AIM:To compare the effect of AT TORBI 709M and Tecnis ZMT intraocular lenses on astigmatism correction in patients with corneal astigmatism at 3 mo after operation based on the standard astigmatism vector analysis.METHODS: This was a retrospective case-control study. The clinical data of 69 patients(69 eyes)with corneal astigmatism who underwent phacoemulsification and implantation of toric intraocular lens(IOL)from June 2021 to December 2021 in Day Surgery Center of Xi'an No.1 Hospital was analyzed. The patients were divided into two groups. In group one, 38 cases(38 eyes)were implanted with AT TORBI 709M, and 31 patients(31 eyes)with Tecnis ZMT in group two. The axial length, preoperative astigmatism and axis, and the degree of intraocular lens were recorded. The uncorrected distance visual acuity(UCDVA), best corrected distance visual acuity(BCDVA), diopter, residual astigmatism and axis were recorded preoperatively and at 1 wk, 1 and 3 mo postoperatively. The postoperative surgical indicators, including spherical equivalent(SE), target induced astigmatism vector(TIA), surgically induced astigmatism vector(SIA), magnitude of error(ME), absolute value of angle of error(|AE|), absolute value of difference vector(|DV|), correction index(CI), and index of success(IOS)were evaluated by the standard astigmatism vector analysis.RESULTS:Postoperative UCDVA and BCDVA were significantly improved(all P<0.001), and there were statistically significant differences compared to preoperative UCDVA and BCDVA(all P<0.001). While, there was no significant difference in UCDVA and BCDVA between the two groups(P=0.275, 0.124). The standard astigmatism vector analysis showed that a good astigmatism correction was achieved in both AT TORBI 709M group and Tecnis ZMT group, and both |DV| and IOS were close to 0(P=0.329, 0.288). The CI of the AT TORBI 709M group was closer to 1, indicating a better astigmatism correction, while the CI of the Tecnis ZMT group was higher than 1, suggesting an overcorrection of astigmatism. However, the difference between the two groups was not statistically significant(P=0.193). The mean residual astigmatism at 3 mo postoperatively was -0.11±0.91 D in the AT TORBI 709M group and -0.46±0.76 D in the Tecnis ZMT group, respectively, showing no statistically significance difference(t=1.732, P=0.088).CONCLUSION:Both the flat loop AT TORBI 709M and the double C-loop Tecnis ZMT intraocular lenses can effectively improve postoperative visual acuity in patients with regular corneal astigmatism, showing good rotational stability and comparable correction abilities for both astigmatism with the rule and against-the-rule astigmatism.

Objective: To evaluate the effects of dietary intervention on blood pressure and renal function in patients with hypertensive nephropathy, so as to provide dietary and nutritional guidances for this population. Methods: Hypertensive nephropathy patients who were treated at Zhucheng People's Hospital from March 2023 to February 2024 were selected as the study subjects and randomly divided into the intervention group and the control group. The control group received routine antihypertensive treatment and health lifestyle guidance. On the basis of the treatment and guidance received by the control group, the intervention group implemented dietary intervention in accordance with the Clinical Practice Guidelines for Nutritional Therapy of Chronic Kidney Disease in China (2021 edition) for a period of 3 months. Systolic blood pressure (SBP), diastolic blood pressure (DBP) were measured before and after the intervention, and serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), cystatin and β2-microglobulin were detected. Differences of indicators before and after intervention between the two groups were compared using generalized estimation equation. Results: A total of 83 patients with hypertensive nephropathy were followed up, including 43 cases in the intervention group and 40 cases in the control group. There were no statistically significant differences in gender, age, body mass index, duration of hypertension, family history of hypertension, hypertension grade, physical activity index, or smoking status between the two groups (all P>0.05). The differences in SBP, DBP, Scr, BUN, and UA between the two groups, as well as the differences before and after the intervention, were statistically significant, and there was an interaction between the groups and the intervention time (all P<0.05). After intervention, the levels of SBP, DBP, Scr, BUN, and UA in the intervention group were lower than those in the control group (all P<0.05). The differences in cystatin and β2-microglobulin between the two groups and before and after the intervention were not statistically significant, and there was no interaction between the groups and the intervention time (all P>0.05). Conclusion Dietary intervention has a certain effect on reducing blood pressure and improving renal function indicators in patients with hypertensive nephropathy.

Chemical investigation of the stems of Fritillaria unibracteata P.K. Hsiao & K.C. Hsia resulted in the isolation of nine compounds, by means of silica gel column chromatography, and preparative HPLC. Based on spectroscopic and chemical evidence, these compounds were identified as: 27-hydroxychlorogenone (1), sieboldogenin (2), (3β, 25S)-spirost-5-ene-3,17,27-triol (3), laxogenin (4), tigogenone (5), cerevisterol (6), ergosterol peroxide (7), stigmaterol (8), and β-sitosterol (9). Compound 1 was a new compound, and compounds 2-9 were isolated from the stems of Fritillaria unibracteata for the first time. The inhibitory effects of compounds 1−9 on A549 cells were determined using the MTT method. The results show that compound 6 exhibits moderate inhibitory activity with an IC50 value of (14.16 ± 1.11) μmol/L.

In this study, Saccharomyces cerevisiae R0 was used as the chassis cell to synthesize oleanolic acid from scratch through the heterologous expression of β-amyrin synthase(β-AS) from Glycyrrhiza uralensis, cytochrome P450 enzyme CYP716A154 from Catharanthus roseus, and cytochrome P450 reductase AtCPR from Arabidopsis thaliana. The engineered strain R1 achieved shake flask titres of 5.19 mg·L~(-1). By overexpressing enzymes in the pentose phosphate pathway(PPP)(ZWF1, GND1, TKL1, and TAL), the NADH kinase gene in the mitochondrial matrix(POS5), truncated 3-hydroxy-3-methylglutaryl-CoA reductase(tPgHMGR1) from Panax ginseng, and farnesyl diphosphate synthase gene(SmFPS) from Salvia miltiorrhiza, the precursor supply and intracellular reduced nicotinamide adenine dinucleotide phosphate(NADPH) supply were enhanced, resulting in an 11.4-fold increase in squalene yield and a 3.6-fold increase in oleanolic acid yield. Subsequently, increasing the copy number of the heterologous genes tPgHMGR1, β-AS, CYP716A154, and AtCPR promoted the metabolic flow towards the final product, oleanolic acid, and increased the yield by three times. Shake flask fermentation data showed that, by increasing the copy number, precursor supply, and intracellular NADPH supply, the final engineered strain R3 could achieve an oleanolic acid yield of 53.96 mg·L~(-1), which was 10 times higher than that of the control strain R1. This study not only laid the foundation for the green biosynthesis of oleanolic acid but also provided a reference for metabolic engineering research on other pentacyclic triterpenoids in S. cerevisiae.
Oleanolic Acid/biosynthesis* ; Saccharomyces cerevisiae/metabolism* ; Industrial Microbiology ; Microorganisms, Genetically-Modified/metabolism* ; Plants/enzymology* ; Fermentation ; Metabolic Engineering

Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis* ; Saccharomyces cerevisiae/genetics* ; Triterpenes/metabolism* ; Metabolic Engineering ; Oleanolic Acid/biosynthesis* ; Ursolic Acid

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

A qualitative analysis by high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was performed for the identification of main constituents in Gentiana veitchiorum. High-performance liquid chromatography (HPLC) was developed for the quantification of seven major components, including loganic acid (1), swertiamarin (2), gentiopicroside (3), sweroside (4), isoorientin (5), isoscoparin (6), and gentiournoside A (7). A total of 42 compounds, including 31 flavonoids, and 11 Iridoids, were identified based on their retention behaviors, and MS fragment information. Furthermore, regression equations for these seven chemical components were established, with good linear relationships (r2 > 0.9999), and the sample recovery rate was 97.02%-103.08%. This method was successfully applied for simultaneous determination of seven components in 7 batches of G. veitchiorum samples by HPLC-UV method. The method established in this study is simple and reliable, capable of qualitatively and quantitatively analyzing the main chemical components of G. veitchiorum, and is applicable to its quality evaluation.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.