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.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

OBJECTIVE: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). METHODS: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. RESULTS: C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. CONCLUSION We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Humans ; Colorectal Neoplasms/diagnosis* ; Cyclin-Dependent Kinase 4/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/genetics* ; Aged ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.

Plant-derived nanovesicles (PDNVs) derived from natural green products have emerged as an attractive nanoplatform in biomedical application. They are usually characterized by unique structural and biological functions, such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups, immune-modulation, and long-term circulation. With the rapid development of nanotechnology, materials, and synthetic chemistry, PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells, which represent an innovative biomaterial with high biocompatibility for fighting against cancer. In this review, we provide an overview of the state-of-the-art studies concerning the development of PDNVs for cancer therapy. The original sources, methods for obtaining PDNVs, composition and structure are introduced systematically. With an emphasis on the featured application, the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail. Finally, some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed, which are expected to promote the further development of PDNVs in clinical translation.

Objective To evaluate the clinical efficacy of oral use of Jiawei Puji Xiaodu Granules(mainly composed of Lonicerae Japonicae Flos,Forsythiae Fructus,Taraxaci Herba,Violae Herba,Schizonepetae Herba,Arctii Fructus,Gleditsiae Spina,Paeoniae Radix Rubra,Moutan Cortex,and Phragmitis Rhizoma)combined with external application of Xiaozhong Sanjie Ointment(mainly composed of Scutellariae Radix,Coptidis Rhizoma,Phellodendri Chinensis Cortex,and Gleditsiae Spina,etc.)in the treatment of acute tonsillitis in children,and to observe their effects on the immune function and related inflammatory indexes of the patients.Methods A total of 116 children with acute tonsillitis of heat stagnation in the lung and stomach type were randomly divided into the control group and the observation group,with 58 cases in each group.The control group was treated with Cefixime Dispersible Tablets,while the observation group was treated with Jiawei Puji Xiaodu Granules for oral use and Xiaozhong Sanjie Ointment for external application.Both groups were treated for 14 days and then were followed-up for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,white blood cell(WBC)count,T lymphocyte subset CD3+,CD4+,CD8+ and CD4+/CD8+ levels,and serum levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),interleukin 6(IL-6)and C-reactive protein(CRP)in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and time for the disappearance of clinical symptoms were compared between the two groups,and the occurrence of adverse reactions and the recurrence of tonsillitis in the two groups were monitored at the same time.Results(1)During the trial,there were 8 cases falling off in the control group but none case falling off in the observation group,and eventually 50 cases in the control group and 58 cases in the observation group completed the full course of treatment.(2)After 14 days of treatment,the total effective rate of the observation group was 98.28%(57/58),while that of the control group was 90.00%(45/50).The intergroup(tested by rank sum test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the time for the disappearance of sore throat,time for the disappearance of purulent spots,time for subsiding fever and time for the tonsils recovering to normal in the observation group were all significantly shorter than those in the control group(P＜0.05).(4)After treatment,the scores of primary and secondary symptoms and the overall symptom scores in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction of the scores in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the levels of T lymphocyte subset CD3+,CD4+ and CD4+/CD8+ in the two groups were significantly higher(P＜0.05)while the level of CD8 + was significantly lower(P＜0.05)than those before treatment,and the increase in the levels of CD3+,CD4+ and CD4+/CD8+ and the reduction of the CD8+ level of the observation group were significantly superior to those of the control group(P＜0.05).(6)After treatment,the levels of WBC,TNF-α,IL-1β,IL-6 and CRP in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the treatment period,no skin allergy,nausea,vomiting or other gastrointestinal adverse reactions occurred in the two groups,which showed a high degree of safety.(8)The 6-month follow-up showed that the recurrence rate of tonsillitis in the observation group was 5.17%(3/58),which was significantly lower than that of 24.00%(12/50)in the control group,and the difference was statistically significant(χ2 = 8.330,P＜0.05).Conclusion The efficacy of Jiawei Puji Xiaodu Granules combined with Xiaozhong Sanjie Ointment exert notable curative effect for children with acute tonsillitis of heat stagnation in the lung and stomach type.The combined therapy can significantly shorten the duration of the disease,improve the clinical symptoms of the children and effectively reduce the recurrence rate of tonsillitis.The therapeutic mechanism may be related to the enhancement of the immune function and the inhibition of inflammatory response.

Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3％,and the complete remission(CR)rate after treatment was 33.3％.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.

AIM To study the chemical constituents from the stems of Gnetum parvifolium(Warb.)C.Y.Cheng ex Chun and their xanthine oxidase inhibitory activities.METHODS The 95%ethanol extract from the stems of G.parvifolium was isolated and purified by silica gel,MCI and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The inhibitory activities on xanthine oxidase was determined by ultraviolet spectrophotometry.RESULTS Seventeen compounds were isolated and identified as isorhapontigenin(1),resveratrol(2),4-hydroxybenzaldehyde(3),cycloeucalenol(4),(E)-1-(3',5'-dimethoxyphenyl)-2-(3,4-dimethoxyphenyl)ethene(5),stigmast-4-en-3-one(6),medioresinol(7),chrysin(8),aurantiamide acetate(9),(-)-pinoresinol(10),methyl 4-hydroxybenzoate(11),2-methoxybenzene-1,4-diol(12),gnetumontain C(13),syringaresinol(14),homoeriodictyol(15),vanillin(16),β-sitosterol(17).The IC50 values of compounds 1-3,15-16 were(11.4±0.54),(14.1±1.06),(320.4±0.75),(360.6±0.78),(386.3±0.71)μmol/L,respectively.CONCLUSION Compounds 3-4 are isolated from this plant for the first time.Compounds 5-13 are first isolated from genus Gnetum.Compounds 1-3,15-16 have xanthine oxidase inhibitory activities.

Humans ; Retrospective Studies ; Tetanus/epidemiology* ; China/epidemiology*