Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective To investigate the therapeutic effects and mechanisms of Jianyang Tablets(mainly with the functions of tonifying the kidneys,replenishing essence,invigorating yang,and alleviating erectile dysfunction)on erectile dysfunction(ED)in rats with liver depression and kidney deficiency syndrome.Methods The 60 male SD rats were randomly divided into a normal group,a model group,a Tadalafil group,and low-,medium-,and high-dose Jianyang Tablets groups.Except for the normal group,all other groups underwent a 14-day composite modeling protocol combining intramuscular hydrocortisone injections and limb immobilization to induce ED with liver depression and kidney deficiency syndrome.Treatments were administered for 28 consecutive days after successful modeling.The body mass differences were recorded and compared before and after the experiment.Behavioral assessments included open-field test and mounting test were conducted.Enzyme-linked immunosorbent assay(ELISA)was used to measure nitric oxide synthase(NOS),cyclic adenosine monophosphate(cAMP),and cyclic guanosine monophosphate(cGMP)levels in penile cavernous tissues.Nitric oxide(NO)level was quantified using the Griess reagent colorimetric method.Results Compared with the normal group,the model group exhibited reduced horizontal activity grid counts in the open-field test,prolonged mounting latency,decreased mounting frequency,decreased body mass,and reduced levels of NOS,NO,cGMP,and cAMP in penile cavernous tissues,with statistical significance(P＜0.05 or P＜0.01).Compared with the model group,the Tadalafil group and medium-and high-dose Jianyang Tablets groups showed increased horizontal activity grid counts and vertical activity counts in the open-field test,shortened mounting latency,elevated mounting frequency,increased body mass,and upregulated levels of NOS,NO,cGMP,and cAMP in penile cavernous tissues,with statistical significance(P＜0.05 or P＜0.01).No significant differences were observed among the intervention groups for the aforementioned indices(P＞0.05).Conclusion Jianyang Tablets effectively improves erectile function in rats with liver depression and kidney deficiency syndrome,potentially mediated by modulation of the NO-cGMP signaling pathway.

Psoriasis is a chronic,recurrent,systemic inflammatory skin disease that is immune-media-ted.The balance and communication between the intestinal microbiota and its metabolites and the host play an important role in maintaining the body's normal functions,such as immune homeostasis and vitamin synthe-sis.Recent studies have found that compared with the healthy individuals,the psoriasis patients have experi-enced significant changes in the abundance and diversity of intestinal microbiota,including an imbalance in in-testinal microbiota,reduced production of short-chain fatty acids(SCFAs),and abnormal Firmicutes/Bacte-roidetes(F/B)ratio.The gut microbiota also changed after systematic medication treatment,biologic agents treatment and small molecule chemotherapy,indicating that the gut microbiota could be a potential biomarker for assessing treatment efficacy.The relationship between psoriasis and gut microbiota is not fully under-stood,and further research is needed.

Poststroke cognitive impairment (PSCI) is a common complication after ischemic stroke, which seriously affects the recovery of neurologic function and lowers the quality of daily life of patients. In a considerable portion of patients, the PSCI is reversible. This article reviews the influencing factors of cognitive impairment after ischemic stroke, including genetic predisposition, demographic factors, lifestyles, clinical manifestations, imaging findings and drug administration, etc. to provide references for prevention and intervention of PSCI.

Objective To explore the role and mechanism of cardiac resident macrophages in heart repair after myocardial infarction in mice.Methods Macrophage-specific Cre tool mice(CX3CR1CreER-YFP mice)with doubly transgenic mice(R26tdTomato/DTR mice)were hybridized to obtain cardiac resident macrophage-specific red fluorescent labels in mice.Sixty Cx3crlCreER-YFP:R26Td/DTR hybrid mice were randomly divided into 4 groups:Sham group,DT+Sham group,MI group,and DT+MI group,with 15 mice in each group.MI group and DT+MI group underwent myocardial infarction modeling by ligating the left anterior descending coronary artery.The DT+MI group mice were induced to deplete resident macrophages in the heart tissue using diphtheria toxin(DT)to establish a cardiac resident macrophage knockout model.On the 5th day after myocardial infarction modeling,heart tissue slices of mice were stained with H-E to observe inflammation infiltration and myocardial infarct size were calculated;on the 14th day of modeling,echocardiography was used to measure cardiac function-related parameters in mice,and mRNA expression levels of inflammatory cytokines were detected.Results Compared with the MI group,the DT+MI group mice showed a significant reduction in cardiac resident macrophages([53.75±4.62]vs[6.37±1.25],P＜0.05).On the 14th day after myocardial infarction modeling,compared with the Ml group,the DT+MI group mice had significantly increased left ventricular end-diastolic diameter([5.11±0.22]mm vs[5.92±0.26]mm,P＜0.05)and left ventricular end-systolic diameter([4.77±0.17]mm vs[5.38±0.16]mm,P＜0.05),while the ejection fraction significantly decreased([27.76±1.20]％vs[17.61±0.94]％,P＜0.05);in addition,the DT+MI group mice showed increased expression levels of inflammatory cytokines,increased inflammatory cell infiltration,and significantly larger myocardial infarct size.The protein expression levels of NF-KB/p-P65 in DT+MI group mice were significantly higher than those in the MI group([0.28±0.14]vs[1.09±0.12],P＜0.05).Conclusions Cardiac resident macrophages play an important role in heart tissue repair after myocardial infarction by reducing inflammation cell infiltration and myocardial infarct size.

ObjectiveTaking Shengxuebao as the model traditional Chinese medicine（TCM）， this study aims to explore the methodologies and transfer patterns in the composition changes of TCM compound preparations from liquid to solid dosage forms. MethodBased on the previously established ultra-high performance liquid chromatography（UPLC） qualitative and quantitative methods for Shengxuebao， the fingerprint profiles of three preparations of Shengxuebao（homemade decoction， commercially available granules and mixtures） were established， and nineteen components were quantitatively analyzed. The similarities of fingerprint profiles among these three preparations were assessed using the Similarity Evaluation System for Chromatographic Fingerprint of TCM（2012 edition） and the total quantum statistical moment similarity method， respectively. The molecular connectivity index （MCI） and the average molar MCI of the chemical components in the three preparations were calculated. Seventy-two MCI values across 0-8 orders， including 8 subclasses， were calculated. The average molar MCI of 0-3 orders was used to study the "imprint template" structural characteristics and transfer patterns of the medicinal component groups. ResultThe similarities of the fingerprint profile of the decoction with those of the control， granules， and mixtures were 0.971， 0.888 and 0.799， respectively， indicating that the chemical composition of the granules and mixtures differed from that of the decoction， and that the 19 components were able to basically respond to the overall situation of the component group of Shengxuebao decoction. The total mass fractions of the detectable major components in Shengxuebao decoction， granules and mixtures was measured to be 5.498 6， 2.282 0， 1.416 6 mg·g^-1， respectively. The average molar MCI of 0-3 orders showed a gradual decrease across the three preparations， with the trend of decoction>granules>mixtures， indicating subtle changes in the overall structural characteristics of the chemical components in the samples of the three preparations. ConclusionAmong the three formulations of Shengxuebao， the traditional decoction contained the highest variety and quantity of components and carried the most substantial amount of component information， with a decreasing order observed in the granules and mixtures. This study further validates that traditional decoction is a reliable and fundamental dosage form， providing a reference for the modernization of TCM dosage forms and the quality consistency evaluation of compound preparations.

Objective:To investigate the clinicopathological and molecular genetic features of POLE mutant endometrioid carcinoma.Methods:Genetic test data of 230 cases of endometrial carcinoma that underwent surgical resection and molecular typing by next generation sequencing in the First Medical Center of Chinese PLA General Hospital from January 2021 to June 2023 were retrospectively analyzed. Seventeen cases of endometrioid carcinoma with POLE mutation were selected. Clinical and prognostic information was collected. The paraffin-embedded tissue and immunohistochemical sections were reviewed, and the gene detection data were analyzed.Results:In the 17 cases of endometrioid carcinoma with POLE mutations, 16 cases (16/230, 6.9%) had mutations at known pathogenic sites, and 1 case had a mutation site (S459Y) that had not been reported, which was inferred to be pathogenic based on clinical prognosis. The 17 patients aged from 48 to 79 years (median 56 years, mean 58 years). All cases had typical histological features of endometrioid carcinoma, including 7 cases (7/17) of poorly-differentiated, 4 cases (4/17) of moderately-differentiated and 6 cases (6/17) of well-differentiated. Squamous differentiation was noted, mucous differentiation was less commonly found and often accompanied by superficial muscle infiltration. The number of stromal lymphocyte infiltration was variable. Lymph-vascular embolus was found in 6 cases, and lymph node metastasis was only detected in 1 case. According to the FIGO staging system for endometrial cancer in 2023, all the cases were in FIGO stage ⅠA m-POLEmut except for one case in FIGO stage ⅢC1. There were 8 cases with genetic co-mutation, 5 cases with TP53 mutation (immunohistochemically subclonal expression pattern), 1 case with MSI-H, and 2 cases with both TP53 mutation and MSI-H. Five of 7 patients with POLE mutation (poorly-differentiated) received postoperative chemotherapy and/or radiotherapy, 4 patients received endocrine therapy, and 8 patients had no treatment after surgery. One of the stage ⅠA m-POLEmut tumor patients was found to have pelvic recurrence one year after surgery, and the other 16 patients were followed up for 10-38 months without recurrence or metastasis. Conclusions:POLE mutant endometrioid carcinoma may have different differentiation, and most patients have good prognosis. Correct interpretation of molecular results, accurate identification and classification are important for predicting prognosis and avoiding overtreatment. However, a small number of cases may have recurrence and metastasis, and therefore it is necessary to make a reasonable treatment plan based on the comprehensive judgment of other high risk factors.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.