As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To investigate the effect of berberine and its mechanism in delaying silica-induced lung injury via network pharmacology and molecular docking, followed by verification with animal experiments. Methods i) Targets of berberine and silicosis were obtained from multiple databases, and the common targets were identified. A protein-protein interaction network was constructed using the STRING database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the common targets via the DAVID database. Molecular docking was conducted using AutoDock software for validation. ii) Specific pathogen-free Wistar rats were randomly divided into five groups, with six rats in each group. Rats in the model group, pirfenidone group, and low- and high-dose berberine groups received a single non-exposure intratracheal instillation of 1.00 mL silica suspension at a mass concentration of 100 g/L, whereas rats in the control group received an equal volume of 0.9% sodium chloride solution. Rats in the pirfenidone group were administered with pirfenidone solution at a dose of 100 mg/kg body weight, and rats in the low- and high-dose berberine groups were administered with berberine solutions at doses of 100 and 200 mg/kg body weight, respectively. The remaining two groups received equal volumes of 0.9% sodium chloride solution. All treatments were administered by gavage once daily for 28 consecutive days from 24 hours after silica exposure. After intervention, rats in each group were sacrificed. Histopathological changes in lung tissues were observed, and the lung organ coefficient was detected. Serum malondialdehyde (MDA) was detected by colorimetry. Serum inflammatory cytokine were detected by enzyme-linked immunosorbent assay. The expression of fibrosis markers in lung tissues was detected by immunohistochemistry. The protein expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and phosphorylated AKT (p-AKT) in lung tissues was determined by Western blot. Results i) Network pharmacology analysis identified 46 potential targets. The core targets included AKT1, tumor protein p53, caspase-3, matrix metalloproteinase-9, and albumin. GO enrichment analysis revealed that the targets related to the anti-fibrotic effect of berberine against silicosis were mainly enriched in biological processes including signal transduction, negative regulation of apoptosis, extracellular matrix degradation, and response to reactive oxygen species. KEGG enrichment analysis showed that berberine exerted anti-silicosis effects through multiple signaling pathways, such as the PI3K/AKT pathway, hypoxia-inducible factor-1 pathway, and advanced glycation end product (AGE)-receptor for AGE pathway. ii) Histopathological examination revealed that rats in the model group presented typical pulmonary fibrotic lesions. Pathological lung injury of rats was alleviated in all three intervention groups (pirfenidone group, low- and high-dose berberine group) compared with the model group. The improvement in the high-dose berberine group was superior to that in the low-dose berberine group and was comparable with that in the pirfenidone group. rats in the model group showed increased lung organ coefficient, serum MDA, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) (all P<0.05), as well as increased expression of typeⅠcollagen (COLⅠ), α-smooth muscle actin (α-SMA) and PI3K, and p-AKT/AKT ratio in lung tissues (all P<0.05) when compared with the control group. The above indicators were lower in rats in both the low- and high-dose berberine groups than those in the model group (all P<0.05). Serum MDA, IL-1β, and TNF-α, as well as relative expression of COLⅠ and α-SMA in lung tissues, were lower in the high-dose berberine group than in the low-dose berberine group (all P<0.05). Conclusion Berberine may alleviate pulmonary inflammation and fibrosis in rats through regulation of the PI3K/AKT signaling pathway, thereby delaying the progression of silicosis.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Nitrogen narcosis is a neurological syndrome that manifests when humans or animals encounter hyperbaric nitrogen, resulting in a range of motor, emotional, and cognitive abnormalities. The anterior cingulate cortex (ACC) is known for its significant involvement in regulating motivation, cognition, and action. However, its specific contribution to nitrogen narcosis-induced hyperlocomotion and the underlying mechanisms remain poorly understood. Here we report that exposure to hyperbaric nitrogen notably increased the locomotor activity of mice in a pressure-dependent manner. Concurrently, this exposure induced heightened activation among neurons in both the ACC and dorsal medial striatum (DMS). Notably, chemogenetic inhibition of ACC neurons effectively suppressed hyperlocomotion. Conversely, chemogenetic excitation lowered the hyperbaric pressure threshold required to induce hyperlocomotion. Moreover, both chemogenetic inhibition and genetic ablation of activity-dependent neurons within the ACC reduced the hyperlocomotion. Further investigation revealed that ACC neurons project to the DMS, and chemogenetic inhibition of ACC-DMS projections resulted in a reduction in hyperlocomotion. Finally, nitrogen narcosis led to an increase in local field potentials in the theta frequency band and a decrease in the alpha frequency band in both the ACC and DMS. These results collectively suggest that excitatory neurons within the ACC, along with their projections to the DMS, play a pivotal role in regulating the hyperlocomotion induced by exposure to hyperbaric nitrogen.
Animals ; Gyrus Cinguli/drug effects* ; Male ; Mice, Inbred C57BL ; Locomotion/drug effects* ; Neurons/drug effects* ; Mice ; Nitrogen/toxicity* ; Inert Gas Narcosis/physiopathology* ; Corpus Striatum/physiopathology*

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans ; Colitis, Ulcerative/immunology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cell Transformation, Neoplastic

To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry* ; Starch/chemistry* ; Multivariate Analysis ; Water/chemistry* ; Terpenes/analysis* ; Plant Roots/chemistry* ; Plant Tubers/chemistry* ; Drugs, Chinese Herbal/chemistry*