Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

Shengma Gegentang is one of the classic formulas in the Catalogue of Ancient Classic Prescriptions （Second Batch）. This study reviewed ancient and modern literature and used literature tracing and bibliometric methods to analyze the historical evolution， efficacy， indications， dosage decoctions， and modern clinical disease spectrum of Shengma Gegentang. The results indicated that the earliest record of Shengma Gegentang can be found in the Taiping Huimin Heji Jufang of the Song dynasty， but its origin can be traced back to the Shaoyao Siwu Jiejitang in the Beiji Qianjin Yaofang of the Tang dynasty. The composition dosage of Shengma Gegentang is 413 g of Cimicifugae Rhizoma， 619.5 g of Puerariae Lobatae Radix， 413 g of Paeoniae Radix Alba， and 413 g of Glycyrrhizae Radix et Rhizoma， which are ground into coarse powder. Each dose is 12.39 g， and the amount of water added is 300 mL. 100 mL of solution is decocted and taken at the right time. The four drugs in the formula play the role of relieving exterior syndrome， penetrating pathogenic factors， and detoxicating together. Its indications are widely involved in internal medicine， pediatrics， surgery， ophthalmology and otorhinolaryngology， obstetrics and gynecology， sexually transmitted diseases， and other diseases， such as measles， sores， acne， spots， surgical gangrene， red eyes， toothache， chancre， and fetal poison. The epidemic diseases treated by Shengma Gegentang are complicated， including rash， pox， macula， numbness， summer diarrhea， dysentery， sha disease， febrile symptoms， spring warmth， winter warmth， and cold pestilence. At the same time， it is a plague prevention formula. Although Shengma Gegentang has a wide range of indications， it cannot be separated from the pathogenic mechanism of evil Qi blocking the muscle surface and heat in the lungs and stomach. The modern clinical disease spectrum of Shengma Gegentang involves the ophthalmology and otorhinolaryngology system， nervous system， pediatric-related diseases and syndromes， skin system， hepatobiliary system， and digestive system. It plays a key role in the treatment of epidemic diseases such as measles， chronic hepatitis B， dysentery， and tetanus.

Objective To investigate the efficacy of leaflet augmentation technique to repair the recurrent mitral valve (MV) regurgitation after mitral repair in children. Methods A retrospective analysis was conducted on the clinical data of children who underwent redo MV repair for recurrent regurgitation after initial MV repair, using a leaflet augmentation technique combined with a standardized repair strategy at Fuwai Hospital, Chinese Academy of Medical Sciences, from 2018 to 2022. The pathological features of the MV, key intraoperative procedures, and short- to mid-term follow-up outcomes were analyzed. Results A total of 24 patients (12 male, 12 female) were included, with a median age of 37.6 (range, 16.5–120.0) months. The mean interval from the initial surgery was (24.9±17.0) months. All children had severe mitral regurgitation preoperatively. The cardiopulmonary bypass time was (150.1±49.5) min, and the aortic cross-clamp time was (94.0±24.2) min. There were no early postoperative deaths. During a mean follow-up of (20.3±9.1) months, 3 (12.5%) patients developed moderate or severe mitral regurgitation (2 severe, 1 moderate). One (4.2%) patient died during follow-up, and one (4.2%) patient underwent a second MV reoperation. The left ventricular end-diastolic diameter was significantly reduced postoperatively compared to preoperatively [ (43.5±8.6) mm vs. (35.8±7.8)mm, P<0.001]. Conclusion The leaflet augmentation technique combined with a standardized repair strategy can achieve satisfactory short- to mid-term outcomes for the redo mitral repair after previous MV repair. It can be considered a safe and feasible technical option for cases with complex valvular lesions and severe pathological changes.

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To investigate the diagnosis value of contrast-enhanced ultrasound (CEUS) in the differentiation of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) of the liver with ≤3 cm of maximum diameter. Methods The image characteristics in 48 lesions of HCC with maximum diameter≤3 cm and 48 lesions of FNH with maximum diameter≤3 cm confirmed by pathology were retrospectively analyzed. The phase changes, enhancement patterns and enhancement characteristics of the lesions in the two groups were compared. Results All lesions in the two groups showed high-echo in the arterial phase. The contrast arrival time in HCC group and FNH group was 17(15, 19) s and 15(12, 18.75) s (P＝0.017); the peak time in the two groups was 21(17, 25) s and 22(19, 26) s (P＞0.05). The main enhancement patterns of HCC group and FNH group in arterial phase were homogeneous enhancement and centrifugal enhancement, respectively. All HCC lesions showed homogeneous enhancement, which was significantly higher than FNH (2.08%, P＜0.05); 97.91% of FHN lesions showed centrifugal enhancement, which was higher that of HCC lesions (0, P＜0.05). During the CEUS process, 87.5% of HCC lesions showed “rapid fill-in and rapid wash-out”, which was significantly higher than that of FNH lesions（8.33%，P＜0.05）; 91.67% of FNH lesions showed “rapid fill-in” and “synchronous/slow wash-out” which was significantly higher than that of HCC lesions （12.50%，P＜0.05）. Conclusion CEUS is helpful in the differential diagnosis of FNH and HCC with maximum diameter≤3 cm．

The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC ( OR value 1.319, 95% CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.

Heart failure （HF） is a group of syndromes caused by cardiac dysfunction with impaired ventricular pumping， seriously affecting patients' health and quality of life. The pathogenesis of HF is complex， including myocardial contractility decline， myocardial fibrosis， and ventricular remodeling， and it is related to neuroendocrine regulation， inflammation， and cardiomyocyte autophagy. Autophagy is a key regulatory mechanism by which cells degrade themselves to maintain body homeostasis. In the process of HF， moderate autophagy can remove aging and damaged cardiomyocytes and maintain the balance of myocardial energy metabolism， while abnormal autophagy may lead to functional decline and pathological changes of cardiomyocytes. The adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway is one of the classical pathways regulating autophagy. This pathway can mediate the autophagy of cardiomyocytes and play a role in protecting the cardiac function and delaying HF progression. Traditional Chinese medicine （TCM） with a long history has a unique theoretical system and shows satisfactory therapeutic effects and wide application prospects amid the integration with modern medicine. The clinical practice of TCM has accumulated rich experience in the treatment of cardiovascular diseases. A large number of studies have shown that the active components and compound prescriptions of TCM and Chinese patent medicines can mediate autophagy by regulating the AMPK/mTOR signaling pathway to treat HF. This article explains the role of AMPK/mTOR signaling pathway-mediated autophagy in the treatment of HF， introduces the understanding of autophagy， AMPK/mTOR signaling pathway， and HF based on TCM theories， and reviews the research progress in the regulation of autophagy by TCM in the treatment of HF via the AMPK/mTOR pathway. This review is expected to tap the potential of TCM in the treatment of cardiovascular diseases， provide theoretical support for subsequent experimental studies， and demonstrate the advantages of TCM in clinical practice to achieve more accurate treatment.