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.

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

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

OBJECTIVE: Burning solid cooking fuel contributes to household air pollution and is associated with frailty. However, how solid cooking fuel use contributes to the development of frailty has not been well illustrated. METHODS: This study recruited 8,947 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study, 2011-2018. Group-based trajectory modeling was employed to identify frailty trajectories. Multinomial logistic regression was used to assess the association between solid cooking fuel use and frailty trajectories. Population-attributable fractions were used to estimate the frailty burden from solid fuel use. RESULTS: We identified three frailty trajectories: low-stable ( n = 5,789), moderate-increasing ( n = 2,603), and fast-increasing ( n = 555). Solid fuel use was associated with higher odds of being in the moderate-increasing ( OR: 1.24, 95% CI: 1.08-1.42) and fast-increasing ( OR: 1.48, 95% CI: 1.14-1.92) trajectories. These associations were strengthened by longer solid fuel use ( P for trend < 0.001). Switching to clean fuel significantly reduced the risk of being in these trajectories compared with persistent solid fuel users. Without solid fuel, 8% of moderate- and 19% of fast-increasing trajectories demonstrated frailty development like the low-stable group. CONCLUSION Solid cooking fuel use is associated with frailty trajectories in middle-aged and older Chinese populations.
Humans ; China/epidemiology* ; Cooking ; Male ; Female ; Middle Aged ; Aged ; Air Pollution, Indoor/adverse effects* ; Frailty/etiology* ; Longitudinal Studies ; Cohort Studies

Objective This project aimed to study the Miao medicine helleborus thibetanus franchon,including investigating its anti-inflammatory activity in collagen-induced arthritis CIA rats and its mechanism of VEGF/VEGFR2/P38 MAPK pathway regulation.Methods Sixty female Wistar rats were randomly divided into six groups:normal;model;positive drug;and low,medium,high dose groups,with 10 rats in each group.Bovine type Ⅱ collagen solution was injected into the tail of rats to construct the rheumatoid arthritis model,and the positive drug group was given MTX2.0 mg/(kg·d)by gavage once every other day.The three groups of helleborus thibetanus franchon low,medium,and high dose were gavaged with helleborus thibetanus franchon ethanol extract at 0.25,0.5 and 1 g/(kg·d)once a day.The normal and model groups were given an equivalent volume of NaCl solution,with continuous administration lasting for 28 days.During treatment,the general condition of the rats was observed,body weight changes recorded,and foot thickness measured.After treatment and euthanasia,the rats'hind limbs were removed for Micro-CT to detect bone destruction;hematoxylin and eosin staining for pathological investigattion of the synovial membrane;immunohistochemistry to observe neovascularization in the synovium;quantitative reverse-transcription PCR to detect mRNA levels of VEGF-A,VEGFR2,TNF-α in the synovial tissue;and Western Blot to detect the expression of VEGF,VEGFR2,p-P38,p-AKT.The analyses were used to explore the potential mechanisms of action of the Miao medicine helleborus thibetanus franchon in treating rheumatoid arthritis.Results Compared with the normal group,the model group showed significant weight loss(P＜0.01),increased foot swelling(P＜0.01),visible proliferative synovial tissue with inflammatory cell infiltration,erosive lesions on bone surfaces,increased neovascularization in the synovium,and significant bone destruction in Micro-CT,with reduced bone percentage,trabecular thickness,and bone density.The levels of VEGF-A,VEGFR2,TNF-α mRNA and VEGF-A,VEGFR2,p-P38,p-AKT proteins were significantly elevated(P＜0.01).Compared with the model group,the helleborus thibetanus franchon ethanol extract-treated groups showed improvements in these conditions in a dose-dependent manner,with the high-dose group receiving the best effect.There was a significant increase in the rats'body weight(P＜0.05);reduction in foot swelling(P＜0.05);amelioration of synovial and erosive bone lesions;reduction in neovascularization in the synovium;and significantly lower levels of VEGF-A,VEGFR2,and TNF-α mRNA,and VEGF-A,VEGFR2,p-P38,and p-AKT protein(P＜0.01).Conclusions The Miao medicine plant helleborus thibetanus franchon may alleviate joint inflammatory damage in CIA rats by modulating the VEGF/VEGFR2 signaling pathway,thereby exerting therapeutic effects on rheumatoid arthritis.

Objective To research superconducting magnetocardiography signal measurement technology and coronary heart disease screening for solving the difficulties in weak magnetocardiography signal measurement,and to verify the value of clinical application.Methods The principle of superconducting magnetocardiography signal measurement technology was analyzed for constructing a framework for superconducting magnetocardiography signal measurement technology.Then,the key circuits such as the host controller,magnetic flux-locked loop,and signal conditioning module were designed,and software systems and core algorithms were developed.Finally,a total of 255 volunteers with healthy hearts,mild myocardial ischemia and severe myocardial ischemia were enrolled in the study,and a comparative experiment was performed between synchronous magnetocardiography and coronary angiography(CAG).Results The peer-to-peer bipolar structure was only observed in the current density vector distribution of healthy subjects instead of myocardial ischemia subjects.The overall coincidence rate,total Kappa value,severe ischemia coincidence rate,mild ischemia coincidence rate and negative coincidence rate of magnetocardiography with CAG were 86.22%,78.21%,86.79%,84.09%and 86.67%,respectively.Magnetocardiography had a sensitivity,specificity,positive rate,negative rate,positive likelihood ratio and negative likelihood ratio of 87.16%,84.41%,86.00%,86.67%,5.98 and 0.08,respectively.Conclusion Magnetocardiography has a high coincidence rate and consistency with CAG in the diagnosis of myocardial ischemia.Superconducting magnetocardiography signal measurement technology can be served as an accurate and reliable screening method for coronary heart diseases.

AIM To investigate the clinical effects of Modified Mahuang Lianqiao Chixiaodou Decoction on patients with chronic eczema.METHODS One hundred and ninety-five patients were randomly assigned into Chinese medicine group(65 cases)for 3-week administration of Modified Mahuang Lianqiao Chixiaodou Decoction,western medicine group(65 cases)for 3-week administration of Levocetirizine Hydrochloride,and combined group(65 cases)for 3-week administration of both Modified Mahuang Lianqiao Chixiaodou Decoction and Levocetirizine Hydrochloride.The changes in clinical effects,clinical indices(EASI score,DQOLS score,TCM syndrome score,PINS score),skin physiological function indicesssss(OCTS,TEWL,WCTC),inflammatory factors(EOT,EOS,NK-κB,CCR3),T lymphocyte subsets(Treg,Th1,Th17,Th22),p38MAPK signaling pathway indices(ERK1,ERK2,mMEK 1,MEK2),recurrence rate and incidence of adverse reactions were detected.RESULTS The combined group demonstrated higher total effective rate than the Chinese medicine group and the western medicine group(P＜0.05),along with lower recurrence rate(P＜0.05).After the treatment,the combined group displayed lower EASI score,TCM syndrome score,PINS,TEWL,inflammatory factors,Th1,Th17,Th22 and p38MAPK signaling pathway indices than the control group(P＜0.05),along with higher DQOLS score,OCTS,WCTC,Treg(P＜0.05).The Chinese medicine group exhibited lower incidence of adverse reactions than the other two groups(P＜0.05).CONCLUSION For the patients with chronic eczema,Modified Mahuang Lianqiao Chixiaodou Decoction can safely and effectively alleviate skin lesion degree,enhance skin physiological functions,improve T lymphocyte subset,inflammatory factors levels,and regulate p38MAPK signaling pathway based on"Four-in-One"therapy,which exhibits synergistic effect when combined with Levocetirizine Hydrochloride.

Cerebroprotein hydrolysate oral liquid (COL) is a neuroprotective preparation composed of various amino acids and peptides, which has beneficial effects on diverse central system diseases. However, the therapeutic effect and potential mechanism of oral COL on ischemic stroke (IS) still need to be explored. This study aims to investigate the therapeutic effects and underlying mechanisms of COL on IS in vivo and in vitro. An IS rat model was established through middle cerebral artery occlusion (MCAO) surgery, and triphenyltetrazolium chloride (TTC) staining, behavioral scoring, Evans blue leakage, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining were performed to investigate the effects of COL on cerebral infarct size, neurological function, blood-brain barrier (BBB) and neuroinflammation in IS rats. An in vitro model of IS was established on hCMEC/D3 cells through oxygen-glucose deprivation/reperfusion (OGD/R), and cell counting kit-8 assay, reactive oxygen species (ROS) detection, scratch test and Transwell test were conducted to examine the influence of COL on cell viability, oxidative stress and migration ability. Lipidomics technology, real-time quantitative PCR and Western blot experiments were used to investigate the regulation and mechanism of COL on lipid metabolism in the brain of IS rats. All the animal experiments were approved by Ethical Committee of Animal Experiments of China Pharmaceutical University (No.2022-02-23). Our results showed that intragastric administration of COL could significantly reduce the area of cerebral infarction, improve neurological deficits, lower the levels of inflammatory factors, and protect against the blood-brain barrier damage of rats with IS. OGD/R modeling resulted in a significant decrease in the viability, an elevation in intracellular ROS levels, and a weakened cell migration ability of hCMEC/D3 cells. COL treatment could effectively protect hCMEC/D3 cells from damage caused by OGD/R. More importantly, cerebral ischemia led to significant lipid metabolism disorders in the brain of rats, and significant accumulation of intracerebral triglycerides (TAG) and ceramides (Cer) was observed in IS rats. COL was proved to significantly reverse lipid metabolism disorders in the brain of IS rats and reduce the content of cytotoxic lipid Cer by upregulating the intracerebral levels of an acid ceramidase called N-acylsphingosine amidehydrolase 1 (ASAH1). In summary, COL was proved to be a promising and effective candidate for IS treatment, which could alleviate cerebral ischemic injury by regulating abnormal lipid metabolism.