ObjectiveTo establish an animal model of atrial fibrillation（AF） that accurately reflects the phlegm-heat and blood stasis（TRYZ） pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups：the control group， the TRYZ+AF group，the AF group and the TRYZ group， with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide（LPS） injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride（Ach-CaCl₂） via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration， echocardiography evaluated left atrial dimensions and cardiac function， fully automated biochemical analyzer measured the levels of total cholesterol（TC）， triglycerides（TG）， high-density lipoprotein cholesterol（HDL-C） and low-density lipoprotein cholesterol（LDL-C）， hemoreometer analyzed the whole blood viscosity， plasma viscosity， and whole blood reduced viscosity， a coagulation analyzer assessed prothrombin time（PT）， activated partial thromboplastin time（APTT）， thrombin time（TT）， and fibrinogen（FIB）， enzyme-linked immunosorbent assay（ELISA） was used to determine the levels of C-reactive protein（CRP）， interleukin（IL）-1β， IL-6， IL-17， tumour necrosis factor（TNF）-α， matrix metalloproteinase-9（MMP-9）， galectin-3（Gal-3）， Collagen Ⅰ， and α-smooth muscle actin（α-SMA）. Hematoxylin-eosin（HE） staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium， Western blot was employed to detect MMP-9， Collagen Ⅰ and α-SMA protein expression in myocardial tissue， real-time quantitative polymerase chain reaction（Real-time PCR） evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight， tongue color［red（R）， green（G）， and blue（B）］， and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling， compared with the control group， rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight， dry faeces， elevated rectal temperature， dark red tongue， decreased RGB values on the tongue surface， and markedly elevated TC and LDL-C levels（P<0.05， P<0.01）. The TRYZ+AF， TRYZ， and AF groups exhibited significantly decreased TT， APTT and PT， along with markedly elevated whole blood viscosity and FIB（P<0.05， P<0.01）. Rats in the TRYZ+AF and AF groups exhibited AF rhythm， markedly decreased heart rate， prolonged RR intervals， enlarged left atrium， and significantly reduced ejection fraction and shortening fraction（P<0.05， P<0.01）. Serum levels of CRP， IL-1β， IL-6， IL-17， TNF-α， MMP-9， Gal-3， Collagen Ⅰ， and α-SMA were elevated in rats from the TRYZ+AF， TRYZ， and AF groups compared to the control group， with the most pronounced increase observed in the TRYZ+AF group（P<0.05， P<0.01）. Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF， TRYZ and AF groups was higher than that in the control group（P<0.05， P<0.01）. Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9， Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups（P<0.05， P<0.01）. Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group， primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome， demonstrating the pathological process where the interactions of phlegm， heat and stasis jointly trigger tremor， this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Huachansu (Cinobufacini) is active extract isolated from the dry skin of Bufo Bufo gargarizans. It has now been widely used in clinical treatment of cancer, this study is to clarify the material basis of down-regulation of thymidylate synthase (TYMS) induced by Huachansu. METHODS: Our study utilized UPLC-MS/MS to identify major bioactive components from Huachansu. Cell Counting Kit 8 (CCK-8) assay and clone formation assay were used to examine the cell viability of tumor cells. TYMS and γ-H2AX level were detected by using quantitative real-time RT-PCR and/or western blotting. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of TYMS could enhance the suppressive effect of Huachansu on cell growth of HCC cells. RESULTS: In our study, firstly, we identify 21 major bioactive components from Huachansu. CCK-8 assay results showed that Huachansu and its bioactive bufadienolides (Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin) significantly inhibited the proliferation of HepG2 and SK-HEP-1 cells in a dose- and time-dependent manner. Further molecular mechanistic investigation demonstrates that Huachansu significantly suppresses thymidylate synthase (TYMS), the enzyme which provides the sole de novo source of thymidylate for DNA synthesis. The inhibition of TYMS could lead to cell-cycle block and DNA damage of HCC cells. Furthermore, we identified that Huachansu markedly increased γ-H2AX expression, which indicated the presence of DNA damage. Moreover, we confirmed that transfection of cells with small interfering RNA specific to TYMS could increase the suppressive effects of Huachansu on the HCC cells proliferation. Quantitative RT-PCR analysis showed that Huachansu treatment had no effect on the transcription level of TYMS. Furthermore, proteasomal inhibitor MG132 could block TYMS inhibition induced by Huachansu, and concomitant administration of protein synthesis inhibitor cycloheximide (CHX) with Huachansu could further suppress the protein level of TYMS, indicating that Huachansu promotes proteasome-dependent degradation of TYMS in liver cancer cells. More importantly, the bioactive bufadienolides of Huachansu such as Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin could also significantly restrain the protein level of TYMS, revealing the material basis of inhibition of TYMS exposed to Huachansu. 5-Fluorouracil (5-FU) is a TYMS inhibitor, we also evaluate the effects of the combined treatment of Huachansu with 5-FU, the results show that interactions between Huachansu and 5-FU are synergistic or antagonistic. Thus, in clinical, attention should be paid to the dosage of Huachansu in combination with 5-FU. CONCLUSION Huachansu inhibits the growth and induces DNA damage of human HCC cells through proteasome-dependent degradation of TYMS, bioactive bufadienolides are the material basis of down-regulation of TYMS induced by Huachansu.

Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans ; Sleep Initiation and Maintenance Disorders/blood* ; Aged ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Middle Aged ; Tumor Necrosis Factor-alpha/blood* ; Sleep Aids, Pharmaceutical/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Interleukin-6/blood* ; Interleukin-1beta/blood* ; Neurotransmitter Agents/blood* ; Aged, 80 and over ; C-Reactive Protein/metabolism*

Objective Based on the Ancient and Modern Medical Case Cloud Platform V2.3.7,analyze the medication pattern and mechanism of action of Chinese medicines commonly used in famous medical cases for the treatment of Alzheimer's disease(AD).Methods The core Chinese medicines for AD were screened according to the inclusion and exclusion criteria by searching the famous Chinese medicine cases in the platform,then established the disease-core Chinese medicines-active ingredients-common targets network.The protein-protein interaction network(PPI)was established through the common targets.Gene oncology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed by David platform.Molecular docking and dynamics simulations were employed to evaluate the binding affinity and stability between key targets and active ingredients.Results Data mining was performed on all the famous medical cases from the time of database construction to October 2023,and the results were summarized as follows.The high-frequency regulating Qi medications and tonifying Qi medications were Citri Reticulatae Pericarpium and Aurantii Fructus Immaturus;Panax ginseng,Ziziphi Jujubae Fructus,Codonopsis pilosula,Astragali Radix,Atractylodis Macrocephalae Rhizoma,Dioscoreae Rhizoma,and Glycyrrhizae Radix et Rhizoma.The core herbs contained 778 active ingredients and 377 targets;1986 disease targets;79 common targets were obtained after intersection with AD targets,and 7 core targets were identified through PPI network topology analysis,including TNF,AKT1,TP53,PPARG,etc.GO and KEGG pathway enrichment analyses confirmed that the targets of the active ingredients of the core herbs involved 138 pathways,and the core herbs could regulate chemical carcinogenesis-receptor activation、serotonergic synapse、chemical carcinogenesis-reactive oxygen species pathways to treat AD.Molecular docking and molecular dynamics simulation results showed good binding ability and stability between the key targets and the core components.Conclusion Through data mining to analyze the core herbs for the treatment of AD,the present investigation showing the pharmacological mechanism of 12-O-Nicotinoylisolineolone and Odoratin in the treatment of Alzheimer's disease at the molecular level,lay a certain theoretical foundation of 12-O-Nicotinoylisolineolone and Odoratin in the future.

Objective:To compare the impact of the AlignRT-based optical guidance method with the traditional marker line method on the accuracy of positioning, and explore the effect of patient′s different thoracic characteristic parameters on the precision of optical guidance positioning.Methods:A total of sixty breast cancer patients who received post breast-conserving radiotherapy at Anhui Cancer Hospital from July 2022 to September 2023 were retrospectively selected. Then these patients were equally divided into traditional cross hairs set-up (marker line group) and surface-guided set-up (SGRT group). The cone-beam CT scanning results were used as the gold standard, the three-dimensional set-up errors and the CTV-PTV target area external radiotherapy boundaries of two groups were studied comparatively. Multiple patient′s thoracic characteristic parameters were defined and the correction between each parameter and set-up error of SGRT was analyzed.Results:The mean value of three-dimensional set-up errors in the SGRT group and the marker line group was within 0.2 cm and 0.5 cm, respectively. The differences in three-dimensional set-up errors and total displacements between two groups were statistically significant ( z=-2.93, -3.21, -2.59, -4.76, P<0.05). The SGRT group reduced the CTV-PTV boundary from 0.5 cm of conventional marker line group to 0.3 cm. The thoracic aspect ratio H/W, the affected side pinch angle α1, and the healthy side pinch angle α2 were positively correlated with the x-direction posing error ( r=0.49, 0.59, 0.71, P<0.05); whereas, the affected side and the healthy side mammary gland heights D1 and D2 were negatively correlated with the z-direction posing error ( r=-0.46, -0.49, P<0.05). Conclusions:For breast-conserving postoperative radiotherapy patients, SGRT can obtain a more accurate radiotherapy set-up than the traditional marker line method, and can effectively reduce the target area externally expanded range. Meanwhile, the monitoring accuracy of SGRT is affected by the patient′s thoracic characteristic parameters, and clinical attention should be paid to breast-conserving radiotherapy patients with thick body shape, narrow body width, and small breast glands.

Objective:To compare the impact of the AlignRT-based optical guidance method with the traditional marker line method on the accuracy of positioning, and explore the effect of patient′s different thoracic characteristic parameters on the precision of optical guidance positioning.Methods:A total of sixty breast cancer patients who received post breast-conserving radiotherapy at Anhui Cancer Hospital from July 2022 to September 2023 were retrospectively selected. Then these patients were equally divided into traditional cross hairs set-up (marker line group) and surface-guided set-up (SGRT group). The cone-beam CT scanning results were used as the gold standard, the three-dimensional set-up errors and the CTV-PTV target area external radiotherapy boundaries of two groups were studied comparatively. Multiple patient′s thoracic characteristic parameters were defined and the correction between each parameter and set-up error of SGRT was analyzed.Results:The mean value of three-dimensional set-up errors in the SGRT group and the marker line group was within 0.2 cm and 0.5 cm, respectively. The differences in three-dimensional set-up errors and total displacements between two groups were statistically significant ( z=-2.93, -3.21, -2.59, -4.76, P<0.05). The SGRT group reduced the CTV-PTV boundary from 0.5 cm of conventional marker line group to 0.3 cm. The thoracic aspect ratio H/W, the affected side pinch angle α1, and the healthy side pinch angle α2 were positively correlated with the x-direction posing error ( r=0.49, 0.59, 0.71, P<0.05); whereas, the affected side and the healthy side mammary gland heights D1 and D2 were negatively correlated with the z-direction posing error ( r=-0.46, -0.49, P<0.05). Conclusions:For breast-conserving postoperative radiotherapy patients, SGRT can obtain a more accurate radiotherapy set-up than the traditional marker line method, and can effectively reduce the target area externally expanded range. Meanwhile, the monitoring accuracy of SGRT is affected by the patient′s thoracic characteristic parameters, and clinical attention should be paid to breast-conserving radiotherapy patients with thick body shape, narrow body width, and small breast glands.

Objective Based on the Ancient and Modern Medical Case Cloud Platform V2.3.7,analyze the medication pattern and mechanism of action of Chinese medicines commonly used in famous medical cases for the treatment of Alzheimer's disease(AD).Methods The core Chinese medicines for AD were screened according to the inclusion and exclusion criteria by searching the famous Chinese medicine cases in the platform,then established the disease-core Chinese medicines-active ingredients-common targets network.The protein-protein interaction network(PPI)was established through the common targets.Gene oncology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed by David platform.Molecular docking and dynamics simulations were employed to evaluate the binding affinity and stability between key targets and active ingredients.Results Data mining was performed on all the famous medical cases from the time of database construction to October 2023,and the results were summarized as follows.The high-frequency regulating Qi medications and tonifying Qi medications were Citri Reticulatae Pericarpium and Aurantii Fructus Immaturus;Panax ginseng,Ziziphi Jujubae Fructus,Codonopsis pilosula,Astragali Radix,Atractylodis Macrocephalae Rhizoma,Dioscoreae Rhizoma,and Glycyrrhizae Radix et Rhizoma.The core herbs contained 778 active ingredients and 377 targets;1986 disease targets;79 common targets were obtained after intersection with AD targets,and 7 core targets were identified through PPI network topology analysis,including TNF,AKT1,TP53,PPARG,etc.GO and KEGG pathway enrichment analyses confirmed that the targets of the active ingredients of the core herbs involved 138 pathways,and the core herbs could regulate chemical carcinogenesis-receptor activation、serotonergic synapse、chemical carcinogenesis-reactive oxygen species pathways to treat AD.Molecular docking and molecular dynamics simulation results showed good binding ability and stability between the key targets and the core components.Conclusion Through data mining to analyze the core herbs for the treatment of AD,the present investigation showing the pharmacological mechanism of 12-O-Nicotinoylisolineolone and Odoratin in the treatment of Alzheimer's disease at the molecular level,lay a certain theoretical foundation of 12-O-Nicotinoylisolineolone and Odoratin in the future.

Objective To analyze the medication law of Professor Yuan Jinsheng,a renowned TCM practitioner in China,for treating palpitations through data mining methods.Methods Clinical prescriptions for treating palpitations by Professor Yuan Jinsheng from January 2016 to May 2023 were collected.The prescriptions were screened based on inclusion and exclusion criteria,a prescription compatibility network was constructed based on R Studio 4.3.1,and the medication law of prescriptions was analyzed.Results Totally 331 prescriptions were screened,involving 180 types of Chinese materia medica,with a total frequency of 3 625.The most frequently used drugs(≥30 times)were mainly tonics.The main properties were warm and neutral,the main tastes were sweet,bitter,and pungent,which belonged to heart,spleen and lung meridians.The top 5 drugs with high correlation were tonifying,blood circulation-activating and stasis-resolving,qi-regulating,and heat-clearing.Correlation analysis reveals high-frequency drugs,which were mainly Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Rehmannine Radix,Ophiopogonis Radix,Astragali Radix and Codonopsis Radix.The clustering analysis results showed that the efficacy was mainly tonifying deficiency,regulating qi,activating blood circulation,and resolving stasis.Conclusion Professor Yuan Jinsheng's prescription compatibility for treating palpitations primarily focuses on tonics,qi-regulating,and blood circulation-activating and stasis-resolving herbs,embodying the principles of treating palpitations from the perspective of the heart and spleen and the combined use of multiple organs.

Objective: To explore the clinical dosimetry advantages of automated plan of IMRT for postoperative esophageal cancer and the dose prediction accuracy of the constructed 3D U-Res-Net model． Methods: A total of 110 postoperative esophageal cancer (middle and upper) cases treated by IMRT were considered in the study，of which 90 cases were randomly selected for training of deep learning prediction model．The deep learning prediction model and Auto-Plan module ( Philips pinnacle3 16. 2 ) were used to predict the three-dimension dose distribution and redesigned the remaining 20 cases respectively ，and the results obtained were compared with manual plan. Results : The average DSC value between the deep learning prediction plan and the manual plan was greater than 0. 92 in isodose surface，and the average Hausdorff distance HD95 of the isodose surface was 0. 58－0. 62 cm ; The V20 ，V30 ，Dmean of total lung were slightly lower than those of manual plan (P ＜0. 05 ) for the prediction model， meanwhile，the D2 ，D50 ，Dmean，HI of the target area and V30 of total lungs were better than those of manual plan(P ＜0. 05) for Auto-Plan ; Three-dimensional dose distribution of the three groups and the corresponding DVH curve showed that the three-dimensional dose distribution of the three groups had a little differences，and the DVH curves of the target area and organs at risk had a good agreement． Conclusion Auto-Plan can realize the design of automated plan for postoperative esophageal cancer，while the deep learning prediction model can realize the accurate prediction of the 3D dose distribution.

Hypertensive intracerebral hemorrhage (ICH) is mostly single in basal ganglia, thalamus and pons. Simultaneous hemorrhage in other brain regions is relatively rare, accounting for only 5.6% of all hemorrhagic strokes, while bilateral symmetrical hemorrhage is extremely rare. A case of bilateral basal ganglia symmetrical hemorrhage is reported for clinical reference.