Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Objective: To analyze the distribution and related factors of spherical equivalent(SE) anisometropia in school aged children in ethnic minority areas of Yunnan Province, so as to provide a scientific basis for the intervention and control of SE anisometropia. Methods: In October 2021,a total of 1 852 school aged children in three counties/cities(Lijiang City,Dali City,Xishuangbanna) in Yunnan Province were examined by multi stage cluster random sampling method for computer optometry visual acuity examination for non ciliary paralysis and questionnaire survey.Demographic characteristics, ocular biological parameters and SE data were obtained for SE anisometropia. Group comparisons were conducted using Mann-Whitney U test or Kruskal-Wallis H test, and Logistic regression was used to explore the related factors of anisometropia in SE. Results: The prevalence of SE anisometropia among school age children was 23.0%, and the prevalence was higher in girls (24.2%) than that in boys (21.6%). Compared with non anisometropic children, school aged children with SE anisometropia had longer axial length (AL) [24.03 (23.41, 24.76), 23.93 (23.26, 24.61) mm] and corneal curvature radius (CR) [43.42 (42.43, 44.42), 43.14 (42.23, 44.04)mm], SE[-1.75(-2.75,-1.00),-0.94(-2.63,-0.25)D], smaller spherical scope [-1.38(-2.38,-0.75),-0.75(-2.38,0)D], deeper anterior chamber depth(ACD)[3.77(3.62, 3.93), 3.72(3.55, 3.89)mm], and grater differences in AL[0.58(0.32,0.82), 0.13( 0.06 ,0.22)mm], ACD[0.05(0.02,0.08), 0.03(0.01,0.06)mm] and AL/CR[0.01(0.01,0.02), 0.01(0.00,0.01)]( Z =-22.47 to -2.41, all P <0.05). The results of Logistic regression showed that mild myopia( OR =2.74), moderate myopia( OR =3.52), and high myopia( OR =8.92) had a relatively high risk of anisometropia SE in school aged children(all P <0.05). Conclusion The prevalence of SE anisometropia in school aged children in ethnic minority areas of Yunnan Province is relatively high, and the prevalence and degree of anisometropia were closely related to myopia degree and related refractive parameters.

The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Quality Control

OBJECTIVE: To screen novel diagnostic marker or therapeutic target for multiple myeloma (MM). METHODS: Sel1L, SPAG4, KCNN3 and PARM1 were identified by bioinformatics method based on GEO database as high expression genes in MM. Their RNA and protein expression levels in bone marrow mononuclear cells from myeloma cell lines U266, NCI-H929, MM.1s, RPMI8226 and leukemia cell line THP1, as well as 31 MM patients were evaluated by RT-PCR and Western blot, respectively. Meanwhile, 5 samples of bone marrow from healthy donors for allogeneic hematopoietic stem cell transplantation were employed as controls. RESULTS: Compared with leukemia cell line THP1, the expression levels of KCNN3, PARM1 and Sel1L mRNA were significantly increased in myeloma cell lines U266, NCI-H929 and MM.1s, while PARM1 was further increased in myeloma cell lines 8226. Western blot showed that the 4 genes were all expressed in the 4 myeloma cell lines. Compared with healthy controls, the expression levels of Sel1L, SPAG4, KCNN3 and PARM1 mRNA were significantly higher in MM patients (all P < 0.05). Western blot showed that the 4 genes were all expressed in MM patients, and the protein expression level of Sel1L and KCNN3 were significantly different compared with healthy donors (all P < 0.01). CONCLUSION Sel1L, SPAG4, KCNN3 and PARM1 may be potential diagnostic markers and therapeutic targets for MM.
Humans ; Multiple Myeloma/genetics* ; Cell Line, Tumor ; Proteins/metabolism* ; Computational Biology ; RNA, Messenger/genetics*

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To explore the relationship between lipid metabolism molecules in plasma and carotid atherosclerotic plaques,traditional cardiovascular risk factors and possible dietary related factors.Methods:Firstly,among 1 312 community people from those who participated in a 10-year follow-up study of subclinical atherosclerosis cohort in Shijingshan District,Beijing,85 individuals with 2 or more carotid soft plaques or mixed plaques and 89 healthy individuals without plaques were selected according to the inclusive and the exclusive criteria(＜70 years,not having clinical cardiovascular disease and other diseases,etc.).Secondly,10 cases and 10 controls were randomly selected in the above 85 and 89 individuals respectively.Carotid plaques were detected using GE Vivid i Ultrasound Machine with 8L de-tector.Lipid metabolism molecules were detected by high performance liquid chromatography-mass spec-trometry.The detection indexes included 113 lipid metabolism molecules.Traditional cardiovascular risk factors were collected by unified standard questionnaires,and dietary related factors were collected by main dietary frequency and weight scale.The difference of lipid metabolism molecules between the case group and the control group was analyzed by Wilcoxin rank test.In the control group,the Spearman cor-relation method was used to analyze the correlation between statistically significant lipid metabolism molecules and traditional cardiovascular risk factors and dietary factors.Results:Among the 113 lipid metabolism molecules,53 lipid metabolism molecules were detected.C24∶0 sphingomyelin(SM),C22∶0/C24∶0 ceramide molecules,C18∶0 phosphoethanolamine(PE)molecules,and C18∶0/C18∶2(Cis)phosphatidylcholine(PC)were significantly higher in the carotid atherosclerotic plaque group than in the control group.The correlation analysis showed that C24∶0 SM was significantly positively correlated with low density lipoprotein cholesterol(LDL-C,r=0.636,P＜0.05),C18∶2(Cis)PC(DLPC)was sig-nificantly positively correlated with systolic pressure(r=0.733,P＜0.05),C18∶0 PE was significantly positively correlated with high sensitivity C-response protein(r=0.782,P＜0.01),C22∶0,C24∶0 ce-ramide and C18∶0 PE were negatively correlated with vegetable intake(r=-0.679,P＜0.05;r=-0.711,P＜0.05;r=-0.808,P＜0.01),C24∶0 ceramide was also negatively correlated with beans food intake(r=-0.736,P＜0.05)in the control group.Conclusion:The increase of plasma C24∶0 SM,C22∶0,C24∶0 ceramide,C18∶0PE,C18∶2(Cis)PC(DLPC),C18∶0PC(DSPC)may be new risk factors for human atherosclerotic plaques.These molecules may be related to blood lipid,blood pres-sure or inflammatory level and the intake of vegetables and soy products,but the nature of the association needs to be verified in a larger sample population.