BACKGROUND:Liver organoids are of great significance to elucidate the exact pathological mechanism of liver diseases and the treatment of liver diseases. OBJECTIVE:To summarize the basic research in this field at home and abroad,review the important research progress in the construction of liver organoids,disease modeling and transplantation therapy,and discuss the application prospect of combined tissue engineering technology of liver organoids. METHODS:The relevant articles included in PubMed and CNKI databases were searched.The English and Chinese search terms were"liver,organoids,liver diseases."The main search time was from April 2018 to April 2024.Duplicate literature was excluded by manual reading.Finally,94 articles were included for review and analysis. RESULTS AND CONCLUSION:The seed cells constructed by liver organoids are mainly concentrated in adult cells and pluripotent stem cells,which promote the generation of organoids by assisting various cytokines to participate in signal guidance and providing 3D microenvironment by extracellular matrix.However,the overall maturity is not high,which is expected to improve this problem by combining tissue engineering technology.In vitro disease modeling is mainly studied in the field of simple diseases and single-gene genetic diseases.Organoids highly retain patient genetic characteristics,and it is expected to simulate more complex liver diseases and clarify deeper pathological mechanisms by combining CRISPR-Cas9 gene correction and other emerging technologies.In vivo transplantation treatment,liver organoids can be safely and effectively implanted,showing amazing liver function replacement potential,tissue regeneration ability,and may also be combined with other tissue engineering materials to achieve therapeutic purposes.

AIM:To evaluate the clinical efficacy of lamellar keratectomy and corneal collagen crosslinking(LKCCC)in treating superficial fungal keratitis.METHODS: Retrospective analysis. Totally 79 patients(79 eyes)with superficial fungal keratitis who underwent LKCCC in our hospital from January 2014 to October 2023 were included. After admission, routine antifungal drug treatment for 7 d showed no obvious improvement or progressive aggravation. The maximum diameter of corneal lesions in all patients was ≤7 mm, the maximum depth was no more than 50% of the corneal thickness at the location, and the remaining healthy corneal thickness was ≥300 μm. The follow-up time was 90 to 112 d.RESULTS:Among the included 79 eyes, the lesions were located in the central region of the cornea in 6 eyes, in the paracentral region in 61 eyes, and in the peripheral region in 12 eyes. Hypopyon was observed in 5 cases. LKCCC was successfully administered in 79 eyes, cured in 76 eyes(96%), and failed in 3 eyes(4%). The healing time of corneal epithelium in 76 cured eyes was 3-15 d, of which 51 eyes(67%)healed within 7 d and 24 eyes(32%)healed within 3 d. The uncorrected visual acuity(UCVA)and best corrected visual acuity(BCVA)of 76 eyes of cured patients were statistically significant compared with those preoperatively(P<0.0167). Two of the 3 failed eyes were located at the edge of the lesion and recovered after re-keratectomy. One eye was located in the center of the lesion and recovered after being covered by bulbar conjunctival flap. At the last follow-up, no other complications were observed in all patients except superficial cloud and thinning of cornea.CONCLUSION:LKCCC is a rapid and effective treatment for superficial fungal keratitis and can be considered a new treatment option.

AIM: To assess the impact of optimized pulsed technology(OPT)on the morphological and functional changes of meibomian glands in patients with meibomian gland dysfunction(MGD).METHODS: This prospective case-control study enrolled 60 MGD patients(60 right eyes)treated at Weifang Eye Hospital from September 2023 to February 2024. Patients were categorized into mild, moderate, and severe groups based on the extent of meibomian gland loss, with 20 cases(20 eyes)per group. Treatments consisted of bilateral OPT combined with meibomian gland massages, administered biweekly over four sessions. Ocular surface function indicators including the ocular surface disease index(OSDI), corneal fluorescein staining(CFS), non-invasive average tear break-up time(NIBUTav), and non-invasive tear meniscus height(NITMH), as well as meibomian gland function parameters such as meibomian gland expressibility score(MGES)and meibomian gland secretion score(MGYSS)were observed and recorded before treatment and at 3 mo after final treatment. Cellular-level assessments using in vivo confocal microscopy(IVCM)examined meibomian gland acinar unit density(MGAUD), inflammatory cell density(ICD), meibomian gland acinar longest diameter(MGALD)and meibomian gland acinar shortest diameter(MGASD).RESULTS: At baseline, no significant differences were found in NITMH across groups(P>0.05). Statistical significance were observed in NIBUTav, MGES, MGYSS, MGAUD, MGALD, and MGASD(all P<0.05). Compared to the mild group, the moderate and severe groups showed significant differences in OSDI, CFS, and ICD(all P<0.05), though no significant differences existed between moderate and severe groups(all P>0.05). At 3 mo after treatment, all groups showed no significant differences in NITMH(all P>0.05). All parameters improved significantly in the mild group(all P<0.05); all indicators improved in the moderate group(P>0.05), except for MGASD before and after treatment(all P<0.05); significant improvements were noted in OSDI, CFS, and NIBUTav in the severe group(all P<0.05), while MGES and MGYSS did not differ significantly(all P>0.05). IVCM parameters(MGAUD, ICD, MGALD, and MGASD)showed no significant change in the severe group(all P>0.05).CONCLUSION:OPT effectively enhances various ocular surface functions and improves gland expressibility and secretion quality in mild to moderate MGD cases, while also positively impacting certain cellular parameters. In severe cases, where most acinar functions are lost and structural reversibility is limited, OPT can still mitigate MGD symptoms and decelerate disease progression.

Objective To analyze the distribution characteristics and trends of occupational exposure types of medical radiation workers in Gansu Province, China, and to provide a basis for administrative departments to formulate and adjust radiation protection policies. Methods According to the radiation health information platform, the data of occupational exposure types of radiation workers in Gansu Province from 2014 to 2023 were obtained. The proportions of occupational exposure types in each physical examination year was statistically analyzed. Results From 2014 to 2023, the number of medical radiation workers accounted for more than 70% of the total number of radiation workers. The proportion of X-ray imaging diagnostic radiation workers in the total number of medical radiation workers gradually decreased but remained the highest, exceeding 68% annually. The proportion of interventional radiology workers in the total number of medical radiation workers increased from 13.8% to 25.5%. The proportions of radiation therapy and nuclear medicine workers in the total number of medical radiation workers increased slowly. The numbers of interventional radiology and radiotherapy workers in tertiary hospitals both accounted for more than 70% of the total number of such workers in the province. The proportion of interventional radiology workers increased and then decreased. The proportion of radiotherapy workers increased significantly from 70.5% to 93.0%. The number of nuclear medicine workers in tertiary hospitals accounted for more than 80% of such workers in the province. Conclusion Radiation protection policies and measures should be adjusted according to the changes in the types of occupational exposure. The focus of these policies and measures should differ depending on the level of healthcare institutions, the type of radiological diagnostic and therapeutic services, and the characteristics of various occupational exposure types .

Intrahepatic cholangiocarcinoma （ICC） is a highly malignant liver tumor， and due to the absence of symptoms in its early stage and the lack of effective treatment measures， patients tend to have an extremely low 5-year survival rate. The tumor stroma-immune microenvironment （TSIME） is a complex ecosystem that changes dynamically during tumorigenesis and evolution and consists of a variety of cellular and non-cellular components， and it plays an important role in the development， proliferation， invasion， and progression of ICC and determines the heterogeneity and malignancy of ICC to a certain degree. This article reviews the cellular components （such as T cells， B cells， natural killer cells， dendritic cells， neutrophils， macrophages， myeloid-derived suppressor cells） and non-cellular components （such as chemokines and cytokines） within the ICC TSIME， as well as the complex mechanisms of interaction between these components， and it also reviews the spatial interactions between immune cells and tumor cells， in order to provide potential research directions for ICC immunotherapy and new ideas for the effective and precise treatment of ICC in the future.

AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Tumor immunotherapy has achieved breakthroughs in the treatment of malignant tumors by activating the host immune system’s antitumor response mechanism. Among various strategies, Toll-like receptor (TLR) agonists have garnered substantial attention due to their unique immunomodulatory capabilities. This work reviews the research progress on the combination of TLR agonists with radiotherapy in tumor immunotherapy, focusing on the clinical translational potential of intratumoral injection strategies. Clinical studies have shown that the in-situ injection of TLR agonists in combination with radiotherapy can effectively suppress primary and metastatic lesions by inducing immunogenic cell death, releasing tumor antigens, activating local immune responses, and triggering abscopal effects. Moreover, novel extended-release formulations and “endogenous vaccine” designs further enhance the safety and durability of treatment. Despite several challenges such as tumor microenvironment suppression and dose optimization, TLR agonists hold promise for the treatment of “cold” tumors lacking innate immunity through combinations with immune checkpoint inhibitors, nanodelivery technologies, and precise biomarker screening.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To investigate the improvement effect of the freeze-dried garlic powder on acute myocardial ischemia and its effect on phosphatidylinositol 3 kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (PI3K/Akt/Nrf2) signaling pathway.Methods:SD rats were randomly divided into sham-operation group, model group, positive drug group, and garlic freeze-dried powder low-, medium-, and high-dosage groups using a random number table method, with 12 rats in each group. The garlic freeze-dried powder low-, medium-, and high-dosage groups were orally administered with 0.58, 1.16, and 2.32 g/kg of garlic freeze-dried powder solution, the positive reference drug group was orally administered with 0.26 g/kg of compound Danshen tablet solution, and the model group and sham-operation group were orally administered with equal volumes of distilled water once a day for 14 consecutive days. Except for the sham-operation group, all other groups were prepared with acute myocardial ischemia models in rats by ligating the left anterior descending coronary artery. Electrocardiogram testing was performed. The incidence of ventricular premature beats, ventricular tachycardia, and ventricular fibrillation in each group was counted. Myocardial infarction was observed through TTC staining, and the myocardial infarction rate was calculated; serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), LDH, cardiac troponin T (cTnT), total antioxidant capacity (T-AOC), SOD, MDA, IL-1β, TNF-α levels were detected, and Western blot was used to detect myocardial tissue p-PI3K, p-Akt, Nrf2, HO-1 and Keap1 proteins.Results:Compared with the model group, the incidence of premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation in rats in each treatment group was reduced. Compared with the model group, the positive drug group and garlic freeze-dried powder medium- and high-dosage groups showed a decrease in myocardial infarction rate in rats ( P<0.05); compared with the model group, the levels of serum T-AOC and SOD in each treatment group increased ( P<0.05 or P<0.01), while the level of MDA decreased ( P<0.05 or P<0.01); the levels of CK, LDH, cTnT, IL-1β, and TNF-α in the serum of rats in the positive drug group and garlic freeze-dried powder high-dosage group decreased ( P<0.05 or P<0.01), while the expressions of p-PI3K, p-Akt, Nrf2, and HO-1 proteins in myocardial tissue increased ( P<0.05 or P<0.01), and the expression of Keap1 protein decreased ( P<0.05 or P<0.01). Conclusions:Garlic freeze-dried powder can improve acute myocardial ischemia of rats by reducing the release of serum myocardial enzymes and exerting antioxidant and anti-inflammatory effects. The mechanism may be related to regulating PI3K/Akt/Nrf2 signaling pathway.

This paper conducts a pooled analysis of information related to orphan drugs approved for marketing in 2024 by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan. It systematically sorts out the scope of indications, therapeutic area distribution, and special review and approval pathways of these drugs, as well as their research and development progress and marketing status in China, thus providing a reference for researchers, regulatory authorities, and industry stakeholders in the field of rare disease drugs.