19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

ObjectiveTo investigate the clinical features and outcomes of critically ill pregnant and parturient women with chronic hepatitis B virus （HBV） infection， and to provide clinical experience for the rescue of critically ill pregnant and parturient women and the prevention and treatment of the severe exacerbation of liver disease. MethodsA total of 41 pregnant and parturient women with chronic HBV infection who were admitted to Department of Critical Care Medicine， Nanjing Second Hospital， from March 2013 to March 2023 were enrolled in this study， and their clinical data were collected through the electronic medical record system of hospital to summarize the main causes of transfer to the intensive care unit （ICU）， the causes of death， and treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 41 patients， 13 （31.71%） did not receive regular antenatal examination and 8 （19.51%） with a high viral load （HBV DNA ≥2×10⁵ IU/mL） did not receive antiviral therapy. Cesarean section was the main mode of delivery in 32 patients （78.05%）； 23 patients （56.10%） had premature delivery， and 5 patients died （12.20%）. The top three causes of transfer to the ICU were liver failure， postpartum hemorrhage， and hypertensive disorders of pregnancy. Liver failure mainly occurred in late pregnancy， with hepatic encephalopathy as the most common complication （28.57%） and intrahepatic cholestasis of pregnancy as the most common comorbidity （21.43%）； among the 14 patients with liver failure， 6 （42.86%） received regular antenatal examination， and 13 （92.86%） did not receive antiviral therapy before admission. The mean length of ICU stay was 3.31±1.65 days for the patients with postpartum hemorrhage， among whom the patients with severe liver disease had coagulation disorders before delivery， which were difficult to correct after 48 hours of treatment. ConclusionPregnant and parturient women with chronic HBV infection tend to have complex conditions and a relatively high mortality rate. For pregnant and parturient women with chronic HBV infection， assessment of liver status， regular antenatal examination， and timely antiviral therapy are of vital importance to reduce severe exacerbation and mortality rate.

The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.

Objective To systematically evaluate the efficacy and safety of plum-blossom needle therapy for vitiligo by using the systematic review and meta analysis.Methods The randomized controlled trials(RCT)on plum-blossom needle for treating vitiligo were systematically retrieved from the databases of the PubMed,China Biological Medicine Database,CNKI,Wanfang Data and VIP database from the database estab-lishment to June 2,2022.The literatures were screened according to the inclusion and exclusion criteria.The finally included literatures conducted the data extraction.The RevMan 5.4 software was used for conducting the data analysis.The methodological quality evaluation on the included trials was performed by the ROB tool.The GRADE method was used to assess the evidence level.Results A total of 7 trials involving 469 pa-tients were finally included.The meta analysis results showed that the plum-blossom needle combined with other therapies(including laser or ultraviolet irradiation,tacrolimus ointment,compound Kaliziran tincture)was superior to the other therapies alone in the aspects of improving vitiligo skin lesion including reducing the of white spot skin lesion area(MD=-1.11,95％CI:-1.92 to-0.30,P=0.007),increasing the repigment-ation rate of vitiliginous lesions(MD=18.09,95％CI:1.55 to 34.63,P=0.030)and enhancing the pigment deposition in vitiligo lesions(MD=0.92,95％CI:0.32 to 1.52,P=0.003),and improving the patients'quali-ty of life(MD=-7.48,95％CI:-8.04 to-6.92,P＜0.001),and the differences were statistically signifi-cant.In terms of safety,there was no statistically significant difference in adverse events between plum blos-som acupuncture combined with other therapies and other therapies alone(RR=1.20,95％CI:0.77 to 1.84,P=0.420).Conclusion Low or very low evidence shows that plum-blossom needle combined with other therapies for treating vitiligo may enhance the effect in the aspects of improving the white spot skin lesions and quality of life in the patients with vitiligo,moreover which is relatively safe.

The quality control of traditional Chinese medicine(TCM)is the core issue to ensure the modernization,industrialization and internationalization of TCM.Compared with other detection methods,electrochemical analysis method has many advantages such as high sensitivity,fast detection speed and low cost,making it an important means of quality control for TCM and having broad development prospects.This article reviewed the research progress of electrochemical methods in quality control of TCM in recent years,discussed the application of electrochemical fingerprinting technique in identification of TCM,and comprehensively summarized the application of electrochemical technology in analyzing effective components and harmful substances in TCM,including flavonoids,alkaloids,quinones,glycosides,heavy metals and pesticide residues.Finally,the development prospects of electrochemical methods in the field of quality control of TCM were discussed.

Objective To observe the therapeutic effect and mechanism of Guhuaisi Kangfu Pills on rats with steroid-induced osteonecrosis of the femoral head(SONFH).Methods Sixty rats were randomly divided into blank group,model group,Xianling Gubao Capsules group and Guhuaisi Kangfu Pills low-,medium-and high-dose groups,10 rats in each group.Except for the blank group,the SONFH model was established by lipopolysaccharide combined with Glucocorticoid induction method in all other groups of rats.At the end of the intervention,for the femoral head,blood vessel radiography was performed to observe the microvascular changes in the bone marrow,and hematoxylin-eosin(HE)staining and calculation of the empty bone trap rate,Micro-CT scanning analysis,and compression experiments were carried out,and the real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the gene expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)1,vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule 1(CD31)in whole blood.Results Compared with the blank group,the blood supply in the femoral head medullary cavity of the model group was poor,the empty bone lacuna rate was increased(P＜0.05),the bone mineral density and bone volume fraction were significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were decreased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in whole blood were decreased(P＜0.05).Compared with the model group,the blood supply in the femoral head medullary cavity was relatively good,the empty bone lacuna rate was decreased(P＜0.05),the bone mineral density,bone volume fraction,trabecular number and trabecular thickness were significantly increased(P＜0.05),the trabecular separation was significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were increased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in the whole blood were increased(P＜0.05)in the high-dose group of Guhuaisi Kangfu Pills and Xianling Gubao Capsules group.There was no significant difference in the above indexes between the high-dose group of Guhuaisi Kangfu Pills and the Xianling Gubao Capsules group(P＞0.05).Conclusion Guhuaisi Kangfu Pills improves SONFH in rats,and its mechanism is related to the promotion of VEGF/PI3K/Akt pathway gene expression,thereby promoting angiogenesis.

Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Objective To investigate the clinical effect in treating AO type B and C distal radius fractures with modified Henry approach.Methods Retrospectively analysis of 20 patients with AO type B and C distal radius fractures between June 2021 and May 2022,they were treated by modified Henry approach.There were 6 males and 14 females,aged from 35 to 78 years old,8 patients on the left and 12 on the right.The patients'general data,fracture healing time,postoperative complica-tions,last-time follow up radiographic parameters(volar inclination angle,ulnar deviation angle and radius height),wrist range of motion,range of forearm rotation and functional outcoming of the wrist joint according to Mayo scoring were observed of each patient.Results All patients were followed-up,the time was(13.3±2.3)months,ranged from 12 to 18 months.All the fractures were healed,the fracture healing time was(12.6±2.5)weeks,ranged from 10 to 16 weeks.There were no complications such as poor wound healing,incision infection,iatrogenic median nerve injury,delayed union,nonunion and malunion during the post-operative follow up.According to the X-ray measurement in the last-time follow up,the volar inclination angle was(11.4±4.0)°,the ulnar deviation angle was(20.9±2.2)° and the radius height was(10.3±1.2)mm.The wrist range of motion was(65.3±5.8)° for volar flexion,(60.2±4.2)° for dorsal extension,(37.8±4.1)° for ulnar deviation,(27.0±3.7)° for radial deviation.The range of forearm rotation was(80.4±4.1)° for pronation,(78.6±3.7)° for supination.According to Mayo scoring,the wrist function was evaluated as excellent in 12 cases,good in 6 cases and fair in 2 cases,the excellent and good rate was 90％.Con-clusion Modified Henry approach can better expose the ulnar and volar fragments in distal radius,especially useful for reduct-ing the distal radius with complex bi-columnar fractures.

Objective To investigate the surgical method and clinical outcome using the free anterolateral thigh flap with the medial gastrocnemius artery as the recipient artery for the repair of complex wounds in the lower leg. Methods A retrospective analysis was conducted on the clinical data of 11 patients with complex wounds in the lower leg admitted to Suzhou Ruihua Orthopedic Hospital from October 2020 to September 2022. All patients had extensive skin and subcutaneous soft tissue defects in the lower leg and received free anterolateral thigh flap repair with the medial gastrocnemius artery as the recipient artery. The skin of donor site was directly sutured. Results All 11 free skin flap survived in 11 patients, and both the donor and recipient sites healed in stage I. All patients were followed up after discharge, with a follow-up time of 12 to 35 months. The follow-up results at 12 months postoperatively showed good wound healing, good flap appearance and elasticity, restoration of normal knee and ankle joint function, and independent living ability. The donor site wounds healed well without significant scar hyperplasia. At the last follow-up, the flap sensory function was graded as S₃ in 2 patients and S₂ in 9 patients. The functional score of the affected limb was excellent in 5 patients and good in 6 patients, with an excellent and good rate of 100%. Conclusion The medial gastrocnemius artery has a suitable vessel caliber for anastomosis and a constant location. The use of the free anterolateral thigh flap with this artery as the recipient artery for the repair of severe wounds in the lower leg can effectively cover soft tissue defects and avoid injuring the residual main vessels in the lower leg, resulting in satisfactory outcomes.