in uncorrected visual acuity and higher subjective visual quality scores.Multiple linear regression analysis showed that capsule-CTR fit and preoperative corneal astigmatism were the main independent factors affecting the rotation angle of Toric IOL(R2=0.52)and residual astigmatism(R2=0.46).Conclu-sion For patients with high myopia cataract,precise capsule-CTR matching based on CASIA2 measurement helps improve the rotational stability of Toric IOLs,reduce residual astigmatism,and enhance postoperative visual quality.Personalized CTR model selection is worth promoting and applying.

ObjectiveAutoimmune thyroiditis （AIT） is a complex and immune-mediated disorder， with no established treatment protocol. Both Western and traditional Chinese medicine （TCM） focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM， using a novel evaluation method. Additionally， it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models， using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM， and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization， iodine induction， heterologous thyroid antigen immunization， and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%， 60%， 54%， and 63%， with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common， with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory， meeting the surface and structural effectiveness criteria of Western medicine. However， there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine， with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine， creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM， providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.

[摘 要] 目的：探讨甲硫氨酸限制对肺腺癌（LUAD）细胞增殖、凋亡及磷酸戊糖途径的影响。方法：将H1299、A549细胞分为Met+组和Met−组，分别用含100 μmol/L或不含甲硫氨酸的培养基连续培养4 d，采用细胞计数法评估甲硫氨酸处理对H1299和A549细胞增殖的影响，PI染色法检测细胞周期分布，Annexin Ⅴ-PE/7AAD标记细胞凋亡，利用DCFH-DA探针检测细胞内ROS水平，WST-8法和DTNB法分别测定细胞内NADPH与GSH含量；通过癌症基因组图谱（TCGA）数据库分析葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）表达与甲硫氨酸代谢通路的关系；采用WB法检测甲硫氨酸处理及回补甲硫氨酸下游代谢产物S-腺苷甲硫氨酸（SAM）对LUAD细胞中磷酸戊糖途径关键酶G6PD和6PGD表达的影响。结果：甲硫氨酸限制显著抑制H1299和A549细胞增殖（均P < 0.01），将细胞周期阻滞于G2/M期（均P < 0.05），显著升高细胞内总ROS水平（均P < 0.001）并促进细胞凋亡（均P < 0.001）；同时，甲硫氨酸限制显著降低了细胞内NADPH和GSH水平（均P < 0.01），抑制DNA合成（均P < 0.01）。分析TCAG数据发现，G6PD和6PGD表达水平与甲硫氨酸代谢通路呈正相关（均P < 0.001），甲硫氨酸限制下调G6PD和6PGD蛋白表达（均P < 0.01），而回补SAM可部分逆转甲硫氨酸限制对G6PD和6PGD的表达的抑制（均P < 0.01），提示甲硫氨酸通过SAM合成调控磷酸戊糖途径。结论：甲硫氨酸限制通过抑制磷酸戊糖途径抑制LUAD细胞增殖，为甲硫氨酸限制疗法治疗LUAD提供实验依据。

ObjectiveTo explore the mechanism of action of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma in the treatment of recurrent spontaneous abortion （RSA） through network pharmacology， molecular docking， and cell experiment verification. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and UniPort databases were used to screen and organize the active ingredients and corresponding targets of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma. The potential therapeutic targets of RSA were screened in Online Mendelian Inheritance in Man （OMIM）， GeneCards database， DrugBank database， DisGeNET database， and Therapeutic Target Database （TTD）. The potential core targets of Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma for treating RSA were further screened by constructing a protein-protein interaction （PPI） network and topological analysis. Meanwhile， the Database for Annotation， Visualization and Integrated Discovery （DAVID） was chosen to perform enrichment analysis on intersection targets. On this basis， AutoDock software was used for molecular docking， and the data were imported into PyMOL software for visualization and composition. Finally， the cell counting kit-8 （CCK-8） experiment， Transwell cell invasion assay， and Western blot were used to detect the effects of serum containing Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma on HTR-8/SVneo cells and observe the effects on the interleukin （IL）-6/signal transducer and activator of transcription 3（STAT3） signaling pathway and related proteins. ResultsThrough network pharmacology analysis， a total of 69 active ingredients， 73 potential therapeutic targets， and 17 core targets， including IL-6， IL-10， and STAT3， were collected. The 73 common targets were enriched in 614 Gene Ontology （GO） entries and 57 Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways. The molecular docking results indicated that IL-6 and STAT3 had good binding ability with the main active ingredients， including matrine， cryptotanshinone， and tanshinone Ⅱ_A. The cell experiment results showed that， compared with those of the control group， after 24 hours of treatment with the drug-containing serum， the survival and invasion rates of HTR-8/SVneo cells were significantly increased （P<0.05）， and the expression of IL-6/STAT3 signaling pathway and related proteins IL-10 and c-Myc was significantly elevated （P<0.05）. Moreover， the trend of action in the drug-containing serum group was consistent with that of pathway agonists. ConclusionCuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma may enhance the survival rate and invasive activity of HTR-8/SVneo cells to further prevent and treat RSA by activating the IL-6/STAT3 signaling pathway and upregulating the expression of downstream factors IL-10 and c-Myc in the pathway.