Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

Frontopsylla(Frontopsylla)ochotona sp.nov.is closely related to Frontopsylla(Fr.)adixsterna Liu,Shao et Liu,1976,but can be distinguished by the following characteristics:1.In males,the immutable processes exhibit a wide,finger-like shape with asymmetrical anterior and posterior edges at their ends.The posterior edge of st.VIII lacks a deep depression,and the distal arm of st.IX is split into two lobes.2.In females,the posterior edge of the st.VII abdominal plate lacks a deep sinus,but the posterior end has a truncated or arc-shaped broad leaf.The posterior edge of t.VIII has a wide sinus,distinguishing it from F.adixsterna and other species in this genus.The type specimen was collected in Linzhi City,Xizang Autonomous Region of China,in November 2018,from an agricultural area at an altitude of approximately 3 000 m.The host species include Ochotona sp.,Niviventer confucianus,and Pitymys leucurus.

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

This study adopted a three-dimensional "effect-dose-mechanism" evaluation system to screen the optimal regimen of Yuxuebi Tablets(YXB) combined with ibuprofen(IBU) for chronic musculoskeletal pain(CMP) intervention and elucidate its pharmacological mechanism, so as to provide a scientific basis for the clinical application of the regimen. The experiments were conducted using 8-week-old ICR mice, which were randomly divided into sham operation(sham) group, model(CFA) group, IBU group, YXB group, stasis paralysis tablets combined with ibuprofen low-dose group(IBU-L-YXB), stasis paralysis combined with ibuprofen high-dose group(IBU-H-YXB), stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen discontinuation on the 10th day of administration(IBU-10-YXB), and stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen halving on the 10th day of administration(IBU-1/2-YXB) group. An animal model was established using the CFA plantar injection method. On D0(the second day post-modeling), the success of model establishment was assessed, followed by continuous drug administration for 18 consecutive days from D1 to D18. During this period, mechanical pain threshold was measured by the Von Frey test; thermal hyperalgesia was detected by the hot plate test, and depression-like behavior was observed by the tail suspension test. After treatment, peripheral blood was collected from all groups for complete blood biochemical analysis, and the injected feet of the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups were subjected to oxylipin metabolomics analysis. Immunofluorescence double staining was further performed to detect the co-expression of key oxylipin metabolic enzymes(COX2, LTA4H, and 5/12/15-LOX) and macrophage marker CD68 in the sham, CFA, IBU, and YXB-L/M/H groups. Subsequently, confirmatory analysis of positive indicators was conducted in the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups. On D6(acute phase), mechanical pain sensitivity data showed that compared with the CFA group, only the three combination groups(IBU-YXB, IBU-10-YXB, and IBU-1/2-YXB) exhibited significantly increased paw withdrawal thresholds. On D17(chronic phase), only the IBU-10-YXB group showed a mechanical pain threshold significantly higher than all other monotherapy and combination groups. On D17, thermal pain data showed that compared with the CFA group, all groups except IBU-1/2-YXB had significantly prolonged paw withdrawal latency. On D18, tail suspension data showed that compared with the CFA group, the YXB, IBU-YXB, and IBU-10-YXB groups had significantly reduced immobility time. In summary, IBU-10-YXB stably improved the core symptoms of acute and chronic inflammatory pain. Complete blood count data showed that compared with the sham group, the CFA group had significantly increased mean platelet volume(MPV), while compared with the CFA group, the IBU-YXB and IBU-10-YXB groups had significantly reduced MPV. Moreover, the platelet distribution width(PDW) of the IBU-10-YXB group was further reduced compared with the CFA group. These data suggest that the IBU-10-YXB combination regimen has superior effects on inflammation and blood circulation improvement compared with other treatment groups. At the mechanistic level, each treatment group differentially regulated pro-inflammatory and pro-resolving oxylipin(SPM). Specifically, compared with the CFA group, the IBU and IBU-YXB groups significantly inhibited the synthesis of the prostaglandin family downstream of COX2, reducing pro-inflammatory oxylipins PGD2 and 6-keto-PGF1α but inhibiting PGE1 and PGE2, which played positive roles in peripheral circulation, vasodilation, and inflammation resolution. Compared with the CFA group, the YXB group tended to inhibit the pro-inflammatory oxylipin LTB4 downstream of LTA4H and increase SPMs such as LXA4. The IBU-10-YXB group bidirectionally regulated pro-inflammatory oxylipins and SPMs. Compared with IBU, IBU-10-YXB significantly inhibited the pro-inflammatory mediator 5-HETE. Meanwhile, IBU-10-YXB broadly upregulated SPMs, as evidenced by significant upregulation of LXA4 compared with the CFA group, significant upregulation of LXA5 compared with the IBU and IBU-YXB groups, significant upregulation of RvD1 compared with the CFA group and all other treatment groups, and significant upregulation of RvD5 compared with the sham group. Immunofluorescence double staining results were as follows: compared with the CFA group, the IBU group specifically inhibited the oxylipin metabolic enzyme COX2. In the YXB group, COX2, LTA4H, and 5/12-LOX were significantly inhibited. Within the optimal analgesic dose range, YXB's inhibitory effects on COX2 and LTA4H were dose-dependent, while its inhibitory effects on 5/12-LOX were inversely dose-dependent. The two combination groups(IBU-YXB and IBU-10-YXB) inhibited COX2 and LTA4H without significantly affecting 5-LOX, while IBU-10-YXB further significantly inhibited 12-LOX. These results suggest that the IBU-10-YXB combination regimen effectively maintains stable inhibition of COX2, LTA4H, and 12-LOX while enhancing 5-LOX expression. This combinatorial strategy effectively suppresses pro-inflammatory oxylipins and promotes SPM biosynthesis, overcoming IBU's analgesic ceiling effect and its blockade of pain resolution pathways while compensating for YXB's inability to effectively intervene in acute pain and inflammation. Therefore, it achieves more stable anti-inflammatory, analgesic, and antidepressant effects.
Animals ; Ibuprofen/administration & dosage* ; Mice ; Mice, Inbred ICR ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Musculoskeletal Pain/immunology* ; Tablets ; Humans ; Chronic Pain/metabolism* ; Drug Therapy, Combination ; Disease Models, Animal

This study explores whether the current external quality assessment (EQA) level and acceptable bias for basic semen analysis in China are clinically useful. We collected data of semen EQA from Andrology laboratories in the Hunan Province (China) in 2022 and searched for data in the published literature from January 2000 to December 2023 in China. On the basis of these data, we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics. We compared these findings with quality specifications based on biological variation from optimal, desirable, and minimum levels of bias to seek a unified and more suitable semen EQA bias evaluation standard for China's national conditions. Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories, ranging from 8.2% to 56.9%. A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility (PR), whereas 100.0% and 75.0% of laboratories met only the minimum quality specifications for sperm concentration and total motility (nonprogressive [NP] + PR), respectively. The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification, whereas the Z value for PR was equivalent only to the minimum performance specification. This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation. These specifications should be unified among external quality control (EQC) centers based on biological variation.
Semen Analysis/standards* ; Humans ; China ; Male ; Quality Control ; Sperm Motility ; Sperm Count/standards*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration