Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To evaluate the design and application of the superior thyroid artery perforator flap (STAPF) for reconstruction after head and neck oncological resection.Methods:A retrospective analysis was performed on 24 consecutive patients (22 men, 2 women; age 40-72 years) treated at Hunan Cancer Hospital between June 2018 and December 2023. Their primary tumors included buccal carcinoma ( n=7), tongue carcinoma ( n=8), oropharyngeal carcinoma ( n=2), floor-of-mouth carcinoma ( n=3), laryngeal carcinoma ( n=3), and hypopharyngeal carcinoma ( n=1). Flap design, venous drainage strategy, and postoperative outcomes were assessed. SPSS 19.0 software was used for statistical analysis. Results:Flap dimensions were length of 9.4±0.5 cm, width of 3.3±0.6 cm, thickness of 0.5±0.2 cm, and pedicle length of 7.3±0.6 cm. Fifteen flaps were based on a single perforator (diameter ≥0.5 mm), whereas, nine fascial flaps incorporated multiple perforators (capillary diameter ≤0.5 mm). Venous drainage routes were as follows: superior thyroid vein ( n=12, retrograde in 3), facial vein ( n=5, all retrograde), anterior jugular vein ( n=4, retrograde in 1), and external jugular vein ( n=3, retrograde in 2). All 24 flaps survived completely. Donor sites were closed primarily and all cervical wounds healed. No flap-related complications, inculding orocutaneous, pharyngocutaneous, laryngocutaneous fistula and wound infection, were observed. Final pathologic stages were T1N0M0 ( n=2), T2N0M0 ( n=16), T2N1M0 ( n=3), and T3N0M0 ( n=3). With follow-up of 12-46 months, aside from one patient with tongue cancer died of contralateral cervical and parapharyngeal lymph-node metastases at 6 months, others remained disease-free. Patients with laryngeal or hypopharyngeal carcinoma had their tracheostomy tubes removed within 4 weeks postoperatively. Conclusion:STAPF offers flexible design, with minimal donor-site morbidity and low functional impairment. It is particularly advantageous for reconstruction of small-to-moderate defects following head and neck tumor ablation.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a significant threat to public health. Advances in medical science and increased screening awareness have improved early-stage diagnosis rates, allowing more patients to undergo radical treatment at initial diagnosis. Concurrently, ongoing developments in treatment modalities have expanded the options available for both patients and clinicians. The challenge now lies in making informed decisions to achieve individualized precision medicine, which merits thorough exploration. This article aims to review the latest research on personalized treatment strategies for early-stage HCC, providing a reasonable reference and valuable insights for clinicians.

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer. Hepatic resection is the preferred treatment for colorectal cancer liver metastasis (CRLM). However, a disappointingly small proportion of patients are deemed suitable for surgical resection upon initial consultation. Failure to adequately address these metastatic tumors results in a dire 5-year survival rate of less than 5%. In recent times, thermal ablation, a minimally invasive procedure aimed at controlling local tumor progression, has undergone rigorous validation and garnered recognition for its effectiveness and safety in managing CRLM. This article endeavors to review the advancements in research concerning thermal ablation in the treatment of CRLM, exploring its efficacy, safety profile, and the promising avenues for its clinical application.

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

By reconstructing the integrated Chinese and western medicine diagnostic and treatment system， the "Two Reconstructions" theoretical framework establishes a standardized pathway of "classification-staging-syndrome differentiation"， which improves the accuracy of disease identification and strengthens the capacity for full-course intervention； in addition， by reconstructing the modern materia medica system， it innovatively integrates the traditional properties and efficacy of Chinese herbal medicinals with modern pharmacological mechanisms， forming a "state-target co-regulation" precise medication model， and builds a dose-effect theoretical system for prescriptions and medicinals， thereby enhancing both the targeting accuracy and dosage precision of therapeutic interventions. The "Two Reconstructions" theorecitcal framework is a key strategy for enhancing clinical efficacy. It can precisely identify "states" and "targets" for directed intervention， shift the focus of prevention and treatment earlier to enable full-cycle management， establish standardized paradigms for reproducible and evaluable efficacy， and expand the scope of clinical practice to address conditions without typical syndromes and critical illnesses. As a systematic pathway for innovation in TCM， this theoretical framework provides valuable insights and references for promoting the high-quality development of integrative Chinese and western medicine.

Objective To investigate the potential value of a deep learning(DL)model based on non-contrast CT images in predicting contrast medium extravasation in contrast-enhanced CT scans of tumor patients.Methods A total of 298 tumor patients were retrospectively selected,including 90 patients with extravasation and 208 without extravasation,and divided into training set(207 patients),validation set(46 patients),and external test set(45 patients)in a ratio of 7︰1.5︰1.5.U-Net was employed to segment the right common carotid artery/internal jugular vein and right subclavian artery/vein in non-contrast CT images,and ResNet50 was utilized to extract imaging features to construct the DL model,which was subsequently integrated with independent clinical predictors to establish the combined model.The segmentation performance of the DL model was evaluated using Dice similarity coefficient(DSC)and Intersection over Union(IoU),while the area under the curve(AUC),accuracy,sensitivity,and specificity of the model were calculated.Results The DL model demonstrated superior vascular segmentation(DSC 0.81-0.95,IoU 0.79-0.90).The combined model achieved optimal predictive performance,with AUC of 0.961[95%confidence interval(CI)0.924-0.983],0.949(95%CI 0.840-0.992),and 0.891(95%CI 0.762-0.964)in the training,validation,and external test sets,respectively.Its accuracy,sensitivity,and specificity were consistently higher than those of the standalone clinical model.Conclusion The DL model based on non-contrast CT images shows significant potential value in predicting contrast medium extravasation risk in tumor patients,providing an objective and intelligent tool for clinical risk assessment.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Objective:To evaluate the design and application of the superior thyroid artery perforator flap (STAPF) for reconstruction after head and neck oncological resection.Methods:A retrospective analysis was performed on 24 consecutive patients (22 men, 2 women; age 40-72 years) treated at Hunan Cancer Hospital between June 2018 and December 2023. Their primary tumors included buccal carcinoma ( n=7), tongue carcinoma ( n=8), oropharyngeal carcinoma ( n=2), floor-of-mouth carcinoma ( n=3), laryngeal carcinoma ( n=3), and hypopharyngeal carcinoma ( n=1). Flap design, venous drainage strategy, and postoperative outcomes were assessed. SPSS 19.0 software was used for statistical analysis. Results:Flap dimensions were length of 9.4±0.5 cm, width of 3.3±0.6 cm, thickness of 0.5±0.2 cm, and pedicle length of 7.3±0.6 cm. Fifteen flaps were based on a single perforator (diameter ≥0.5 mm), whereas, nine fascial flaps incorporated multiple perforators (capillary diameter ≤0.5 mm). Venous drainage routes were as follows: superior thyroid vein ( n=12, retrograde in 3), facial vein ( n=5, all retrograde), anterior jugular vein ( n=4, retrograde in 1), and external jugular vein ( n=3, retrograde in 2). All 24 flaps survived completely. Donor sites were closed primarily and all cervical wounds healed. No flap-related complications, inculding orocutaneous, pharyngocutaneous, laryngocutaneous fistula and wound infection, were observed. Final pathologic stages were T1N0M0 ( n=2), T2N0M0 ( n=16), T2N1M0 ( n=3), and T3N0M0 ( n=3). With follow-up of 12-46 months, aside from one patient with tongue cancer died of contralateral cervical and parapharyngeal lymph-node metastases at 6 months, others remained disease-free. Patients with laryngeal or hypopharyngeal carcinoma had their tracheostomy tubes removed within 4 weeks postoperatively. Conclusion:STAPF offers flexible design, with minimal donor-site morbidity and low functional impairment. It is particularly advantageous for reconstruction of small-to-moderate defects following head and neck tumor ablation.

Objective To investigate the potential value of a deep learning(DL)model based on non-contrast CT images in predicting contrast medium extravasation in contrast-enhanced CT scans of tumor patients.Methods A total of 298 tumor patients were retrospectively selected,including 90 patients with extravasation and 208 without extravasation,and divided into training set(207 patients),validation set(46 patients),and external test set(45 patients)in a ratio of 7︰1.5︰1.5.U-Net was employed to segment the right common carotid artery/internal jugular vein and right subclavian artery/vein in non-contrast CT images,and ResNet50 was utilized to extract imaging features to construct the DL model,which was subsequently integrated with independent clinical predictors to establish the combined model.The segmentation performance of the DL model was evaluated using Dice similarity coefficient(DSC)and Intersection over Union(IoU),while the area under the curve(AUC),accuracy,sensitivity,and specificity of the model were calculated.Results The DL model demonstrated superior vascular segmentation(DSC 0.81-0.95,IoU 0.79-0.90).The combined model achieved optimal predictive performance,with AUC of 0.961[95%confidence interval(CI)0.924-0.983],0.949(95%CI 0.840-0.992),and 0.891(95%CI 0.762-0.964)in the training,validation,and external test sets,respectively.Its accuracy,sensitivity,and specificity were consistently higher than those of the standalone clinical model.Conclusion The DL model based on non-contrast CT images shows significant potential value in predicting contrast medium extravasation risk in tumor patients,providing an objective and intelligent tool for clinical risk assessment.