By tracing back to the classical literature of traditional Chinese medicine （TCM）， this paper proposes a TCM philosophy integrating "dao （道）-shen（神）-formula" as a unified whole. It systematically elaborates the formula-constructing thought that "the monarch drug follows dao， and the formula carries dao"， analyzes shen （spirit/ life vitality） from the perspectives of its substance， manifestation and function， and explains the pivotal role of shen in connecting dao and formula. Taking Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》） as an example， the paper explores how the "dao-shen-formula" union is implemented in classics. Based on the Inner Canon of Yellow Emperor （《黄帝内经》）， the paper articulates a practical pathway for the "dao-shen-formula" union， namely "observing shen to differentiate the mechanism → restoring dao to regulate shen → achieving harmony of shen and restoration of dao"， thereby transforming abstract concepts into operable and verifiable practical approaches. It is hoped that this study will provide theoretical foundation and practical guidance for the shift from treating diseases to treating the person， and from correcting deviations to restoring dao in TCM.

By tracing back to the classical literature of traditional Chinese medicine （TCM）， this paper proposes a TCM philosophy integrating "dao （道）-shen（神）-formula" as a unified whole. It systematically elaborates the formula-constructing thought that "the monarch drug follows dao， and the formula carries dao"， analyzes shen （spirit/ life vitality） from the perspectives of its substance， manifestation and function， and explains the pivotal role of shen in connecting dao and formula. Taking Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》） as an example， the paper explores how the "dao-shen-formula" union is implemented in classics. Based on the Inner Canon of Yellow Emperor （《黄帝内经》）， the paper articulates a practical pathway for the "dao-shen-formula" union， namely "observing shen to differentiate the mechanism → restoring dao to regulate shen → achieving harmony of shen and restoration of dao"， thereby transforming abstract concepts into operable and verifiable practical approaches. It is hoped that this study will provide theoretical foundation and practical guidance for the shift from treating diseases to treating the person， and from correcting deviations to restoring dao in TCM.

ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To compare the contents of malonyl-ginsenosides Rb3 （MG-Rb3） in different parts, including roots, stems, leaves and flowers, of Panax ginseng, P. quinquefolium and P. notoginseng and explore the effects of two drying methods, constant temperature drying and vacuum freeze drying on their contents. Methods The contents of MG-Rb3 in P. ginseng, P. quinquefolium and P. notoginseng were compared based on HPLC analysis, using enzymatically synthesized MG-Rb3 as the reference standard. Results The buds of P. ginseng and P. quinquefolium exhibited relatively high levels of MG-Rb3, which were approximately 7.3-18.1 times and 2.8-4.3 times higher than those found in the roots, respectively, and the lowest contents were detected in the stems. The content of MG-Rb3 in P. notoginseng flower buds was about 31.2 times higher than that in leaves. The content of MG-Rb3 in the buds treated by constant temperature drying was about 1-1.1 times that of using vacuum freeze drying. Conclusion The highest content of MG-Rb3 was detected in the flower buds of P. ginseng and P. notoginseng, and the content of MG-Rb3 in leaves of P. quinquefolium was the highest. Content of MG-Rb3 in the buds after constant temperature drying was slightly higher than that of using vacuum freeze drying.

Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

ObjectiveTo observe the clinical efficacy of modified Xiangsha Liujunzi Decoction （香砂六君子汤， XLD） in the treatment of abemaciclib-related diarrhea of spleen-stomach deficiency type， and its regulatory effect on immune function in patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative （HR+/HER2-） breast cancer. MethodsA prospective， randomized， open-label， blinded-endpoint （PROBE） study was conducted. A total of 70 patients with advanced HR+/HER2- breast cancer and abemaciclib-related diarrhea were randomly divided into two groups， with 35 cases in each group. In addition to abemaciclib， the control group was treated with oral loperamide， while the trial group was treated with oral modified XLD. Both groups received treatment for 7 days as one course. The efficacy for diarrhea after treatment was compared between groups. Traditional Chinese medicine （TCM） syndrome score， Karnofsky performance status （KPS） score， inflammatory markers including interleukin-6 （IL-6） and C-reactive protein （CRP）， and immune function indicators including CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio were compared between groups before and after treatment. Adverse events during the study were recorded， and safety was assessed. ResultsDuring the study， 1 case in the trial group and 2 cases in the control group， were lost to follow-up leaving 34 cases in the trial group and 33 cases in the control group for final analysis. The total effective rate of diarrhea in the trial group was 94.12% （32/34）， higher than 72.73% （24/33） in the control group （P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， increased KPS scores， increased CD4⁺， CD8⁺， and CD4⁺/CD8⁺ ratio， and decreased IL-6 and CRP levels （all P＜0.05）. Compared to the control group， the trial group had higher KPS scores， CD4⁺ levels， and CD4⁺/CD8⁺ ratios， and lower TCM syndrome scores and IL-6， CRP， and CD8⁺ levels （P＜0.05）. The incidence of adverse events in the trial group was 20.59% （7/34）， with an incidence of adverse drug reactions of 14.71% （5/34） after causality assessment； in the control group， the corresponding rates were 45.45% （15/33） and 39.39% （13/33）， respectively. The incidence of adverse events in the trial group was significantly lower than that in the control group （P＜0.05）. ConclusionModified XLD can effectively alleviate abemaciclib-related diarrhea in patients with advanced HR+/HER2- breast cancer of the spleen-stomach deficiency type， reduce levels of inflammatory cytokines， and regulate immune function， with a favorable safety profile.

Objective:To investigate the effects of propionic acid produced by Akkermansia muciniphila on the radiosensitivity of colorectal cancer and the underlying mechanism. Methods:Normal human colon mucosal epithelial cells (NCM460) were used to determine the appropriate concentration of propionic acid. Human colorectal cancer cells (HCT-8) were treated with A. muciniphila-conditioned medium or propionic acid, followed by exposure to 6 Gy γ-ray irradiation, and cell survival and proliferation were measured by clone formation assay and Cell Counting Kit-8 (CCK-8) assay, respectively. A mouse model of colorectal cancer was established using azoxymethane/dextran sodium sulfate. The mice were divided into control model group, irradiation group, and irradiation+ propionic acid group. Their body weight, colorectal length, tumor count, and tumor area were recorded. The radiosensitizing effect of propionic acid was assessed with HE staining, immunohistochemical staining, and enzyme-linked immunosorbent assay. The mechanism was explored by using RT-PCR and flow cytometry. Results:CCK-8 assay showed that 1-mmol/L propionic acid had no significant effect on the proliferation of NCM460 cells ( P>0.05), which was used for subsequent experiments. Pretreated with A. muciniphila-conditioned medium or propionic acid, the survival and proliferation abilities of irradiated HCT cells were significantly decreased ( t=3.14-34.98, P<0.05). Compared with the irradiation group, the colorectal cancer mice in the irradiation+ propionic acid group showed a significantly longer colorectal length ( t=3.50, P<0.05) and a significantly smaller number of tumors ( t=3.48, P<0.05); the two groups had significantly smaller tumor areas than the control model group ( t=5.97, 7.30, P<0.05). HE staining and immunohistochemical staining showed that propionic acid restored colorectal structure, and decreased Ki67 expression in colorectal tissue ( t=14.50, 3.40, P<0.05). Propionic acid treatment significantly reduced the levels of the inflammatory factors interleukin-6 and tumor necrosis factor-α, as compared with the mice receiving irradiation alone ( t=4.86, 5.06, P<0.05). Irradiation plus propionic acid treatment significantly increased p53 expression and significantly aggravated G 2/M phase block and cell apoptosis ( t=20.35, 13.05, P<0.05). Conclusions:The A. muciniphila metabolite propionic acid plays a sensitizing role in radiation therapy for colorectal cancer by promoting G 2/M phase block and apoptosis in colorectal cancer cells.

Objective To explore the predictive value of growth differentiation factor 15(GDF-15)for atrial fibrillation(AF)in patients with coronary heart disease(CHD).Methods A prospective observation cohort of 1261 elderly CHD patients was randomly sampled from the First Medical Center of Chinese PLA General Hospital from January 2012 to December 2015.ELISA was used to detect GDF-15 level in all the subjects,and their baseline data were collected.Until March 2023,93 patients were lost during the follow-up period,and finally 1168 patients completed the follow-up,with a median time of 9.4 years.According to AF occurred or not during the period,the eligible patients were divided into an AF group(197 cases)and a non-AF group(971 cases),and based on their medical history,also assigned into a stable angina pectoris(SAP,n=304)and an acute coronary syndrome group(ACS,n=864).Logistic regression analysis was used to determine whether GDF-15 is a risk factor for AF in elderly CHD patients.ROC curve was plotted to assess the predictive value of GDF-15,guideline recommended CHARGE-AF scoring model,and their combination for AF events in the patients.Results The AF group had significantly advanced age,larger proportions of smoking history,type 2 diabetes,hypertension,old myocardial infarction,stroke,ACS and administration of statins,higher ratio of angiotensin converting enzyme inhibi-tor/angiotensin receptor blocker,and elevated levels of GDF-15 and N-terminal pro-B-type natri-uretic peptide,and lower left ventricular ejection fraction,SAP incidence,and low-density lipopro-tein cholesterol,total cholesterol and triglycerides levels when compared with the non-AF group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that GDF-15 was not a risk factor for AF in elderly CHD patients(OR=0.92,95％CI:0.74-1.16,P=0.489),but was a risk factor for AF in SAP patients(OR=1.38,95％CI:1.07-2.79,P=0.015),and in ACS patients,still not a risk factor for AF(OR=0.81,95％CI:0.63-1.05,P=0.814).ROC curve analysis showed that the AUC value of GDF-15 combined with the CHARGE-AF scoring model in predic-ting AF was 0.682 in the elderly CHD patients,0.746 in the SAP patients,and 0.680 in the ACS patients.Conclusion Elevated GDF-15 level is an independent risk factor and predictor of AF in elderly SAP patients.In SAP patients,the combination of GDF-15 and CHARGE-AF scoring model further improves the predictive performance of AF occurrence.

Microplastics are widely present in various environments such as water bodies,land,and atmosphere,which pose threats to the ecological environment and human health through transmission and accumulation in the food chain.The existing detection techniques for microplastics face challenges such as complex preparation procedure of samples,low efficiency in processing large batches of samples,and difficulties in handling complex samples.Therefore,there is an urgent need for rapid and efficient detection techniques suitable for complex microplastics samples in the field of environmental monitoring.Raman spectroscopy,known for its advantages such as rapidity,accuracy,high sensitivity,non-destructiveness,and non-contact,demonstrates great application potential in detection of microplastics.Deep learning,an artificial intelligence method known for its large-scale data processing,nonlinear modeling and automatic feature extraction capabilities,is receiving increasing attention in the analysis of Raman spectroscopy signals.The application of deep learning-based Raman spectroscopy has significantly improved performance indicators such as detection efficiency and accuracy.This article introduced the existing Raman enhancement techniques,summarized the deep learning methods applied in Raman spectroscopy signal analysis,reviewed the recent research and application progress of deep learning-based Raman spectroscopy in detection of microplastics,and finally discussed the challenges and future prospects of deep learning-based Raman spectroscopy in detection of microplastics.