1.siRNA micelleplexes-mediated glutamine metabolism re-engineering for vascular normalization-boosted photo-immunotherapy.
Yunfei YI ; Zhangwen PENG ; Yuanqi LIU ; Huisong HAO ; Liu YU ; Simin WEN ; Shengjie SUN ; Jianlin SHI ; Meiying WU ; Lin MEI
Acta Pharmaceutica Sinica B 2025;15(4):2237-2252
Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.
2.Effect of virtual reality combined with body weight-supported treadmill training on phantom limb pain and lower limb dynamics in amputees
Qiongying LI ; Simin LI ; Jingru ZENG ; Xuyi WU ; Zhongjie LEI ; Chunping DU
Journal of Clinical Medicine in Practice 2025;29(9):65-69,74
Objective To investigate the impact of virtual reality combined with body weight-supported treadmill training on phantom limb pain,lower limb dynamics,gait stability,balance func-tion,and quality of life in amputees.Methods A prospective study enrolled 100 unilateral lower limb amputees as participants,who were randomly divided into experimental group(n=50)and con-trol group(n=50).The experimental group received virtual reality combined with body weight-sup-ported treadmill training,while the control group received conventional rehabilitation training.Out-comes,including phantom limb pain intensity[Visual Analogue Scale(VAS),Douleur Neuropathique 4 Questions(DN4)scores],lower limb dynamics[vertical ground reaction force(Fz),anteroposterior ground reaction force(Fy),joint moments],gait parameters,static balance(Berg Balance Scale score),dynamic balance(stability time,proportion of gait support time),quality of life[12-Item Short-form Health Survey(SF-12)score],and activities of daily living[Modified Barthel Index(MBI)score]were assessed before intervention and at 4,8,and 12 weeks post-intervention.Results At 4,8,and 12 weeks post-intervention,the experimental group exhibited significantly lower VAS and DN4 scores compared to baseline and the control group(P<0.05).Gait speed,stride length,ca-dence,stance time,Berg Balance Scale score,stability time,and proportion of gait support time improved in the experimental group compared to baseline and the control group(P<0.05).SF-12 score,MBI score,peak Fz,peak Fy,knee flexion moment,ankle abduction moment,and stance phase proportion also increased significantly in the experimental group compared to baseline and the control group(P<0.05).Conclusion Virtual reality combined with body weight-supported tread-mill training effectively alleviates phantom limb pain,improves lower limb dynamics,gait stability,and balance function,and enhances quality of life in amputees.
3.NK cell-specific knockout of UTX modulates pulmonary metastasis of melanoma in a sex-dependent manner
Pei HUANG ; Hongchen WANG ; He HUANG ; Jiaxin XIE ; Yu WU ; Simin ZHOU ; Xinyi LIAO ; Xiao GUAN
Journal of Army Medical University 2025;47(8):807-815
Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.
4.Recent advance in NLRP3 inflammatome in neuropathic pain after spinal cord injury
Simin CHEN ; Hongyu QUAN ; Mai LI ; Qian CHEN ; Ying WU ; Yongmei LI
Chinese Journal of Neuromedicine 2025;24(1):94-99
The mechanism of neuropathic pain after spinal cord injury is still unclear, which might be closely related to ion channel changes, central sensitization and decreased function of descending inhibitory system after injury. Existing studies have shown that the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome play a key role in neuropathic pain after spinal cord injury; therefore, targeting NLRP3 inflammasome is a promising therapeutic strategy. This review analyzes the molecular mechanism and treatment of NLRP3 inflammasome in neuropathic pain after spinal cord injury, aiming to provide references for pathogenesis and treatment of neuropathic pain after spinal cord injury.
5.T cell factor 1 regulates CD8 +T cell immunological and stemness
Yuning DAI ; Ming GAO ; Yanshi WU ; Simin YUN ; Siman HUANG ; Yibei ZHU
Chinese Journal of Microbiology and Immunology 2025;45(11):974-978
T cell factor 1(TCF-1)is a downstream transcription factor of the Wnt/β-catenin signaling pathway,and plays an important role in the development,differentiation,and memory formation of T cells. Recent studies have shown that TCF-1 can regulate the formation and maintenance of stem-like memory T cells(Tscm),and has potential application value in evaluating the prognosis of tumor immunotherapy and as a target for tumor immunotherapy. This article reviews the regulatory effects of TCF-1 on the immune memory as well as stemness formation and maintenance of CD8 +T cells,summarizes the transcription network centered on TCF-1,and further elucidates the application and value of TCF-1 in tumor immunotherapy.
6.Related factors of drug detoxification motivation in methamphetamine-dependent female youth
Yidan ZHANG ; Xuan LIU ; Simin HOU ; Lushi JING ; Yong DENG ; Yuxi WU ; Wenting ZHOU ; Lan DENG
Chinese Mental Health Journal 2025;39(1):81-86
Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.
7.Related factors of drug detoxification motivation in methamphetamine-dependent female youth
Yidan ZHANG ; Xuan LIU ; Simin HOU ; Lushi JING ; Yong DENG ; Yuxi WU ; Wenting ZHOU ; Lan DENG
Chinese Mental Health Journal 2025;39(1):81-86
Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.
8.T cell factor 1 regulates CD8 +T cell immunological and stemness
Yuning DAI ; Ming GAO ; Yanshi WU ; Simin YUN ; Siman HUANG ; Yibei ZHU
Chinese Journal of Microbiology and Immunology 2025;45(11):974-978
T cell factor 1(TCF-1)is a downstream transcription factor of the Wnt/β-catenin signaling pathway,and plays an important role in the development,differentiation,and memory formation of T cells. Recent studies have shown that TCF-1 can regulate the formation and maintenance of stem-like memory T cells(Tscm),and has potential application value in evaluating the prognosis of tumor immunotherapy and as a target for tumor immunotherapy. This article reviews the regulatory effects of TCF-1 on the immune memory as well as stemness formation and maintenance of CD8 +T cells,summarizes the transcription network centered on TCF-1,and further elucidates the application and value of TCF-1 in tumor immunotherapy.
9.Recent advance in NLRP3 inflammatome in neuropathic pain after spinal cord injury
Simin CHEN ; Hongyu QUAN ; Mai LI ; Qian CHEN ; Ying WU ; Yongmei LI
Chinese Journal of Neuromedicine 2025;24(1):94-99
The mechanism of neuropathic pain after spinal cord injury is still unclear, which might be closely related to ion channel changes, central sensitization and decreased function of descending inhibitory system after injury. Existing studies have shown that the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome play a key role in neuropathic pain after spinal cord injury; therefore, targeting NLRP3 inflammasome is a promising therapeutic strategy. This review analyzes the molecular mechanism and treatment of NLRP3 inflammasome in neuropathic pain after spinal cord injury, aiming to provide references for pathogenesis and treatment of neuropathic pain after spinal cord injury.
10.Surveillance of parasitic infections in market-sold aquatic products and knowledge and practice towards food-borne parasitic diseases among residents in Shanghai Municipality from 2020 to 2023
Simin DAI ; Qing YU ; Zhenyu WANG ; Yaoguang ZHANG ; Jiawei YANG ; Zixin WEI ; Xiaojiang MA ; Qian ZHU ; Jian CHEN ; Hao PAN ; Huanyu WU
Chinese Journal of Schistosomiasis Control 2024;36(6):631-636
Objective To investigate the prevalence of parasitic infections in market-sold aquatic products in Shanghai Municipality, and to understand the knowledge and practice towards food-borne parasitic diseases among residents, so as to provide insights into the surveillance and control of food-borne parasitic diseases. Methods Freshwater products, seawater products and pickled products were randomly obtained from agricultural trade markets, supermarkets, retail stores and restaurants in Huangpu, Putuo, Minhang and Qingpu districts of Shanghai Municipality from 2020 to 2023. Parasite metacercariae and larvae were detected in these aquatic products using pressing method, digestion method and the dissection method, and the detection of parasitic infection was compared in different types of aquatic products. In addition, the knowledge and practice towards food-borne parasitic diseases were investigated among residents aged 10-80 years old who randomly selected from agricultural trade markets, supermarkets, community streets and other population concentration areas in these four districts by questionnaire in 2023, and the awareness of food-borne parasitic diseases knowledge and percentage of healthy behaviors formation were analyzed. Results A total of 2 109 aquatic products sampled from Huangpu, Putuo, Minhang and Qingpu districts of Shanghai Municipality from 2020 to 2023 were detected, and there were 317 products detected with parasitic infections, with an overall detection rate of 15.03%. There were 8 products detected with parasitic infections in 1 221 freshwater products, with a detection rate of 0.66%, and Clonorchis sinensis was the predominant parasite, which was detected in Pseudorasbora parva, Rhodeus amarus and Carassius auratus. There were 82 products detected with parasitic infections in 501 seawater products, with a detection rate of 16.37%, and Anisakis was the predominant parasite, which was detected in Trichiurus lepturus, Larimichthys polyactis, Pneumatophorus japonicus, Collchthys lucidus, Mugil cephalus, Larimichthys crocea, Scomberomorus niphonius, Stromateoides argenteus and Cololabis saira. There were 227 products detected with parasitic infections in 387 pickled products, with a detection rate of 58.66%, and the prevalence rates of Echinostoma metacercariae were 76.27% (225/295) in Bullacta exarata and 11.11% (2/18) in crab pastes, respectively (χ2 = 159.511, P < 0.05). No Paragonimus infection was found in freshwater shrimps, crabs and pickled products, and no Diphyllobothrium latum larvae infection was detected in freshwater and seawater fish. Questionnaire surveys showed that the awareness of food-borne parasitic diseases knowledge was 79.00% (222/281), and the percentages of washing hands before and after meals, not drinking filtered water or tap water directly, not eating raw or semi-raw food, being willing to change special dietary preferences or bad living habits for health, and being willing to learn more about food-borne parasitic diseases knowledge were 99.64% (280/281), 72.24% (203/281), 56.23% (158/281), 96.80% (272/281) and 97.51% (274/281) among residents living in Huangpu, Putuo, Minhang and Qingpu districts, respectively. Conclusions There are food-borne parasite contaminations in market-sold aquatic products in Shanghai Municipality. Although residents are aware of food-borne parasitic diseases knowledge, sustainable surveillance of food-borne parasitic diseases and improved health education are required to minimize the risk of human parasitic infections.

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