Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

This paper focuses on the necessity and feasibility of the multidimensional integration of clinic, culture and language in the international education of acupuncture-moxibustion within a cross-cultural context. In view of the current gap between theory and practice, and the barrier of culture and language in the international education of acupuncture-moxibustion, it proposes the specific integration approaches, such as the "trinity teaching method" and "modularization of acupuncture courses", which develops the framework of international education of acupuncture-moxibustion, guided by "cultural exploration" in macroscopic view and implemented through "cultural experience", aiming to achieve a seamless integration of clinic, culture, and language. This initiative not only inherits and promotes Chinese acupuncture-moxibustion, maintains its unique position in global healthcare, but also fosters dialogue and exchange between Eastern and Western medicine. Ultimately, it enhances the international recognition of Chinese acupuncture-moxibustion. By offering fresh perspectives and methodologies, this paper paves the way for a more comprehensive and systematic approaches to international education of acupuncture-moxibustion, presenting the theoretical and practical significance in advancing the globalization of traditional Chinese medicine.
Humans ; Moxibustion ; Language ; Acupuncture/education* ; Acupuncture Therapy ; Culture ; China

Objective:This study aims to construct a quality evaluation index system for specialized disease databases. Through systematic assessment and optimization, it seeks to comprehensively enhance the quality and standardization of specialized disease cohort data. This initiative will provide more precise and reliable data support for disease research, the development of innovative drugs and medical devices, as well as policy formulation.Methods:By conducting a thorough analysis of domestic and international literature and policies related to clinical research data quality evaluation systems, preliminary quality evaluation indicators for specialized disease databases were established. Utilizing the Delphi method in two rounds, a quality evaluation system for specialized disease databases was constructed. The Analytic Hierarchy Process (AHP) and YAAHP 7.5 software were then employed to calculate the relative weights of indicators at various levels and their composite weights.Results:The two rounds of expert consultation achieved a 100.00% valid response rate, with an expert authority coefficient of 0.81 in both rounds. In the second round, the Kendall′s coordination coefficients for the first-level and second-level indicators reached 0.311 and 0.218, respectively ( P<0.05), indicating a good level of consensus among experts. The final specialized disease database quality evaluation system consists of 3 first-level indicators, 10 second-level indicators, and 32 third-level indicators. The first-level indicators include database construction, data quality, and cohort development, with weight coefficients of 31.82%, 41.49%, and 26.69%, respectively. The scientific validity of the indicator system was confirmed through reliability and validity analyses. When applied to assessing 58 specialized disease database projects from 36 medical institutions in a certain city, the results showed significant improvements in scores for database construction, data quality, and cohort development, with the most notable improvement observed in database construction. Conclusions:This study successfully developed a scientific, practical, and rationally weighted quality evaluation system for specialized disease databases, demonstrating high expert consensus and broad applicability.Validation studies have shown that this system effectively enhances the standardization and data quality of databases, providing robust technical support and assurance for specialized disease research and data resource sharing.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:This study aims to construct a quality evaluation index system for specialized disease databases. Through systematic assessment and optimization, it seeks to comprehensively enhance the quality and standardization of specialized disease cohort data. This initiative will provide more precise and reliable data support for disease research, the development of innovative drugs and medical devices, as well as policy formulation.Methods:By conducting a thorough analysis of domestic and international literature and policies related to clinical research data quality evaluation systems, preliminary quality evaluation indicators for specialized disease databases were established. Utilizing the Delphi method in two rounds, a quality evaluation system for specialized disease databases was constructed. The Analytic Hierarchy Process (AHP) and YAAHP 7.5 software were then employed to calculate the relative weights of indicators at various levels and their composite weights.Results:The two rounds of expert consultation achieved a 100.00% valid response rate, with an expert authority coefficient of 0.81 in both rounds. In the second round, the Kendall′s coordination coefficients for the first-level and second-level indicators reached 0.311 and 0.218, respectively ( P<0.05), indicating a good level of consensus among experts. The final specialized disease database quality evaluation system consists of 3 first-level indicators, 10 second-level indicators, and 32 third-level indicators. The first-level indicators include database construction, data quality, and cohort development, with weight coefficients of 31.82%, 41.49%, and 26.69%, respectively. The scientific validity of the indicator system was confirmed through reliability and validity analyses. When applied to assessing 58 specialized disease database projects from 36 medical institutions in a certain city, the results showed significant improvements in scores for database construction, data quality, and cohort development, with the most notable improvement observed in database construction. Conclusions:This study successfully developed a scientific, practical, and rationally weighted quality evaluation system for specialized disease databases, demonstrating high expert consensus and broad applicability.Validation studies have shown that this system effectively enhances the standardization and data quality of databases, providing robust technical support and assurance for specialized disease research and data resource sharing.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

AIM:To research the effects of cyti-dine deaminase(CDA)C435T polymorphism on the long-term effectiveness of gemcitabine in non-small cell lung cancer(NSCLC).METHODS:Enrolled 145 NSCLC patients received gemcitabine-platinum regiments at the Affiliated Hospital of Xuzhou Med-ical University from August 2016 to February 2019,characteristics recorded such as:age,gender,path-ological type,clinical stage(Ⅰ-ⅢA/ⅢB-Ⅳ)and so on.Followed-up and evaluated according to RECIST1.1,the disease-free survival(DFS),progression-free survival(PFS)and overall survival(OS)was study endpoint.Cases were categorized into wild-type CC and mutant CT/TT group.Kaplan-Meier method and log-rank test were utilized to analyze the rela-tionship between CDA C435T and DFS/PFS/OS.A cox model was implemented to analyze the prog-nostic factors.RESULTS:In stage Ⅰ-ⅢA,median DFS of CT/TT compared with CC was not obvious(16.8 vs.35.7 months,P=0.294),same in median OS(54.3 vs.81.9 months,P=0.256).In stage ⅢB-Ⅳ,the median PFS in CT/TT was longer than CC(10.4 vs.5.0 months,P=0.009),the median OS was undiffer-entiated(16.2 vs.24.3 months,P=0.087).No differ-ence of overall median OS in CC and CT/TT geno-types was seen(21.5 months vs.25.3 months,P=0.077).Cox regression model showed CDA C435T polymorphism was an independent factor of PFS in stage ⅢB-Ⅳ(P=0.019).CONCLUSION:CDA C435T polymorphism shows a function as a prediction in-fluencing PFS of gemcitabine in ⅢB-Ⅳ NSCLC,CT/TT genotype is significantly prolonged.