The quality of drugs is a crucial premise for ensuring the safety and effectiveness of clinical medication, while quality control during the pharmaceutical process directly affects the quality and consistency of the final product formulation. However, there is a lack of a comprehensive and scientific system for assessing and optimizing the quality control level during the manufacturing process in the field of drug quality control. Therefore, this study proposed the concept of "pharmaceutical process omics", clarified its advantages in guiding drug production, and explored in depth the research approaches, diverse analytical techniques, and broad range of applications in drug quality control. In addition, this study anticipated the broad application prospects of pharmaceutical process omics in the field of drug quality control, aiming to provide a scientific basis for the development of pharmaceutical process quality control standards.
Quality Control ; Humans ; Drugs, Chinese Herbal/chemistry*

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum (I. dunnianum) resulted in the isolation of five pairs of new lignans (1-5), and 7 known analogs (6-12). The separation of enantiomer mixtures 1-5 to 1a/1b-5a/5b was achieved using a chiral column with acetonitrile-water mixtures as eluents. The planar structures of 1-2 were previously undescribed, and the chiral separation and absolute configurations of 3-5 were reported for the first time. Their structures were determined through comprehensive spectroscopic data analysis [nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass (HR-ESI-MS), infrared (IR), and ultraviolet (UV)] and quantum chemistry calculations (ECD). The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide (LPS)-stimulated BV-2 cells. Compounds 1a, 3a, 3b, and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner. Western blot and real-time polymerase chain reaction (PCR) assays revealed that 1a down-regulated the messenger ribonucleic acid (mRNA) levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), COX-2, and iNOS and the protein expressions of COX-2 and iNOS. This research provides guidance and evidence for the further development and utilization of I. dunnianum.
Lignans/isolation & purification* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/isolation & purification* ; Mice ; Animals ; Molecular Structure ; Plant Extracts/pharmacology* ; Illicium/chemistry* ; Cyclooxygenase 2/immunology* ; Interleukin-6/immunology* ; Nitric Oxide/metabolism* ; Cell Line ; Tumor Necrosis Factor-alpha/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Lipopolysaccharides

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Analyze the changes in phenolic components and gene expression profiles of Tetrastigma hemsleyanum leaves with supplemental blue light, and screen differentially expressed genes related to phenolic metabolism, providing a basis for improving the quality of T. hemsleyanum leaves. Using the leaves of T. hemsleyanum under supplemental blue light and visible light as research materials, the content of phenolic components such as neochlorogenic acid, chlorogenic acid, and 3-O-coumaroyl quinic acid was significantly increased by supplemental blue light. A total of 102 949 unigenes were obtained from the transcriptome, including 14 564 differentially expressed unigenes. They can be divided into 52 subclasses by gene ontology (GO) function, kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis showed that these differentially expressed unigenes were significantly enriched in phenolic metabolic pathways such as phenylpropane biosynthesis, flavonoid biosynthesis and isoflavone biosynthesis. A total of 63 differentially expressed unigenes were identified in the pathways related to the biosynthesis of phenolic cpmponents, including 19 key enzymes such as phenylalanine ammonia-lyase (PAL), cinnamyl-alcohol dehydrogenase (CAD), flavonol synthase (FLS), and so on. This study greatly enriched the genetic data information of T. hemsleyanum and laid a foundation for analyzing the mechanism of blue light promoting the biosynthesis of phenols and molecular breeding of T. hemsleyanum.

The objective of this study was to observe the effect of Astragalus membranaceus on high sugar-induced Caenorhabditis elegans, and to explore its mechanism of action. UPLC-MS method was used to identify the components of Astragalus membranaceus. A high glucose model was established by using Caenorhabditis elegans as a model organism, and the effects of Astragalus membranaceus on body length, body bending, swallowing frequency, and reactive oxygen species (ROS) of the nematode were determined; the effects of Astragalus membranaceus on the expression of mRNA of genes related to the protein skinhead-1 (SKN-1) signaling pathway were examined by using the real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that compared with the normal group, the nematode body length, body bending, and swallowing frequency expression were significantly reduced and the ROS content in the body was significantly increased in the high glucose state; after the administration of Astragalus membranaceus, the body length, body bending, and swallowing frequency expression were significantly increased, and the ROS content was significantly reduced (P < 0.01). Compared with the normal group, SKN-1, superoxide dismutas-3 (SOD-3), glutathione S-transferase 4 (GST-4), and glutathione S-transferase 7 (GST-7) expression were significantly decreased in Caenorhabditis elegans in the high glucose condition; SKN-1, SOD-3, GST-4, and GST-7 expression were significantly increased after administration of Astragalus membranaceus (P < 0.01). In the present study, we demonstrated that Astragalus membranaceus has an effect on high glucose-induced Caenorhabditis elegans nematodes, and its mechanism of action may be through the modulation of the SKN-1 signaling pathwaym in order to ameliorate the oxidative stress response induced by high glucose.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Objective To investigate the effect of microRNA-454-3p(miR-454-3p)on the proliferation,invasion,and migration ability of endometrial cancer(EC)cells and its mechanism.Methods Analyze the expression levels of miR-454-3p in various tissues using the miTED database.Analyze the survival rates of high expression miR-454-3p and low expression miR-454-3p groups in EC patients using the starBase database.Use Targetscan to predict downstream target genes of miR-454-3p.Use the Kaplan Meier Plotter database to analyze the survival rates of the high expression detection of phosphatase and tensin homolog(PTEN)group(average expression level in the high cohort:2 412.45)and the low expression of PTEN(average expression level in the low cohort:733.15)in EC patients.Ishikawa cells were divided into NC-mimics group(transfected with NC-mimics),mimics group(transfected with miR-454-3p mimics),NC-inhibitor group(transfected with NC-inhibitor),and inhibitor group(transfected with miR-454-3p inhibitor).Detect the proliferation ability of cells using cell counting kit-8(CCK-8)assay;evaluate cell invasion and migration abilities using Transwell and scratch experiments,respectively;detection of PTEN RNA expression levels using real-time quantitative polymerase chain reaction(qRT-PCR).Results Compared with normal tissue,the expression level of miR-454-3p in tumor tissue of EC patients increased(1.57 vs 3.26,P＜0.05),and the survival rate of EC patients with low expression of miR-454-3p increased(0.74 vs 0.42,P＜0.05).The cell proliferation ability of the NC mimics group,mimics group,NC inhibitor group and inhibitor group were 3.73±0.02,5.40±0.02,2.06±0.05 and 1.95±0.05;the number of invading cells were 116±17,154±19,855±165 and 447±44;the number of migrating cells were 116±8,154±27,1 518±50 and 1 132±175;the scratch healing rates were(20.00±8.00)％、(39.00±2.00)％、(84.00±1.00)％and(52.00±1.00)％;the expression levels of PTEN mRNA were 1.16±0.03,0.94±0.02,0.85±0.14 and 1.22±0.07,respectively.The differences in the above indicators between the mimics group and the NC mimics group,as well as between the inhibitor group and the NC inhibitor group,were statistically significant(all P＜0.05).The expression level of PTEN in tumor tissue of EC patients decreased(33.45 vs 17.17,P＜0.05),and the survival rate of EC patients with low expression of PTEN increased(41％vs 93％,P＜0.05).Conclusion miR-454-3p may promote the proliferation,invasion,and migration of EC cells by negatively regulating the expression of PTEN.

Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

Objectives:Present study aimed to use quantitative flow ratio based on Murray's law to analyze the risk factors of impaired side branches perfusion without naked eye visible slowing of blood flow in branches after interventional treatment of true bifurcation lesions of the coronary arteries. Methods:A total of 211 patients with non-left main coronary artery true bifurcation coronary artery disease who underwent percutaneous coronary intervention(PCI)in Hunan Provincial People's Hospital from June 2022 to September 2023 were continuously enrolled,with a total of 234 bifurcation lesions.The general clinical indicators,anatomical characteristics of coronary artery bifurcation lesions,branch protection methods,postoperative branch TIMI blood flow and other data were collected,and quantitative flow ratio(μQFR)was measured for postoperative branch blood vessels.Post-PCI μQFR<0.8 was considered as impaired branch perfusion and was included in the postoperative impaired branch perfusion group(n=51,53 branch lesions).Patients with μQFR≥0.8 were included in the postoperative normal branch perfusion group(n=160,181 branch lesions).Multivariate Logistic regression analysis was used to evaluate the effects of various clinical and anatomical factors on branch perfusion after PCI. Results:The post-PCI branch flow grading of all patients was TIMI grade Ⅲ.The postoperative branch μQFR of 53 vessels(22.6％)in the group with impaired postoperative branch perfusion was 0.70±0.10,and 0.93±0.05 in the group with normal postoperative branch perfusion,and the difference between the two groups was statistically significant(P<0.001).Compared with the postoperative group with normal branch perfusion,the postoperative group with impaired branch perfusion was featured with an elevated branch lesion length,branch reference diameter,postoperative branch opening diameter stenosis rate,postoperative branch narrowest lumen diameter stenosis rate,and a lower main branch-to-branch diameter ratio,preoperative branch narrowest lumen diameter stenosis rate,and preoperative main branch μQFR,all of which were statistically significant(all P<0.05).The postoperative branch opening diameter stenosis rate(r=-0.490,P<0.001),postoperative branch narrowest lumen diameter stenosis rate(r=-0.788,P<0.001),preoperative branch narrowest lumen diameter stenosis rate(r=-0.280,P<0.001),branch narrowest lumen diameter(r=-0.469,P<0.001),branch lesion length(r=-0.157,P=0.016)were negatively correlated with postoperative branch μQFR,and branch reference diameter(r=0.173,P=0.008),main branch/side branch diameter ratio(r=0.194,P=0.003),and branch opening diameter(r=0.328,P<0.001)were positively correlated with postoperative branch μQFR,and none of them were significantly correlated with clinical baseline data(all P>0.05).Multifactorial logistic regression analysis showed that following four factors were independent risk factors for impaired branch perfusion:postoperative stenosis of the narrowest branch lumen diameter(OR=1.228,95％CI:1.144-1.318,P<0.001),postoperative stenosis of the branch opening diameter(OR=1.110,95％CI:1.055-1.168,P<0.001),postoperative stenosis of the narrowest lumen diameter of the main branch(OR=1.115,95％CI:1.042-1.192,P=0.001),and length of the branch lesion(OR=1.121,95％CI:1.021-1.231,P=0016). Conclusions:Some of the patients whose branch flow reached TIMI grade Ⅲ after PCI are still faced the risk of hemodynamical impairment and should be functionally evaluated after PCI.The postoperative stenosis rate of the narrowest branch lumen diameter,postoperative stenosis rate of the branch opening diameter,postoperative stenosis rate of the narrowest lumen diameter of the main branch,and branch lesion length are the risk factors of branch perfusion impairment after PCI for coronary bifurcation lesions.