Mitofusin 2 (MFN2) residing on the outer mitochondrial membrane is a pivotal factor participating in mitochondrial fusion and maintaining mitochondrial morphology. Due to its multifaceted cellular functions, MFN2 is implicated in the pathogenesis of diverse maladies, notably type 2 Charcot-Marie-Tooth disease, which has catalyzed a surge in pharmaceutical endeavors directed towards MFN2. This article reviews the function of MFN2 and its role in a variety of diseases, outlines the current status of drug discovery against MFN2, and summarizes potential drug molecules currently in preclinical research, aiming to provide some reference for the research and development of drugs and therapies targeting MFN2.

Objective: To explore the clinical safety and efficacy of a single-position robot-assisted radical nephroureterectomy (RRUN) in the treatment of upper tract urothelial carcinoma (UTUC). Methods: A retrospective study was conducted on 136 UTUC patients who underwent RRUN (n=35) and laparoscopic radical nephroureterectomy (LRUN，n=101) in our hospital during Dec.2020 and Aug.2023.The perioperative and safety indicators of the two groups were compared.The intravesical recurrence-free survival (IVRFS)，recurrence-free survival (RFS)，and overall survival (OS) of the two groups were compared using Kaplan-Meier method. Results: There were no significant differences in the baseline data between the two groups (P>0.05).All surgeries were successfully completed without conversion to open surgery.RRUN demonstrated superior perioperative outcomes compared to LRUN in overall postoperative complication rate [37.1%(13/35) vs. 56.4%(57/101)]，postoperative hospital stay [6(5,7) days vs. 7(6,8) days]，and catheter indwelling time [3(2，4) days vs. 4(3，5) days]，with statistically significant differences (P<0.05).Safety indicators of both surgical approaches were similar (P>0.05).Survival analysis showed no significant difference in oncological outcomes between the two groups [IVRFS (1 year：92.1%，2 years：85.2%)，RFS (1 year:82.4%，2 years:74.9%)，OS (1 year:90.6%，2 years:84.2%)] (P>0.05). Conclusion: Compared with retroperitoneal LRUN，single-position RRUN for UTUC demonstrates comparable safety and oncological efficacy，while offering significant advantages in perioperative outcomes such as reducing postoperative complication rate and shortening hospital stay.

Objective To establish the drug use evaluation(DUE)criteria of recombinant human prourokinase(rhPro-UK),and to provide reference for the rational clinical application of rhPro-UK.Methods Based on the drug instructions of rhPro-UK,DUE standard rules were established by referring to relevant guidelines,expert consensus,authoritative literature and expert consultation.The medical records of hospitalized patients treated with rhPro-UK from January 2019 to May 2022 in Xilin Gol League Central Hospital were evaluated by retrospective investigation.The effectiveness of rhPro-UK was evaluated based on clinical outcome,and its safety was evaluated based on the incidence and severity of adverse reactions.Results A total of 230 cases were included,and 4 cases fully met the evaluation criteria(medication indication,medication process,medication results),accounting for 1.74％.There were 226 patients(98.26％)with irrational drug use,mainly manifested in two aspects of drug indication and drug process(administration mode and dosage).Treatment was effective in 221 patients,with an overall effective rate of 96.09％;139 patients experienced adverse reactions,with an incidence rate of 60.43％.Conclusion The clinical use of rhPro-UK in our hospital is irrational in the indication of medication and the process of medication,and the establishment of the DUE standard rules of rhPro-UK can provide a reference to standardize the clinical application of rhPro-UK and promote its rational use.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Objective To explore association between childhood trauma,resilience and non-suicidal self-injury in adolescents.Methods One hundred and fifty-eight first-episode adolescent patients with mood disorders were selected and divided into NSSI group(n=94)and non-NSSI group(n=64)based on presence or absence of NSSI.The Hamilton depression scale(HAMD),Hamilton anxiety scale(HAMA),childhood trauma questionnaire(CTQ-SF)and Connor-Davidson resilience scale(CD-RISC)were used to evaluate the depression and anxiety symptoms,childhood trauma and resilience.Results There were more cases of younger age(16.17±1.67 vs.16.73±1.37),lower education level(30.9% vs.15.6% ),left behind experience(48.9% vs.29.7% ),school bullying(46.8% vs.25.0% ),suicide ideation(85.1% vs.37.5% )and history of attempted suicide(29.8% vs.6.3% )in the group with NSSI compared to those without NSSI.The HAMD score(27.99±5.94 vs.24.19±5.19),HAMA score(18.02±5.94 vs.15.45±4.99),CTQ total score(48.43±15.40 vs.41.97±9.75),emotional abuse score(12.77±6.06 vs.10.19±4.06),and emotional neglect score(11.40±5.34 vs.9.14±3.55)were higher in the group with NSSI,and the differences between the two groups were significant(P<0.05).The total scores of psychological resilience(39.83±10.27 vs.28.66±12.75),resilience(19.59±4.92 vs.12.28±6.47),strength(12.03±3.98 vs.9.99±4.67),and optimism(8.98±2.97 vs.6.47±3.73)in the group without NSSI were higher than those in the group with NSSI(P<0.05).Logistic regression analysis showed that left behind experience(OR=4.494,95% CI:1.192-16.940),school bullying(OR=5.983,95% CI:1.329-26.945),suicidal ideation(OR=13.225,95% CI:2.908-60.146),history of attempted suicide(OR=16.769,95% CI:1.845-152.379),HAMD(OR=1.264,95% CI:1.046-1.626),emotional abuse(OR=1.327,95% CI:1.093-1.612),and resilience(OR=0.468,95% CI:0.266-0.823)were significantly associated with adolescent mood disorders with NSSI(P<0.05).Conclusion Left behind experience,campus bullying,suicidal ideation and attempted suicide,emotional abuse,degree of depression,and psychological resilience may be associated with NSSI behavior in adolescents with mood disorders.

Objective:To explore the quality improvement in the organization structure and management model of the integrated community child health services.Methods:This was a qualitative study, including two parts: cause analysis and service improvement suggestions. In the analysis part the data mining was conducted to identify valuable patterns and relationships in the comprehensive child health services. Semi-structured interviews were conducted with 12 relevant department heads and health workers of the comprehensive child health service team at Gumei Community Health Service Center in December 2023, and the causes of the key problems were explored. In the service improvement part, focus group discussions were held to propose suggestions, then improvement measures were formulated to address the identified problems.Results:Through data mining and semi-structured interviews, the key problems were identified: information isolation among multiple departments and lack of coordination mechanism in the comprehensive child health service team. A team organizational structure based on the "three definite" principle was established. The organizational structure should include the pediatric family doctor team, general practitioner management team and departments of pediatrics, maternal and child health care, immunization and child rehabilitation; the management model should include a cross-department resource and information sharing mechanism, the pediatric family doctor model, optimization and integration of physical space, and enhancement of publicity activities for the comprehensive child health services.Conclusion:Based on the analysis in Gumei health service center, this study identified key problems in community integrated child health services, and proposes the quality improvement measure in the organizational structure and management model of the service team.

Objective:To analyze the association between periampullary diverticula (PAD) and the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), and to further classify diverticula types, and explore the impact of different types of diverticula on PEP.Methods:Data of 505 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for various reasons in General Hospital of Ningxia Medical University from May 2021 to May 2022 were retrospectively analyzed. Patients were classified into the diverticula group ( n=133) and the non-diverticula group ( n=372) based on the presence of PAD. The diverticula group was subdivided into types Ⅰ ( n=29), Ⅱ ( n=57), Ⅲ ( n=34), Ⅳ ( n=13) according to the Li-Tanaka classification. The incidences of PEP were compared between the diverticula group and the non-diverticula group, as well as among the four subgroups within the diverticula group. Multivariate logistic regression analysis was used to identify the independent risk factors for PEP. Results:There were significant differences in median age (72 years VS 66 years, Z=-4.626, P<0.001), common bile duct stones [80.45% (107/133) VS 59.94% (223/372), χ2=18.191, P<0.001], acute cholangitis [81.20% (108/133) VS 67.10% (231/372), χ2=16.208, P<0.001], malignant biliary stricture [8.27% (11/133) VS 23.39% (87/372), χ2=14.314, P<0.001] and pancreatic malignant diseases [7.52% (10/133) VS 18.55% (69/372), χ2=9.032, P=0.003] between the diverticula group and the non-diverticula group. The incidence of PEP in the diverticula group was significantly higher than that in the non-diverticula group [24.81% (33/133) VS 7.26% (27/372), χ2=28.835, P<0.001]. The incidence of PEP (36.84%,21/57) in type Ⅱ PAD patients was the highest, showing a significant difference compared with that of type Ⅲ [11.76% (4/34), χ2=6.984, P=0.008]. PAD ( OR=5.045, 95% CI: 2.898-11.194, P<0.001) and difficult cannulation ( OR=4.123, 95% CI: 1.968-8.490, P<0.001) were independent risk factors for PEP. In the Li-Tanaka classification, type Ⅰ ( OR=3.055, 95% CI: 1.131-8.251, P=0.028) PAD and type Ⅱ PAD ( OR=6.082, 95% CI: 3.468-13.344, P<0.001) had a higher risk of PEP compared with non-PAD patients. Conclusion:PAD is one of the independent risk factors for PEP. Types Ⅰ and Ⅱ PAD, according to the Li-Tanaka classification, are associated with an elevated risk of PEP when compared with non-PAD patients.

AIM:To investigate the role of specific long noncoding RNA SLC25a6(lncSLC25a6)in homocys-teine(Hcy)-induced cuproptosis in cardiomyocytes.METHODS:Rat cardiomyocytes were cultured in vitro and divided into control group and Hcy group.After 48 h of intervention,the expression levels of cuproptosis-related proteins,ferre-doxin 1(FDX1)and heat shock protein 70(HSP70),were detected by Western blot and immunofluorescence staining.The oxidative stress state of cardiomyocytes was assessed using fluorescence staining,and the intracellular Cu2+levels were measured using a copper ion assay kit.Furthermore,the impact of Hcy on the expression of cuproptosis-related proteins in cardiomyocytes was analyzed following overexpression of lncSLC25a6.RESULTS:Compared with the control group,80 μmol/L Hcy significantly accelerated cardiomyocyte damage,with a notable underexpression of lncSLC25a6(P<0.05).Western blot results indicated that,compared with the control group,the expression level of FDX1 in the Hcy intervention group was significantly reduced(P<0.05),while the expression level of HSP70 was significantly elevated(P<0.05),and the expression level of copper ions in cardiomyocytes of the Hcy group was increased(P<0.05).Immunofluorescence staining showed a significant reduction in FDX1 fluorescence intensity and a significant increase in HSP70 fluorescence in-tensity in the Hcy group.Further overexpression of lncSLC25a6 significantly mitigated Hcy-induced cuproptosis in cardio-myocytes,resulting in elevated expression of FDX1 and reduced expression of HSP70(P<0.05).Pearson correlation analysis demonstrated that the expression level of lncSLC25a6 was negatively correlated with FDX1 protein expression(r=-0.676,P=0.046)and positively correlated with HSP70 expression(r=0.680,P=0.044).CONCLUSION:lnc-SLC25a6 significantly mitigates Hcy-induced cuproptosis in cardiomyocytes,positioning it as a potential therapeutic target for managing Hcy-induced cardiac injury.

Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring.Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group,and the offspring mice were fed normally for 16 weeks after the mother gave birth.Western blot and RT-qPCR were used to detect the expression and transcription of related proteins,and immunofluorescence and im-munohistochemical staining were used for pathological analysis.Results Compared with the offspring of maternal nor-mal diet during pregnancy,the expressions of vascular inflammatory factors,macrophage infiltration,monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet(OHF)during pregnancy(P＜0.05).Vas-cular endothelial nitric oxide synthase(eNOS)activity,nitric oxide(NO)level were dramatically reduced(P＜0.05).Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal marker α-smooth muscle actin(α-SMA)in OHF.Western blot analysis further confirmed the results,which showed that maternal high fat diet reduced vascular endothelial-cadherin(VE-cadherin)and CD31 and increased α-SMA and Vimentin in the offspring(P＜0.05).The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta(TGF-β)/Smad signaling in endothelium(P＜0.05).Moreover,the maternal high fat diet reduced Kruppel-like factor 2(KLF2)expression by 76％in mRNA level and 59％in protein level(P＜0.05).Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta.The results provide a clue for prevention of vascular disease in early stage.

Objective To observe the value of feature pyramid network(FPN)for automatic segmentation and semantic feature classification of spontaneous intracerebral hemorrhage(sICH)hematoma showed on non-contrast CT.Methods Non-contrast CT images of 408 sICH patients in hospital A(training set)and 103 sICH patients in hospital B(validation set)were retrospectively analyzed.Deep learning(DL)segmentation model was constructed based on FPN to segment the hematoma region,and its efficacy was assessed using intersection over union(IoU),Dice similarity coefficient(DSC)and accuracy.Then DL classification model was established to identify the semantic features of sICH hematoma.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of DL classification model for recognizing semantic features of sICH hematoma.Results The IoU,DSC and accuracy of DL segmentation model for 95％sICH hematoma in training set was 0.84±0.07,0.91±0.04 and(88.78±8.04)％,respectively,which was 0.83±0.07,0.91±0.05 and(88.59±7.76)％in validation set,respectively.The AUC of DL classification model for recognizing irregular shape,uneven density,satellite sign,mixed sign and vortex sign of sICH hematoma were 0.946-0.993 and 0.714-0.833 in training set and validation set,respectively.Conclusions FPN could accurately,effectively and automatically segment hematoma of sICH,hence having high efficacy for identifying semantic features of sICH hematoma.