1.Development status and ethical challenges of artificial intelligence in traditional Chinese medicine
Jiaqing DAI ; Yuxuan JIANG ; Jingnan HU ; Liu YANG ; Lifang GUO
Chinese Medical Ethics 2025;38(2):173-178
In the context of the rapid development of 5G technology, the development of artificial intelligence (AI) in traditional Chinese medicine (TCM) faces new opportunities and challenges. Focusing on how to uphold tradition while innovating in the development of AI in TCM, starting from the current development status of AI in Chinese medicine, including the integration of four diagnostic methods, syndrome differentiation and treatment, auxiliary diagnosis and treatment, research and development of Chinese herbal medicine, prevention and treatment of diseases, knowledge inheritance, and other aspects, this paper discussed the support of policies and technical advancements, as well as development opportunities such as increased demand for health. Regarding machine ethics, data ethics, regulatory review, and other aspects, it also proposed some suggestions that the training algorithm should be improved to assist medical work; data ownership should be clarified to ensure data security; and an AI ethics committee should be set up to improve the review system, aiming to maximize the advantages of smart healthcare and accelerate the modernization of TCM for the benefit of patients and the service of human health.
2.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
3.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
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.
4.An electrostatically coupled polypeptide affinity multimodal chromatography medium for the purification of antibodies and their separation efficiency.
Yuxuan CHENG ; Liuyang WANG ; Kaixuan JIANG ; Songping ZHANG ; Hongbo YAN ; Jian LUO
Chinese Journal of Biotechnology 2025;41(8):3262-3274
As the need for antibody production rises, there is an urgent need to lower the costs and enhance the efficiency of the separation process. Currently, the chromatographic media used for antibody separation and purification often focus on individual properties of antibodies, such as affinity, hydrophobicity, and charge, leading to issues like low purification efficiency or inadequate adsorption capacity. To address this, an electrostatically coupled polypeptide affinity medium (FD7-3, 5-diaminobenzoic acid n-sepharose, FD7-DA-Sepharose) was developed for rapid purification of antibodies from cell culture supernatant. This medium utilized 3, 5-diaminobenzoic acid as a spacer to attach the heptapeptide-affinity ligand (FYEILHD, FD7) to agarose microspheres. Antibodies could be adsorbed through charge interactions with the carboxyl functional group of the FD7-DA-Sepharose spacer, while FD7 enhanced electrostatic coupling and affinity adsorption through synergistic effects, significantly increasing the adsorption capacity while maintaining the affinity and specificity. The influences of pH and ionic strength on adsorption capacity were investigated with human immunoglobulin as a model protein. The static adsorption capacity (Qm) of FD7-DA-Sepharose in the solution of pH 6.0 reached 67.73 mg/mL, representing a 52.68% increase compared with that (44.36 mg/mL) of the commercial Protein A affinity medium. Furthermore, the elution conditions for FD7-DA- Sepharose were mild (20 mmol/L PB, 0.5 mol/L NaCl, pH 6.0), in contrast to the harsh acidic elution (pH 2.7-3.6) typically associated with Protein A, which can damage antibody integrity. The FD7-DA-Sepharose medium was then employed to purify antibodies from cell culture supernatant, achieving the yield of 94.8% and the purity of 98.4%. The secondary structure of the purified antibody was determined by circular dichroism spectroscopy. The results demonstrated that FD7-DA-Sepharose enabled efficient purification of antibodies from cell culture supernatant, which provided a cost-effective solution (approximately one-third the price of commercial Protein A affinity medium) with gentle elution conditions that preserve the natural conformation of antibodies. This approach paves a novel, economical, and efficient way for the separation and purification of antibodies from cell culture supernatant.
Chromatography, Affinity/methods*
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Static Electricity
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Humans
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Sepharose/analogs & derivatives*
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Peptides/chemistry*
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Adsorption
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Antibodies/isolation & purification*
5.Efficacy of red and blue lights combined with Yufa Shengfa solution and 5% minoxidil solution in treating type Ⅰ female androgenetic alopecia
Chenlei DAI ; Jun LIU ; Xiaoming SUN ; Jinghui YANG ; Jiang MA ; Yuxuan WANG ; Juping CHEN
Journal of Clinical Medicine in Practice 2024;28(24):10-14
Objective To investigate the efficacy of red and blue lights combined with Yufa Shengfa solution and 5% minoxidil solution in treating Ludwig type Ⅰ female androgenetic alopecia. Methods A total of 160 patients with Ludwig type Ⅰ female androgenetic alopecia were randomly divided into group A (Yufa Shengfa solution combined with 5% minoxidil solution), group B (red and blue lights therapy combined with Yufa Shengfa solution), group C (red and blue lights therapy combined with 5% minoxidil solution) and group D (red and blue lights therapy combined with Yufa Shengfa solution and 5% minoxidil solution), with 40 cases in each group. All the patients orally took compound glycyrrhizin tablets and Centrum multivitamins, and the therapeutic period was 3 months. Differences in hair diameter, hair density, and the number of hair follicles with multiple hairs were compared before and after treatment. Results The hair density, hair diameter, and the number of hair follicles with multiple hairs improved significantly in 4 groups compared with those before treatment, and group D showed the best improvement in these parameters, with significant between-group differences (
6.Improvement effect and mechanism of Shuhou tongqi formula on intestinal injury in mice with postoperative ileus
Yuxuan LU ; Zhiwei JIANG ; Yijun XIE ; Yizhu WANG ; Jingwen HA ; Yachun SHU
China Pharmacy 2024;35(17):2108-2113
OBJECTIVE To study the improvement effect and mechanism of Shuhou tongqi formula on intestinal injury in mice with postoperative ileus (POI). METHODS Mice were randomly divided into sham operation group, model group, positive control group (Mosapride citrate tablets, 1.95 mg/kg), and Shuhou tongqi formula group (1.88 g/kg), with 6 mice in each group. Except for the sham operation group, POI model was induced in other groups by typical small intestinal interference. Each group was given relevant drug liquid/water, once a day, for consecutive 2 days. After the last medication, the percentage of carbon powder propulsion in small intestine was detected, and pathomorphological changes in ileum tissue of mice were observed. The serum levels of interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α), motilin (MTL) and somatostatin (SS) were all detected; the expression levels of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB p65) and p38 mitogen-activated protein kinase (p38 MAPK) were determined in ileal tissue of mice; the gut microbiota of colon contents was analyzed in each group of mice. RESULTS After the intervention of Shuhou tongqi formula, pathological damage such as intestinal wall atrophy and mucosal capillary congestion in ileum tissue were improved significantly; the percentage of carbon powder propulsion and the serum level of IL-10 and MTL were increased significantly (P<0.05); however, serum levels of TNF-α, IL-6 and SS, the expressions of TLR4, NF-κB p65 and p38 MAPK were decreased significantly (P<0.05). The analysis of gut microbiota showed that Shuhou tongqi formula could significantly increase ACE, Chao1, Shannon and PD indexes, and relative abundance of Akkermansia (P<0.05), but decreased relative abundance of Proteobacteria, Ligilactobacillus and Escherichia-Shigella significantly (P<0.05). CONCLUSIONS Shuhou tongqi formula can improve intestinal injury and inflammatory reaction of POI mice, the mechanism of which may be associated with inhibiting the activity of TLR4/ NF-κB/MAPK signaling pathway, regulating the levels of gastrointestinal hormones and improving the disturbance of intestinal flora in mice. E-mail:1643589936@qq.com
7.The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.
Xiaoxuan ZHONG ; Xiang WEI ; Yan XU ; Xuehai ZHU ; Bo HUO ; Xian GUO ; Gaoke FENG ; Zihao ZHANG ; Xin FENG ; Zemin FANG ; Yuxuan LUO ; Xin YI ; Ding-Sheng JIANG
Acta Pharmaceutica Sinica B 2024;14(2):712-728
Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
8.Chaihu Shugansan and Its Modified Formulas in Treatment of Functional Dyspepsia: A Review
Wei ZHAO ; Yaxi ZHANG ; Yuxuan JIANG ; Jiaqing DAI ; Lifang GUO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):248-255
Chaihu Shugansan composed of Bupleuri Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, Aurantii Fructus, Citri Reticulatae Pericarpium, Cyperi Rhizoma, and Glycyrrhizae Radix et Rhizoma has the effects of soothing liver, relieving depression, regulating Qi movement, and relieving pain. It is a classic formula for treating gastric distension recommended by doctors of later ages. This article systematically reviews the clinical application and basic experimental progress of Chaihu Shugansan in the treatment of functional dyspepsia. In modern clinical practice, Chaihu Shugansan and its modified formulas are used to treat functional dyspepsia, and they can be applied in combination with other formulas (Si Junzitang, Jinlingzisan, Zhizhuwan, etc.), western medicine (domperidone tablets, deanxit, Saccharomyces boulardii, etc.), traditional Chinese medicine (TCM) acupuncture and other therapies. The results of clinical studies have shown that Chaihu Shugansan and its modified formulas can significantly reduce the Hamilton depression scale (HAMD) score, Hamilton anxiety scale (HAMA) score, and TCM syndrome score, ameliorate the symptoms, improve the quality of life, and decrease the recurrence rate. The experimental pharmacological studies have demonstrated that Chaihu Shugansan can inhibit the autophagy of Cajal interstitial cells, regulate the endoplasmic reticulum stress signaling pathway, and modulate the brain-gut peptide level to improve the gastrointestinal motility. Chaihu Shugansan can inhibit the expression of 5-hydroxytryptamine in the colon tissue and reduce the abdominal withdrawal reflex (AWR) score to improve visceral hypersensitivity. Furthermore, Chaihu Shugansan can lower the levels of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α to repair duodenal mucosal inflammation. In addition, it can regulate intestinal flora to maintain intestinal flora balance. The main active ingredients such as saikosaponin, paeoniflorin, hesperidin, and naringin in Chaihu Shugansan can exert anti-inflammatory, antioxidant, and antimicrobial effects.
9.Statistical analysis of disability-adjusted life years for stomach and colorectal cancers in Changning District of Shanghai
Jing WU ; Lei ZHANG ; Yu JIANG ; Dandan TANG ; Yuxuan XIAO ; Yun ZHANG ; Honglan LI ; Wensui ZHAO ; Qinghua XIA ; Yongbing XIANG
Chinese Journal of Oncology 2024;46(2):168-176
Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P<0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P>0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P<0.05) and females showing a downward trend (AAPC=-1.67%, P<0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.
10.Decoding the Molecular Mechanisms of BRAFV600E-Induced Nevi Formation
Liang WEIZHENG ; Liu YUXUAN ; Xu DANDAN ; Jiang WENJIE ; Ran RENSEN
Biomedical and Environmental Sciences 2024;37(7):774-784
Melanocytes derived from neural crest cells harbor the BRAFV600E mutation,which is the predominant driver of nevus formation in humans.This mutation leads to malignant cell proliferation and subsequent cell cycle arrest,culminating in oncogene-induced senescence and nevus development.Nevertheless,emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAFV600E-induced senescent melanocytes.Moreover,the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAFV600E,via the mitogen-activated protein kinase signaling pathway,triggers nevus formation.This study provides an overview and discussion of the molecular mechanisms underpinning BRAFV600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation.It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAFV600E animal models created through gene editing technologies.


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