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.

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.

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.

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.

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.

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.

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.

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.

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.

Objective To report and analyze the clinical characteristics of kidney transplant recipients(KTRs)combined with novel coronavirus Omicron variant strain infection of novel coronavirus(SARS-CoV-2),and to investigate the possible factors affecting the serum creatinine change.Methods The patients under-going allogeneic kidney transplantation and complicating Omicron variant strain infection in this hospital from October 2022 to December 2023 were retrospectively observed.Their clinical data,basic complications and prognosis,etc.were collected and analyzed.The possible factors affecting the serum creatinine change were an-alyzed.Results Among the 114 cases of KTRs combined with Omicron variant strain infection included in this study,there were 90 cases(78.9％)in the home management group(group A),18 cases(15.8％)in the non-intensive isolation ward group(group B)and 6 cases(5.3％)in the ICU group(group C).The most common symptoms were in turn fever(90.4％),fatigue(65.8％)and cough(61.4％),the clinical manifesta-tions were mainly upper respiratory tract infection symptoms.The overall mortality rate was 2.6％(3/114),moreover the dead patients all were in the group C.The number of basic comorbidities in the group C was higher than that in the group B and group A(P＜0.05).The patients were re-divided into 33 cases(28.9％)in the creatinine increase group(group D),71 cases(62.3％)in the creatinine unchange group(group E)and 10 cases(8.8％)in the creatinine decrease group(group F).The patients in the F group were the patients with mild and moderate Omicron variant strain infection in the group A,and a larger proportions of the pa-tients in the group D and group F discontinued or reduced the calcineurin inhibitor(CNI)type drugs than in the group E.Conclusion The hazard of Omicron variant strains to KTRs has been greatly reduced compared with previous other variant strains.Realizing the immune balance between anti-infection and anti-rejection is the effective measure for preventing renal function damage in KTRs.