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.

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.

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.

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 (Q_m) 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* ; Static Electricity ; Humans ; Sepharose/analogs & derivatives* ; Peptides/chemistry* ; Adsorption ; Antibodies/isolation & purification*

Mid-to-late stage ankle arthritis is a chronic degenerative disease that is extremely common in clinical practice.It is characterized by significant cartilage degeneration and subchondral bone sclerosis,accompanied by the formation of osteophytes around the joint,often leading to joint deformity.This condition causes severe pain in the patients during walking,severely restricts their activities,and affects their qualities of life.In recent years,with the continuous improvement of medical standards,the treatment methods for mid-to-late stage ankle arthritis have shown a diversified development trend.Non-surgical treatments primarily include activity restriction,orthotic devices,oral non-steroidal anti-inflammatory drugs(NSAIDs),and intra-articular injections of the talocrural joint.The surgical treatments primarily include joint distraction arthroplasty,periacetabular osteotomy,total ankle arthroplasty,and ankle arthrodesis.Tissue engineering therapy,as an emerging method,has also received considerable attention.This article systematically reviewed the selection principles and research progress of various treatment options for mid-to-late stage ankle arthritis,including traditional treatments,non-surgical treatments,surgical treatments,and tissue engineering treatments.By deeply analyzing the basic principles and advantages and disadvantages of each treatment method,and combining the latest research findings on clinical outcomes,a scientific and comprehensive clinical decision-making reference system was constructed to provide clearer and more comprehensive treatment choices for both doctors and patients,thereby effectively improving treatment outcomes and enhancing the quality of life for the patients.

Objective To investigate the organ protective role and the underlying mechanism of nafamostat mesylate(NM)in a renal ischemia-reperfusion injury(RIRI)model.Methods A total of 21 healthy male Sprague-Dawley(SD)rats were randomly assigned to 3 groups(n=7 in each group),including the sham operation group(Sham group),the RIRI group,and the NM intervention group(NM group).The RIRI and NM groups underwent ischemia-reperfusion injury(IRI)modeling.The NM group was given an intraperitoneal injection of NM at 0.75 mg/kg before modeling.Venous blood and renal tissue samples were then collected from the rats 24 hours after modeling.The levels of serum creatinine,cystatin C,and serum inflammatory factors were determined using the serum samples.Hematoxylin-eosin(HE)staining and TUNEL stainings were performed on the renal tissues to evaluate the damage of the renal tissues.The localization and expression of HMGB1 were analyzed by immunofluorescence and Western blotting,respectively.Single-cell RNA sequencing of the nuclei was performed to obtain the single-cell transcriptome of the kidneys from the rats in the RIRI and the NM groups and to acquire the RIRI cell profile.The cells were annotated according to the cell marker genes to explore the cell type composition in the disease model and the functional status of immune cells between the groups.Results 1)Compared with those of the Sham group,the levels of cystatin C,creatinine,and inflammatory factors in the RIRI and NM groups were significantly increased,and the expression levels in the NM group were lower than those in the RIRI group(P＜0.05).Compared with those of the RIRI group,the tubular injury score and apoptosis rate in the NM group were significantly decreased(P＜0.05),but those of both the NM and RIRI groups were higher than those of the sham group.Compared with that in the RIRI group,the expression of HMGB1 in the NM group was significantly decreased(P＜0.05),but the expression levels in both the RIRI and NM groups were higher than that in the sham group.Immunofluorescence showed that there was increased cytoplasmic expression of HMGB1 in both the NM and RIRI groups,with the increase being more prominent in the RIRI group.2)A total of 13 major cell populations were identified through the single-nucleus sequencing results.The proportion of tubular cells in the NM group was higher,with the HMGB1 gene being highly expressed in the damaged proximal convoluted tubular cells.The proportion of the polarized Macro3 cell subpopulation in the macrophages in the NM group was lower compared to that in the RIRI group.Conclusion NM may play a protective role in a rat model of RIRI,and its underlying mechanisms may be related to the regulation of the functional abnormalities of HMGB1-mediated macrophages.

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

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.

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.

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 (P < 0.001). There were no serious adverse events or side effects during treatment in all the patients. Conclusion Red and blue lights therapy combined with Yufa Shengfa solution and 5% minoxidil solution is an effective non-surgical treatment for Ludwig type Ⅰ female androgenetic alopecia.