Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

Respiratory syncytial virus (RSV) is a ubiquitous respiratory virus that affects individuals of all ages; however, there is a notable lack of targeted treatments. RSV infection is associated with a range of respiratory symptoms, including bronchiolitis and pneumonia. Baicalin (BA) exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action. Nonetheless, the clinical application of BA is constrained by its low solubility and bioavailability. In this study, we prepared BA nanodrugs (BA NDs) with enhanced water solubility utilizing the supramolecular self-assembled strategy, and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA. Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA, attributed to prolonged lung retention, improved cellular uptake, and increased targeting affinity. Our study confirms that the nanosizing strategy, a straightforward approach to enhance drug solubility, can also increase biological activity compared to free drugs with the same content, thereby providing a potential ND for RSV treatment. This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.

ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy but inherent toxicity, primarily due to its alkaloid content. Traditional and modern detoxification methods for CW include proper processing, rational compatibility, and specialized decoction techniques, among which honey-boiled CW is particularly distinctive. However, research on the detoxification mechanism of honey-boiled CW remains limited. This study investigated this mechanism by analyzing alkaloid transformation and supramolecular aggregation. Honey-boiled and water-boiled CW preparations were compared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non-esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy was employed to observe and identify supramolecular aggregates in the honey-boiled CW decoction. In vivo absorption of water-boiled, honey-boiled, and NADES-boiled CW was compared. Median lethal dose (LD₅₀) tests assessed toxicity, including hepatotoxicity and nephrotoxicity. In vitro experiments evaluated the safety, anti-inflammatory, and analgesic effects of CW-medicated serum on RAW264.7 cells, with in vivo validation in mice. Results showed that honey promoted the conversion of highly toxic DDAs to less toxic MDAs and prevented MDAs from hydrolyzing into NDAs. Honey-boiled CW formed approximately 250 nm supramolecular aggregates that encapsulated MDAs, inhibiting their conversion to NDAs. These encapsulated MDAs acted as a stable delivery system with higher bioavailability than free benzoylmesaconine. Subsequent mouse experiments confirmed that honey-boiled CW significantly increased the LD₅₀ of CW while reducing hepatotoxicity and nephrotoxicity. Additionally, honey-boiled CW significantly improved cell safety and enhanced anti-inflammatory and analgesic effects. Our findings reveal that honey-boiled CW exhibits a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This study lays the groundwork for developing detoxification or synergistic strategies within honey-boiled TCM.

ObjectiveTo observe the efficacy of Huoxue Jiedu Formulas （活血解毒方药， HJF） as an adjunctive treatement for patients with binding of stasis and toxin syndrome during the vulnerable period after acute myocardial infarction （AMI） percutaneous coronary intervention （PCI） surgery， and to explore its potential mechanism from the perspective of serum neutrophil extracellular traps （NETs）. MethodsA total of 129 patients with binding of stasis and toxin syndrome within 6 months after PCI for AMI were enrolled and divided into a treatment group （65 cases） and a control group （64 cases） based on patients' willingness to take Chinese herbal medicine. The control group received standard western medical therapy alone， while the treatment group additionally received HJF， one dose daily. Both groups were treated for four weeks. Before and after treatment， TCM syndrome scores were assessed. Seattle angina questionnaire （SAQ） was used to record angina stability and frequency scores， while the short form-36 health survey （SF-36） was employed to assess quality of life across eight dimensions， including physical functioning， role-physical， bodily pain， general health， vitality， social functioning， role-emotional， and mental health. The Pittsburgh sleep quality index （PSQI） was used to evaluate sleep quality， and the patient health questionnaire-15 （PHQ-15） was used to assess psychosomatic symptoms； Duke activity status index （DASI） was used to measure daily physical activity. Serum levels of neutrophil extracellular traps （NET） markers including myeloperoxidase-DNA （MPO-DNA）， neutrophil elastase-DNA （NE-DNA）， and citrullinated histone H3 （CitH3） were measured in 20 patients from the treatment group. ResultsAfter treatment， TCM syndrome score， PSQI score and PHQ-15 score in both groups significantly decreased， while DASI score， angina stability and frequency scores， and all eight dimensions of the SF-36 scale significantly increased （P＜0.05）. Compared to the control group， the treatment group had significantly lower TCM syndrome scores and significantly higher DASI， angina stability and frequency scores （P＜0.05）， as well as higher scores in the SF-36 dimensions of physical functioning， role-physical， social functioning， bodily pain， and vitality （P＜0.05）. After treatment， serum levels of MPO-DNA， CitH3， and NE-DNA in the treatment group were significantly reduced （P＜0.05）. ConclusionHJF combined with conventional therapy can significantly improve angina symptoms， TCM syndrome scores， and psychosomatic conditions in patients with binding of stasis and toxin syndrome during the vulnerable period after AMI. It also enhances quality of life， sleep quality， and daily physical activity. The underlying mechanism may be associated with the inhibition of serum NETs level.

BACKGROUND: Lung cancer is one of the most common malignant tumors worldwide and a major cause of cancer-related deaths. Early-stage lung cancer is often manifested as pulmonary nodules, and accurate assessment of the malignancy risk is crucial for prolonging survival and avoiding overtreatment. This study aims to construct a model based on image feature parameters automatically extracted by artificial intelligence (AI) to evaluate its effectiveness in predicting the malignancy of part-solid nodule (PSN). METHODS: This retrospective study analyzed 229 PSN from 222 patients who underwent pulmonary nodule resection at Lanzhou University Second Hospital between October 2020 and February 2025. According to pathological results, 45 cases of benign lesions and precursor glandular lesion were categorized into the non-malignant group, and 184 cases of pulmonary malignancies were categorized into the malignant group. All patients underwent preoperative chest computed tomography (CT), and AI software was used to extract imaging feature parameters. Univariate analysis was used to screen significant variables; variance inflation factor (VIF) was calculated to exclude highly collinear variables, and LASSO regression was further applied to identify key features. Multivariate Logistic regression was used to determine independent risk factors. Based on the selected variables, five models were constructed: Logistic regression, random forest, XGBoost, LightGBM, and support vector machine (SVM). Receiver operating characteristic (ROC) curves were used to assess the performance of the models. RESULTS: The independent risk factors for the malignancy of PSN include roughness (ngtdm), dependence variance (gldm), and short run low gray-level emphasis (glrlm). Logistic regression achieved area under the curves ( AUCs) of 0.86 and 0.89 in the training and testing sets, respectively, showing good performance. XGBoost had AUCs of 0.78 and 0.77, respectively, demonstrating relatively balanced performance, but with lower accuracy. SVM showed an AUC of 0.93 in the training set, which decreased to 0.80 in the testing set, indicating overfitting. LightGBM performed excellently in the training set with an AUC of 0.94, but its performance declined in the testing set, with an AUC of 0.88. In contrast, random forest demonstrated stable performance in both the training and testing sets, with AUCs of 0.89 and 0.91, respectively, exhibiting high stability and excellent generalizability. CONCLUSIONS The random forest model constructed based on independent risk factors demonstrated the best performance in predicting the malignancy of PSN and could provide effective auxiliary predictions for clinicians, supporting individualized treatment decisions.
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Humans ; Male ; Female ; Lung Neoplasms/pathology* ; Middle Aged ; Retrospective Studies ; Artificial Intelligence ; Aged ; Tomography, X-Ray Computed ; Adult ; Solitary Pulmonary Nodule/diagnostic imaging* ; ROC Curve

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.
Humans ; Neoplasms/metabolism* ; Cyclin-Dependent Kinases/antagonists & inhibitors* ; Cyclins/metabolism* ; Proteolysis ; Antineoplastic Agents/pharmacology* ; Molecular Targeted Therapy ; Proteasome Endopeptidase Complex/metabolism* ; Animals

Objective To determine the effect of limb dominance on landing biomechanics and lower limb functional outcomes in patients with anterior cruciate ligament reconstruction(ACLR).Methods Forty-nine participants were recruited and divided into the ACLR on dominant limb(ACLR-D)group,ACLR on nondominant limb(ACLR-ND)group and healthy control group.Single-leg jump landing,knee isokinetic muscle strength,Y balance,and single-leg hop distance were tested on both limbs of all participants.Kinematics and kinetics data during the single-leg jump landing were collected by an infrared motion capture system and a force platform,and knee joint muscle strength was collected using the isokinetic muscle strength testing system.Two-way mixed-design ANOVAs were used to observe the effects of limb and group on the outcomes of each test.Results The non-surgical limbs had greater knee valgus,knee external rotation angles and knee valgus moments during single-leg jump landing in the ACLR-D group compared with those in the ACLR-ND group,and the ACLR-D group had significantly smaller bilateral knee flexion angles than the control group.There were no differences in knee muscle strength,Y-balance composite scores and single-leg hop distance between ACLR-D and ACLR-ND groups,but the Y balance scores in the ACLR-ND group were smaller than those in the control group.Conclusions Limb dominance has no effects on knee muscle strength,dynamic postural control,and single-leg hop function in ACLR patients.The non-surgical limbs of ACLR-D patients are at a higher risk of ACL injury due to the presence of greater knee valgus and external rotation angles and knee valgus moments.

Objective To evaluate the efficacy of non-ablative vaginal erbium-doped yttrium aluminum garnet(Er:YAG)laser therapy in improving symptoms in women with mild-to-moderate stress urinary incontinence(SUI).Methods A prospective,multicenter,randomized controlled trial was conducted.A total of 126 female SUI patients were enrolled and randomized in a 2∶1 ratio to the treatment group(n=84,receiving Er:YAG laser therapy)and the sham control group(n=42,undergoing non-energized laser device with shielded beam).Efficacy outcomes were compared between the two groups,including the International Consultation on Incontinence Questionnaire-Short Form(ICI-Q-SF)scores at baseline and 1,3,6 months after treatment,response rate 3 month after treatment,urine leakage volume,daily incontinence episodes and visual analog scale(VAS).Results One month and 3 months after treatment,the ICI-Q-SF scores in the treatment group(8.07±3.33 and 7.04±3.04,respectively)were significantly lower than those in the control group(9.57±4.03 and 9.65±3.27,respectively;both P＜0.05).The 3-month response rate was significantly higher in the treatment group(71.43％)compared to the control group(35.71％,P＜0.05).Improvements in urine leakage volume 1 and 3 months after treatment were significantly greater in the treatment group versus the control group(both P＜0.05).A statistically significant reduction in daily incontinence episodes was observed in the treatment group 1 month after treatment compared to the control group[2(0,5)times vs.4(2,8)times,P＜0.05].VAS score in the treatment group markedly decreased 1 month after treatment,comparable to the level observed in the control group[0(0,2.45)vs.0(0,0),P＜0.05].Conclusion Non-ablative vaginal Er:YAG laser therapy significantly alleviates symptoms in women with mild-to-moderate SUI and represents a viable treatment option for this condition.

Objective:To compare four postmastectomy radiotherapy plans with different arc angles for left-sided breast cancer prepared using deep inspiration breath hold (DIBH) technique, in order to explore the feasibility of selecting optimal arc angles based on the parameters of patients′ anatomical structures.Methods:A total of 51 patients who underwent postmastectomy radiotherapy for left-sided breast cancer using DIBH at the Second Affiliated Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangzhou Medical University were selected. Among these, 40 patients selected using simple random sampling were treated with four radiotherapy plans with different arc angles, labeled as SV120, SV100, SV80, and SV60, while the remaining 11 patients were treated with only the SV60 plans. The dose parameters of the target volumes (TVs) and organs at risk (the heart, lungs, and contralateral breast), as well as the beam-on times of individual arcs, in these plans were compared. The parameters of the anatomical structures (i.e., the heart, lung, and breast) of the 51 patients, including PHeart, PLungl, and PBreast, were extracted. Taking these parameters as independent variables and the quality of the SV60 plans as the dependent variable, fitting was conducted using P(SV60)—a multivariate logistic regression model—based on a training set (45 patients) and a testing set (six patients). The classification threshold of the plans was set at 0.5. Results:As the arc angle increased, the plans exhibited improved modulation capabilities for TVs and the left lung. However, the V5 of the right lung and the average beam-on time of a single arc also increased. The SV120 plans demonstrated significantly better V107% of planning target volume (PTV; 6.84%), homogeneity index (HI; 0.13), conformity index (CI; 0.81), and mean dose to the left lung (1 330.97 cGy) compared to the other three types of plans, with statistically significant differences ( W = 0-99, P < 0.001). The SV60 plans displayed lower mean doses to the contralateral breast (198.97 cGy) and the heart (440.35 cGy) and lower V5 of the right lung (0.27%) than the other three types of plans, with significant differences in V5 of the right lung and the mean dose to the contralateral breast ( W = 0-157, P < 0.001). In contrast, no significant difference was observed in these parameters (except for V5 of the right lung) among the other three types of plans. The four types of plans exhibited average beam-on times of individual arcs of 22.0, 19.1, 16.1, and 14.4 s, respectively, with statistically significant differences ( χ2= 93.0, P < 0.001). A multivariate logistic regression model revealed that PLungl, PHeart, and PBreast were negatively correlated with the quality of the SV60 plans ( t = -64.84, -28.20, -24.45, P<0.001). This model yielded an accuracy of 93.33% and a precision of 92.86% in the training set, while its accuracy and precision reached 100% in the testing set. Conclusions:For patients treated with postmastectomy radiotherapy for left-sided breast cancer using DIBH, it is feasible to select appropriate arc angles based on patients’ anatomical structures.

Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respi-ratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.