Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.

AIM: To analyze the factors affecting non-contact intraocular pressure(IOPNCT)measurements after femtosecond laser-assisted small incision lenticule extraction(SMILE), explore the correlation of IOPNCT with central corneal thickness(CCT)and corneal curvature after SMILE, and construct the corresponding regression model which will provide scientific basis for clinical evaluation of the true IOP of patients after SMILE.METHODS: Data from a retrospective analysis of 107 myopic patients(206 eyes)who underwent SMILE and 107 myopic patients(201 eyes)received femtosecond laser-assisted in situ keratomileusis(FS-LASIK)surgery from June 2023 to May 2024 were examined. IOPNCT, CCT, and corneal curvature before surgery and at 1 and 3 mo were collected. The preoperative and postoperative IOPNCT, CCT and corneal curvature were analyzed by ANOVA and Pearson correlation analysis, and multiple linear regression models were constructed to evaluate the association of postoperative changes of IOPNCT, CCT and corneal curvature.RESULTS: There were significant differences in IOPNCT, CCT, and corneal curvature of both SMILE and FS-LASIK patients(all P<0.001), there was no significant difference between two groups and interaction effects(all P>0.05), and the IOPNCT, CCT and corneal curvature at 1 and 3 mo post-surgery were significantly lower than preoperative(all P<0.05). Pearson correlation analysis showed a positive correlation between IOPNCT and CCT at 1 and 3 mo after SMILE(r=0.261, 0.267, all P<0.001), but no significant correlation with corneal curvature(all P>0.05). Multiple linear regression analysis of IOPNCT with CCT and corneal curvature at 1 mo after SMILE indicated that the regression equation was: Y=3.426+0.019X1-0.058X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistical significant difference in the equation(F=7.654, P=0.001); the regression equation for 3 mo after surgery was: Y=2.056+0.020X1-0.038 X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistically significance in the equation(F=7.903, P<0.001). The regression equation of postoperative IOPNCT change(△IOPNCT)and intraoperative cutting corneal thickness(△CCT)and corneal curvature at 1 mo was Y=-2.252+0.008X1+0.587X2(Y represents △IOPNCT, X1 stands for the △CCT, X2 represents the corneal curvature change value), with statistical significant difference in the equation(F=17.550, P<0.001); the regression equation for 3 mo after surgery was: Y=-2.168+0.024X1+0.281X2(Y represents △IOPNCT, X1 represents △CCT, X2 indicates the corneal curvature change values), with statistical significant difference in the equation(F=16.030, P<0.001).CONCLUSION: After SMILE and FS-LASIK surgery, the IOPNCT value of patients was mainly affected by CCT compared with preoperative surgery, and the short-term use of hormone eye drops, fluorometholone, did not cause a significant increase in IOP; both the IOP correction formula at 1 and 3 mo postoperatively can be used clinically to evaluate and correct actual IOP in patients after SMILE.

AIM: To analyze the factors affecting non-contact intraocular pressure(IOPNCT)measurements after femtosecond laser-assisted small incision lenticule extraction(SMILE), explore the correlation of IOPNCT with central corneal thickness(CCT)and corneal curvature after SMILE, and construct the corresponding regression model which will provide scientific basis for clinical evaluation of the true IOP of patients after SMILE.METHODS: Data from a retrospective analysis of 107 myopic patients(206 eyes)who underwent SMILE and 107 myopic patients(201 eyes)received femtosecond laser-assisted in situ keratomileusis(FS-LASIK)surgery from June 2023 to May 2024 were examined. IOPNCT, CCT, and corneal curvature before surgery and at 1 and 3 mo were collected. The preoperative and postoperative IOPNCT, CCT and corneal curvature were analyzed by ANOVA and Pearson correlation analysis, and multiple linear regression models were constructed to evaluate the association of postoperative changes of IOPNCT, CCT and corneal curvature.RESULTS: There were significant differences in IOPNCT, CCT, and corneal curvature of both SMILE and FS-LASIK patients(all P<0.001), there was no significant difference between two groups and interaction effects(all P>0.05), and the IOPNCT, CCT and corneal curvature at 1 and 3 mo post-surgery were significantly lower than preoperative(all P<0.05). Pearson correlation analysis showed a positive correlation between IOPNCT and CCT at 1 and 3 mo after SMILE(r=0.261, 0.267, all P<0.001), but no significant correlation with corneal curvature(all P>0.05). Multiple linear regression analysis of IOPNCT with CCT and corneal curvature at 1 mo after SMILE indicated that the regression equation was: Y=3.426+0.019X1-0.058X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistical significant difference in the equation(F=7.654, P=0.001); the regression equation for 3 mo after surgery was: Y=2.056+0.020X1-0.038 X2(Y represents IOPNCT, X1 represents the CCT, and X2 represents the corneal curvature), with statistically significance in the equation(F=7.903, P<0.001). The regression equation of postoperative IOPNCT change(△IOPNCT)and intraoperative cutting corneal thickness(△CCT)and corneal curvature at 1 mo was Y=-2.252+0.008X1+0.587X2(Y represents △IOPNCT, X1 stands for the △CCT, X2 represents the corneal curvature change value), with statistical significant difference in the equation(F=17.550, P<0.001); the regression equation for 3 mo after surgery was: Y=-2.168+0.024X1+0.281X2(Y represents △IOPNCT, X1 represents △CCT, X2 indicates the corneal curvature change values), with statistical significant difference in the equation(F=16.030, P<0.001).CONCLUSION: After SMILE and FS-LASIK surgery, the IOPNCT value of patients was mainly affected by CCT compared with preoperative surgery, and the short-term use of hormone eye drops, fluorometholone, did not cause a significant increase in IOP; both the IOP correction formula at 1 and 3 mo postoperatively can be used clinically to evaluate and correct actual IOP in patients after SMILE.

OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9％.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P＜0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Depression,characterized by high incidence,high re-lapse rate and high suicide rate,is an affective disorder mainly characterized by low mood and often accompanied by suicidal tendency,which seriously endangers human health.In recent years,more and more evidence suggests that microglia regulate synaptic plasticity and play an important role in depression.Here we outline the recent research progress of microglia regula-ting synaptic plasticity to exert antidepressant effects,focusing on three main types of molecular signals regulating synaptic pruning in microglia,including"Find Me"signaling,"Eat Me"signaling and"Don't Eat Me"signaling.By reviewing recent studies on how microglia regulate synaptic plasticity in depression,hopeful-ly,the understanding of microglia-mediated synaptic plasticity can be strengthened,which can help to provide new strategies for the treatment of depression by targeting microglia or microglia-associated signaling pathways.

Objective: To investigate the efficacy and incidence of adverse reactions of therapeutic erythrocytapheresis in high altitude polycythemia (HAPC) population. Methods: A retrospective study was conducted on 243 HAPC patients who were either native residents or long-term workers in Xizang and underwent therapeutic erythrocytapheresis in the Chengdu Office Hospital of the People's Government of Xizang Autonomous Region from 2021 to 2023. A comparative study was carried out on the changes in blood routine, vital signs, skin color, serum iron metabolism data, and the incidence of adverse reactions before and after the procedure. Results: After erythrocytapheresis, significant decreases were observed in red blood cell (RBC) count (7.06±0.89×10 vs 6.08±0.93×10 /L, P<0.001], hemoglobin (HGB, 211.59±17.99 vs 182.76±19.83 g/L, P<0.001), hematocrit (Hct) [(65.30±6.45)% vs (55.56±8.12)%, P<0.001], serum iron (14.46±4.38 vs 11.77±3.78 μmol/L, P=0.003), total iron-binding capacity (126.62±4.47 vs 123.73±3.77 μmol/L, P=0.002), transferrin (1.88±0.41 vs 1.77±0.12 g/L, P=0.023), transferrin saturation [(11.32±3.11)% vs (9.43±2.78)%, P=0.004], serum ferritin (832.4±295.6 vs 665.3±249.2 ng/mL, P<0.001), systolic blood pressure (123.86±14.43 vs 118.51±13.68 mmHg, P<0.001) and diastolic blood pressure (81.68±9.54 vs 74.28±7.61 mmHg, P<0.001). In contrast, platelet count (Plt, 137.21±46.21 ×10 vs 147.94±50.66 ×10 /L, P<0.001) and oxygen saturation [(93.97±3.29)% vs (95.84±2.27)%, P<0.001] increased. No significant differences were found in white blood cell (WBC) count [5.35 (4.59, 6.44)×10 /L vs 5.43 (4.54, 6.53) ×10 /L, P=0.690], unsaturated iron-binding capacity (112.15±0.50 vs 111.96±0.25 μmol/L, P=0.074) and pulse rate (73.42±11.28 vs 73.19±7.18 beats/min, P=0.750). Furthermore, skin color of the face (conjunctiva, lips) and palms mitigated after therapeutic erythrocytapheresis, changing from purplish-red to red. The total incidence of adverse reactions during erythrocytapheresis was 13.98% (34/243), including citrate toxicity 12.75% (31/243), puncture site hematoma 0.82% (2/243) and blood volume imbalance 0.41% (1/243). Conclusion: Therapeutic erythrocytapheresis could rapidly decrease HCT, Hb, serum iron, transferrin and transferrin saturation levels in HAPC patients, with a low incidence of adverse reactions. Therefore, therapeutic erythrocytapheresis has broad clinical application prospects in Xizang Autonomous Region.

Objective:To investigate the efficacy of volar anatomical locking plates combined with dorsal mini-plates in treating com-plex distal radius fractures.Methods:We retrospectively included patients with complex distal radius fractures who had been treated with volar locking plates and dorsal mini-plates at Chongqing General Hospital from January 2019 to June 2023.The quality of articu-lar surface fragment reduction was assessed through image analysis.Follow-up data included the Mayo wrist score,Disabilities of the Arm,Shoulder,and Hand Questionnaire(DASH)score,wrist range of motion,time to fracture healing,and complications.Results:Twenty-eight patients[19 males,9 females;mean age,(45.4±11.9)years]were included,with a mean follow-up of 1(4.9±3.6)months.Their injury mechanisms included falls from height(11 cases),traffic accidents(9 cases),and simple falls(8 cases).After op-eration,the volar tilt was(5.1±4.9)°,and the ulnar inclination was(19.8±2.8)°;at the final follow-up,the angles were(5.2±4.8)° and(19.3±2.5)°,respectively,neither showing any significant change(P>0.05).At the final follow-up,all fractures healed,with a mean healing time of 3.6 months.At 1 year after operation,the wrist extension was(50.7±6.3)°;the wrist flexion was(49.4±6.1)°;the DASH score was 15.0±6.3;the Mayo wrist scores were excellent or good in 24 cases;the grip strength of the affected side averaged 84.4%of that of the contralateral side.No implant loosening occurred.Two cases of superficial wound infection and one case of exten-sor tendon irritation were reported.Conclusion:Locked volar plat-ing combined with dorsal mini-plating provides stable fixation for comminuted articular surface fragments in complex distal radius fractures,enabling early functional rehabilitation with favorable wrist recovery and low rates of dorsal tendon irritation.

Risks of food safety induced by small molecule drug residues in animal food and environment have become an increasing public concern,so it is necessary to develop highly sensitive and easy-to-operate techniques to detect small molecules.Herein,a metasurface plasma resonance(MetaSPR)sensor chip coupled with gold nanoparticles(AuNPs)was developed for detection of enrofloxacin(ENR)based on competitive immunoassay.The detection range of the sensor for ENR was 0.025-3.2 ng/mL,and the detection limit(3σ)was 20 pg/mL.The biosensor showed excellent performance including high selectivity,good stability,ease to operate and high throughput,etc.The developed method was applied to detection of ENR residues in real samples,with recoveies of 96.0% -105.0%.The proposed sensing strategy provided new technique reference for detection of other small molecules in the field of residue analysis in food safety and environment monitoring.

Objective:To investigate the effect of human epidermal growth factor receptor 2 (HER2) on bladder cancer by regulating phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway via tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon peptide (YWHAE) and to examine its mechanism.Methods:The gene expression profiling interactive analysis (GEPIA) database was used to analyze HER2 expression in 408 bladder cancer tissues and 19 adjacent normal tissues. HER2 expression was then compared between 215 tumor protein 53 ( TP53) mutant and 193 TP53 non-mutant bladder cancer tissues. Tissue samples were obtained from patients who underwent surgical resection for bladder cancer in Tianjin Medical University General Hospital between June 2010 and March 2015. Immunohistochemistry and Western blotting were performed to validate HER2 and p53 protein expression, as well as analyze their correlation. Bladder cancer T24 cells were transfected with short hairpin RNA targeting HER2 (shHER2) control (shCon) or shHER2, designated as shCon and shHER2 groups. Bladder cancer UMUC3 cells were transfected with overexpression control (oeCon), HER2 overexpression (oeHER2), oeYWHAE, or short hairpin RNA targeting murine double minute 2 (MDM2) (shMDM2), and were designated as the oeCon, oeHER2, oeYWHAE and shMDM2 groups, respectively. UMUC3 cells were then treated with either 0.1% dimethyl sulfoxide or 100 mmol/L dihydrotestosterone and designated as the solvent control and dihydrotestosterone groups, respectively. Additionally, oeCon and oeYWHAE UMUC3 cells were treated with the PI3K inhibitor LY294002 (25 μmol/L), designated as the LY294002 and LY294002+oeYWHAE groups. On this basis, shHER2 was transfected into the oeCon and oeYWHAE groups, which were then designated as the shHER2-2 and shHER2-2+oeYWHAE groups. The relative expression levels of HER2, YWHAE mRNA, and HER2, p53, YWHAE, MDM2, phosphorylated Akt (p-Akt), and Akt proteins were determined using quantitative reverse transcription PCR and Western blotting. Cell Counting Kit-8, Transwell, and wound-healing assays were performed to evaluate the impact of HER2 on the proliferation, invasion, and migration of bladder cancer cells. Mass spectrometry and co-immunoprecipitation assays were performed to confirm the interaction between YWHAE and HER2, and immunofluorescence was used to detect p53 expression. BALB/c nude mice were subcutaneously injected with 5×10 6 UMUC3 cells in the scapular region. According to the random number table method, they were divided into negative the control group and the transfection group, with 3 mice in each group, and transfected with oeCon and oeHER2, respectively. Tumor volume and weight were measured and calculated, and HER2 and p53 protein expression in bladder cancer tissues was validated by immunohistochemistry and Western blotting. Independent sample t test or Mann-Whitney U test was used to compare the two groups. One-way analysis of variance or Kruskal-Wallis test was used for comparison of multiple groups. Results:GEPIA database analysis demonstrated significantly higher levels of HER2 expression in bladder cancer tissues and in TP53 mutant bladder cancers compared with adjacent normal tissues (both P<0.01). HER2 expression was inversely correlated with p53 expression ( r=?0.6). Immunohistochemistry and Western blotting confirmed that p53 expression level in the bladder cancer tissues (5.32±0.11) was higher than that in the adjacent normal tissues (2.00±0.01), while HER2 expression level in the bladder cancer tissues (1.13±0.02) was lower than that in the adjacent normal tissues (6.20±0.06) (both P<0.01). HER2 mRNA and protein expression, absorbance at 450 nm wavelength ( A450) values, and cell invasion number and cell migration distance in the shHER2 group were all lower than those in the shCon group [0.25±0.01 vs 1.00±0.05, 1.00± 0.01 vs 3.26±0.09, 1.36±0.04 vs 1.65±0.06, (107.00±5.51) vs (202.70±11.61) cells, and (298.70±6.94) vs (454.30±7.84) μm] ( P<0.05, 0.01). HER2 mRNA and protein expression, absorbance ( A450) values, and cell invasion number and cell migration distance in the oeHER2 group were all higher than those in the oeCon group [0.78±0.02 vs 0.46±0.01, 2.05±0.02 vs 1.00±0.00, 1.23±0.06 vs 0.78±0.03, (136.30±5.24) vs (59.00±5.51) cells, and (153.70±7.27) vs (66.33±33.84) μm] ( P<0.05, 0.01). HER2 protein expression level in the dihydrotestosterone group was higher than that in the solvent control (1.83±0.19 vs 1.00±0.00), while p53 protein expression level in the dihydrotestosterone group was lower than that in the solvent control group (1.10±0.10 vs 1.53±0.15) (both P<0.01). The differentially expressed protein between the dihydrotestosterone group and solvent control group was YWHAE. The expression levels of YWHAE mRNA and protein in the dihydrotestosterone group (1.10±0.12 and 3.05±0.03) were higher than those in the solvent control group (0.30±0.12 and 1.00±0.00) (both P<0.01). YWHAE protein expression level in the oeHER2 group was higher than that in the oeCon group (1.37±0.08 vs 1.00±0.00) ( P<0.01) and YWHAE expression level in the bladder cancer tissues was higher than that in the adjacent normal tissues ( P<0.01). YWHAE expression positively correlated with HER2 expression ( r=0.4). Co-immunoprecipitation confirmed direct binding between HER2 and YWHAE. Overexpression of YWHAE significantly reduced p53 expression. The relative expression level of MDM2 protein in the oeYWHAE group (2.73±0.09) was lower than that in the oeCon group (3.43±0.12) ( P<0.01). The relative expression level of MDM2 protein in the shMDM2 group (1.00±0.00) was lower than that in the oeYWHAE group, and the relative expression level of p53 protein (2.00±0.00) was higher than that in the oeYWHAE group (1.07±0.07) (both P<0.01). The relative expression levels of YWHAE and p-Akt protein in the oeYWHAE group (1.23±0.09, 3.00±0.06) were higher than those in the oeCon group (1.00±0.00, 1.13±0.03) ( P<0.05, 0.01). The relative expression level of p-Akt protein in LY294002 group (2.20±0.06) was lower than that in the oeCon group (3.30±0.10), and the relative expression level of p53 protein (2.10±0.06) was higher than that in the oeCon group (1.00±0.00) (both P<0.01). The relative expression level of p-Akt protein in LY294002+oeYWHAE group (2.00±0.06) was lower than that in the oeYWHAE group (3.53±0.14), and the relative expression level of p53 protein (2.10±0.06) was higher than that in the oeYWHAE group (1.00±0.06) (both P<0.01). The relative expression levels levels of YWHAE, p-Akt and MDM2 protein in the shHER2-2 group (1.60±0.15, 1.70±0.06, 0.80±0.06) were lower than those in the oeCon group (2.30±0.06, 2.30±0.06, 1.13±0.09), and the relative expression level of p53 protein (1.83±0.12) was higher than that in the oeCon group (1.00±0.00) ( P<0.05, 0.01). The relative expression level of YWHAE protein in the shHER2-2+oeYWHAE group (2.00±0.06) was lower than that in the oeCon group ( P<0.01), and the relative expression levels of MDM2 and p53 protein (2.63±0.15, 1.13±0.03) were higher than those in the oeCon group ( P<0.05, 0.01). The tumor volume, tumor weight, and relative expression levels of HER2, YWHAE, p-Akt, and MDM2 proteins on day 28 in the transfection group [(5 133.0±185.6) mm 3, (0.65±0.12) g, 2.23±0.02, 4.00±0.12, 3.33±0.06 and 2.24±0.02] were higher than those in the negative control group [(2 633.0±88.2) mm 3, (0.33±0.07) g, 0.98±0.02, 1.27±0.03, 1.29±0.02 and 1.46±0.06] (all P<0.01). The relative expression level of p53 protein (1.21±0.04) was lower than that in the negative control group (3.29±0.04) ( P<0.01). Conclusions:HER2 may promote the malignant progression of bladder cancer by regulating the PI3K-Akt pathway via YWHAE, thereby facilitating MDM2 nuclear translocation and p53 degradation. This ultimately enhances the proliferative, migratory, and invasive capacities of bladder cancer cells.