ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

Objective To study the impact of a Western diet-type feed on biological indicators and histopathology in APOE-/-mice.Methods Forty-eight female and 48 male APOE--mice,and 48 female and 48 male C57BL/6J mice were divided into eight breeding groups:APOE-/-breeding feed group,APOE-/-Western dietary feed group,C57BL/6J breeding feed group,and C57BL/6J Western dietary feed group(24 male and 24 female mice per group).Mice were fed the respective diets from 3 weeks until the end of the experiment at 20 weeks.After the experiment,serum was collected for measurement of biochemical indicators.Aortas were removed for oil red O staining and gross examination and the aorta root was paraffin sectioned and stained with hematoxylin and eosin.Results A Western diet did not significantly increase body weight in APOE-/-mice,but did significantly improve the blood lipid index and total cholesterol,low-density lipoprotein,and high-density lipoprotein levels,and promoted the formation of atherosclerotic plaques.Male mice were suitable for modeling gross aortic plaques while female mice were suitable for modeling aortic arch root plaques.Conclusions A Western diet can promote atherosclerosis in APOE-/-mice,increase the aortic plaque area ratio,shorten modeling time,and improve modeling uniformity.

A total of 44 patients with diabetic foot ulcers were treated in the Traumatic Orthopedics Department of Weifang People′s Hospital from January 2019 to December 2022. After debridement of foot ulcers the wounds were soaked in alkaline water of pH 7.5-8.0 (study group, n=22) or covered with vaseline gauze following iodophor disinfection (control group, n=22). The therapeutic effects of the two methods were compared. Four weeks after debridement, the wound area of study group was smaller than that of control group (3.15 (0, 7.60) vs. 6.75 (3.50, 9.32)cm 2, P<0.05), and the proportion of positive wound bacterial culture was lower than that of control group (40.9% (9/22) vs. 72.7% (16/22), P<0.05). At 12 weeks after surgery, there was no statistically significant difference in the wound healing rate between the two groups (72.7% (16/22) vs. 63.6% (14/22)), but the healing time of the study group was significantly shorter than that of the control group ((6.56±2.68) vs. (9.50±3.87) weeks, P<0.05). It is suggested that immersion of weak alkaline solution is helpful to promote wound healing for patients with diabetic foot ulcers after debridement surgery.

Objective:The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) .Methods:Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed.Results:①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34 + cells [7.62×10 6 (2.26×10 6-37.20×10 6) /kg vs 2.73×10 6 (0.53×10 6-9.85×10 6) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) ( P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34 + cells infused in the two groups was 4.62×10 6 (2.14×10 6-19.89×10 6) /kg versus 2.62×10 6 (1.12×10 6-5.31×10 6) /kg ( P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d ( P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d ( P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion:The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34 + cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

Objective:To investigate the prognosis of newly diagnosed multiple myeloma (MM) patients with t (14;16) abnormality.Methods:Clinical data from 564 patients diagnosed with initial MM from January 2018 to November 2020 at Beijing Chaoyang Hospital affiliated with Capital Medical University and the First Affiliated Hospital of Sun Yat-sen University were collected and retrospectively analyzed. The prognoses of patients with t (14;16) were analyzed and compared with the prognoses of patients with normal FISH, and those with t (4;14) and del (17p) .Results:Among 564 newly diagnosed MM patients, 19 (3.4%) exhibited t (14;16) abnormalities, with 14 cases diagnosed with 1q21+ and three cases with del (17p). Progression-free survival (PFS) and overall survival (OS) of patients with t (14;16) were significantly shorter compared with patients with normal FISH (the median PFS: 14 months vs not reached, P<0.001; the median OS: 42 months vs not reached, P=0.002). No statistically significant difference was detected in PFS and OS between the 15 patients with t (14;16) and the 15 with t (4;14) after propensity score matching (the median PFS: 13.0 months vs not reached, P=0.247; the median OS: 42 months vs not reached, P=0.609). Similarly, no statistically significant difference was observed in PFS and OS between 15 patients with t (14;16) and 15 with del (17p) (the median PFS: 13 months vs 31 months, P=0.939; the median OS: 42 months vs 37.3 months, P=0.557). Propensity score matching indicated that when combined with 1q21+, no statistically significant differences were present in PFS and OS between patients with t (14;16) and patients with t (4;14) or patients with del (17p) (all P>0.05). Whether or not the patients with t (14;16) had undergone auto-HSCT did not significantly impact the PFS and OS (all P>0.05) . Conclusion:t (14;16) is often associated with high-risk cytogenetic abnormalities in newly diagnosed MM patients, and its adverse prognostic value is similar to that of t (4;14) and del (17p) .

Objective:To investigate the necessity of internal fixation of the fibular fracture in the treatment of degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification in children.Methods:A retrospective study was conducted to analyze the data of 69 children with ankle fracture (degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification) who had been treated at Department of Orthopedic Trauma, The People's Hospital of Weifang and Department of Pediatric Orthopedics, Tianjin Hospital from January 2015 to October 2021. There were 41 males and 28 females with an age of (10.1±1.4) years, and 37 left and 32 right sides affected. The patients were divided into 2 groups according to whether internal fixation of the fibular fracture was performed. Group A consisted of 21 cases with fibular internal fixation and group B of 48 cases without fibular internal fixation. The preoperative data, operation time and operation expenses were recorded and compared between the 2 groups. At the last follow-up, the anteroposterior and lateral radiographs of bilateral full length lower limbs and ankle joints were taken; the lateral distal tibial angle (LDTA) and the anterior distal tibial angle (ADTA) on the affected side, and the disparity between bilateral ankle tibiotalar angles were measured; ankle function was assessed according to the ankle-hindfoot score of American Association of Foot and Ankle Surgery (AOFAS); the occurrence of premature physeal closure (PPC) was recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (19.5±4.1) months. At the last follow-up, the LDTA on the affected side was 89.6° (87.9°, 90.5°) in group A and 88.6°±1.9° in group B; the ADTA on the affected side was 80.9° (79.0°, 81.4°) in group A and 80.0° (78.6°, 81.2°) in group B; the disparity between bilateral ankle tibiotalar angles was 1.1°±0.5° in group A and 1.2°±0.5° in group B; the AOFAS ankle-hindfoot score was (89.5±5.2) points in group A and 89.0 (87.0, 92.0) points in group B. There was no statistically significant difference between the 2 groups in the above items ( P>0.05). The incidence of PPC was, respectively, 14.3% (3/21) and 14.6% (7/48) in groups A and B, showing no statistically significant difference ( P>0.05). Conclusions:In the treatment of degree Ⅱ ankle supination-external rotation injury in children, internal fixation of the fibular fracture has no significant effect on the imaging angles or the function of the ankle joint. After anatomic reduction of the distal tibia, the fibular fracture can be treated without internal fixation to reduce operational trauma, shorten operation time and reduce operation expenses.

Objective:To investigate the efficacy of staged treatment of infectious femoral defects of Cierny-Mader type Ⅳ using bone transport combined with locking plating after En-Bloc resection debridement.Methods:A retrospective analysis was conducted of the 10 patients with distal femoral traumatic bone infection who had been treated at Department of Orthopedics, The People's Hospital of Weifang from January 2020 to January 2023. There were 8 males and 2 females with an age of (48.5±11.4) years. All cases were classified as Cierny-Mader type Ⅳ. At the first stage, En-Bloc resection debridement was performed in all cases to remove previous internal fixation devices and fill the defects with antibiotic bone cement. After infection control, the second stage involved removal of bone cement, re-fixation with internal devices, and external fixation support for bone transport. After the bone segments met, freshening of the bone ends, minor bone grafting, and screw locking of the transported bone segments were performed. Outcomes observed included bone defect length, frame carrying time and index, bone healing time, limb function, and complications.Results:After the first stage of debridement, a bone defect of (9.1±2.1) cm was created in 10 patients. All patients were followed up for (19.8±6.6) months. The duration for carrying external fixation frame was (107.2±25.1) days, and the frame index (11.8±0.5) d/cm. No recurrence was observed postoperatively. Bone union was achieved in 9 patients within 8 months, but in 1 patient only after secondary bone grafting due to poor healing at the meeting ends. All patients returned to their previous life or physical labor with no complications like pain or re-fracture. Three patients experienced varying degrees of knee joint stiffness, but were able to meet needs of daily life; one requested joint release surgery which resulted in satisfactory therapeutic efficacy.Conclusion:Staged treatment of infectious femoral defects of Cierny-Mader type Ⅳ using bone transport combined with locking plating after En-Bloc resection debridement is simple and effective.

Objective To explore the effects of different types of drinking water on the growth and fecal flora of mice.Methods Specific pathogen-free NIH mice were randomly divided into five groups,32 mice each group,with half males and half females in each group.The group were given either purified water(control group),acidified water,alkalized water,weakly acidic water or solid water.Diet and body weight were monitored continuously for 20 days.After the experiment,animal fecal samples were collected,and the V3-V4 region was amplified with bacterial 16S rDNA universal primers.An Illumina Miseq high-throughput sequencing platform was used for high-throughput sequencing,and microbial community,α diversity and β diversity were analyzed by bioinformatics method.Results The body weight of female mice given different pH values of weakly acidic water was higher,while the weight of the other groups was lower,than that of the control group(P＞0.05).The body weight of male mice in the acidified water group was higher,while that of other groups was lower,than that of control group,but there was no statistical difference between the groups(P＞0.05).The body weights of male and female mice in the solid water group were lower than those in the control group(P＜0.05).The food and water intake of the female animals in the alkaline water group and the water intake of female animals in the solid water group were lower than those of the other groups.OTU clustering analysis showed that the data volume of the sequencing was reasonable,and the fecal flora species of NIH mice were divided into five phyla,among which Bacteroides and Firmicutes were dominant.Unclassified Pseudopurpuromonas,Lactobacillus and Alistipes were the main genera.There were differences in fecal flora abundance and diversity among the mice given the five drinking water types.α analysis showed that the acidified water group had the highest flora abundance and diversity,while the solid water group had the lowest flora diversity.β analysis showed that the fecal flora composition in the solid water group was the closest to that of the control group,followed by the alkalized water group,acidified water group and weakly acidic water group.Conclusions Through an exploration of the effects of consuming different forms of water,this study revealed that solid water consumption had the greatest effects on body weight,feed intake,water consumption,and fecal flora of mice.The abundance and diversity of fecal flora in mice were affected by different pH values of drinking water,especially acidified water.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.