The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVES: To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of Buyang Huanwu Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition. METHODS: Forty normal Wistar rats were randomized into two groups (n=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O₂) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum. AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells, and the changes in ROS, ATP level, mitochondrial membrane potential and Ca²⁺ homeostasis were analyzed. The changes in mRNA and protein expressions of BNIP3, PI3K and AKT and mRNA expressions of LC3, Beclin-1 and P62 were detected using RT-qPCR and Western blotting. RESULTS: Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure. The treatment significantly decreased T-AOC concentration, increased ROS production, autophagosome formation and ATPase levels, and lowered mitochondrial membrane potential and Ca²⁺ level in the cells. In IL-1β-induced FLS-RA with hypoxic exposure, treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression, decreased the protein expressions of PI3K and AKT, increased the mRNA expressions of BNIP3 and P62, and lowered the mRNA expressions of PI3K, AKT, LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression. The cells treated with 5% and 10% BYHWT-medicated serum showed no significant changes in LC3 expression. CONCLUSIONS BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.
Drugs, Chinese Herbal/pharmacology* ; Arthritis, Rheumatoid/pathology* ; Animals ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Humans ; Fibroblasts/cytology* ; Rats, Wistar ; Membrane Proteins/metabolism* ; Rats ; Phosphatidylinositol 3-Kinases/metabolism* ; Mitochondria/metabolism* ; Cells, Cultured ; Proto-Oncogene Proteins/metabolism* ; Apoptosis/drug effects* ; Cell Hypoxia ; Synovial Membrane/cytology* ; Male ; Mitochondrial Proteins

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Alcoholic liver disease(ALD), a major cause of chronic liver disease worldwide, poses a serious threat to human health. Despite the availability of various drugs for treating ALD, their efficacy is often uncertain, necessitating the search for new therapeutic approaches. Traditional Chinese medicine polysaccharides have garnered increasing attention in recent years due to their versatility, high efficiency, and low side effects, and they have demonstrated significant potential in preventing and treating ALD. Emerging studies have suggested that these polysaccharides exert their therapeutic effects through multiple mechanisms, including the inhibition of oxidative stress and the regulation of lipid metabolism, gut microbiota, and programmed cell death. This review summarizes the recent research progress in the pharmacological effects and regulatory mechanisms of traditional Chinese medicine polysaccharides in treating ALD, aiming to provide a scientific basis and theoretical support for their application in the prevention and treatment of ALD.
Humans ; Liver Diseases, Alcoholic/metabolism* ; Polysaccharides/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Oxidative Stress/drug effects* ; Medicine, Chinese Traditional ; Gastrointestinal Microbiome/drug effects* ; Lipid Metabolism/drug effects*

This study aimed to investigate the associations between the post-wash total progressively motile sperm count (TPMSC) in the first intrauterine insemination (IUI) cycle and pregnancy outcomes of the second IUI cycle. Data were retrieved from the clinical database at the Reproductive Center of Peking University Third Hospital (Beijing, China) between January 2011 and December 2022. Couples were included in this retrospective cohort study if they had unexplained or mild male factor infertility and were treated with IUI for two consecutive cycles using the same protocol. A total of 8290 couples were included in the analysis. The mean ± standard deviation (s.d.) age of women was 32.0 ± 3.5 years. We categorized groups based on the post-wash TPMSC (×10 6 ) levels in the first IUI cycle: group 1 (0 < TPMSC < 1, n = 1290), group 2 (1 ≤ TPMSC < 2, n = 863), group 3 (2 ≤ TPMSC < 3, n = 800), group 4 (3 ≤ TPMSC < 4, n = 783), group 5 (4 ≤ TPMSC < 5, n = 1541), group 6 (5 ≤ TPMSC < 6, n = 522), group 7 (6 ≤ TPMSC < 7, n = 547), group 8 (7 ≤ TPMSC < 8, n = 175), group 9 (8 ≤ TPMSC < 9, n = 556), group 10 (9 ≤ TPMSC < 10, n = 192), and group 11 (TPMSC ≥ 10), n = 1021). The primary outcome was live birth rate of the second IUI cycle. Live birth rates were 7.9%, 5.8%, 7.6%, 7.4%, 7.3%, 8.4%, 7.5%, 7.4%, 8.8%, 8.9%, and 7.6% in each group, respectively. There were no statistically significant differences in clinical pregnancy rates or live birth rates between any groups and those with the post-wash TPMSC <1 × 10 6 . In an IUI program for unexplained and mild male factor infertility, the post-wash TPMSC in the first IUI cycle was not significantly associated with the live birth rate in the second IUI cycle.
Humans ; Female ; Male ; Pregnancy ; Adult ; Retrospective Studies ; Sperm Count ; Pregnancy Rate ; Sperm Motility/physiology* ; Insemination, Artificial/methods* ; Pregnancy Outcome ; Infertility, Male/therapy* ; Insemination, Artificial, Homologous ; Live Birth

Objective To investigate the distribution characteristics and future trends of clinical trials related to TCM prevention and treatment of constipation by analyzing the clinical trials registered in the Chinese Clinical Trial Registry(ChiCTR).Methods The clinical trials data related to TCM prevention and treatment of constipation in the ChiCTR database were retrieved from the establishment of the database to April 15,2024.Excel 2019 was utilized for de-duplication.Subsequently,SPSS 26.0 was employed to analyze the general characteristics,research types,intervention measures,etc.of the included trials,charts were drawn,and the clinical trial characteristics were summarized.Results A total of 107 clinical trials were included,with 102 being pre-registered,involving 21 provincial-level administrative regions and 75 clinical institutions.The top five regions in terms of the number of registered clinical trials were Beijing(19.63%),Shanghai(15.89%),Guangdong(14.02%),Sichuan(10.28%)and Jiangsu(9.35%).The top three sources of funding were local finance(28.97%),self-raised funds(18.69%)and hospital-funded funds(15.89%).The research types were mostly intervention studies(92.52%),of which 41 explicitly stated the use of blinding methods,and the main research design type is randomized parallel controlled trial.Conclusion The number of clinical trials related to TCM prevention and treatment of constipation registered in ChiCTR is on an upward trend.However,there is a noticeable geographical imbalance in the distribution of these trials,and there is a need for further improvement in the quality of trial design and the standardization of registration information.

Objective:To investigate the application and safety of cardiopulmonary bypass precharge with 4% succinylated gelatin during surgery for children with cyanotic congenital heart disease (CCHD).Methods:A prospective case-control study was conducted. One hundred and thirty children with CCHD undergoing cardiac surgery admitted to Shaanxi Provincial People's Hospital in 2021-2024 were selected as study participants. Participants were divided into control group ( n=65) and gelatin group ( n=65) by random number table method based on the principle of matching baseline characteristics between groups. Children in the control group were pre-filled with 10-20 ml/kg of fresh frozen plasma, while the gelatin group was pre-filled with 10-20 ml/kg of 4% succinyl gelatin. Thrombelastogram parameters [fibrin formation time, blood clot strength, fibrinogen maximum amplitude, fibrinogen content], hematological parameters [platelet count, prothrombin time (PT), prothrombin activity (PTA), hemoglobin], myocardial function [troponin, creatine kinase, creatine kinase isoenzyme (CK-MB)] and liver-kidney function were compared before and after treatment.Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:Comparison between groups showed that before treatment, the difference of various thromboelastography parameters, haematological parameters, myocardial function indexes, liver and kidney function indexes were not statistically significant ( P>0.05). Compared to before treatment, R, PTA, troponin and creatine kinase increased in both groups after treatment [control group:(51±4) s vs. (43±3) s, (98±15)% vs. (95±12)%, (0.624±0.085) μg/L vs. (0.040±0.005) μg/L, (711±50) U/L vs. (96±11) U/L, (60±7) U/L vs. (22±4) U/L, t values were -17.92、-2.13、-104.63、-165.15、-57.43, respectively, all P<0.001; gelatin group: (51±4) s vs. (42±3) s, (100±16)% vs. (94±13)%, (0.631±0.113) μg/L vs. (0.041±0.004) μg/L, (717±52) U/L vs.(97±11) U/L, (62±7) U/L vs.(24±4) U/L, t values were -19.79、-3.09、-81.31、-157.70、-54.67, respectively, all P<0.001], while MA, MAf, FLEV, platelet count, PT and hemoglobin decreased [control group: (50±4) mmHg vs. (57±5) mmHg、(5.5±0.9) mmHg vs. (13.8±1.3) mmHg、(1.58±0.22) g/L vs.(2.64±0.31) g/L、(217±21)×10 9/L vs. (275±25)×10 9/L、(13.3±0.5) s vs.(14.7±0.8) s、(116±12) g/L vs.(127±17) g/L, t values were 14.79、61.26、32.25、20.58、17.21、6.09,respectively, all P<0.001; gelato group: (49±3) mmHg vs. (57±5) mmHg、(5.7±0.8) mmHg vs. (14.0±1.4) mmHg、(1.62±0.27) g/L vs.(2.59±0.26) g/L、(214±20)×10 9/L vs.(273±23)×10 9/L、(13.4±0.5) s vs.(14.7±0.8) s、(114±12) g/L vs.(128±17) g/L, t values were 16.34、62.05、29.51、22.77、14.91、7.41, respectively, all P<0.001], but the differences between groups were not statistically significant (all P>0.05). The difference of albumin, alanine aminotransferase, aspartate aminotransferase and creatinine before and after treatment were not statistically significant (all P>0.05). Conclusion:4% succinylated gelatin does not increase the risk of coagulation dysfunction during perioperative period in children with CCHD. It has small influence on liver-kidney function and has high safety.

[Objective]To explore the medication patterns of Zhejiang school of febrile diseases school in treating epidemic diseases through data mining in relevant articles in the Great Compendium of Febrile Diseases.[Methods]By reviewing TCM professional monographs and related literature with search terms such as"epidemic","plague"and"febrile disease",the monographs on the Zhejiang school of febrile disease and plague in the Great Compendium of Febrile Diseases were organized and summarized.Taking into account the regional climate and specific political and social factors in Zhejiang,the plague types were categorized.Using the R language platform(version 4.3.2),frequency statistics,classification statistics and systematic clustering analysis of Chinese medicine prescriptions were conducted.[Results]The study included a total of 14 monographs,and the selected prescriptions were obtained 84 in total,with 209 kinds of Chinese herbs.The plague types were categorized into wind-heat evil toxin syndrome,summer-dampness syndrome and lingering evil syndrome.Among them,there were 34 prescriptions for wind-heat evil toxin syndrome,26 for summer-dampness syndrome and 24 for lingering evil syndrome.In the classification of Chinese herbs,wind-heat evil toxin syndrome was mainly dominated by heat-clearing and exterior-releasing herbs,summer-dampness syndrome was mainly dominated by heat-clearing and diuretic and dampness-dispelling herbs,and lingering evil syndrome was most widely dominated by tonifying and heat-clearing herbs.Cluster analysis yielded a total of 8 core prescription groups,mainly focusing on heat-clearing herbs,diuretic and dampness-dispelling herbs,and tonifying herbs.[Conclusion]The treatment of plague by Zhejiang school of febrile disease is mostly combined with heat-clearing,dampness-percolating,deficiency-tonifying and exterior-releasing herbs.The wind-heat evil toxin syndrome is treated with pungent-cool and bitter-cold herbs to clear and relieve stagnated heat,combined with a small amount of pungent-warm herbs.In the summer-dampness syndrome,the three methods of promoting the upper-Jiao,unblocking the middle-Jiao and seeping the lower-Jiao are used to open and promote tri-Jiao,and aromatic herbs may also be combined to promote Qi movement and resolve dampness.In the case of the syndrome with lingering pathogenic factors,the therapeutic principle of clearing and dispersing to resolve and ventilate is adopted to expel the residual pathogenic factors.At the same time,the method of tonifying deficiency and promoting the production of body fluids is applied to support the healthy Qi,thereby achieving the effect of tonifying the healthy Qi and dispelling pathogenic factors These principles not only provide new methods for the clinical diagnosis and treatment of different types of plague,but also expand the ideas for subsequent medical research.

Most of the medical colleges and universities in China follow the traditional three-stage teaching mode centering on subjects, and a number of colleges and universities have implemented the teaching mode of organ-system-based curriculum (OSBC). With the OSBC course for the nervous system in our university as an example, this article analyzes the advantages and challenges of OSBC course of the nervous system in the context of integrative medicine.
Neurology