ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

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.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.
Humans ; Heart Failure ; Stroke Volume/physiology* ; Hypertrophy, Left Ventricular/metabolism* ; Ventricular Dysfunction, Left/metabolism* ; Inflammation/complications* ; Obesity ; Hypertension

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Periostin (POSTN), an evolutionary conserved and secreted extracellular matrix protein, can be easily detected by humoral samples such as blood, urine, interstitial fluid etc., which was firstly found in bone tissues.POSTN is expressed in various tissues and its expression level is closely related to oc¬currence and development of various diseases, which will be a potential molecular marker in early diagnosis of diseases.'Hie paper systematically summarizes the relationship of the expres¬ sion level of POSTN and some diseases including myocardial in¬farction, vascular calcification, diseases related to bone metabo¬lism, chronic nephrosis and various cancers, and explores its function as well as mechanism, which provides scientific basis for the early diagnostic kits or new drug development of diseases based on POSTN.

OBJECTIVE: To compare the clinical efficacy and safety of hypomenthylating agents (HMA) combined with Venetoclax (VEN) and half dose priming regimen (CAG-like) in the treatment of elderly patients with newly diagnosed acute myeloid leukemia (AML) who were not suitable for intensive chemotherapy. METHODS: The clinical data of 43 newly diagnosed elderly patients with AML who were not suitable for intensive chemotherapy in our hospital from April 2019 to October 2020 were retrospectively analyzed. Among them, 16 cases received HMA-VEN regimen and 27 cases received HMA-CAG-like regimen. The remission rate, early mortality and survival were compared between the two groups. And, the patients were grouped according to HCT-CI score. The effects of two different regimens in different groups on the efficacy and survival of patients were compared, and the prognosis of patients was further analyzed. RESULTS: After one course of treatment, the total remission rate of HMA-VEN group and HMA-CAG-like group was 81.3% (13/16) and 51.9% (14/27), respectively, and the difference between the two groups was statistically significant (χ2=4.650, P=0.045). The median overall survival (OS) time of HMA-VEN group had not yet reached, while that of HMA-CAG-like group was 11.2 months, and the HMA-VEN group had a longer OS (P=0.055). There was no tumor lysis syndrome occurred in both groups. The main adverse reactions were digestive tract reaction, bone marrow suppression and infection. The amount of agranulocytosis infection, pulmonary infection and platelet infusion in HMA-VEN group were significantly lower than those in HMA-CAG-like group (P<0.05), while the time of agranulocytosis and amount of erythrocyte infusion were similar (P>0.05). In HMA-Ven group 1 case died early, while in HMA-CAG-like group 8 cases died early due to pulmonary infection, respiratory failure, cerebral hemorrhage, and alveolar hemorrhage, the mortality in HMA-CAG-like group was significantly higher than that in HMA-VEN group (P=0.043). Among 43 patients, there was a significant difference in OS between HCT score 0-2 group and ≥3 group (P=0.033). In HMA-CAG-like group, patients with HCT score ≥3 had a worse prognosis (P=0.01), while in HMA-VEN group patients showed no statistically significant difference in prognosis (P=0.681). In HCT score 0-2 group, 9 cases receiving HMA-VEN regimen and 22 cases receiving HMA-CAG-like regimen showed no statistical difference in OS (P=0.281). In HCT score ≥3 group, 7 cases receiving HMA-VEN regimen had a longer OS than 5 cases receiving HMA-CAG-like regimen (P=0.015). CONCLUSION Venetoclax combined with HMA can achieve higher response rate, lower early mortality, and longer OS, especially in those with more comorbidities and poor tolerability.
Humans ; Aged ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy*