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.

Investigator initiated trial （IIT） represents a primary format for clinical research in traditional Chinese medicine （TCM）. As key implementation sites for TCM-based IIT targeting malignant tumors， western medicine institutions often face unique challenges in conducting such studies， which limit their feasibility and standardization. This paper reviews the registration status of TCM-based IIT for malignancies conducted in western medical institutions and analyzes key difficulties， including complex project initiation and management processes， limited TCM knowledge and skills among western medicine physicians， and relatively low patient acceptance of TCM. From a practical perspective， the study proposes several optimization strategies. These include improving the review and management mechanisms of TCM-related IIT within western medical institutions， establishing multidisciplinary clinical research teams that integrate TCM and western medicine， and enhancing investigators' training in TCM theory and clinical skills. Additionally， the study suggests standardizing IIT operational procedures， objectifying the collection of TCM diagnostic information， refining subject recruitment methods， and increasing TCM involvement in patient follow-up and management. These investigator-oriented， TCM-featured， and operable strategies aim to promote the high-quality development of TCM-based IIT in western medicine institutions and enhance the clinical application of TCM.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

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.

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Objective:To investigate the patterns of mutation evolution in patients with acute myeloid leukemia (AML) during treatment and the possible clinical significances.Methods:A retrospective case series study was conducted. A total of 103 AML patients who were hospitalized at the Affiliated Yuebei People's Hospital of Medical College of Shantou University from November 2019 to August 2021 and underwent high-throughput next-generation sequencing (NGS) technology to detect the mutations of 128 AML-related genes in bone marrow samples were selected. Based on the NGS results, the somatic gene mutations in samples of patients collected at initial diagnosis (73 cases), complete remission (CR) (30 cases), non-remission (NR) (23 cases), and recurrence (12 cases) were analyzed, and the targeted drugs involved in the gene mutations detected in NR and recurrence samples were summarized.Results:The median age [ M ( Q1, Q3)] of onset for 103 patients was 58 (48, 66) years, including 64 males (61%) and 39 females (39%); 86 cases (83%) were primary AML, and 17 cases (17%) were secondary AML; at the initial diagnosis, 51 cases (50%) had normal karyotypes, 34 cases (33%) had abnormalities, and 18 cases (17.5%) were unknown. Compared with the CR samples, the mutation frequencies of FLT3 [29% (21/73) vs. 3% (1/30)], NPM1 [27% (20/73) vs. 3% (1/30)], NRAS [22% (16/73) vs. 3% (1/30)], and IDH2 [14% (10/73) vs. 0 (0/30)] were all higher in the initial diagnosis samples, and the differences were statistically significant (all P < 0.05); compared with the initial diagnosis sample, the median number of gene mutations in each CR sample was lower [4 (2, 5) vs. 7 (5, 9)], and the difference was statistically significant ( P < 0.001). However, there was no statistically significant difference in the median number of gene mutations in each patient between the initial diagnosis samples and the NR samples, the initial diagnosis samples and the recurrence samples, and the NR samples and the recurrence samples (all P > 0.05). Analysis of 14 patients with NGS data at initial diagnosis and CR showed that the same gene mutations could be detected at initial diagnosis and CR, such as DNAH23 (3 cases), USH2A (3 cases), etc; partial gene mutations were detected at initial diagnosis but were not detected at CR, including NRAS (5 cases), FLT3 (3 cases), ANKRD26 (3 cases), NPM1 (3 cases), ETV6 (3 cases), etc; ARID1B (1 case) and DNMT3A (1 case) were negative for mutations at initial diagnosis but positive upon reaching CR. Analysis of 14 patients with NGS data at initial diagnosis and NR showed that most gene mutations persisted at initial diagnosis and NR, such as DNMT3A (5 cases), NRAS (5 cases), KRAS (3 cases), RUNX1 (3 cases), etc; the mutant genes detected at initial diagnosis but not detected at NR included USH2A (2 cases), PCLO (2 cases), ATM (2 cases), FAT1 (2 cases), etc; partial gene mutations were not detected at initial diagnosis but were detected at NR, such as FAT1 (2 cases), TCF3 (2 cases), etc. Analysis of 5 patients with NGS data at CR and recurrence showed that some gene mutations were detected at both CR and recurrence, such as BCORL1 (1 case), ARID2 (1 case), SETD2 (1 case), VEGFC (1 case), etc; FLT1 (1 case) and GNAS (1 case) gene mutations were detected at CR but not detected at recurrence; at recurrence, some gene mutations that were not detected at CR were also detected, such as ANKRD26 (1 case), WT1 (1 case), etc. Among the 23 NR samples and 12 recurrence samples, the targets of drugs approved by US Food and Drug Administration or in clinical trials were detected in 14 (61%) and 5 (42%) samples respectively, including IDH1, IDH2, FLT3, KIT, KRAS, NRAS, SF3B1, U2AF1, and SRSF2. Conclusions:The number of gene mutations in AML patients during CR is significantly less than that at initial diagnosis, some gene mutations disappear when CR is achieved through treatment, but the majority of gene mutations persist during the treatment period, including NR and recurrence, suggesting that monitoring through NGS technology can help understand the evolution of gene mutations during AML treatment and discover the potential therapeutic targets.

Objective To compare animal models of chronic heart failure(CHF)prepared by three different protocols,to establish a stable,reliable,and reproducible mouse model of CHF.Methods Twenty-five male C57BL/6J mice were divided randomly into four groups:a blank group,model A group(MA group),model B group(MB group),and model C group(MC group).The model groups adopted different preparation protocols for continuous injection of isoprenaline.The MA group and MB group were dose-decreasing models:MA group:subcutaneous injection of 10 mg/kg on day 1,5 mg/kg on day 2,2.5 mg/(kg·d)on days 3～30,total 30 days;and MB group:subcutaneous injection of 20 mg/kg on day 1,10 mg/kg on day 2,5 mg/(kg·d)on days 3～14,total 14 days.The MC group used a constant dose of intraperitoneal injection of 7.5 mg/(kg·d)for 28 days.The day after the final injection,the survival and model-formation rates for each group of mice were calculated.Cardiac function was measured by cardiac ultrasound and serum levels of N-terminal pro B-type natriuretic peptide,interleukin-6,and tumor necrosis factor-α were measured.Results CHF was successfully induced in all the model groups after all injections at the end of the fourth week.However,comprehensive test result showed that the MC model was the most stable.Conclusions An isoprenaline-induced mouse model of CHF using constant intraperitoneal injection of 7.5 mg/(kg·d)for 28 days may be the most suitable model for subsequent research on traditional Chinese medicine.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

ObjectiveTo explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription. MethodEight patients with colorectal adenoma in damp-heat accumulation syndrome， 11 patients with non-damp-heat accumulation syndrome， and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained， and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases. The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome， damp-heat accumulation syndrome， and colorectal cancer， and functional enrichment analysis and signaling pathway enrichment analysis were carried out. Real-time polymerase chain reaction （Real-time PCR） was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes. ResultBy comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome， a total of 384 differentially expressed genes were screened， of which 203 were up-regulated genes， and 181 were down-regulated genes. By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome， a total of 2 965 differentially expressed genes were screened， of which 2 460 were up-regulated genes， and 505 were down-regulated genes. The intersection of differentially expressed genes of the two groups was taken， and a total of 58 differentially expressed genes with the same changes were screened. The gene ontology functions were mainly enriched in UDP-galactose： β-N-acetylglucosamine beta-1，3-galactosyltransferase activity， N-acetyllactosaminide beta-1，3-N-acetylglucosaminyltransferase activity， and poly-N-acetyllactosamine biosynthetic process. Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways were mainly enriched in glycosphingolipid biosynthesis-globo and isoglobo series， glycosphingolipid biosynthesis-lacto and neolacto series， and IL-17 signaling pathway. Shenbai Jiedu prescription significantly inhibited the expression of key genes involved in the enrichment， such as FOSB and B3GALT5， in a dose-dependent manner （P<0.05）. ConclusionGlycolipid metabolism may be the biological foundation of colorectal adenoma in damp-heat accumulation syndrome， and Shenbai Jiedu prescription may inhibit colorectal adenoma carcinogenesis by down-regulating the expression of FOSB and B3GALT5.

ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets. MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription， their clinical symptoms were observed， and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry （LC-MS） were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients. ResultThe total scores of traditional Chinese medicine （TCM） syndromes of patients after drug administration decreased significantly （P<0.01）. The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration， and a total of 106 differential metabolites were screened out （P<0.05）. The Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis revealed that arginine-proline metabolism， ferroptosis， glycine， and serine and threonine metabolism were significantly enriched metabolic pathways （P<0.05）. Notably， L-4-hydroxyglutamate semialdehyde， glutathione， isopentenyl pyrophosphate， creatinine， 4-acetamido-2-aminobutanoic acid， and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore， the association between these metabolites and different intestinal flora was analyzed， and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium， Eggerthella， and Dialister （P<0.05）. ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria， reducing the abundance of harmful bacteria， and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.