Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Objective To investigate the effects of exosome(Exo)secreted by cholangiocarcinoma(CCA)cells under hypoxic conditions on the proliferation,migration,invasion,and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway of CCA cells.Methods Exo secreted by CCA cells was extracted and identified.Exo under normoxic and hypoxic conditions were co-cultured with CCA cells and divided into normal oxygen group,hypoxic group,hypoxic+inhibitor group,and blank group.The proliferation,migration,and invasion abilities of CCA cells were tested separately.Immunoblotting was applied to detect the expression levels of relevant proteins.Results Exo carrying fluorescent dye 3,3'-dioctadecyloxacarbocyanine perchlorate was detected in CCA cytoplasm.Compared with blank group,the number of clone formation,cell migration and invasion cells in normoxic group increased,the expression of proliferating cell nuclear antigen(PCNA),matrix metallopeptidase(MMP)-2,MMP-9,neural cadherin(N-Cadherin),Vimentin,phosphorylated JAK2(p-JAK2)/JAK2,phosphorylated STAT3(p-STAT3)/STAT3 increased,and the expression of epithelial cadherin(E-Cadherin)decreased(P＜0.05);Compared with normal oxygen group,the number of clone formation,cell migration and invasion cells in hypoxia group increased,the expression of PCNA,MMP-2,MMP-9,N-Cadherin,Vimentin,p-JAK2/JAK2 and p-STAT3/STAT3 increased,and the expression of E-Cadherin decreased(P＜0.05).Compared with hypoxia group,the number of clone formation,cell migration and invasion cells in hypoxia+inhibitor group decreased,the expression of PCNA,MMP-2,MMP-9,N-Cadherin,Vimentin,p-JAK2/JAK2 and p-STAT3/STAT3 decreased,and the expression of E-Cadherin increased(P＜0.05).Conclusion Exo secreted by CCA cells under hypoxic conditions promote proliferation,migration,invasion,and epithelial mesenchymal transition of CCA cell by activating the JAK2/STAT3 pathway.

Objective:To compare the clinical application of the anterolateral thigh perforator flap (ALTPF) and the calf pedicled propeller perforator flap (PPPF) in reconstruction of soft tissue defect of foot and ankle.Methods:A retrospective observational study was conducted. From March 2013 to June 2019, 48 patients with soft tissue defect around ankle and in foot were reconstructed with ALTPF and PPPF in the Department of Orthopaedics, 920th Hospital of the Joint Logistic Support Force, People's Liberation Army of China. According to the types of flap, the patients were divided into 2 groups: ALTPF group (21 patients,13 males and 8 females, aged 16-67 years, mean 38.71 years±15.30 years. Donor sites were all directly sutured.) and PPPF group (27 patients, 12 males and 15 females, aged 12-69 years, mean 35.18 years±13.96 years. Five cases in the donor site required partial skin grafting, and the rest 22 cases were repaired by directly suture.). The wound size of the former was 5 cm×6 cm-15 cm×18 cm, and at 2 cm×3 cm-14 cm×17 cm for the latter. The surgical time and flap size of the 2 groups were recorded during the surgery. The survival and complications of the flap were observed, and the days of hospital stay were recorded after surgery. Follow-ups were conducted by outpatient clinic and via telephone and WeChat interviews. The colour, texture, appearance, donor scar, complications and thinning of the flap were observed during the follow-up. The ankle function was evaluated according to the score of American Orthopaedic Foot and Ankle Society (AOFAS), and the donor scar was evaluated according to the score of Vancouver Scar Scale (VSS). SPSS 22.0 statistical software was used for data analysis, and P<0.05 was considered statistically significant. Results:The surgical time for the ALTPF group was 118-203 (154.71±25.42) min, and that for the PPPF group was 52-92 (72.78±10.04) min. The size of the flap in the ALTPF group was 5 cm×8 cm-8 cm×18 cm (75.00 cm 2±8.69 cm 2), while it was 3 cm×7 cm-7 cm×17 cm (53.56 cm 2±19.49 cm 2) in the PPPF group. In the ALTPF group, 3 flaps had vascular complications within 24 hours after surgery, which survived after exploration and thrombectomy. Partial necrosis occurred in 1 flap. The rest 17 flaps survived uneventfully. In the PPPF group, 2 flaps had partial necrosis due to infection and they healed after dressing changes, 3 flaps had venous occlusion and survived after phlebotomy, partial suture removal and massage. The rest 22 flaps in 2 groups survived uneventfully. The postoperative days of hospital stay for the ALTPF group was 6-14 (8.71±2.03) days, and that was 4-12 (6.03±2.16) days in the PPPF group. Flap thinning was performed on 19 flaps in the ALTPF group and 2 in the PPPF group. Follow-up was performed for 7 to 21 months. All the flaps were good in colour, shape and texture. All donor sites healed well. At the final follow-up, 19 patients achieved ankle function of excellent, 1 of good and 1 of fair in the ALTPF group, and 21 patients achieved ankle function of excellent, 4 of good and 2 of fair in the PPPF group, according to the AOFAS. According to the VSS, scores of donor site scar was rated 4-8 (6.33±1.35) points for the ALTPF group, and 3-10 (5.92±1.80) points for the PPPF group. Statistical analysis showed no significant differences between the 2 groups in terms of early postoperative complications, flap survival rate, ankle function, and VSS scores ( P>0.05). However, there were statistically significant differences between the 2 groups in terms of surgical time, hospital stay, flap size, and the number of flap thinning ( P<0.05). Conclusion:Both ALTPF and PPPF have good clinical effects in reconstruction of soft tissue defect of foot and ankle. For small to medium-sized wounds, PPPF is the preferred choice due to the advantages in surgical time and postoperative hospital stay. For larger wounds, the ALTPF is the first choice with multiple surgery.

Objective:To evaluate the lung ultrasound characteristics of mycoplasma pneumoniae pneumonia in children and to investigate the value of lung ultrasound monitoring in clinical diagnosis and treatment.Methods:A retrospective analysis of 62 children with mycoplasma pneumoniae pneumonia admitted to Xi'an Chest Hospital from 7 November to 30 November 2023 was performed，and the characteristic parameters of bedside lung ultrasound and their related clinical data were collected. Pathological lung ultrasound features such as interrupted pleural line，well-spaced B-lines，coalescent B-lines，small subpleural patchy pulmonary consolidation，large pulmonary consolidation and pleural effusion in 12 scan areas of both lungs were observed. The maximum upper and lower diameters，right and left diameters，and anterior and posterior diameters of the large pulmonary consolidations were measured，and the changes in the above signs before and after treatment were measured and compared.Results:In sixty-two children with mycoplasma pneumoniae pneumonia，including 32 males and 30 females，with a mean age of（8.18 ± 2.05）years old and a mean hospital stay of（8.79 ± 2.93）days，lung ultrasound showed interrupted pleural line，well-spaced B-lines，coalescent B-lines，small subpleural patchy pulmonary consolidation，large pulmonary consolidation and pleural effusion，with the incidence of 93.5%（58 /62），33.9%（21/62），32.3%（20/62），59.7%（37/62），66.1%（41/62）and 17.7%（11/62），respectively，in which the large pulmonary consolidations presented rich blood supply were more common in the L6 and L4 areas，while the pleural effusions were more common in the L6 area.The signs of interrupted pleural line，coalescent B-lines，large pulmonary consolidation and pleural effusion were significantly improved after treatment compared with before treatment（all P<0.05）. The upper and lower diameters，left and right diameters，and anterior and posterior diameters of large pulmonary consolidations were significantly reduced after treatment compared with before treatment［（4.19 ± 2.42）cm vs.（2.84 ± 2.31）cm， t=2.613， P=0.011；（2.80 ± 1.82）cm vs.（1.96 ± 1.62）cm， t=2.226， P=0.029；（3.41 ± 2.11）cm vs.（2.12 ± 1.82）cm， t=2.972， P=0.004］.With the process of treatment，the dynamic observation of lung ultrasound showed that the well-spaced B-lines/coalescent B-lines gradually decreased until they completely disappeared or a small number of B-lines remained，and the area of the large pulmonary consolidation showed a dynamic downward trend（all P<0.001），and the area of large pulmonary consolidations gradually decreased until they completely disappeared or only small subpleural patchy pulmonary consolidations and well-spaced/coalescent B-lines remained，and at the same time，the pleural effusion gradually absorbed until it disappeared. Conclusions:Lung ultrasound can detect the distribution area of lung lesions，morphology and blood supply characteristics of children with mycoplasma pneumoniae pneumonia，as well as the dynamic changes after treatment，and lung ultrasound can dynamically monitor and evaluate the progression and regression of the disease in real time，providing a reliable imaging evidence for clinical practice.

Objective:To establish a pure water direct dilution-inductively coupled plasma mass spectrometry (ICP-MS) detection method for rapid determination of urinary iodine.Methods:Pure water was used to directly dilute the urine samples. The washing solution was 5.0 g/L ascorbic acid, the internal standard solution was 5.0 g/L ascorbic acid and 100 μg/L 128Te, the standard solution was prepared with the solution of lyophilized urine iodine biological component analysis reference material. The method was evaluated in terms of linear range, detection limit, quantification limit, precision and method comparision experiment. Results:The linear correlation coefficient of the standard curve for iodine concentration range from 0 to 50.0 μg/L was 0.999 7, with a detection limit of 0.2 μg/L and a quantification limit of 0.6 μg/L. The spiked recovery rates of low, medium, and high concentration iodine standard solutions added to actual urine samples were 100.8%, 99.1% and 99.7%, respectively, with relative standard deviations of 0.8%, 1.3% and 1.6%, respectively. There was no statistically significant difference ( t = - 0.14, P = 0.890) between the results of measuring actual urine and assessment urine using this method and "Determination of Iodine in Urine-Part 2: Inductively Coupled Plasma Mass Spectrometry (WS/T 107.2-2016)". Conclusions:We have successfully established a pure water direct dilution-ICP-MS method for determining urinary iodine. This method provides accurate and highly sensitive results, making it suitable for sudden public health emergencies and large-scale clinical measurement of urinary iodine.

Objective To investigate the effects of exosome(Exo)secreted by cholangiocarcinoma(CCA)cells under hypoxic conditions on the proliferation,migration,invasion,and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway of CCA cells.Methods Exo secreted by CCA cells was extracted and identified.Exo under normoxic and hypoxic conditions were co-cultured with CCA cells and divided into normal oxygen group,hypoxic group,hypoxic+inhibitor group,and blank group.The proliferation,migration,and invasion abilities of CCA cells were tested separately.Immunoblotting was applied to detect the expression levels of relevant proteins.Results Exo carrying fluorescent dye 3,3'-dioctadecyloxacarbocyanine perchlorate was detected in CCA cytoplasm.Compared with blank group,the number of clone formation,cell migration and invasion cells in normoxic group increased,the expression of proliferating cell nuclear antigen(PCNA),matrix metallopeptidase(MMP)-2,MMP-9,neural cadherin(N-Cadherin),Vimentin,phosphorylated JAK2(p-JAK2)/JAK2,phosphorylated STAT3(p-STAT3)/STAT3 increased,and the expression of epithelial cadherin(E-Cadherin)decreased(P＜0.05);Compared with normal oxygen group,the number of clone formation,cell migration and invasion cells in hypoxia group increased,the expression of PCNA,MMP-2,MMP-9,N-Cadherin,Vimentin,p-JAK2/JAK2 and p-STAT3/STAT3 increased,and the expression of E-Cadherin decreased(P＜0.05).Compared with hypoxia group,the number of clone formation,cell migration and invasion cells in hypoxia+inhibitor group decreased,the expression of PCNA,MMP-2,MMP-9,N-Cadherin,Vimentin,p-JAK2/JAK2 and p-STAT3/STAT3 decreased,and the expression of E-Cadherin increased(P＜0.05).Conclusion Exo secreted by CCA cells under hypoxic conditions promote proliferation,migration,invasion,and epithelial mesenchymal transition of CCA cell by activating the JAK2/STAT3 pathway.