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.

Objective:To establish a serum detection method of surface-enhanced Raman spectroscopy (SERS) combining with machine learning for early screening of colorectal cancer (CRC).Methods:Serum samples were collected from 150 CRC patients diagnosed at Jiangdu People′s Hospital, Affiliated to Yangzhou University, and also from 37 healthy subjects. Gold nanohexapod (AuNHs) arrays were prepared using an oil-water interface self-assembly method. A 5 μl serum sample was applied onto the AuNHs array. Scatheless and rapid detection for serum were performed using a Renishaw inVia Raman spectrometer at room temperature with a laser wavelength of 785 nm, exposure time of 10 s, and power of 5 mW. The raw SERS spectra were preprocessed using Savitzky-Golay smoothing, AsLS baseline correction, and Min-Max normalization with Origin 2019 software. Furthermore, the principal component analysis (PCA)-support vector machine (SVM) model was constructed using Python′s scikit-learn library. Leave-One-Out Cross-Validation (LOOCV) was used to evaluate the model′s accuracy, sensitivity, specificity, and area under the curve (AUC).Results:The AuNHs arrays exhibited uniform morphology. The relative standard deviation (RSD) of the SERS intensity at 1 080 cm -1 was 5.69%, and the RSD of the SERS intensity at 1 340 cm -1 was 6.20%. The limit of detection (LOD) of the AuNHs array was 9.42×10 -12 mol/L. The PCA-SVM model achieved an accuracy of 90.91% (170/187), sensitivity of 96.79% (181/187), specificity of 99.47% (186/187), and an AUC of 0.98. The most significant characteristic peaks distinguishing different CRC stages were at 747, 940, 1 000, 1 447, and 1 612 cm -1. Conclusion:The serum detection method based on SERS combined with machine learning can accurately screen CRC with higher accuracy, sensitivity, and specificity, demonstrating potential clinical application value.

A variety of plants are used as Gymnadenia conopsea(L.)R.Br medicine in some areas.According to statistics,there are 7 genera and 16 species of Orchidaceae.There is confusion in medicinal varieties,which seriously affects drug safety and rational utilization of resources.Based on the national standards,this article conducted a textual research from the aspects of ancient herbs,modern monographs,the name of the reference,base,property and taste and efficacy and other aspects.The results showed that,the Gymnadenia conopsea(L.)R.Br medicine is named Erheten nai gar,and the Tibetan medicine is named Wangla,and most of the herbs take"Gymnadenia conopsea(L.)R.Br"as the name.The mainstream varieties of Gymnadenia conopsea(L.)R.Br,a plant of the genus Gymnadenia of Orchidaceae,were born in arid grassland or wetland and meadow,with palmlike roots,green stems and leaves and pink and white flowers.Gymnadenia conopsea(L.)R.Br is different in property and taste and efficacy when used as different ethnic medicines,but it has the commonness of tonifying kidney,producing sperm and strengthening yang and nourishing.The conclusion of textual research could provide references for the resource conservation,rational research and utilization,and artificial cultivation of Gymnadenia conopsea(L.)R.Br resources.

Objective To investigate the safety parameters of the air-powered electrocautery hook and its advantages in laparoscopic surgery.Methods In pressure trauma experiments,21 healthy New Zealand White Rabbits were randomly divided into three groups.In each group,three sites(liver,intestine,and kidney)were selected from each rabbit,and the air-powered electrocautery hook was used under laparoscopy to apply pressure and time gradients in a cross-combination manner.The three groups of experimental rabbits were dissected at three time points:immediately after application,3 d post-application,and 7 d post-application.Pathological sections were prepared from the corresponding treated sites,and the extent of injury was assessed.In rabbit renal capsule removal experiment,another 20 healthy New Zealand White Rabbits were randomly divided into 2 groups.Renal capsule removal was performed by using an air-powered electrosurgical hook and a conventional electrosurgical hook,respectively,to compare the two groups in terms of surgical time,intraoperative bleeding volume,intraoperative complications,and the number of times of wiping speculum.Results In pressure trauma experiment,except for the intestinal tract at 3 seconds(P=0.060),the histopathological scores under 0.3 MPa pressure were significantly higher than those under 0.1 MPa(P<0.05)and 0.2 MPa(P<0.05)in all the tissues.In the tissue sampling groups at 3 d and 7 d post-surgery,no tissue damage was observed in any tissue at any time point under 0.1 MPa pressure.In rabbit renal capsule removal experiment,the aerodynamic electrocautery group had less intraoperative bleeding volume than the conventional electrocautery group[(2.9±0.5)ml vs.(3.4±0.5)ml,t=-2.280,P=0.035].There were no significant differences between the two groups in terms of surgical time,intraoperative complication rates,and the number of times of wiping speculum(P>0.05).Conclusions The safe pressure range for using the air-powered electrosurgical hook on the surfaces of the kidney and intestinal tract is within 0.2 MPa.Within the safe pressure range,blowing on tissue for 6 seconds or less is relatively safe.Using the air-powered electrosurgical hook in surgeries requiring the separation of loose connective tissue can reduce intraoperative bleeding.

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r＞0.990 0),whose average recoveries were 83.74％-105.12％with the RSDs of 1.10％-4.8％.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

Objective:To explore the applicability of modified comprehensive interventions in the treatment of non-severe dry eye syndrome in military pilots.Methods:A total of 88 military pilots with non-severe dry eye syndrome admitted to the Special Service Department of the 988th Hospital of the Joint Logistic Support Force between December 2021 and December 2023 were divided into an intervention group and a control group using the random number table method, with 44 cases in each. The intervention group received modified comprehensive interventions, while the control group underwent conventional treatment. The Ocular Surface Disease Index (OSDI), break-up time, tear meniscus height, changes in meibomian gland function, and levels of satisfaction of military pilots were compared between the 2 groups. The correlations between the OSDI, break-up time, tear meniscus height and levels of satisfaction were analyzed.Results:Before treatment, there was no significant difference in the OSDI between the 2 groups ( P>0.05). After 4 weeks of treatment, the changes in the OSDI of military pilots were smaller in the intervention group than in the control group ( t=3.21, P=0.002). After 2 and 4 weeks of treatment, the break-up time (both P<0.001) and tear meniscus height ( P<0.001, =0.012) of pilots in the intervention group exceeded those of the control group. In both groups, the break-up time (all P<0.001) and tear meniscus height (all P<0.001) kept increasing after treatment. After 4 weeks of treatment, there were significant differences in the distribution of meibomian gland function between the 2 groups ( Z=-2.55, -2.41, -2.29, P=0.011, 0.016, 0.022). Clinical care, procedure flow, and health education scored higher in the intervention group than in the control group during the survey on levels of satisfaction with the treatment ( t=6.55, 6.77, 3.63, all P≤0.001). The OSDI was negatively correlated with clinical care, procedure flow and health education ( r=-0.286, -0.275, -0.363, P=0.007, 0.010, 0.001) while the break-up time was positively correlated with clinical care and procedure flow ( r=0.248, 0.278, P=0.020, 0.009). Conclusions:The implementation of modified comprehensive intervention measures for dry eye syndrome in military pilots can effectively improve clinical symptoms and leave military pilots more satisfied.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones