Nucleolar URB1 ensures 3' ETS rRNA removal to prevent exosome surveillance.

The nucleolus is the most prominent membraneless condensate in the nucleus. It comprises hundreds of proteins with distinct roles in the rapid transcription of ribosomal RNA (rRNA) and efficient processing within units comprising a fibrillar centre and a dense fibrillar component and ribosome assembly in a granular component1. The precise localization of most nucleolar proteins and whether their specific localization contributes to the radial flux of pre-rRNA processing have remained unknown owing to insufficient resolution in imaging studies2-5. Therefore, how these nucleolar proteins are functionally coordinated with stepwise pre-rRNA processing requires further investigation. Here we screened 200 candidate nucleolar proteins using high-resolution live-cell microscopy and identified 12 proteins that are enriched towards the periphery of the dense fibrillar component (PDFC). Among these proteins, unhealthy ribosome biogenesis 1 (URB1) is a static, nucleolar protein that ensures 3' end pre-rRNA anchoring and folding for U8 small nucleolar RNA recognition and the subsequent removal of the 3' external transcribed spacer (ETS) at the dense fibrillar component-PDFC boundary. URB1 depletion leads to a disrupted PDFC, uncontrolled pre-rRNA movement, altered pre-rRNA conformation and retention of the 3' ETS. These aberrant 3' ETS-attached pre-rRNA intermediates activate exosome-dependent nucleolar surveillance, resulting in decreased 28S rRNA production, head malformations in zebrafish and delayed embryonic development in mice. This study provides insight into functional sub-nucleolar organization and identifies a physiologically essential step in rRNA maturation that requires the static protein URB1 in the phase-separated nucleolus.

Analysis of cases with co-infection of COVID-19 and pulmonary aspergillosis.

The objective of this study was to investigate the risk factors and diagnosis measure of COVID-19-associated pulmonary aspergillosis (CAPA). This study included 201 COVID-19 patients from December 1, 2022, to January 31, 2023; 7 (3.5%) were diagnosed with CAPA. The main risk factors were age, MV, ICU admission and COPD, and the presence of comorbidities such as ARDS and hypoproteinemia in COVID-19 patients, more susceptible to Aspergillus infection. In addition to specimen culture in the lower respiratory tract, the 1,3-ß-D-glucan antigen test can serve as an important screening indicator for early CAPA diagnosis in non-granulocytopenia patients.

The Edwards volume ensemble in cyclically sheared granular experiments.

We experimentally investigate the Edwards volume ensemble in cyclically sheared bidisperse disks of two friction coefficients (µ ≈ 0.3 and µ → ∞) subjected to a range of shear amplitudes γm. Despite the local and global anisotropy, hysteresis, and the potential long-range correlation of the free volume, the Edwards volume ensemble surprisingly provides an excellent statistical description of disk packings in cyclically sheared systems. Our finding can be better understood from the comprehensive analysis of the geometric and statistical properties of Voronoi cells of individual particles. First, the average degrees of anisotropy of Voronoi cells are weak at both the microscopic and macroscopic scales within a range of shear amplitudes γm of up to γm = 12% regardless of the inter-particle friction coefficients µ even though the azimuthal distributions of the Voronoi cell depend on µ. Second, there is only negligible hysteresis of global compactivity and volume fluctuations. Finally, the spatial correlations of the free volume and the orientation are weakly anisotropic and short ranged for practical purposes. Both results are independent of µ. Interestingly, our free-volume statistical results are consistent with the simple physical picture that the free volume is directly proportional to the compactivity.

Regioselective Fluoroalkylphosphorylation of Unactivated Alkenes by Radical-Mediated Alkoxyphosphine Rearrangement.

A novel distal radical rearrangement of alkoxyphosphine is developed for the first time and applied to the regioselective radical fluoroalkylphosphorylation of unactivated olefins. By employing a one-pot two-step reaction of (bis)homoallylic alcohols, organophosphine chlorides, and fluoroalkyl iodides under CFL (compact fluorescence light) irradiation, a series of fluoroalkylphosphorylated alkyl iodides and alcohols are easily synthesized by regiospecific installing a phosphonyl onto the inner carbon of terminal olefins and further iodination/hydroxylation. Mechanism studies reveal that the migration undergoes a distinctive radical cyclization/ß-scission on the lone electron pair of phosphorus, resulting in C-P bond formation and C-O bond cleavage.

Stress propagation in locally loaded packings of disks and pentagons.

The mechanical strength and flow of granular materials can depend strongly on the shapes of individual grains. We report quantitative results obtained from photoelasticimetry experiments on locally loaded, quasi-two-dimensional granular packings of either disks or pentagons exhibiting stick-slip dynamics. Packings of pentagons resist the intruder at significantly lower packing fractions than packings of disks, transmitting stresses from the intruder to the boundaries over a smaller spatial extent. Moreover, packings of pentagons feature significantly fewer back-bending force chains than packings of disks. Data obtained on the forward spatial extent of stresses and back-bending force chains collapse when the packing fraction is rescaled according to the packing fraction of steady state open channel formation, though data on intruder forces and dynamics do not collapse. We comment on the influence of system size on these findings and highlight connections with the dynamics of the disks and pentagons during slip events.

circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling.

BACKGROUND: Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear. METHODS: circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/ß-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels. RESULTS: circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/ß-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/ß-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes. CONCLUSION: circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.

ß-catenin promotes MTX resistance of leukemia cells by down-regulating FPGS expression via NF-κB.

BACKGROUND: Aberrant activation of ß-catenin has been shown to play important roles in the chemoresistance of acute lymphoblastic leukemia (ALL), but the involvement and mechanism of ß-catenin in methotrexate (MTX) resistance is poorly understood. In the present study, we demonstrate a critical role of ß-catenin-NF-κB-FPGS pathway in MTX resistance in the human T-lineage ALL cell lines. METHODS: Lentivirus sh-ß-catenin was used to silence the expression of ß-catenin. Flow cytometry was performed to detect apoptosis after MTX treatment. Western blot, real-time PCR, Co-immunoprecipitation (Co-IP), Chromatin immunoprecipitation (ChIP), Re-ChIP, and Luciferase assay were utilized to investigate the relationship among ß-catenin, nuclear factor (NF)-κB, and folypoly-γ-glutamate synthetase (FPGS). RESULTS: Depletion of ß-catenin significantly increased the cytotoxicity of MTX. At the molecular level, knockdown of ß-catenin caused the increase of the protein level of FPGS and NF-κB p65. Furthermore, ß-catenin complexed with NF-κB p65 and directly bound to the FPGS promoter to regulate its expression. In addition, ß-catenin repression prolonged the protein turnover of FPGS. CONCLUSIONS: Taken together, our results demonstrate that ß-catenin may contribute to MTX resistance in leukemia cells via the ß-catenin-NF-κB-FPGS pathway, posing ß-catenin as a potential target for combination treatments during ALL therapy.

Sheared Amorphous Packings Display Two Separate Particle Transport Mechanisms.

Shearing granular materials induces nonaffine displacements. Such nonaffine displacements have been studied extensively, and are known to correlate with plasticity and other mechanical features of amorphous packings. A well known example is shear transformation zones as captured by the local deviation from affine deformation, D_{min}^{2}, and their relevance to failure and stress fluctuations. We analyze sheared frictional athermal disc packings and show that there exists at least one additional mesoscopic transport mechanism that superimposes itself on top of local diffusive motion. We evidence this second transport mechanism in a homogeneous system via a diffusion tensor analysis and show that the trace of the diffusion tensor equals the classic D_{min}^{2} when this second mesoscopic transport is corrected for. The new transport mechanism is consistently observed over a wide range of volume fractions and even for particles with different friction coefficients and is consistently observed also upon shear reversal, hinting at its relevance for memory effects.

Frequency distribution of five SNPs in human GGH gene and their effects on clinical outcomes of Chinese pediatric patients with acute lymphoblastic leukemia.

Methotrexate (MTX) is widely used in the treatment of childhood acute lymphoblastic leukemia (ALL). Gamma-glutamyl hydrolase (GGH) plays an important role in the disposition of MTX. The aim of this study was to investigate the frequency distribution of five SNPs in the human GGH gene and their effects on serum MTX concentrations and clinical outcomes in Chinese children with ALL. Genotyping of 149 pediatric patients for GGH rs11545078 C>T, rs11545077 G>A, rs1800909 T>C, rs11545076 T>G, and rs3758149 C>T was performed using the Sequenom MassARRAY system. Serum MTX concentrations were determined using a fluorescence polarization immunoassay. The five SNPs studied were in strong linkage. The minor allele frequencies for rs11545078, rs11545077, rs1800909, rs11545076, and rs3758149 were 5.3, 15.0, 14.3, 15.0, and 15.0%, respectively. Four haplotypes (CGTTC, CACGT, TACGT, and TATGT) were observed at frequencies of 84.9, 9.8, 4.5, and 0.8%, respectively. The median C/D ratios of serum MTX at 24 h and 42 h in children with variant haplotypes (12.30 and 0.08 µmol/L per g/m², respectively) were higher than those in wild haplotype carriers (11.85 and 0.07 µmol/L per g/m², respectively). The event-free survival of patients with variant haplotypes (89.2%) was significantly better than that of patients with wild haplotypes (71.9%, P < 0.05). The relapse rate in children with variant haplotypes (8.1%) was lower than that in children with wild haplotypes (15.6%). These findings have implications for the efficacious use of MTX in childhood ALL patients.

Activated γδ T cells exhibit cytotoxicity and the capacity for viral clearance in patients with acute hepatitis B.

γδ T cells are a unique population of lymphocytes that have regulatory roles in patients with chronic hepatitis B (CHB); however, their role in acute hepatitis B (AHB) infection remains unclear. Phenotype and function of γδ T cells were analyzed in 29 AHB patients, 28 CHB patients, and 30 healthy controls (HCs) using immunofunctional assays. Compared with HCs and CHB patients, decreased peripheral and increased hepatic γδ T cells were found in AHB patients. Increased hepatic γδ T cells in AHB patients were attributed to elevated hepatic chemokine levels. Peripheral γδ T cells exhibited highly activated and terminally differentiated memory phenotype in AHB patients. Consistently, peripheral γδ T cells in AHB patients showed increased cytotoxic capacity and enhanced antiviral activity which was further proved in longitudinal study. Activated γδ T cells in AHB patients exhibited increased cytotoxicity and capacity for viral clearance associated with liver injury and the control of infection.

Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children.

BACKGROUND: Although leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes. METHODS: This study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19+CD10- pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children's Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed. RESULTS: KMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1 + patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively). CONCLUSIONS: Pediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required.

Shear-Jammed, Fragile, and Steady States in Homogeneously Strained Granular Materials.

We study the jamming phase diagram of sheared granular material using a novel Couette shear setup with a multiring bottom. The setup uses small basal friction forces to apply a volume-conserving linear shear with no shear band to a granular system composed of frictional photoelastic discs. The setup can generate arbitrarily large shear strain due to its circular geometry, and the shear direction can be reversed, allowing us to measure a feature that distinguishes shear-jammed from fragile states. We report systematic measurements of the stress, strain, and contact network structure at phase boundaries that have been difficult to access by traditional experimental techniques, including the yield stress curve and the jamming curve close to ϕ_{SJ}≈0.75, the smallest packing fraction supporting a shear-jammed state. We observe fragile states created under large shear strain over a range of ϕ<ϕ_{SJ}. We also find a transition in the character of the quasistatic steady flow centered around ϕ_{SJ} on the yield curve as a function of packing fraction. Near ϕ_{SJ}, the average contact number, fabric anisotropy, and nonrattler fraction all show a change of slope. Above ϕ_{F}≈0.7 the steady flow shows measurable deviations from the basal linear shear profile, and above ϕ_{b}≈0.78 the flow is localized in a shear band.

Probing bianisotropic biomolecules via a surface plasmon resonance sensor.

The transfer matrix method is developed to probe bianisotropic biomolecules via a Kretschmann configuration surface plasmon resonance (SPR) sensor. This method employs wave vectors and 4 × 4 transfer matrices derived by using anisotropic and magnetoelectric coupling constitutive relations. The transfer matrices relate four eigenstates and trace four transverse field components through the multilayer to account for cross-polarization coupling due to the chirality of the biomolecule layer. The validity of the method is confirmed by means of numerical results. It is shown that cross-polarized reflection waves are enhanced around the SPR angle, as the water solution and bianisotropic biomolecules to be detected are placed in contact with the graphene layer of the sensor. The effects of optical activity and bianisotropy on the SPR sensor are investigated. This work enriches the transfer matrix theory for SPR sensors to detect the chirality parameter of bianisotropic chiral material, and may lead to a better design of SPR sensors against the chirality parameter variation.

The prognostic potential of coilin in association with p27 expression in pediatric acute lymphoblastic leukemia for disease relapse.

BACKGROUND: Cajal body (CB) is a nucleic organelle where small nuclear ribonucleoproteins undergo modification, maturation, splicing and/or assembly. Coilin is the marker structural protein of CBs. The expression level and cellular localization of coilin is sensitive to chemotherapeutic reagents, such as cisplatin. The gene of cyclin-dependent kinase inhibitor 1B (p27) is located with a high incidence translocation region of leukemic chromosomes, and its expression was of prognosis values in a variety of adult leukemia types. The exact profile and associated functions of coilin, as well as p27, in children's acute lymphoblastic leukemia (ALL) is obscure. METHODS: Bone marrow samples from 144 patients with ALL were collected. The expression levels of coilin and p27 were detected by qRT-PCR. The patient cohort was divided into low and high groups of coilin and p27 respectively. The prognosis and clinicobiological characteristics of different groups were investigated, especially focused on the treatment outcome. Leukemia cells of Reh or RS4;11 were exposed to different concentrations of DNR, prior to the detection for morphological changes of coilin by immunofluorescence. In Reh cells, lentivirus sh-coilin was used to silence coilin expression. Western blotting was used to detect coilin and p27 expression; flow cytometry was used for cell cycle and apoptosis assay; MTS method was used for measuring cell viability to examine the drug sensitivity of DNR. RESULTS: In this study, we found that daunorubicin was able to induce significant morphological changes of CBs in Reh and RS4;11 cells. Knockdown the expression of coilin increased the sensitivity to daunorubicin and inhibited the expression of p27 in Reh cells, and led to increased apoptosis. Importantly, not only the levels of coilin and p27 mRNA expression at initial diagnosis ALL children are markedly higher than those at complete remission (CR), but also both coilin and p27 expression in the relapsed patients was observed significantly higher comparing to the continuous CR patients. The 4-year EFS and RFS indicated that low levels of both coilin and p27 group favored better prognosis (p < 0.05). CONCLUSIONS: Our results indicated that consideration of coilin and p27 levels could be a prognostic reference for predicting the outcome of pediatric ALL patients, especially for disease recurrence. Reduction of coilin expression was sufficient to increase the sensitivity of leukemic cells to daunorubicin treatments, and during which possibly involved functions of p27 in cell cycle regulation and its effects on cell apoptosis.

Microscopic Origins of Shear Jamming for 2D Frictional Grains.

Shear jamming (SJ) occurs for frictional granular materials with packing fractions ϕ in ϕ_{S}<ϕ<ϕ_{J}^{0}, when the material is subject to shear strain γ starting from a force-free state. Here, ϕ_{J}^{µ} is the isotropic jamming point for particles with a friction coefficient µ. SJ states have mechanically stable anisotropic force networks, e.g., force chains. Here, we investigate the origins of SJ by considering small-scale structures-trimers and branches-whose response to shear leads to SJ. Trimers are any three grains where the two outer grains contact a center one. Branches occur where three or more quasilinear force chain segments intersect. Certain trimers respond to shear by compressing and bending; bending is a nonlinear symmetry-breaking process that can push particles in the dilation direction faster than the affine dilation. We identify these structures in physical experiments on systems of two-dimensional frictional discs, and verify their role in SJ. Trimer bending and branch creation both increase Z above Z_{iso}≃3 needed for jamming 2D frictional grains, and grow the strong force network, leading to SJ.

Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: The first nation-wide prospective multicenter study in China.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)-ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation-wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical-biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%-50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event-free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non-MRD group (5y-EFS: 82.4% vs 78.3%, P = .038; 5y-CIR: 10.7% vs 18.0%, P < .001). Our results demonstrated that the large-scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD-based risk stratification might improve the treatment outcome for childhood ALL.

Force and Mass Dynamics in Non-Newtonian Suspensions.

Above a certain solid fraction, dense granular suspensions in water exhibit non-Newtonian behavior, including impact-activated solidification. Although it has been suggested that solidification depends on boundary interactions, quantitative experiments on the boundary forces have not been reported. Using high-speed video, tracer particles, and photoelastic boundaries, we determine the impactor kinematics and the magnitude and timings of impactor-driven events in the body and at the boundaries of cornstarch suspensions. We observe mass shocks in the suspension during impact. The shock front dynamics are strongly correlated to those of the intruder. However, the total momentum associated with this shock never approaches the initial impactor momentum. We also observe a faster second front associated with the propagation of pressure to the boundaries of the suspension. The two fronts depend differently on the initial impactor speed v_{0} and the suspension packing fraction. The speed of the pressure wave is at least an order of magnitude smaller than (linear) ultrasound speeds obtained for much higher frequencies, pointing to complex amplitude and frequency response of cornstarch suspensions to compressive strains.

Low CREBBP expression is associated with adverse long-term outcomes in paediatric acute lymphoblastic leukaemia.

OBJECTIVES: CREBBP alterations are associated with many diseases including leukaemia. However, CREBBP expression and its clinical relevance in paediatric acute lymphoblastic leukaemia have not been elucidated. METHODS: We studied CREBBP mRNA expression in 349 patients treated with either the BCH-2003 or CCLG-2008 protocol. Using a receiver operating characteristic curve, patients were divided into low- or high-CREBBP. The association among clinicobiological characteristics, outcomes and CREBBP level was analysed. RESULTS: Low expression of CREBBP (<1.0) at diagnosis was found in 97.7% of patients and increased significantly after complete remission. Low-CREBBP patients were associated with unfavourable clinical presentations, poor prednisone response and high minimal residual disease (>10-2 ) after induction. We found significantly poorer event-free survival (EFS) and overall survival (OS) in low-CREBBP group whether administered BCH-2003 or CCLG-2008. Low-CREBBP was an inferior independent prognostic factor in BCH-2003; patients with low-CREBBP had better outcomes on an intermediate-risk regimen than a standard-risk regimen involving the CCLG-2008 protocol. Patients stratified to high-risk with low-CREBBP had the worst EFS and OS. CONCLUSIONS: These findings indicate that low-CREBBP is predictive of unfavourable outcomes; thus, a more intensive treatment protocol is necessitated for standard-risk patients with insufficient CREBBP and that a specific target therapy is necessitated for high-risk patients.

Experimental study on the effect of temperature and flux conditions on moisture distribution in vadose zone soil.

Moisture distribution in vadose zone soil is the most important parameter for land productivity and vegetation status of ecological systems, and is sensitive to temperature variation. In this study, laboratory scale tests were conducted to determine the effect of temperature on variation in moisture distribution in covered and uncovered conditions. The results indicated that soil moisture from 2.65 to 20 cm was positively correlated with temperature and temperature gradient, and the top 2.65 to 5 cm was dramatically influenced by temperature changes in both covered and uncovered conditions. The moisture content when temperature was increasing was higher than that when temperature was decreasing for the same temperature, when the film covered the top of the soil column. In contrast, the moisture content when temperature was increasing was lower than when the temperature was decreasing for the uncovered soil column. The difference between treatments was not maintained as soil depth increased.

[Clinical study on compound prescription with Valerianae Jatamansi Rhizoma et Radix in treatment of generalized anxiety disorder].

This study was aimed to observe the clinical efficacy of anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix (ACPV) in treating liver Qi stagnation and feel ill at ease type generalized anxiety disorder (GAD). Sixty-seven patients diagnosed as GAD with stagnation of liver Qi and feel ill at ease were randomly divided into treatment group and control group. Patients in treatment group (n=34) was treated with ACPV decoction, and patients in control group (n=33) were treated with deanxit. Both groups were treated with respective drugs for 4 weeks. HAMA scale, traditional Chinese medicine (TCM) symptom scale (liver Qi stagnation and feel ill at ease type) and salivary cortisol levels were measured before and 2 weeks and 4 weeks after drug treatment. The life events scale (LES) and drug safety evaluation were performed before and after 4 weeks treatment. Two patients were excluded according to LES, and 5 patients were discontinued. Sixty patients were enrolled in the study finally (30 cases in each group). As compared with baseline, HAMA scores in both groups were significantly decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). After 2 weeks and 4 weeks treatment, the TCM syndrome score in both group was also significantly improved (P<0.01). Moreover, the salivary cortisol levels in both groups were also decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). The total efficiency between two groups had no statistically significant difference after 2 weeks treatment and 4 weeks treatment; moreover, no statistically significant differences were observed between two groups in HAMA scores, TCM syndrome scale scores and salivary cortisol levels between two groups. The incidence of adverse reactions in the treatment group was significantly lower than that in the control group (P<0.01), and there were no obvious side effects in general physical examination during the period of treatment. Thus, anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix is effective for GAD (stagnation of liver Qi and feel ill at ease type).