As a new manner of cell death,cuproptosis depends on the accumulation of copper ions in cells.Copper ion is an essential trace element in normal physiological state of organisms.The excess of free copper in cells not only has toxic effect on normal cells,but also plays its specific killing function on tumor cells.Copper transporter 1(CTR1)is a key transporter of transmembrane uptake of copper ions by cells.As a regulator of cuproptosis,its mutation and expression changes in tumors have an impact on the distribution of copper ions inside and outside the cells.It may participate in multiple biological processes such as proliferation,invasion and migration of tumor cells by regulating the pathway of cuproptosis.This article reviews the cuproptosis pathway mediated by CTR1 and the potential value of CTR1 in tumor treatment,elaborates the importance of copper ion homeostasis regulation for normal life activities and the mechanism of CTR1 in regulating cuproptosis,and discusses the potential value of CTR1 as a new target for tumor therapy,so as to provide a theoretical basis for the treatment of tumor patients.

Objective To investigate the characteristics and clinical significance of serum immunoglob-ulins in patients with Cronkhite-Canada syndrome(CCS).Methods This retrospective study included CCS patients admitted to Peking Union Medical College Hospital from December 2009 to September 2024 who under-went serum immunoglobulin testing.Clinical manifestations and ancillary examination results were analyzed ret-rospectively.Results Fifty-two patients were included(male:36[69.2%],female:16[30.8%]),with median onset age of 60(54-64)years and median diagnostic delay of 5(3-12)months.Common manifesta-tions included diarrhea(86.5%),abdominal pain(40.4%),hematochezia(19.2%),weight loss(86.5%),nail malnutrition(100.0%),pigmentation(88.5%),hair loss(84.6%),and hypogeusia(69.2%).Serum IgG reduction occurred in 21 patients(50.0%),while total IgE elevation was observed in 20(71.4%).Elevated serum IgG4 levels were noted in 11 patients(23.4%),with no significant clinical differences between IgG4-elevated and normal groups.IgG4 levels showed no statistical difference between active(n=43)and remission(n=27)groups.The hair loss rate was significantly higher in the total IgE-ele-vated group than that in the normal total IgE group(P=0.0383).Conclusions CCS patients exhibit periph-eral blood immunoglobulin disorders,with elevated IgE levels correlating with hair loss.This suggests an im-mune-mediated mechanism may underlie hair loss in CCS.

Objective To study the expression characteristics of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.Methods SD rats were randomly divided into sham-operation group(12 rats)and model group.In sham-operation group,surgical thread was passed through the abdominal aorta without constricting it after laparotomy;in model group,establish the heart failure model by abdominal aorta coarctation.The successful model rats were randomly divided into model 1 week(12 rats),model 2 weeks(11 rats),model 4 weeks(11 rats),model 8 weeks(11 rats)and model 12 weeks groups(11 rats).The end point of the study is at week 12.The contents of hydroxyproline(HYP),total myocardial collagen and collagen volume fraction(CVF)were compaired in all proups.The expression levels of OPG,RANKL and RANK proteins in cardiomyocytes were determined by Western blot.Results The contents of HYP in sham-operation,model 1 week,model 2 weeks,model 4 weeks,model 8 weeks and model 12 weeks group were(0.25±0.04),(0.37±0.05),(0.45±0.04),(0.60±0.05),(0.82±0.10)and(1.03±0.07)μg·mg-1;the total myocardial collagen contents were(1.87±0.31),(2.73±0.38),(3.36±0.31),(4.47±0.37),(6.08±0.74)and(7.67±0.49)μg·mg-1;the CVF were(1.95±0.23)％,(2.40±0.25)％,(3.65±0.25)％,(5.43±0.29)％,(6.97±0.36)％and(9.38±0.49)％;the relative expression levels of OPG protein were 0.64±0.07,0.80±0.07,1.02±0.07,1.32±0.11,2.13±0.12 and 2.84±0.16;the relative expression levels of RANKL protein were 0.71±0.08,1.06±0.07,1.53±0.07,2.62±0.12,4.46±0.14 and 6.11±0.16;the relative expression levels of RANK protein were 0.30±0.05,0.45±0.05,0.63±0.06,0.98±0.07,1.43±0.10 and 1.63±0.10.With the extention of time,the above indexs of all model groups were significantly higher than those in the sham-operation group(all P＜0.05).There were positive linear correlation between the relative expression levels of OPG,RANKL,RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure(allP＜0.01).Conclusions In the process of chronic heart failure,the expression of OPG/RANKL/RANK axis is obviously enhanced,in which the up-regulation of RANKL level is most obvious.The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

Objective To explore the effect of galangin(GAL)on bone metabolism by regulating Hippo/Yes associated protein(YAP)signaling pathway in rats with diabetic osteoporosis(DOP).Methods 90 female SD rats were randomly divided into normal control(NC)group,model(Mod)group,low-dose GAL(GAL-L)group,high-dose GAL(GAL-H)group,and high-dose GAL+YAP inhibitor Verteporfin(GAL-H+Verteporfin)group,with 18 rats in each group.Dual energy X-ray was used to detect bone mineral density(BMD).Three-point bending assay was used to evaluate the biomechanics of femur.HE staining was used to test the pathological changes in femoral tissue.ELISA was used to detect serum levels of osteocalcin(OC),alkaline phosphatase(ALP),and tartaric-resistant acid phosphatase(TRAP).Western blot was used to evaluate the expression of YAP protein in femoral tissue.Results Compared with NC group,the BMD,maximum load,elastic modulus,OC,ALP,and YAP protein expression of femur were reduced(P<0.05),and the TRAP was increased in Mod group(P<0.05).Compared with Mod group,BMD,maximum load,elastic modulus,OC,ALP and YAP protein expressions of femur were increased(P<0.05),while TRAP was decreased in GAL-L and GAL-H groups(P<0.05),and the improvement was better in GAL-H group.Compared with GAL-H group,femur BMD,maximum load,elastic modulus,OC,ALP and YAP protein expressions of femur were decreased(P<0.05),while TRAP was increased in GAL-H+Verteporfin group(P<0.05).Conclusions GAL may regulate the Hippo/YAP signaling pathway,increase the expression of YAP,regulate bone metabolism in DOP rats,and inhibit bone resorption.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To study the expression characteristics of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.Methods SD rats were randomly divided into sham-operation group(12 rats)and model group.In sham-operation group,surgical thread was passed through the abdominal aorta without constricting it after laparotomy;in model group,establish the heart failure model by abdominal aorta coarctation.The successful model rats were randomly divided into model 1 week(12 rats),model 2 weeks(11 rats),model 4 weeks(11 rats),model 8 weeks(11 rats)and model 12 weeks groups(11 rats).The end point of the study is at week 12.The contents of hydroxyproline(HYP),total myocardial collagen and collagen volume fraction(CVF)were compaired in all proups.The expression levels of OPG,RANKL and RANK proteins in cardiomyocytes were determined by Western blot.Results The contents of HYP in sham-operation,model 1 week,model 2 weeks,model 4 weeks,model 8 weeks and model 12 weeks group were(0.25±0.04),(0.37±0.05),(0.45±0.04),(0.60±0.05),(0.82±0.10)and(1.03±0.07)μg·mg-1;the total myocardial collagen contents were(1.87±0.31),(2.73±0.38),(3.36±0.31),(4.47±0.37),(6.08±0.74)and(7.67±0.49)μg·mg-1;the CVF were(1.95±0.23)％,(2.40±0.25)％,(3.65±0.25)％,(5.43±0.29)％,(6.97±0.36)％and(9.38±0.49)％;the relative expression levels of OPG protein were 0.64±0.07,0.80±0.07,1.02±0.07,1.32±0.11,2.13±0.12 and 2.84±0.16;the relative expression levels of RANKL protein were 0.71±0.08,1.06±0.07,1.53±0.07,2.62±0.12,4.46±0.14 and 6.11±0.16;the relative expression levels of RANK protein were 0.30±0.05,0.45±0.05,0.63±0.06,0.98±0.07,1.43±0.10 and 1.63±0.10.With the extention of time,the above indexs of all model groups were significantly higher than those in the sham-operation group(all P＜0.05).There were positive linear correlation between the relative expression levels of OPG,RANKL,RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure(allP＜0.01).Conclusions In the process of chronic heart failure,the expression of OPG/RANKL/RANK axis is obviously enhanced,in which the up-regulation of RANKL level is most obvious.The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

Objective To investigate the characteristics and clinical significance of serum immunoglob-ulins in patients with Cronkhite-Canada syndrome(CCS).Methods This retrospective study included CCS patients admitted to Peking Union Medical College Hospital from December 2009 to September 2024 who under-went serum immunoglobulin testing.Clinical manifestations and ancillary examination results were analyzed ret-rospectively.Results Fifty-two patients were included(male:36[69.2%],female:16[30.8%]),with median onset age of 60(54-64)years and median diagnostic delay of 5(3-12)months.Common manifesta-tions included diarrhea(86.5%),abdominal pain(40.4%),hematochezia(19.2%),weight loss(86.5%),nail malnutrition(100.0%),pigmentation(88.5%),hair loss(84.6%),and hypogeusia(69.2%).Serum IgG reduction occurred in 21 patients(50.0%),while total IgE elevation was observed in 20(71.4%).Elevated serum IgG4 levels were noted in 11 patients(23.4%),with no significant clinical differences between IgG4-elevated and normal groups.IgG4 levels showed no statistical difference between active(n=43)and remission(n=27)groups.The hair loss rate was significantly higher in the total IgE-ele-vated group than that in the normal total IgE group(P=0.0383).Conclusions CCS patients exhibit periph-eral blood immunoglobulin disorders,with elevated IgE levels correlating with hair loss.This suggests an im-mune-mediated mechanism may underlie hair loss in CCS.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To explore the effect of galangin(GAL)on bone metabolism by regulating Hippo/Yes associated protein(YAP)signaling pathway in rats with diabetic osteoporosis(DOP).Methods 90 female SD rats were randomly divided into normal control(NC)group,model(Mod)group,low-dose GAL(GAL-L)group,high-dose GAL(GAL-H)group,and high-dose GAL+YAP inhibitor Verteporfin(GAL-H+Verteporfin)group,with 18 rats in each group.Dual energy X-ray was used to detect bone mineral density(BMD).Three-point bending assay was used to evaluate the biomechanics of femur.HE staining was used to test the pathological changes in femoral tissue.ELISA was used to detect serum levels of osteocalcin(OC),alkaline phosphatase(ALP),and tartaric-resistant acid phosphatase(TRAP).Western blot was used to evaluate the expression of YAP protein in femoral tissue.Results Compared with NC group,the BMD,maximum load,elastic modulus,OC,ALP,and YAP protein expression of femur were reduced(P<0.05),and the TRAP was increased in Mod group(P<0.05).Compared with Mod group,BMD,maximum load,elastic modulus,OC,ALP and YAP protein expressions of femur were increased(P<0.05),while TRAP was decreased in GAL-L and GAL-H groups(P<0.05),and the improvement was better in GAL-H group.Compared with GAL-H group,femur BMD,maximum load,elastic modulus,OC,ALP and YAP protein expressions of femur were decreased(P<0.05),while TRAP was increased in GAL-H+Verteporfin group(P<0.05).Conclusions GAL may regulate the Hippo/YAP signaling pathway,increase the expression of YAP,regulate bone metabolism in DOP rats,and inhibit bone resorption.

Objective:To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application.Methods:This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively.Results:All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] ( Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] ( Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] ( Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] ( Z=-2.81, P=0.005). Conclusions:A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.