Pharmaceutical solid form engineering through co-crystallization represents a transformative strategy for enhancing drug bioavailability and physicochemical properties, yet remains hindered by labor-intensive experimental screening and the notable absence of computational models capable of simultaneously classifying co-crystals, salts, and physical mixtures. Here, we present an intelligent multi-modal graph neural network (GNN) framework that synergistically integrates molecular graph representations, molecular fingerprints, and quantum chemical descriptors to enable automated three-class classification of pharmaceutical solid forms, addressing a critical gap in current computational pharmaceutical research. Our innovative feature fusion strategy combines topological molecular graphs with traditional molecular fingerprints and computationally-derived quantum chemical properties, creating a comprehensive multi-dimensional representation of pharmaceutical compounds. The developed integrated model achieves exceptional classification accuracy exceeding 98 % across all evaluation phases, demonstrating the superior performance of combined structural, topological, and electronic feature representations in complex multi-component pharmaceutical systems. Rigorous validation using three independent active pharmaceutical ingredient datasets, theophylline, ligustrazine, and piperazine, yields outstanding success rates, confirming the model's remarkable generalizability and practical applicability across diverse chemical spaces. Most significantly, our artificial intelligence (AI)-driven multi-modal predictions successfully guided the experimental synthesis of two novel co-crystalline phases: Emodin-ligustrazine and emodin-metformin, validating the predictive power of integrated molecular feature representations in real-world pharmaceutical development.

Hyperlipidemia is closely linked to abnormal dietary lipid absorption, and pancreatic lipase (PL) is a key target for inhibiting intestinal lipid hydrolysis. Thus, the efficient discovery of PL inhibitors is crucial for treating the disease. However, existing recognition techniques suffer from false positives and disconnection from subsequent separation, hindering the exploration of natural product active components. This study developed an online high-performance liquid chromatography-fluorescence detection (HPLC-FLD) recognition system. It enables real-time mixing of chromatographic eluents with PL solution, forming protein-ligand complexes that yield characteristic negative peaks due to their lower fluorescence, thus enabling rapid localization of PL-binding components at corresponding retention times. Validation with orlistat as a reference standard confirmed the system's high precision, stability, and specificity. When applied to the crude extract of Sinacalia tangutica, this system recognized 15 active chromatographic peaks in a single analysis. Combined with an activity-guided progressive separation strategy, 16 compounds were obtained and exhibited PL inhibitory activity in vitro enzymatic assays. The therapeutic potential of phlorizin, one of inhibitors identified by our recognition system, was evaluated in hyperlipidemic mice. High-dose phlorizin lowered serum total cholesterol (TC) by 46.3% and triglyceride (TG) by 66.3%, reduced pancreatic PL content by 52.4%, raised fecal TG by 65.7%, alleviated hepatic steatosis and oxidative stress, with efficacy near orlistat. This integrated strategy of online recognition with activity-guided separation provides an efficient solution for the discovery of natural PL inhibitors with therapeutic potential.

4-Methylumbelliferone (4-MU) is used clinically to treat conditions such as biliary dyskinesia, inflammation, autoimmune diseases, cancer, and other conditions. However, 4-MU suffers from poor solubility, low permeability, and suboptimal bioavailability, which limit its pharmacological activity and clinical application. Cocrystallization technology, as an effective method for improving physicochemical properties of drugs, offers a viable approach to address these issues with 4-MU. In this study, four cocrystal formers (CCFs) with druggable potential, namely nicotinamide (NAM), isonicotinamide (INA), theophylline (TP), and piperazine (PPZ), were selected for cocrystallization experiments with 4-MU, leading to the successful preparation of four novel cocrystals: 4-MU-NAM (1:1), 4-MU-INA (1:1), 4-MU-TP (1:1), and 4-MU-PPZ (2:1). Cocrystals were characterized using single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and infrared spectroscopy (IR). Solubility, permeability, and bioavailability were also evaluated for each cocrystal. In vitro results demonstrated that all four cocrystals improved the physicochemical properties of 4-MU, specifically: 4-MU-PPZ increased the water solubility of 4-MU to six times that of the parent drug, enhanced permeability to three times that of the parent drug, and significantly accelerated the drug's permeation rate. In vivo results indicated that 4-MU-TP effectively increased the bioavailability of 4-MU. Unlike traditional 4-MU structural modification methods, cocrystal engineering offers significant advantages of environmental friendliness and operational simplicity. This study effectively improved the key pharmaceutical properties of 4-MU through cocrystal technology, providing a new research direction and technical support for enhancing its druggability and promoting its application in more disease treatment fields.

In the pharmaceutical field, machine learning can play an important role in drug development, production and treatment. Co-crystallization techniques have shown promising potential to enhance the properties of active pharmaceutical ingredients (APIs) such as solubility, permeability, and bioavailability, all without altering their chemical structure. This approach opens new avenues for developing natural products into effective drugs, especially those previously challenging in formulation. Emodin, an anthraquinone-based natural product, is a notable example due to its diverse biological activities; however, its physicochemical limitations, such as poor solubility and easy sublimation, restricted its clinical application. While various methods have improved emodin's physicochemical properties, research on its bioavailability remains limited. In our study, we summarize cocrystals and salts produced through co-crystallization technology and identify piperazine as a favorable coformer. Conflicting conclusions from computational chemistry and molecular modeling method and machine learning method regarding the formation of an emodin-piperazine cocrystal or salt led us to experimentally validate these possibilities. Ultimately, we successfully obtained the emodin-piperazine cocrystal, which were characterized and evaluated by several in vitro methods and pharmacokinetic studies. In addition, experiments have shown that emodin has a certain therapeutic effect on sepsis, so we also evaluated emodin-piperazine biological activity in a sepsis model. The results demonstrate that co-crystallization significantly enhances emodin's solubility, permeability, and bioavailability. Pharmacodynamic studies indicate that the emodin-piperazine cocrystal improves sepsis symptoms and provides protective effects against liver and kidney damage associated with sepsis. This study offers renewed hope for natural products with broad biological activities yet hindered by physicochemical limitations by advancing co-crystallization as a viable development approach.

N-acyl amino acids (N-acyl AAs) are potential bioactive compounds in fermented soybean (FS), but their accurate annotation is challenging due to their structural diversity, the existence of various isomers and wide polarity differences. Herein, we established a novel One-pot Micro Synthesis-Chemical Derivatization (OMSCD)-LC-MS analytical approach for comprehensive profiling of N-acyl AAs. First, the rapid synthesis of 142 N-acyl AA standards combined with in situ DIAAA derivatization in a one-pot manner significantly enhanced ionization and separation efficiency, particularly enabling excellent discrimination of isomers. Next, using this method, 222 N-acyl AAs were rapidly identified in FS, of which 200 were reported for the first time. Among them, N-oleoyl AAs, present at high contents in FS, demonstrated significant anti-liver cancer activity in a cell model, with MAPK1 acting as a promising candidate target. Overall, the OMSCD-LC-MS strategy facilitates the N-acyl AAs profiling, offering new preliminary insights into the functional components of FS.

Oxicam-based non-steroidal anti-inflammatory drugs, including piroxicam and tenoxicam, are known to exhibit tautomerism between zwitterionic and molecular forms. Specifically, tenoxicam in cocrystal exists solely as zwitterions, while piroxicam cocrystals contain both tautomeric forms. A pivotal structural feature is that the zwitterionic cocrystals of these oxicams display a well-predictable "XYYX" tetrameric spatial arrangement, and this specific configuration has been found to be closely associated with their solubility properties. Temozolomide, a novel alkylating agent and first-line drug for malignant gliomas (pKa 14.77), has drawn significant interest for its stability. Through liquid-assisted grinding and rotary evaporation, 1:1 drug cocrystals of temozolomide with the two oxicams were successfully prepared. Comprehensive characterization analyses demonstrated that the oxicam in these newly formed cocrystals maintained the zwitterionic form; however, the characteristic "XYYX" arrangement was absent. This absence of the "XYYX" structure is considered a key factor contributing to the only marginal improvement in solubility observed. It is important to note that the stability of temozolomide shows a positive correlation with the strength and degree of hydrogen bonding interactions involving its amide groups. Additionally, the prepared cocrystals were confirmed to enhance the pharmacokinetic parameters of temozolomide, thereby providing essential foundational data for further related research endeavors.

The structural differences between Gefitinib (GFN) and its positional isomers, specifically N-(2-Fluoro-3-chlorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine (ISOGFN), appear minimal on a twodimensional level. Despite their similar crystallization packing styles, the physical and chemical properties of the two solid states differ significantly, obstructing the development of the isomer into pharmaceutical drugs. Can cocrystallization with an identical ligand bridge this gap? In this study, we first prepared crystal of the GFN positional isomer. We then synthesized two distinct salts of GFN and its isomer using fumaric acid (FA, pKa:3.03) as the ligand, comparing the physicochemical properties of these samples. X-ray diffraction was conducted to characterize these crystals, alongside vibrational spectrum and thermal analysis. Additionally, their dissolution and permeability properties were evaluated to identify and summarize similarities and differences. Theoretical computational studies, including crystal packing similarity, proton transfer, Gibbs free energy, and interaction energy, were employed to elucidate the differences in properties from the structural and energy perspectives. The results indicated that introducing FA diminished the differences in properties between GFN and its positional isomer, especially in terms of solubility, permeability, thermostability, and packing similarity. For the isomer, its improvement in permeability after salt formation, which overcomes its shortcoming, providing a valuable reference for isomer drug research and development.

Emodin (EMO) shows therapeutic promise for ulcerative colitis (UC), yet its clinical utility is hampered by low bioavailability. To rationally overcome this limitation, this study employed cocrystal engineering, strategically selecting tetramethylpyrazine (TMP)—a natural compound from traditional Chinese medicine—as the cocrystal coformer (CCF). The selection of TMP was guided by a systematic CCF screening strategy, incorporating extensive literature analysis of natural compound CCF candidates, computational chemistry methods to predict favorable hydrogen-bonding interactions and interaction sites with EMO, and machine learning assessment of cocrystallization propensity. Utilizing this rational design approach, we successfully synthesized and characterized a novel EMO-TMP cocrystal through comprehensive solid-state characterization techniques. The resulting cocrystal significantly enhanced the aqueous solubility of EMO while preserving its intrinsic bioactivity. Pharmacokinetic studies confirmed that the cocrystal formulation markedly improved the oral bioavailability of EMO. In a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model, the EMO-TMP cocrystal demonstrated superior efficacy compared to EMO alone, effectively alleviating colitis symptoms and associated pathological markers. This enhanced in vivo efficacy is attributed to the significantly improved systemic exposure achieved through the rationally designed cocrystal. Our findings establish the EMO-TMP cocrystal as a highly promising strategy to surmount the physicochemical barriers of EMO, unlocking its full clinical potential for UC treatment. Critically, this work not only validates TMP as an efficient and safe CCF specifically suited for active pharmaceutical ingredients (APIs) rich in hydrogen-bond donors, but also exemplifies the value of leveraging formulation principles and compatible components inherent in traditional Chinese medicine through advanced crystal engineering approaches.

Background Luspatercept, approved by the FDA and EMA for patients with transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS) unresponsive to erythropoiesis-stimulating agents (ESAs), lacks extensive real-world data, particularly in China.Methods We retrospectively analyzed 14 LR-MDS-SF3B1 patients treated with luspatercept for ≥12 weeks.Results Median age was 60 years (range 47-72); 42.9% were male. Before treatment, 78.6% were transfusion-dependent, and 42.9% had prior ESA therapy. At median 24-week follow-up (range 12-44), erythroid response rates were 71.43% (week 12), 75.00% (week 16), and 62.50% (week 24). Hemoglobin levels significantly improved at weeks 12 and 24 (P = 0.013, P = 0.005). No grade 3-4 adverse events occurred. Hematologic improvement-erythroid (HI-E) patients exhibited higher white blood cells, neutrophils, and reticulocytes at week 12 versus non-HI-E patients. Bone marrow analysis revealed erythroid hyperplasia in HI-E patients, with higher erythrocyte percentage (56.00% vs. 34.00%, P = 0.023), lower myeloid-to-erythroid ratio (0.60 vs. 1.59, P = 0.024), and increased polychromatic erythroblasts (19.50% vs. 10.00%, P = 0.034).Conclusions Luspatercept demonstrated efficacy and safety in Chinese LR-MDSSF3B1 patients. Greater erythroid hyperplasia correlated with better clinical response.

Mosapride (Mosa) is an active pharmaceutical ingredient commonly used for the treatment of gastroesophageal reflux disease. The purpose of this study is to investigate the possibility of discovering novel solid forms of Mosa that may arise during the process of drug product development, and subsequently analyze their structure. Five forms are obtained here: one is Mosa monohydrate, which has been reported before, and four are new forms (Mosa anhydrate, Mosa methanol hydrate (1:1:1), Mosa ethanol hydrate (1:1:1), and Mosa DMSO solvate (1:1)). The phase composition of the forms was analyzed by powder X-ray diffraction, thermal analysis, and FTIR analysis. The crystal structures of all five forms were successfully solved using single-crystal X-ray diffraction. To investigate the characteristics of five forms, a combination of X-ray crystallography, 13C solid-state nuclear magnetic resonance, molecular electrostatic potential surface, and Hirshfeld surface analysis methods were employed. It's demonstrated that the conformation of Mosa was changed due to the introduction of solvates. The water molecules play vital roles in the formation of Mosa solvates. The presence of water during the preparation process can result in different forms. Furthermore, DVS data demonstrate that the stability of Mosa solvates was significantly impacted by relative humidity.

The phase transition among different solid forms of active pharmaceutical ingredients can significantly influence their physicochemical properties, potentially leading to clinical safety risks. However, phase transition mechanisms remain under explored, especially in multi-component drugs. Here we report a novel ciprofloxacin-diclofenac salt system and investigate phase transitions among its anhydrate, dihydrate, and methanol solvate forms. The study focused on the influence of water activity and solvent vapor conditions, elucidating the role of guest molecules in driving these transitions. These findings offer new insights into polymorphic phase transitions, advancing our understanding of stability and performance in pharmaceutical formulations.

The green and sustainable production of pharmaceuticals has always been a concern, and mechanochemistry as an effective means of green chemistry can reduce the use of solvents and the environmental hazards of intermediates in drug production. Ligustrazine, also known as 2,3,5,6-tetramethylpyrazine (TMP), is an effective drug for the treatment of cardiovascular and cerebrovascular diseases, but it tends to sublimate under ambient conditions, is unstable under light conditions, and is highly hygroscopic. The cocrystallization technique is an effective method to improve its stability. In this paper, four cocrystals, namely, TMP-MG (1.5:2), TMP-MG-H2O (2.5:1:1), TMP-EG (1:1), and TMP-PG (1:1), were obtained by mechanochemical and cocrystallization techniques, and the stability and hygroscopicity were studied. Characterization and structural analysis were carried out using different techniques. It showed that four new cocrystals showed significantly higher hygroscopicity and improved stability under strong light. In addition, interconversion between TMP-MG and TMP-MG-H2O was found by mechanochemical methods. Cocrystallization combined with mechanochemical technique as a simple and effective green method provides strong support for the improvement of pharmaceutical properties and sustainable production.

Review Research and Prospects on the Evaluation of Drug Cocrystal Permeability Shuang Li 1, Meiru Liu 1, Dezhi Yang 1,*, Li Zhang 1,*, Yang Lu 1,* and Guanhua Du 2 1 Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China 2 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China * Correspondence: ydz@imm.ac.cn (D.Y.); zhangl@imm.ac.cn (L.Z.); luy@imm.ac.cn (Y.L.) Received: 29 August 2024; Revised: 14 October 2024; Accepted: 15 October 2024; Published: 24 February 2025 Abstract: In developing new drugs, drug permeability assessment is crucial. Lead compounds exhibiting inadequate permeability often produce low bioavailability, rendering them inappropriate as drugs. The cocrystallization technique is a valuable tool for optimizing the physical and chemical properties of active pharmaceutical ingredients (APIs) and enhancing drug properties. This technique involves the introduction and weak interaction with cocrystal formers to produce supramolecular substances without altering the chemical structure of APIs, effectively improving their solubility and permeability and thereby significantly increasing their bioavailability. Consequently, drug cocrystal research has become a focal point for researchers in drug development. This study provides a comprehensive overview of four commonly employed methods for evaluating drug permeability and summarizes the applicability of each method to provide a reference for improving and refining the permeability evaluation method of drug cocrystals.

Metal-organic frameworks (MOFs) have emerged as a highly versatile class of porous materials with significant potential to advance pharmaceutical research. This review provides a comprehensive overview of the current landscape of MOFs, encompassing their synthesis strategies, characterization methodologies, and diverse biomedical applications. We detail various synthesis approaches (e.g., hydrothermal, electrochemical, microwave) and essential characterization techniques (e.g., X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area analysis) that are critical for developing well-defined MOF structures. The review highlights the key advantages of MOFs in drug delivery, including their exceptional drug loading capacity, good biocompatibility, and capabilities for sustained, controlled, and targeted release. Their applications in improving drug solubility and stability, enabling pulmonary delivery, and functioning in biosensing, antimicrobial therapy, and nucleic acid delivery are also extensively discussed. Furthermore, we explore the utility of MOFs in drug structure analysis and the development of advanced functional systems, such as stimuli-responsive and self-propelled MOFs. Despite promising preclinical progress, challenges related to scalability, reproducibility, and long-term biosafety remain to be addressed for successful clinical translation. This work aims to bridge the gap between MOF materials science and pharmaceutical applications, offering valuable insights for the rational design of next-generation drug delivery systems and therapeutic platforms.

In this study, crystal engineering was employed to enhance the solubility and druggability of Chrysin (CHR). Four nitrogen heterocyclic compounds, including piperazine (PIP), 4,4 '-bipyridine (BIP), imidazole (IMI), and sophoridine (SOP), were investigated using computational screening methodologies. Screening experiments were conducted to validate the computational screening results, and four CHR crystals were successfully prepared, three of which were reported for the first time. The structures of these cocrystals were characterized by using single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD), and thermal analysis. The spatial structure, arrangement, interactions, and associations were analyzed. Additionally, physical stability, apparent solubility, and biological evaluation were performed to assess those cocrystals. Finally, the CHR-SOP cocrystal shows a significant improvement in solubility and dissolution rate, making it a promising candidate for further study.

Old individuals are at a high risk of developing aplastic anemia, and immunosuppressive therapy (IST) based on anti-human T-lymphocyte immunoglobulin (ATG) and cyclosporine (CsA) is recommended for treating severe aplastic anemia (SAA). Adding the thrombopoietin receptor agonist (TPO-RA) to IST could improve hematologic responses in patients with SAA; however, limited data exist for elder patients. Here, we report on the efficacy and prognostic factors associated with porcine ATG and CsA with or without TPO-RA as first-line therapy in elderly patients with SAA. Porcine ATG was administered intravenously at a dose of 20 mg/kg/d for 5 days. CsA was administered orally, maintaining plasma trough concentrations of 150–250 µg/L. Eltrombopag was administered at a dose of 75–150 mg/day, and hetrombopag was administered orally at a dose of 15 mg/day. One hundred and twenty-eight SAA patients, with a median age of 63 (60–73) years old, were included in this study, including 44 very severe aplastic anemia (VSAA) patients. All patients completed the porcine ATG treatment, and mild serum sicknesses were observed. Ten patients (2 SAA patients and 8 VSAA patients) died within 3 months of ATG initiation (early death), with severe infections being the main cause of death. Sixty-nine patients achieved a hematologic response at 6 months, with an overall response (OR) rate of 53.9

Structural isomers are critical analytes in the biological and chemical arenas. Despite the ability of tandem mass spectrometry to provide fragment ion information, their high structural similarity impedes confident identification. To address this, we developed a novel method leveraging energy-resolved mass spectrometry (ER-MS) of fragment ions generated by electron activation dissociation (EAD). EAD initiated rapid radical chain dissociation via electron excitation and removal mechanisms, delivering superior isomer discrimination compared to conventional collision-induced dissociation (CID). Subsequent energy-resolved analysis further enhanced the distinction by integrating these dissociation mechanisms. Our strategy employed a cosine-based multidimensional spectral similarity algorithm to visualize and quantify subtle spectral differences across multiple energies. This method successfully distinguished many types of isomers, such as linkage, composition, and conformation isomers in disaccharides and flavonoid glycosides and achieved 93.8% top-1 identification accuracy against an in-house library. When applied to pomelo peel and commercial beverages for key metabolite characterization, it provided 44.4-50.0% top-1 annotation accuracy across all detected interest features. These results demonstrate that the multidimensional similarity algorithm that combines EAD and ER-MS significantly advances the depth and accuracy of compound annotation.

Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.

To our best knowledge, acacetin has great potential for market development and clinical application due to its various pharmacological effects including antioxidant, anti-inflammatory, anti-cancer, neuroprotective, hepatoprotective, cardioprotective and so on. However, low solubility and poor bioavailability overshadow its prospect for new drug development and application. In order to optimize the solubility of acacetin, a scientific and reasonable cocrystal design was launched. In this study, the cocrystal of acacetin-4,4 '-bipyridine and acacetin-2,2 '-bipyridine were successfully prepared and systematically characterized by single-crystal X-ray diffraction, powder X-ray diffraction, fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. With the efforts of structural analysis and theoretical calculation, it was found that the two formed cocrystals including acacetin-4,4 '-bipyridine and acacetin-2,2 '-bipyridine possessed significant distinctions in terms of the type of space group and crystal system, the lattice arrangement as well as the forces and hydrogen bonds connections involved in the generation of cocrystals. By the evaluation of stability and dissolution, the results indicated that two cocrystals could keep stable under high temperature, high humidity as well as light condition and significant enhancement in the solubility and dissolution rate of acacetin were achieved by the formation of two new cocrystals which might be contributed to the increase of its bioavailability. This study was of significance to not only investigate the differences of two cocrystals in the aspects of space group, lattice arrangement, intermolecular force and thermodynamic stability, but also provided a new approach to optimize the solubility of acacetin.

A randomized, controlled clinical trial was conducted from 2022 to 2023 at a hospital specializing in Traditional Chinese Medicine in Shanghai. A total of 564 participants were allocated into control and intervention groups in order to determine the effectiveness of Shujing Tongdu massage on patients with chronic lesions or spinal disorders. No significant differences were observed in baseline characteristics between the groups; age, gender and condition type were all distributed in a comparable manner. Following the implementation of Shujing Tongdu massage therapy twice weekly for the duration of 12 weeks, intervention group exhibited noteworthy enhancements. Significantly, rate of lesion healing achieved in the intervention group increased by 30%, while it merely improved by 10% in the control group. The intervention group exhibited decrease in pain intensity from 6.5 to 4.2, whereas control group demonstrated comparatively smaller reduction from 6.7 to 6.0. Range of motion in the intervention group increased substantially from 45 to 60 degrees, whereas it increased from 44 to 46 degrees in the control group. In the intervention group, Quality of Life scores increased from 50 to 75, exceeding the increase of 58 in the control group. There was significant rise in the Mental Well-being Index for intervention group, from 60 to 80, in contrast to rise of 64 from 62 in the control group. Statistically significant outcomes were determined, establishing the massage therapy's efficacy. Mild discomfort and muscle soreness were the most frequent adverse effects in the intervention group, whereas vertigo was more prevalent in the control group. Based on the findings of this research, Shujing Tongdu massage therapy effectively promoted wound healing and mitigated symptoms associated with spinal disorders, indicating its potential as the supplementary therapeutic modality in clinical environments.