Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage， and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation， and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora， short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways， thereby playing an important role in the diagnosis， treatment， and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs， this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE， in order to provide new ideas for optimizing clinical prevention and treatment strategies.

AIM: To evaluate the effects of 3% diquafosol ophthalmic solution(DQS)on the ocular surface and tear film in adolescents with mild dry eye syndrome during the early stage of wearing orthokeratology lenses.METHODS: Prospective study. Totally 60 myopic adolescents(120 eyes)with mild dry eye syndrome who were fitted with orthokeratology lenses for the first time in our hospital from January 2023 to September 2023 were enrolled in this study. They were randomly divided into control group and observation group. Both groups wore the same brand of orthokeratology lenses for 8-9 h a day and 7 d a week. In the control group(30 cases, 60 eyes), the patients were treated by routine eyelid cleaning and warm compresses from the day of fitting. In addition to the control group's treatment, patients in the observation group(30 cases, 60 eyes)were given DQS 6 times a day for 3 mo, and follow-up for 6 mo after discontinuation of DQS. According to the follow-up requirements of orthokeratology lens, uncorrected visual acuity(UCVA), corneal curvature, corneal topography, and corneal fluorescein staining were rechecked. The ocular surface disease index(OSDI)scores, tear meniscus height(TMH)of lower eyelid, non-invasive tear film break-up time [first and average, NIBUT(f)and NIBUT(av)] and corneal fluorescein staining were measured at baseline, 1, 2 and 3 mo after treatment, and 3 and 6 mo after DQS discontinuation.RESULTS: All patients completed follow-up. The NIBUT(f), NIBUT(av)and TMH of lower eyelid in the observation group were higher than those in the control group at 2 and 3 mo after treatment and at 3 and 6 mo after discontinuation of DQ3(all P<0.05). The OSDI scores for both groups decreased significantly at 2 mo after treatment(all P<0.05). At 3 mo after treatment and 3 and 6 mo after discontinuation of DQS, the OSDI scores in the observation group was significantly lower than the control group(all P<0.01). There was no significant difference of corneal fluorescein staining between the two groups(P=0.731).CONCLUSION: The combination of DQS with eyelid hygiene and warm compresses shows better efficacy in enhancing the stability of the tear film for adolescents with mild dry eye syndrome while wearing orthokeratology lenses.

AIM:To observe the defocus state and myopia control in myopic children wearing single-vision, defocus, and orthokeratology lenses using multispectral refraction topography(MRT).METHODS: A total of 279 myopic patients aged 8-14 years old, with a spherical equivalent(SE)from -7.00 to -0.50 D, treated at the Chengdu Aier Eye Hospital from June 2022 to December 2023. Patients who volunteered for the study were assigned to three groups. A total of 94 cases were provided with single-vision spectacle lenses(SVL group), 90 cases received individualized ocular refraction customization(IORC group), and 95 cases received orthokeratology lenses(OK group). Simultaneously, the three groups were further categorized into low(-3.00 to -0.50 D), moderate(-6.00 to -3.25 D), and high myopia(-7.00 to -6.25 D)groups according to different SE. MRT was used to measure and compare the defocus changes of the retina in supperior, inferior, nasal, and temporal quadrants(RDV-S, RDV-I, RDV-N, RDV-T), and three angles of field of view, including 0-15°, 15°-30°, and 30°-45°(RDV-15, RDV-30, RDV-45)in the three groups(the data divide for the connected regions is grouped to the latter group). A one-way analysis of variance was used for intergroup comparisons. Univariate and multivariate linear regression analyses were used to analyze the factors related to changes in the axial length(AL)at 1 a after intervention.RESULTS:There were significant differences in 1-year SE and AL growth among patients in the SVL, IORC, and OK groups before and after intervention(P<0.001). The 1-year SE and the difference of AL growth in patients with low myopia was significantly different among SVL, IORC, and OK groups(P<0.001); however, there was no significant difference between the IORC and OK groups(P>0.05); there were significant differences in the SE and AL growth changes between the OK group and the IORC and SVL groups in moderate myopia(P<0.001); and there were significant differences between the OK group and the IORC and SVL groups in SE and AL growth of high myopia group after wearing lenses for 1 a(P<0.001), while there were no significant differences between the IORC and SVL groups(P>0.05). In addition, there were significant differences in the relative peripheral refractive errors(RPRE)of 4 quadrants and 3 eccentric regions among the three groups of patients in different degrees of myopia groups(P<0.001). Pair-wise comparison of the growth difference of eccentric D-RDV-15 in low myopia group after wearing lenses for 1 a showed significant differences between the SVL, IORC, and OK groups(P<0.001), but no significant differences between the IORC and OK groups(P>0.05). The angle of field of view D-RDV-30 in moderate myopia subgroups was statistically different between the SVL group and the IORC and OK groups after wearing lenses for 1 a(P<0.001), while the IORC and OK groups showed no significant differences(P>0.05); the angle of field of view D-RDV-15 in high myopia subgroups was statistically different between the OK group and the IORC and SVL groups after wearing lenses for 1 a(P<0.001), but there was no significant difference between the IORC and SVL groups(P>0.05). Univariate and multivariate linear regression model analysis showed that the changes in D-TRVD, D-RDV-45, D-RDV-N, and D-RDV-I correlated with the increase in the difference in 1 a AL.CONCLUSION: MRT can be used to guide the clinical control of myopia. Myopia development is related to the peripheral retinal defocus state, and the difference of defocus quantity in the inferior nasal side at 30°-45° eccentricity may be a factor regulating the rapid progression of myopia.

Dormant tumor cells constitute a population of cancer cells that reside in a non-proliferative or low-proliferative state, typically arrested in the G0/G1 phase and exhibiting minimal mitotic activity. These cells are commonly observed across multiple cancer types, including breast, lung, and ovarian cancers, and represent a central cellular component of minimal residual disease (MRD) following surgical resection of the primary tumor. Dormant cells are closely associated with long-term clinical latency and late-stage relapse. Due to their quiescent nature, dormant cells are intrinsically resistant to conventional therapies—such as chemotherapy and radiotherapy—that preferentially target rapidly dividing cells. In addition, they display enhanced anti-apoptotic capacity and immune evasion, rendering them particularly difficult to eradicate. More critically, in response to microenvironmental changes or activation of specific signaling pathways, dormant cells can re-enter the cell cycle and initiate metastatic outgrowth or tumor recurrence. This ability to escape dormancy underscores their clinical threat and positions their effective detection and elimination as a major challenge in contemporary cancer treatment. Hypoxia, a hallmark of the solid tumor microenvironment, has been widely recognized as a potent inducer of tumor cell dormancy. However, the molecular mechanisms by which tumor cells sense and respond to hypoxic stress—initiating the transition into dormancy—remain poorly defined. In particular, the lack of a systems-level understanding of the dynamic and multifactorial regulatory landscape has impeded the identification of actionable targets and constrained the development of effective therapeutic strategies. Accumulating evidence indicates that hypoxia-induced dormancy tumor cells are accompanied by a suite of adaptive phenotypes, including cell cycle arrest, global suppression of protein synthesis, metabolic reprogramming, autophagy activation, resistance to apoptosis, immune evasion, and therapy tolerance. These changes are orchestrated by multiple converging signaling pathways—such as PI3K-AKT-mTOR, Ras-Raf-MEK-ERK, and AMPK—that together constitute a highly dynamic and interconnected regulatory network. While individual pathways have been studied in depth, most investigations remain reductionist and fail to capture the temporal progression and network-level coordination underlying dormancy transitions. Systems biology offers a powerful framework to address this complexity. By integrating high-throughput multi-omics data—such as transcriptomics and proteomics—researchers can reconstruct global regulatory networks encompassing the key signaling axes involved in dormancy regulation. These networks facilitate the identification of core regulatory modules and elucidate functional interactions among key effectors. When combined with dynamic modeling approaches—such as ordinary differential equations—these frameworks enable the simulation of temporal behaviors of critical signaling nodes, including phosphorylated AMPK (p-AMPK), phosphorylated S6 (p-S6), and the p38/ERK activity ratio, providing insights into how their dynamic changes govern transitions between proliferation and dormancy. Beyond mapping trajectories from proliferation to dormancy and from shallow to deep dormancy, such dynamic regulatory models support topological analyses to identify central hubs and molecular switches. Key factors—such as NR2F1, mTORC1, ULK1, HIF-1α, and DYRK1A—have emerged as pivotal nodes within these networks and represent promising therapeutic targets. Constructing an integrative, systems-level regulatory framework—anchored in multi-pathway coordination, omics-layer integration, and dynamic modeling—is thus essential for decoding the architecture and progression of tumor dormancy. Such a framework not only advances mechanistic understanding but also lays the foundation for precision therapies targeting dormant tumor cells during the MRD phase, addressing a critical unmet need in cancer management.

Nuclear factor-kappa B （NF-κB） is an important intracellular transcription factor widely involved in the processes such as immune response， inflammatory response， cell proliferation， and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis， liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds， such as matrine and salvianolic acid B， have shown the potential in suppressing NF-κB activity， thereby exerting anti-inflammatory， anti-fibrotic， and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target， in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.

Objective:To assess the efficiency and safety of combining lenvatinib with DEB-TACE for the treatment of unresectable large hepatocellular carcinoma,accompanied by PVTT,in order to provide insights into its potential as a therapeutic approach.Method:Patients with hepa-tocellular carcinoma and portal vein tumor thrombus,who were diagnosed and treated at Linyi Can-cer Hospital between June 2019 and June 2021,were chosen as the subjects of this study.Patient allocation into the experimental group(23 cases)and control group(27 cases)was based on indi-vidual preferences,ensuring a random distribution of participants.The DEB-TACE treatment was administered to the control group,while the experimental group received a combination of DEB-TACE and lenvatinib.The effectiveness of lenvatinib was assessed in the immediate post-surgery period,the patients'survival was monitored,and any associated side effects were documented.Result:3 months after treatment,the objective remission rates of the experimental group and the control group were 91.31％and 66.67％,and the disease control rates were 100％and 77.78％.The difference was statistically significant(P＜0.05).3 months after treatment,the regression rates of tumor thrombus in the experimental group and the control group were 60.87％and 29.63％,the difference was statistically significant(P＜0.05).The progression free survival time of the experi-mental group and the control group was 11 months and 8 months,the difference was statistically significant(P＜0.05);The median survival time of the experimental group and the control group was 20 months and 14 months,and the difference was statistically significant(P＜0.05).The main ad-verse reactions of the experimental group were hypertension,diarrhea,hand foot syndrome,rash,fatigue,loss of appetite,etc.,all of which were less than or equal to grade 3,and could be basically relieved after symptomatic treatment.Conclusion:The combination of DEB-TACE and lenvatinib is proven to be a safe and well-tolerated treatment for unresectable large hepatocellular carcinoma with portal vein tumor thrombus.This therapy not only effectively controls tumor progression but also prolongs survival time.

Mitochondrial diabetes mellitus (MDM) is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) or nuclear DNA mutations, characterized by multi-system involvement and diverse clinical phenotypes. We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus. Systematic evaluation revealed concurrent bilateral sensorineural hearing loss, bilateral basal ganglia calcification, and electroencephalographic abnormalities. A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion. Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084. This case report is complemented by a literature review focusing on the pathogenesis, genetic characteristics, and therapeutic approaches of mitochondrial diabetes, with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations. Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.