CCL2/CCR2 axis promotes perineural invasion of salivary adenoid cystic carcinoma via ITGß5-mediated nerve-tumor interaction.

Perineural invasion (PNI) is a notorious feature of salivary adenoid cystic carcinoma (SACC) and other neurotropic tumors. The pathogenesis of PNI that involves the molecular communication between the tumor and the suffered nerve is elusive. The in vitro co-culture assays of SACC cells with dorsal root ganglia (DRG) or neural cells showed that nerve-derived CCL2 activated CCR2 expression in SACC cells, promoting the proliferation, adhesion, migration, and invasion of SACC cells via the ERK1/2/ITGß5 pathway. Meanwhile, SACC-derived exosomes delivered ITGß5 to promote the neurite outgrowth of neural cells or DRG. Blocking of CCL2/CCR2 axis or ITGß5 inhibited the PNI of SACC cells in models in vitro by 3D co-culture of DRG with SACC cells and in vivo by xenografting SACC cells onto the murine sciatic nerve. High levels of ITGß5 in tissues or plasma exosomes were significantly correlated with CCL2 and CCR2 expression in the tissues and associated with PNI and poor prognosis of SACC cases. Our findings revealed a novel reciprocal loop between neural and tumor cells driven by the CCL2/CCR2 axis and exosomal ITGß5 during PNI of SACC. The present study may provide a prospective diagnostic and anti-PNI treatment strategy for SACC patients via targeting the nerve-tumor interactions.

Ratiometric fluorescent probe with AIE characteristics for hypochlorite detection and biological imaging.

It is very important and highly valuable to detect ClO- in samples and living cells with accuracy and speed. In this work, a novel fluorescent probe NA was prepared from 4-bromo-1,8-naphthalic anhydride by acylation reaction and Suzuki coupling reaction and used for the detection of ClO-. Thiomethyl serves as the recognition group for probe NA, while naphthalimide serves as fluorescent chromophore. The probe exhibited an extremely pronounced blue shift from yellow to blue fluorescence within 1 min after the addition of hypochlorite (ClO-). The probe demonstrates high sensitivity to ClO- with a limit of detection (LOD) of 1.22 µM. Also, probe NA demonstrates excellent selectivity and immunity to interference. Additionally, simple fluorescent test strips containing probe NA were prepared in this study, enabling rapid detection of ClO- in water samples. And NA had been effectively used to image endogenous and exogenous ClO-fluorescence in living cells. The results suggest that probe NA has significant potential for portable detection and biological applications.

Chemogenetic Evolution of Diversified Photoenzymes for Enantioselective [2 + 2] Cycloadditions in Whole Cells.

Artificial photoenzymes with novel catalytic modes not found in nature are in high demand; yet, they also present significant challenges in the field of biocatalysis. In this study, a chemogenetic modification strategy is developed to facilitate the rapid diversification of photoenzymes. This strategy integrates site-specific chemical conjugation of various artificial photosensitizers into natural protein cavities and the iterative mutagenesis in cell lysates. Through rounds of directed evolution, prominent visible-light-activatable photoenzyme variants were developed, featuring a thioxanthone chromophore. They successfully enabled the enantioselective [2 + 2] photocycloaddition of 2-carboxamide indoles, a class of UV-sensitive substrates that are traditionally challenging for known photoenzymes. Furthermore, the versatility of this photoenzyme is demonstrated in enantioselective whole-cell photobiocatalysis, enabling the efficient synthesis of enantioenriched cyclobutane-fused indoline tetracycles. These findings significantly expand the photophysical properties of artificial photoenzymes, a critical factor in enhancing their potential for harnessing excited-state reactivity in stereoselective transformations.

RGIE: A Gene Selection Method Related to Radiotherapy Resistance in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant tumor with a high degree of malignancy, invasiveness, and metastasis rate. Radiotherapy, as an important adjuvant therapy for HNSCC, can reduce the postoperative recurrence rate and improve the survival rate. Identifying the genes related to HNSCC radiotherapy resistance (HNSCC-RR) is helpful in the search for potential therapeutic targets. However, identifying radiotherapy resistance-related genes from tens of thousands of genes is a challenging task. While interactions between genes are important for elucidating complex biological processes, the large number of genes makes the computation of gene interactions infeasible. METHODS: We propose a gene selection algorithm, RGIE, which is based on ReliefF, Gene Network Inference with Ensemble of Trees (GENIE3) and Feature Elimination. ReliefF was used to select a feature subset that is discriminative for HNSCC-RR, GENIE3 constructed a gene regulatory network based on this subset to analyze the regulatory relationship among genes, and feature elimination was used to remove redundant and noisy features. RESULTS: Nine genes (SPAG1, FIGN, NUBPL, CHMP5, TCF7L2, COQ10B, BSDC1, ZFPM1, GRPEL1) were identified and used to identify HNSCC-RR, which achieved performances of 0.9730, 0.9679, 0.9767, and 0.9885 in terms of accuracy, precision, recall, and AUC, respectively. Finally, qRT-PCR validated the differential expression of the nine signature genes in cell lines (SCC9, SCC9-RR). CONCLUSION: RGIE is effective in screening genes related to HNSCC-RR. This approach may help guide clinical treatment modalities for patients and develop potential treatments.

SALL4 promotes cancer stem-like cell phenotype and radioresistance in oral squamous cell carcinomas via methyltransferase-like 3-mediated m6A modification.

Radioresistance imposes a great challenge in reducing tumor recurrence and improving the clinical prognosis of individuals having oral squamous cell carcinoma (OSCC). OSCC harbors a subpopulation of CD44(+) cells that exhibit cancer stem-like cell (CSC) characteristics are involved in malignant tumor phenotype and radioresistance. Nevertheless, the underlying molecular mechanisms in CD44( + )-OSCC remain unclear. The current investigation demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in CD44(+) cells and promotes CSCs phenotype. Using RNA-sequencing analysis, we further showed that Spalt-like transcription factor 4 (SALL4) is involved in the maintenance of CSCs properties. Furthermore, the overexpression of SALL4 in CD44( + )-OSCC cells caused radioresistance in vitro and in vivo. In contrast, silencing SALL4 sensitized OSCC cells to radiation therapy (RT). Mechanistically, we illustrated that SALL4 is a direct downstream transcriptional regulation target of METTL3, the transcription activation of SALL4 promotes the nuclear transport of ß-catenin and the expression of downstream target genes after radiation therapy, there by activates the Wnt/ß-catenin pathway, effectively enhancing the CSCs phenotype and causing radioresistance. Herein, this study indicates that the METTL3/SALL4 axis promotes the CSCs phenotype and resistance to radiation in OSCC via the Wnt/ß-catenin signaling pathway, and provides a potential therapeutic target to eliminate radioresistant OSCC.

Synthesis and application of hypochlorite ratiometric fluorescence probe based on cellulose.

Cellulose is the most abundant natural polymer with good biocompatibility and easy modification characteristics. In this paper, a novel cellulose fluorescence probe CNS for detecting ClO- was prepared by modifying microcrystalline cellulose (MCC). The fluorescence detection results indicate that CNS exhibits a highly specific "ratiometric" and "colorimetric" fluorescence response to ClO-. In the presence of ClO-, the fluorescence color changes from green to cyan. In addition, the color of the solution changes from yellow to colorless, which can be observed with the "naked eye". Considering the good selectivity and anti-interference ability of CNS, the probe can be used for the detection of ClO- in real water samples. Importantly, CNS composite films and test papers were prepared and showed practicability in the detection of ClO-, highlighting its broad application potentials.

Metabolome and transcriptome analyses identify the characteristics and expression of related saponins of the three genealogical plants of bead ginseng.

Objective: The classification and clinical usage of the different species of bead ginseng are often confused. Therefore, we conducted an integrated metabolomics and transcriptome analysis of three main species of Panax, including Panax japonicas, Panax pseudoginseng, and Panax pseudo-ginseng var. elegantior. Methods: A broad metabolome and transcriptome analysis for three origins of bead ginseng plants was performed using UPLC-ESI-MS/MS, RNA sequencing and annotation, and bioinformatic analysis of transcriptome data. Results: The levels of 830 metabolites were determined. A total of 291 differentially accumulated metabolites (DAMs) between Panax pseudo-ginseng var. elegantior and Panax japonicas (Group A), with 73 upregulated and 218 downregulated. A total of 331 DAMs (110 upregulated and 221 downregulated) were found between Panax pseudoginseng and Panax japonicas (group B). There were 160 DAMs (102 up-regulated and 58 down-regulated) between Panax pseudoginseng and Panax pseudo-ginseng var. elegantior (group C). In addition, RNA sequencing was performed in the above three ways. A total of 16,074 differential expression genes (DEGs) were detected between Group A, in which 7,723 genes were upregulated and 8,351 genes were downregulated by RNA sequencing. Similarly, 15,705 genes were differentially expressed between group B, in which 7,436 genes were upregulated and 8,269 genes were downregulated. However, only 1,294 genes were differentially expressed between group C, in which 531 genes were upregulated and 763 genes were downregulated. We performed differential gene analysis on three groups of samples according to the Venn diagram and found that 181 differential genes were present. A total of 3,698 and 2,834 unique genes were in groups A and B, while 130 unique genes were in group C. Conclusions: This study provides metabolome and transcriptome information for three bead ginseng plants. The analysis of the metabolite content showed differences in the attributes of the three bead ginseng, contained mainly flavonoids, phenolic acids as well as terpenes.

Neural network-based model for evaluating inert nodules and volume doubling time in T1 lung adenocarcinoma: a nested case-control study.

Objective: The purpose of this study is to establish model for assessing inert nodules predicting nodule volume-doubling. Methods: A total of 201 patients with T1 lung adenocarcinoma were analysed retrospectively pulmonary nodule information was predicted by an AI pulmonary nodule auxiliary diagnosis system. The nodules were classified into two groups: inert nodules (volume-doubling time (VDT)>600 days n=152) noninert nodules (VDT<600 days n=49). Then taking the clinical imaging features obtained at the first examination as predictive variables the inert nodule judgement model >(INM) volume-doubling time estimation model (VDTM) were constructed based on a deep learning-based neural network. The performance of the INM was evaluated by the area under the curve (AUC) obtained from receiver operating characteristic (ROC) analysis the performance of the VDTM was evaluated by R2(determination coefficient). Results: The accuracy of the INM in the training and testing cohorts was 81.13% and 77.50%, respectively. The AUC of the INM in the training and testing cohorts was 0.7707 (95% CI 0.6779-0.8636) and 0.7700 (95% CI 0.5988-0.9412), respectively. The INM was effective in identifying inert pulmonary nodules; additionally, the R2 of the VDTM in the training cohort was 0.8008, and that in the testing cohort was 0.6268. The VDTM showed moderate performance in estimating the VDT, which can provide some reference during a patients' first examination and consultation. Conclusion: The INM and the VDTM based on deep learning can help radiologists and clinicians distinguish among inert nodules and predict the nodule volume-doubling time to accurately treat patients with pulmonary nodules.

SEpi-3D: soft epipolar 3D shape measurement with an event camera for multipath elimination.

Multipath in 3D imaging happens when one pixel receives light from multiple reflections, which causes errors in the measured point cloud. In this paper, we propose the soft epipolar 3D(SEpi-3D) method to eliminate multipath in temporal space with an event camera and a laser projector. Specifically, we align the projector and event camera row onto the same epipolar plane with stereo rectification; we capture event flow synchronized with the projector frame to construct a mapping relationship between event timestamp and projector pixel; we develop a multipath eliminating method that utilizes the temporal information from the event data together with the epipolar geometry. Experiments show that the RMSE decreases by 6.55mm on average in the tested multipath scenes, and the percentage of error points decreases by 7.04%.

The development of radioresistant oral squamous carcinoma cell lines and identification of radiotherapy-related biomarkers.

BACKGROUND: In the treatment of oral squamous cell carcinoma (OSCC), radiation resistance remains an important obstacle to patient outcomes. Progress in understanding the molecular mechanisms of radioresistance has been limited by research models that do not fully recapitulate the biological features of solid tumors. In this study, we aimed to develop novel in vitro models to investigate the underlying basis of radioresistance in OSCC and to identify novel biomarkers. METHODS: Parental OSCC cells (SCC9 and CAL27) were repeatedly exposed to ionizing radiation to develop isogenic radioresistant cell lines. We characterized the phenotypic differences between the parental and radioresistant cell lines. RNA sequencing was used to identify differentially expressed genes (DEGs), and bioinformatics analysis identified candidate molecules that may be related to OSCC radiotherapy. RESULTS: Two isogenic radioresistant cell lines for OSCC were successfully established. The radioresistant cells displayed a radioresistant phenotype when compared to the parental cells. Two hundred and sixty DEGs were co-expressed in SCC9-RR and CAL27-RR, and thirty-eight DEGs were upregulated or downregulated in both cell lines. The associations between the overall survival (OS) of OSCC patients and the identified genes were analyzed using data from the Cancer Genome Atlas (TCGA) database. A total of six candidate genes (KCNJ2, CLEC18C, P3H3, PIK3R3, SERPINE1, and TMC8) were closely associated with prognosis. CONCLUSION: This study demonstrated the utility of constructing isogenic cell models to investigate the molecular changes associated with radioresistance. Six genes were identified based on the data from the radioresistant cells that may be potential targets in the treatment of OSCC.

The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial-to-mesenchymal transition.

BACKGROUND: Perineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve-derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC. METHODS: Immunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH-SY5Y cells were co-cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI-specific therapeutic effects by blocking the GAL/GALR2 axis. RESULTS: GAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p < 0.05). Nerve-derived GAL activated GALR2 expression in SACC cells and induced epithelial-to-mesenchymal transition (EMT) in SACC cells. Adding human recombinant GAL to the co-culture system promoted the proliferation, migration, and invasion of SACC cells significantly, but inhibited the apoptosis of SACC cells. Adding M871, a specific antagonist of GALR2, significantly blocked the above effects (p < 0.05) and inhibited the PNI of SACC cells in vitro and in vivo (p < 0.05). CONCLUSIONS: This study demonstrated that nerve-derived GAL activated GALR2 expression, and promoted EMT in SACC cells, thereby enhancing the PNI process. Interruption of the GAL/GALR2 axis might be a novel strategy for anti-PNI therapy for SACC.

Construction of a combined hypoxia and EMT index for head and neck squamous cell carcinoma.

Objectives: In head and neck squamous cell carcinoma (HNSCC), the interaction between epithelial-mesenchymal transformation (EMT) and hypoxia has been confirmed, and corresponding treatment methods have been investigated. Few studies have examined its combined effects and its potential clinical use, however. As a result, we developed a new scoring system based on EMT and hypoxia. Methods: We combined 200 hypoxia-related genes with 1184 EMT-related genes and finally constructed a score risk model containing 14 characteristic factors named the comprehensive index of EMT and hypoxia (CIEH) by the Lasso-Cox regression and univariate Cox regression method, which is used to predict prognosis and to guide treatment planning in HNSCC patients. Furthermore, we examined HNSCC expression of CIEH-related genes using the human protein atlas database. Results: Based on survival analysis results, CIEH value had a high prognostic value in HNSCC patients, a high CIEH value carries a poor prognostic significance in HNSCC. It is noteworthy that the CIEH value was correlated with tumor immune infiltration. Moreover, the CIEH had significant differences in age, stage, N, laterality, and peripheral nerve invasion, and that the CIEH could be an independent prognostic factor. Conclusions: This study constructed a CIEH model containing 14 characteristic factors, including hypoxia-related genes and EMT genes, that may be able to serve as potential biomarkers for HNSCC. According to the 14 characteristic factors in the CIEH model, a diagnostic kit can be packaged in the future to evaluate the survival of patients before tumor surgery and guide the subsequent treatment plan.

Children tongue leiomyosarcoma: A rare case and literature review.

Primary leiomyosarcoma of the tongue is a rare malignant mesenchymal tumor with high recurrence rate and metastatic potential. Through analysis of one case condition and literature review, this paper discusses the clinical characteristics and treatment methods and recommends that expanded resection surgery should be the first intervention. Postoperative adjuvant radiotherapy and combined chemotherapy should be administered if the case specifically requires such an approach.

Melanotic neuroectodermal tumor of infancy: Case report and literature review.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare benign tumor. Here, we report the diagnosis and treatment of 1 case of MNTI in the maxilla and discuss its clinical and pathological features, imaging features, treatment, and prognosis.

Nomogram predicting long-term overall and cancer-specific survival of patients with buccal mucosa cancer.

BACKGROUND: Few models about the personalized prognosis evaluation of buccal mucosa cancer (BMC) patients were reported. We aimed to establish predictive models to forecast the prognosis of BMC patients. METHODS: The complete clinicopathological information of BMC patients from the surveillance, epidemiology and end results program was collected and reviewed retrospectively. Two nomograms were established and validated to predict long-term overall survival (OS) and cancer-specific survival (CSS) of BMC patients based on multivariate Cox regression survival analysis. RESULTS: 1155 patients were included. 693 and 462 patients were distributed into modeling and validation groups with 6:4 split-ratio via a random split-sample method. Based on the survival analysis, independent prognostic risk factors (variables that can be used to estimate disease recovery and relapse chance) influencing OS and CSS were obtained to establish nomograms. Then, we divided the modeling group into high- and low-risk cohorts. The low-risk cohort had improved OS and CSS compared to the high-risk cohort, which was statistically significant after the Log-rank test (p < 0.05). Furthermore, we used the concordance index (C-index), calibration curve to validate the nomograms, showing high accuracy. The decision curve analyses (DCA) revealed that the nomograms had evident clinical value. CONCLUSIONS: We constructed two credible nomogram models, which would give the surgeons reference to provide an individualized assessment of BMC patients.

An animal experiment study on the application of indocyanine green angiography in the harvest of multi-angiosome perforator flap.

Background: This study sought to explore the application value of indocyanine green angiography (ICGA) in the harvest of multi-angiosome perforator flap and the effect of low molecular weight heparin (LMWH) on the survival of postoperative flap. Methods: Twenty-four SD male rats were selected to construct a three-angiosome perforator flap model with the unilateral iliolumbar artery perforator. They were randomly divided into two groups: the control group was injected with indocyanine green (ICG) into the femoral vein during the operation, and the fluorescence signal was collected and quantitatively analyzed using Real-Time Image Guided System to determine the intraoperative fluorescence imaging length. The experimental group was injected subcutaneously with LMWH (400 U/kg) after 0.5 h postoperatively, and the control group was injected with the same amount of normal saline. The injection was repeated at the same time each day from 0 to 7 days postoperatively. After the flap was sutured in situ, ICGA was performed at 0, 1, 3, 5, and 7 days postoperatively to observe the vascular structure of the two groups of flaps. The flap survival length of the control group was counted at 7 days postoperatively, and the correlation between the intraoperative fluorescence imaging length and the survival length at 7 days postoperatively was calculated. The proportion of distal necrosis of the flaps between the two groups was compared at 7 days postoperatively. Results: The average length of intraoperative fluorescence imaging in the control group was 6.29±0.50 cm, and the survival length of the flap at 7 days postoperatively was 8.24±0.52 cm. The actual survival length was higher than the intraoperative fluorescence imaging length, with a ratio of 1.31±0.08. The difference was statistically significant (P<0.05). At 7 days postoperatively, the flap necrosis ratio of experimental group and control group were 10.92%±1.30% and 19.11%±1.19%, and the flap necrosis ratio of experimental group was lower than that of control group (P<0.001). Conclusions: ICGA can locate the position of perforator, and can be used to predict and observe the length of distal survival of multi-angiosome perforator flap postoperatively. LMWH can promote the distal survival of flap and reduce flap necrosis.

LINC01123 promotes immune escape by sponging miR-214-3p to regulate B7-H3 in head and neck squamous-cell carcinoma.

Numerous studies have shown that long noncoding RNAs (LncRNAs) are involved in the development and immune escape of head and neck squamous-cell carcinoma (HNSCC). However, the specific regulatory mechanisms by which LINC01123 regulates HNSCC and its correlation with immunity remain unclear. Therefore, this study's primary purpose was to explore the mechanisms by which LINC01123 regulates the immune escape and progression of HNSCC. This study confirmed that LINC01123 is competitively bound to miR-214-3p, and miR-214-3p specifically targets B7-H3. The effects of LINC01123, B7-H3, and miR-214-3p on tumor progression, CD8+T-cell-mediated immune response, and the tumorigenicity of HNSCC in vitro and in vivo were examined through the downregulation or upregulation of LINC01123, B7-H3, and miR-214-3p. Our results indicated that LINC01123 and B7-H3 were highly expressed in HNSCC and are associated with poor prognosis in patients. Notably, overexpression of LINC01123 or B7-H3 or downregulation of miR-214-3p inhibited the function of CD8+T cells and promoted the progression of HNSCC. Therefore, LINC01123 acts as a miR-214-3p sponge to inhibit the activation of CD8+T cells and promote the progression of HNSCC by upregulating B7-H3.

Inhibition of TRPA1 Attenuates Oxidative Stress-induced Damage After Traumatic Brain Injury via the ERK/AKT Signaling Pathway.

Neuron apoptosis is a feature of secondary injury after traumatic brain injury (TBI). Evidence implies that excess calcium (Ca2+) ions and reactive oxidative species (ROS) play critical roles in apoptosis. In reaction to increased ROS, the anti-oxidative master transcription factor, Transient receptor potential Ankyrin 1 (TRPA1) allows Ca2+ ions to enter cells. However, the effect of TBI on the expression of TRPA1 and the role of TRPA1 in TBI are unclear. In the present study, TBI in the mouse brain was simulated using the weight-drop model. The process of neuronal oxidative stress was simulated in HT22 neuronal cells by treatment with hydrogen peroxide. We found that TRPA1 was significantly upregulated in neurons at 24 h after TBI. Neuronal apoptosis was increased in the in vivo and in vitro models; however, this increase was reduced by the functional inhibition of TRPA1 in both models. After TBI, TRPA1 was upregulated via nuclear factor, erythroid 2 like 2 (Nrf2) in neurons. TRPA1-mediated neuronal apoptosis after TBI might be achieved in part through the CaMKII/AKT/ERK signaling pathway. To sum up, TBI-triggered TRPA1 upregulation in neurons is mediated by Nrf2 and the functional blockade of TRPA1 attenuates neuronal apoptosis and improves neuronal dysfunction, partially mediated through the activation of the calcium/calmodulin dependent protein kinase II (CaMKII) extracellular regulated kinase (ERK)/protein kinase B (AKT) signaling pathway. Our results suggest that functional blockade of TRPA1 might be a promising therapeutic intervention related to ROS and Nrf2 in TBI.

Prediction of active ingredients in Salvia miltiorrhiza Bunge. based on soil elements and artificial neural network.

The roots of Salvia miltiorrhiza Bunge. are commonly used in the treatment of cardiovascular diseases, and tanshinones and salvianolic acids are its main active ingredients. However, the composition and content of active ingredients of S. miltiorrhiza planted in different regions of the soil environment are also quite different, which adds new difficulties to the large-scale and standardization of artificial cultivation. Therefore, in this study, we measured the active ingredients in the roots of S. miltiorrhiza and the contents of rhizosphere soil elements from 25 production areas in eight provinces in China, and used the data to develop a prediction model based on BP (back propagation) neural network. The results showed that the active ingredients had different degrees of correlation with soil macronutrients and trace elements, the prediction model had the best performance (MSE = 0.0203, 0.0164; R2 = 0.93, 0.94). The artificial neural network model was shown to be a method that can be used to screen the suitable cultivation sites and proper fertilization. It can also be used to optimize the fertilizer application at specific sites. It also suggested that soil testing formula fertilization should be carried out for medicinal plants like S. miltiorrhiza, which is grown in multiple origins, rather than promoting the use of "special fertilizer" on a large scale. Therefore, the model is helpful for efficient, rational, and scientific guidance of fertilization management in the cultivation of S. miltiorrhiza.