Atherosclerosis (AS) remains the core pathological basis underlying the high incidence and high rates of mortality and disability associated with cardiovascular disease (CVD) worldwide. Its essence is not merely lipid deposition, but rather an immune-mediated disease of the vascular wall characterized by an interplay of lipid metabolism disorders and chronic inflammation, with damage to vascular endothelial cells serving as the initiating event. As the disease progresses, it involves complex synergistic interactions among various cellular components, including endothelial cells, macrophages, and inflammatory cells, ultimately leading to plaque formation, instability, and even fatal thrombotic events. In recent years, the central driving role of lipid metabolic reprogramming in the progression of AS has garnered increasing attention from the scientific community. Among the vast array of lipid molecules, long-chain fatty acids (LCFAs) have become a primary focus of research due to their exceptional physiological functions. Traditional views have primarily emphasized the basic physiological functions of LCFAs: serving as highly efficient energy substrates through mitochondrial β-oxidation and acting as key structural components of cellular phospholipid membranes. However, emerging evidence clearly indicates that the functions of LCFAs extend far beyond those of mere metabolic fuel. They also act as potent bioactive signaling molecules, playing an indispensable multidimensional role in the pathogenesis of AS. Equally noteworthy and representing a paradigm shift in cardiovascular research is the emerging theory of the “gut-heart axis”. This theoretical framework views the human gut microbiota—comprising trillions of microorganisms—as a critical and metabolically active “bioreactor”. A wealth of clinical and multi-cohort epidemiological studies have conclusively demonstrated that imbalances in the composition and function of the gut microbiota are highly correlated with the clinical risk and severity of AS. Within this axis, the gut microbiota serves as the primary processing hub for dietary lipids. It actively participates in the digestion and biochemical remodeling of LCFAs, thereby altering their saturation and chemical structure and generating a wide variety of gut microbial metabolites. The effects of these gut-derived lipid metabolites extend far beyond the local intestinal microenvironment. Upon entering the bloodstream, these circulating microbiota metabolites act as endocrine signals. Given the extreme complexity of the underlying mechanisms, a comprehensive elucidation of the synergistic and bidirectional interactions between LCFAs and the gut microbiota in vascular pathology is particularly urgent. Therefore, this article aims to provide a systematic review of the multidimensional regulatory mechanisms of LCFAs and their associated gut microbiota metabolites in the onset, progression, and clinical manifestations of AS. By thoroughly exploring the interaction patterns within the “LCFAs-gut microbiota-AS” triad, this review seeks to fundamentally expand our understanding of the pathogenesis of CVDs. More importantly, translating these mechanistic insights into clinical practice holds tremendous promise. We hope to provide a solid theoretical foundation for the future development of novel AS prevention and treatment strategies based on non-traditional approaches. These include precision nutritional interventions (i.e., dietary lipid intake plans tailored to an individual’s unique microbiome profile) and targeted microbiome modulation therapies (such as next-generation probiotics, prebiotics, or specific metabolite supplements). Targeting the gut as a “reactor” to treat vascular wall lesions represents a promising direction for future cardiovascular medicine.

OBJECTIVE: To summarize the methods of ankle hinge position design in the correction of clubfoot deformity by Ilizarov method, and to explore its application value in the prevention of ankle dislocation. METHODS: A retrospective study was conducted including 28 patients with rigid clubfoot deformity (34 feet) who met the selection criteria and admitted between September 2021 and December 2024. There were 19 males and 9 females with an average age of 31.8 years (range, 19-47 years). According to Dimeglio classification, there were 21 feet of degree Ⅲ and 13 feet of degree Ⅳ. The causes were traumatic sequelae in 9 cases, congenital foot deformity in 15 cases, spina bifida sequelae in 1 case, peripheral neuropathy in 1 case, and cerebral palsy sequelae in 2 cases. The malformation lasted from 6 to 46 years, with an average of 29.3 years. All patients were treated with Ilizarov circular external fixator, and the hinge position of ankle joint was planned according to the standard lateral X-ray film of foot and ankle and the principle of Ilizarov limb deformity correction center of rotation angulation (CORA) before operation. The 2008 International Clubfoot Study Group (ICFSG) scoring system was used to evaluate the efficacy. RESULTS: The deformity of rigid clubfoot was completely corrected in all patients, and the patients could walk with plantar weight-bearing, and the ankle weight-bearing walking significantly improved when compared with that before operation. There was no complication such as ankle dislocation, talus impact or extrusion, local skin necrosis, needle tract infection, or numbness of extremities during the correction process. All patients were followed up 5-39 months, with an average of 18.1 months. At last follow-up, according to the ICFSG scoring system, 23 feet were excellent, 10 feet were good, and 1 foot was fair, and the excellent and good rate was 97%. CONCLUSION Designing the position of the ankle hinge according to the principle of CORA can effectively avoid ankle dislocation, talus impingement, tibiotalar joint extrusion, and other ankle adverse events in the process of correcting clubfoot deformity, which has good application value in clinical practice.
Humans ; Male ; Female ; Clubfoot/diagnostic imaging* ; Ilizarov Technique/instrumentation* ; Adult ; Retrospective Studies ; External Fixators ; Ankle Joint/diagnostic imaging* ; Middle Aged ; Joint Dislocations/prevention & control* ; Treatment Outcome ; Young Adult

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

Purpose To investigate the role of 18F-FDG PET/CT in predicting histological grade of invasive pulmonary adenocarcinoma in the WHO(2021)classification.Materials and Methods The Clinical,pathological and PET/CT data of 255 patients with invasive pulmonary adenocarcinoma confirmed by surgical pathology were retrospectively analyzed from May 2015 to August 2023.Tertiary tumor grading was performed according to the WHO(2021)classification.The clinicopathologic features,maximum standardized uptake value(SUVmax),maximum standardized uptake,total lesion glycolysis and CT imaging findings were compared among the three tumor grades.Logistic regression analysis was used to screen the independent predictors for grade 3 tumors,and performance evaluation was performed using receiver operating characteristic curve.Results Higher tumor grade was associated with male sex(χ2=11.803,P=0.003),smoking history(χ2=7.702,P=0.021),maximum tumor diameter(H=20.548,P=0.002),lymph node metastasis(P<0.001),vascular cancer thrombus(χ2=33.270,P<0.001),pleural invasion(χ2=15.116,P=0.001)and airway spread(χ2=17.867,P<0.001).SUVmax(H=71.488,P<0.001),total lesion glycolysis(H=30.658,P<0.001)and the proportion of pure solid tumors on CT image(χ2=28.872,P<0.001)all increased significantly with higher tumor grade.A higher SUVmax(OR=1.234,95%CI 1.141-1.334,P<0.001)and pure solid appearance(OR=2.205,95%CI 1.166-4.171,P=0.015)were independent predictors of grade 3 tumors.The area under the receiver operating characteristic curve for SUVmax,CT solid appearance and the combination for predicting grade 3 tumors was 0.793,0.641 and 0.804,respectively,with the SUVmax cut-off of 6.08.Conclusion SUVmax and CT solid appearance are independent predictive factors for grade 3 invasive pulmonary adenocarcinoma.Preoperative 18F-FDG PET/CT can assist in evaluating the grading of invasive pulmonary adenocarcinoma,which improves treatment decision-making.

Purpose To investigate the role of 18F-FDG PET/CT in predicting histological grade of invasive pulmonary adenocarcinoma in the WHO(2021)classification.Materials and Methods The Clinical,pathological and PET/CT data of 255 patients with invasive pulmonary adenocarcinoma confirmed by surgical pathology were retrospectively analyzed from May 2015 to August 2023.Tertiary tumor grading was performed according to the WHO(2021)classification.The clinicopathologic features,maximum standardized uptake value(SUVmax),maximum standardized uptake,total lesion glycolysis and CT imaging findings were compared among the three tumor grades.Logistic regression analysis was used to screen the independent predictors for grade 3 tumors,and performance evaluation was performed using receiver operating characteristic curve.Results Higher tumor grade was associated with male sex(χ2=11.803,P=0.003),smoking history(χ2=7.702,P=0.021),maximum tumor diameter(H=20.548,P=0.002),lymph node metastasis(P<0.001),vascular cancer thrombus(χ2=33.270,P<0.001),pleural invasion(χ2=15.116,P=0.001)and airway spread(χ2=17.867,P<0.001).SUVmax(H=71.488,P<0.001),total lesion glycolysis(H=30.658,P<0.001)and the proportion of pure solid tumors on CT image(χ2=28.872,P<0.001)all increased significantly with higher tumor grade.A higher SUVmax(OR=1.234,95%CI 1.141-1.334,P<0.001)and pure solid appearance(OR=2.205,95%CI 1.166-4.171,P=0.015)were independent predictors of grade 3 tumors.The area under the receiver operating characteristic curve for SUVmax,CT solid appearance and the combination for predicting grade 3 tumors was 0.793,0.641 and 0.804,respectively,with the SUVmax cut-off of 6.08.Conclusion SUVmax and CT solid appearance are independent predictive factors for grade 3 invasive pulmonary adenocarcinoma.Preoperative 18F-FDG PET/CT can assist in evaluating the grading of invasive pulmonary adenocarcinoma,which improves treatment decision-making.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Objective:To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase(CML-CP).Methods:Clinical data of 41 adult CML-CP patients in Department of Hematology,Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed.The clinical characteristics and prognosis of patients between＜60 years group and ≥ 60 years group were compared.Results:The 41 patients included 27(65.9％)males and 14(34.1％)females.The median age of the patients was 56(19-84)years,with 22 cases(53.7％)＜60 years and 19 cases(46.3％)≥60 years.Univariate analysis indicated that the proportions of patients with comorbidities,intermediate/high-risk Sokal score,myelofibrosis,and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with＜60 years group at initial diagnosis(all P＜0.05).There were no statistical differences in the distribution of sex,ELST score,white blood cell count,platelet count,peripheral blood basophil percentage,peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups(P＞0.05).The proportion of patients taking reduced-dose imatinib in≥60 years group significantly increased(P＜0.001).Patients＜60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors(TKIs)than patients ≥ 60 years(P＜0.001).The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥ 60 years(P＜0.001).Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI.Conclusion:Compared with adult CML-CP patients＜60 years,patients ≥ 60 years gain fewer benefits from TKI treatment and increased adverse reactions.