1.Reconceptualizing Critical Illness in Cancer Through the Lens of Host Unregulated Response
Yun CHU ; Shiyi GONG ; Xin DING ; Hua ZHAO ; Huan CHEN ; Qing ZHANG ; Xiaoting WANG
Medical Journal of Peking Union Medical College Hospital 2026;17(1):1-9
Onco-critical care has emerged as an important subspecialty at the intersection of critical care medicine and oncology, attracting increasing attention in recent years. With continuous innovations in cancer therapies, patient survival has improved significantly; however, the incidence of associated critical complications has also increased. The reasons for cancer patients requiring intensive care unit admission are diverse and can be broadly categorized into three groups: progression of the underlying malignancy, treatment-related complications, and coexisting classical critical illnesses. Traditional critical care concepts and practices face limitations in addressing the multidimensional and heterogeneous challenges of onco-critical care. Based on the core mechanism of critical illness development—host/organ unregulated response (HOUR)—this article systematically elaborates on how this framework advances understanding and clinical practice into onco-critical care, with emphasis on its manifestations in neuroendocrine, immune-inflammatory, and coagulation-metabolic pathways. The review summarizes recent advances in clinical assessment and phenotyping systems for onco-critical illness and discusses a multidisciplinary, integrated management strategy centered on the "Disease Control, Host Response Modulation, Organ Support" triad. Finally, major challenges and future directions in this field are outlined. By integrating existing evidence and theoretical insights, this review aims to provide new perspectives and a theoretical foundation for the clinical management of onco-critical illness, thereby promoting its evolution toward precision and standardization.
2.GEO database-based investigation on the expression and role of mitochondrial metabolism genes AKT1, ATP5F1, and BAG3 in pterygium
Shiyi WANG ; Jing WANG ; Hua WANG ; Yuping CHEN
International Eye Science 2026;26(3):398-404
AIM: To investigate expression differences and mechanism of action of serine/threonine kinase 1(AKT1), ATP synthase F1 subunit(ATP5F1), and Bcl-2-associated anti-apoptotic gene 3(BAG3)in the occurrence and progression of pterygium.METHODS:Pterygium-related gene expression data were retrieved from GEO database to screen differentially expressed genes(DEGs). String and Cytoscape were used to construct protein-protein interaction(PPI)networks and identify core targets. GO/KEGG enrichment analyzed mitochondrial metabolic pathways. The pterygium samples(head/body)were collected; pathological features were evaluated by HE staining, and the expression of AKT1, ATP5F1, and BAG3 was detected via immunohistochemistry(IHC).RESULTS:A total of 1 264 DEGs were identified(585 upregulated, 679 downregulated). GO analysis showed significant enrichment of mitochondrial pathways regarding to biological processes, cell components and molecular functions; KEGG analysis highlighted oxidative phosphorylation and chemical carcinogenesis-reactive oxygen species(ROS)pathways. The head and body pterygium samples were collected from 28 cases(28 eyes)that received pterygium surgery, including 7 males(7 eyes)and 21 females(21 eyes), with a mean age of 69.32±8.98 years. HE staining showed more severe dysplasia, disordered stroma, and inflammation in the pterygium head versus the body. IHC detection confirmed significantly lower AKT1, ATP5F1, and BAG3 expression in the head compared with the body(all P<0.05).CONCLUSION:GEO-based bioinformatics and experiments confirmed that AKT1/ATP5F1/BAG3(mitochondrial genes)had significant differential expression in pterygium, correlating with pathological progression. They may regulate mitochondrial metabolism to mediate pterygium progression, offering new insights for targeted therapy.
3.Lumbar Oscillatory Manipulation for Lumbar Disc Herniation:A Randomized Controlled Trial
Shiyi LIU ; Yuelai CHEN ; Nan ZHOU ; Qiang LYU
Journal of Traditional Chinese Medicine 2025;66(16):1672-1678
ObjectiveTo observe clinical effectiveness and safety of lumbar oscillatory manipulation in the treatment of patients with lumbar disc herniation. MethodsThis study recruited 90 lumbar disc herniation patients who were randomly divided into 45 cases each in the treatment group and the control group. The treatment group was given lumbar oscillatory manipulation, while the control group was given traditional lumbar obliquely pulling manipulation, and both groups were treated twice a week for 4 weeks. The Oswestry dysfunction index (ODI) score, lumbar spine mobility, and the absolute values of difference in hardness between the left and right sides of the lumbar erector spinae muscle were compared between groups of patients before treatment and after 2 and 4 weeks of treatment; the shear wave elastic modulus of multifidus muscle and abdominal muscle thickness were compared between groups before treatment and after 4 weeks of treatment; the clinical effectiveness of the treatment was compared, and the safety evaluation was carried out. ResultsCompared with the group before treatment, the ODI scores and the the absolute values of difference in hardness between the left and right sides of the lumbar erector spinae muscle decreased after 2 and 4 weeks treatment in both groups, and the mobility of the lumbar vertebrae in all directions of anterior flexion, posterior extension, left lateral flexion, and right lateral flexion increased; the shear wave elastic modulus of bilateral multifidus muscles of the fourth lumbar vertebral segments decreased, and the thickness of abdominal muscle increased after 4 weeks of treatment in both groups (P<0.05). Compared with the control group, the ODI score of the treatment group decreased after 2 weeks of treatment, and the shear wave elastic modulus value of bilateral multifidus muscle of the fourth lumbar vertebral segment decreased and the thickness of abdominal muscle increased after 4 weeks of treatment (P<0.05). The total effective rate was 90.48% (38/42) in the treatment group and 71.43% (30/42) in the control group, and the clinical effectiveness of the treatment group was better than that of the control group (P<0.05). No adverse events occurred in both groups during the study. ConclusionLumbar oscillatory manipulation is superior to traditional lumbar obliquely pulling manipulation in relieving symptoms of lumbar disc herniation and improving lumbar spine function, which may be related to its improvement in the elasticity of the multifidus muscle.
4.Study on nonlinear spatiotemporal response characteristics of acupoint electrical signals to multi-mode acupuncture and moxibustion stimulation based on array multichannel data.
Shiyi QI ; Jinwen LIN ; Shihao WANG ; Jianguo CHEN ; Lili LIN ; Youcong NI ; Xin DU ; Dong LIN
Chinese Acupuncture & Moxibustion 2025;45(9):1209-1217
OBJECTIVE:
To elucidate the rules of temporal and spatial variations in distal skin potential at Hegu (LI4) under different stimulation modes by extracting nonlinear characteristic parameters from array multichannel data and adopting multivariate statistical analysis.
METHODS:
Seven healthy subjects were selected and the surface potential at the left Quchi (LI11) was collected using 14×9 array multichannel electrodes. Using Hegu (LI4) on the left as the stimulation point, four stimulation modes were applied, i.e. being quiescent, point pressing, moxibustion, and manual needling manipulation. Electrical signals were collected for 30 s in each mode, with a 5-min interval between operations, and a sampling frequency of 16 384 Hz. The data was denoised using ensemble empirical mode decomposition (EEMD), and sample entropy (SaEn) features were extracted. Statistical analysis was conducted on these data using factor analysis and multivariate analysis of variance.
RESULTS:
The SaEn values of most electrode channels were higher under point pressing, moxibustion and manual needling manipulation compared with those under quiescent condition. Under manual needling manipulation, the SaEn value of the electrode channel reached the peak in the first time interval (1-5 s) and it was declining thereafter. Factor analysis showed that the specificity of activation channels was concentrated at the left Quchi (LI11) (loading capacity ≥0.90). Analysis of variance indicated that the significant differences were presented in average sample entropy (SaEn()) values of activation channels among different stimulation modes at Hegu (LI4) (P<0.001), but there was no statistically significant interaction effect between groups and time intervals (P>0.05).
CONCLUSION
Through nonlinear characteristic parameter extraction and multivariate statistical analysis, we have uncovered the complex temporal and spatial dynamical rules of distal skin potential at Hegu (LI4) under various stimulation modes and successfully identified the specific activation characteristics at Quchi (LI11).
Humans
;
Moxibustion
;
Acupuncture Points
;
Male
;
Adult
;
Female
;
Young Adult
;
Acupuncture Therapy/instrumentation*
5.Study on distribution characteristics of pressure-sensitive points on body surface around acupoints in patients with chronic non-specific low back pain based on Euclidean distance.
Dong LIN ; Shiyi QI ; Youcong NI ; Xin DU ; Zijuan HUANG ; Xiang ZHAO ; Jianguo CHEN ; Lili LIN
Chinese Acupuncture & Moxibustion 2025;45(12):1743-1750
OBJECTIVE:
To explore the pain-location interaction between pressure-sensitive points on the body surface and traditional acupoints in patients with chronic non-specific low back pain (CNLBP) under different disease courses, using Euclidean distance and multivariate statistical analysis.
METHODS:
A pressure-sensitive point detection was performed on 30 CNLBP patients with varying disease courses. A constant pressure was applied using an FDK20 algometer within a designated lumbar area, a total of 50 points were tested, and the tested points were numbered; the visual analogue scale (VAS) pain score was recorded simultaneously. MatlabR2022a9.12. software was used to extract the positions of pressure-sensitive points, and preprocessing and normalization of point location and VAS scores data were conducted. Under constraint conditions (VAS≥8.0 ∩ Euclidean distance to acupoint≤0.5), the proportion of pressure-sensitive points within the Euclidean distance threshold to each acupoint (PVDacupoint) was calculated, followed by multivariate statistical analysis.
RESULTS:
①Constrained analysis of PVDacupoint showed that PVDQihaishu (BL24) and PVDDachangshu (BL25) were positively correlated with disease course (r=0.55, P<0.01). ②Factor analysis and silhouette analysis revealed that PVDShenshu (BL23) and PVDDachangshu (BL25) exhibited trends consistent with disease course progression (P>0.05), with different degree (P<0.01).
CONCLUSION
The PVDacupoint value based on Euclidean distance can characterize the pressure sensitivity features of traditional acupoints associated with disease. Multivariate statistical analysis of PVDacupoint confirms that selecting the acupoint combination of Shenshu (BL23) and Dachangshu (BL25) for CNLBP is associated with the distribution of surrounding pressure-sensitive points and the pathological characteristics of the condition.
Humans
;
Acupuncture Points
;
Low Back Pain/physiopathology*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Aged
;
Acupuncture Therapy
;
Young Adult
;
Pressure
7.Research on attention-enhanced networks for subtype classification of age-related macular degeneration in optical coherence tomography.
Minghui CHEN ; Wenyi YANG ; Shiyi XU ; Yanqi LU ; Zhengqi YANG ; Fugang LI ; Zhensheng GU
Journal of Biomedical Engineering 2025;42(5):901-909
Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.
Tomography, Optical Coherence/methods*
;
Humans
;
Macular Degeneration/diagnostic imaging*
;
Neural Networks, Computer
8.Structural insights into the binding modes of lanreotide and pasireotide with somatostatin receptor 1.
Zicheng ZENG ; Qiwen LIAO ; Shiyi GAN ; Xinyu LI ; Tiantian XIONG ; Lezhi XU ; Dan LI ; Yunlu JIANG ; Jing CHEN ; Richard YE ; Yang DU ; Thiansze WONG
Acta Pharmaceutica Sinica B 2025;15(5):2468-2479
Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.
9.Role of"HA coat"in modulating stemness and endocrine resistance in ER+breast cancer
Shiyi WU ; Si CHEN ; Bohan LIU ; Yuting LIU ; Yiwen LIU ; Yiqing HE ; Yan DU ; Guoliang ZHANG ; Qian GUO ; Feng GAO ; Cuixia YANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(10):1298-1307
Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.
10.Serotyping,virulence factors and drug resistance analysis of Pasteurella multocida of porcine origin of Zhejiang Province
Yizhen XU ; Xiufang YUAN ; Lihua XU ; Bin YU ; Fei SU ; Shiyi YE ; Hongchao SUN ; Yijie CHEN ; Qiaodan CHEN ; Hui ZHANG ; Junxing LI
Chinese Journal of Veterinary Science 2025;45(7):1378-1387
The aim of this paper was to investigate the serotypes,virulence factors and drug resist-ance of clinical isolates of Pasteurella rnultocida of porcine origin in recent years.Morphological screening and polymerase chain reaction(PCR)were used to isolate and identify 119 isolates from nasal swabs and lung tissue samples sent from swine farms in Zhejiang Province from 2010 to 2024.The isolates of Pasteurella multocida were subjected to capsular polysaccharide serotyping,lipopolysaccharide serotyping,virulence factor detection and drug resistance analysis by PCR and Kirby-Bauer disc agar diffusion method(K-B).The results showed that there were 64 strains(53.7%)of A-type,54 strains(45.3%)of D-type and 1 strain(0.9%)of F-type among the capsu-lar polysaccharide serotypes,and 10 strains(8.4%)of L1-type,20 strains(16.8%)of L3-type,86 strains(72.2%)of L6-type,and 3 strains(2.6%)of undetermined type among the lipopolysaccha-ride serotypes.The amplification results of 10 virulence genes showed that the detection rate of virulence genes hgbA,higbB and fimA was over 86.0%,the detection rate of toxA was 8.4%,while the virulence gene tbpA was not detected.There were also differences in the distribution vir-ulence genes in different capsular polysaccharide serotypes.Virulence factor pfhA was detected in type A and F but not in type D.The detection rate of adhesin gene tadD in serotype A(92.2%)was significantly higher than that of type D(9.3%),and,on the contrary,the detection rate of ad-hesin gene hsf-l in serotype D(90.7%)was significantly higher than that of type A(20.3%).Drug resistance analysis revealed that Pasteurella multocida showed high susceptibility to antimi-crobial drugs such as amoxicillin,ampicillin,cephalosporins,doxycycline,fosfenicol and ciprofloxa-cin,and showed strong resistance to antimicrobial drugs such as lincomycin,cotrimoxazole,genta-micin and amikacin,and there were 54 multi-drug resistant strains(78.3%).In summary,capsular polysaccharide serotypes were dominated by type A and D,lipopolysaccharide serotypes were dom-inated by L6,the distribution of some virulence genes varied greatly among different serotypes,and the proportion of multi-resistant strains was high,which provide reference for the prevention and control of this disease.

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