As a distinctive resource of Chinese civilization， traditional Chinese medicine （TCM） technology transfer faces significant opportunities under the background of digital and intelligent transformation， while also being constrained by unique challenges such as the complexity of its theoretical system， lengthy industrial chains， and multidimensional policy restrictions， resulting in a "high-value-high-threshold" paradox. At present， TCM technology transfer is deeply trapped in a "threefold reluctance" dilemma， i.e.， unwillingness to transfer， inability to transfer， and lack of capacity to transfer. Specifically， the disconnection between scientific research evaluation systems and market demand leads to low conversion rates of research achievements， unclear ownership and compliance risks suppress innovation incentives， and the absence of professional services intensifies supply-demand mismatches. This article systematically analyzes the specific characteristics of TCM technology transfer and proposes a breakthrough pathway centered on full-chain digital and intelligent transformation. By integrating technologies such as intelligent sorting systems， blockchain-based traceability， and AI diagnostic models， the TCM ecosystem spanning "cultivation-production-service" can be reconstructed. In terms of standardization， promoting the progression from "experience-based data conversion" to "data standardization" and further to "intelligent standardization" is advocated to resolve quality control challenges. For example， a "three-no-one-full" certification system can strengthen quality trust. Policy coordination should focus on optimizing mechanisms for the transformation of scientific and technological achievements， while exploring intellectual property securitization and risk-sharing models to stimulate research momentum. In terms of internationalization， reliance on the Belt and Road Initiative platform to promote the export of geo-authentic medicinal material brands and standards is recommended to build a dual-driven model of "technology plus culture". Looking ahead， through the construction of national-level databases， the cultivation of interdisciplinary talent， and the mutual recognition of international standards， a new paradigm of "scientific intelligent manufacturing" can be formed， providing systematic solutions for the modernization of TCM and global health governance.

Ten-eleven translocation 2 （TET2）， as a core enzyme in epigenetic regulation， dynamically regulates the differentiation and function of CD4⁺ T cells by mediating DNA demethylation. Recent studies have shown that TET2 deficiency can promote the progression of autoimmune hepatitis （AIH） by disrupting the Th17/Treg balance and activating inflammatory signals along the gut-liver axis. This article systematically reviews the bridging role of TET2 between CD4⁺ T cells and gut microbiota， explores the molecular mechanisms by which it drives AIH through the gut microbiota-epigenetics-immunity network， and discusses the potential intervention strategies targeting the TET2-microbiota axis.

Standardizing the emergency assessment and management process for patients with implantable continuous-flow left ventricular assist device (LVAD) in emergency and intensive care settings is of great significance for reducing delays in diagnosis and treatment, lowering the mortality associated with LVAD-related emergencies, and improving overall prognosis and long-term survival. To this end, a multidisciplinary expert committee was convened to develop this consensus, integrating international evidence-based findings with clinical practice experience in China, with an emphasis on highlighting the characteristics of domestically manufactured devices. The aim is to establish an actionable standardized emergency management protocol to enhance clinical identification and response efficiency, reduce the risk of LVAD-related emergencies, and improve patient outcomes. Using a modified Delphi method, this consensus proposes a structured decision-making pathway that integrates an "ABC" rapid assessment with parallel device troubleshooting, prioritizing the use of point-of-care echocardiography for hemodynamic evaluation and complication assessment. Key emergency scenarios covered include low-flow alarms, pump thrombosis, right heart dysfunction, bleeding and anticoagulation imbalance, arrhythmias, and cardiac arrest. This consensus applies to implantable continuous-flow LVADs commonly used in China, including domestically manufactured devices such as Corheart 6, CH-VAD, EVAHEART, and HeartCon, as well as the imported device HeartMate 3.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective:To compare the impact of preoperative pulmonary vascular resistance(PVR) levels on the prognosis of patients undergoing left ventricular assist device(LVAD)implantation.Methods:A retrospective analysis was conducted on the clinical data of 33 patients among September 2021 and June 2024, who underwent LVAD implantation at Zhongshan Hospital, Fudan University. 29 males and 4 females, with a mean age of(53.61±9.65)years old. The cohort included 30 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 1 case of noncompaction cardiomyopathy. Patients were grouped based on a preoperative PVR threshold of 3 WU, Preoperative data from Swan-Ganz catheterization, liver and renal function indicators, as well as other relevant clinical parameters were recorded. Patients were followed up to assess differences in survival outcomes.Results:Preoperative PVR was elevated in 18 cases(60%)of the patients, with a mean preoperative PVR of(3.16±1.71)WU. Immediate postoperative right heart catheterization was performed in 20 patients, showing a significant reduction in PVR from(3.85±1.72)WU preoperatively to(1.80±1.38)WU postoperatively( P<0.05). The cardiac index improved significantly from(1.95±0.63)L·min -1·m -2 preoperatively to(4.25±1.26)L·min -1·m -2 postoperatively( P<0.001). The mean follow-up duration was(14.78±12.06)months, no significant difference in postoperative survival was observed between the two groups(100% vs. 80%, P=0.667). Conclusion:Increased pulmonary resistance is often secondary to left heart dysfunction. After the implantation of a LVAD, pulmonary resistance can be improved. For patients with relatively normal right heart function before surgery, elevated pulmonary resistance does not affect the short-term outcomes of the implantation.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

To investigate the infection status of two arboviruses,akabane orthobunyavirus(AKAV)and bluetongue virus(BTV),in cattle herds of Guizhou Province,we employed the indirect ELISA method to detect AKAV and BTV antibody levels in the present experiment.A total of 1504 bovine serum samples from 37 large-scale farms and 88 free-range households from 26 districts or coun-ties of 7 cities(prefectures)of Guizhou Province were collected to detect AKAV antibody levels.Additionally,1 241 serum samples from 30 large-scale farms and 15 free-range households in 19 districts or counties of 3 cities(prefectures)were tested for BTV antibody levels.Moreover,two influencing factors,breeding mode and sampling season,were statistically analyzed for their effects.The results showed that the overall positive rate of AKAV antibodies was 11.64％(175/1 504),with individual positive rates of 13.20％(123/934)and 9.12％(52/570)in large-scale farms and free-range households,respectively.No significant differences were observed between the two groups.However,the farm positive rate(64.86％,24/37)in large-scale farms was significantly higher than that(26.14％,23/88)in free-range households.Seasonal statistics showed that the positive rate was highest during the summer season at 60.00％(12/20).The total positive rate of BTV antibodies was 25.42％(222/1 241).The farm positive rate and individual positive rate in free-range households were 66.67％(10/15)and 41.91％(57/136),respectively.For large-scale farms,these rates were 60.00％(18/30)and 14.93％(165/1 105),respectively.The individual pos-itive rate in free-range households was significantly higher than that in large-scale farms.Seasonal statistics showed that the positive rates in summer and autumn seasons were 50.00％(5/10)and 72.41％(21/29),respectively,both of which were significantly higher than those in winter and spring seasons.All these findings indicated that both AKAV and BTV were present to a certain ex-tent in Guizhou Province,with seasonality.Furthermore,differences were observed between the different breeding modes.Our results could provide a data reference for the formulation of preven-tion and control measures for the two insect-borne diseases.

To establish a rapid visual detection method for Akabane virus(AKAV)on site,specific primers and probes based on the S fragment of AKAV were designed in this experiment.Corre-sponding groups were added to the primers or probes to fulfil the requirement of the combination of recombinase polymerase amplification(RPA)with lateral flow dipstick(LFD).The reaction temperature and time,concentrations of the primer and probe were optimized to establish the RPA-LFD method for detecting AKAV.After that,the specificity,sensitivity and clinical reliability of the method were evaluated.The results showed that after 20 minutes of reaction at 37 ℃,the test results could be read on LFD paper.There was no cross reaction against blue tongue virus,Pasteurella multocida,bovine infectious rhinotracheitis virus and bovine Mycoplasma bovis,and the detection limit was 2.5 × 100 copies/μL of standard plasmid.Detection of clinical samples showed a consistent results with that by RT-PCR method.These findings indicated that the RPA-LFD method established had the advantages of good specificity,high sensitivity,simple operation and visualization,and could be applied to clinical detection,which provides new technical support for the rapid diagnosis and prevention and control of AKAV.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Autoimmune hepatitis （AIH） is an inflammatory disease caused by immune dysfunction， and its pathogenic mechanism remains unclear. In recent years， a large number of studies have shown that iron homeostasis imbalance and ferroptosis are closely associated with the pathogenesis and progression of AIH. This article reviews the pathological mechanism and impact of iron overload and ferroptosis in AIH， in order to provide new insights and theoretical bases for research on the mechanism and clinical treatment of AIH.