Objective:To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN).Methods:A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion:The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

Objective To evaluate the efficacy and safety of anlotinib monotherapy and combined therapy in patients with advanced pheochromocytoma/paraganglioma.Methods Nine patients with advanced pheochromo-cytoma/paraganglioma(PPGL)who were admitted to the Department of Urology,Sun Yat-sen University Cancer Center from January 2018 to June 2023 were collected.Patients were divided into four groups according to different treatments:anlotinib monotherapy group(3 patients),anlotinib combined with PD-1 monoclonal antibody immuno-therapy group(3 patients),anlotinib combined with immunotherapy and chemotherapy group(2 patients),and anlotinib combined with chemotherapy group(1 patients).The effectiveness and safety of different treatment regiments of anlotinib were analyzed.Results Objective response rate(ORR):(44%),Partial response(PR):(44%),Stable disease(SD):(44%),Progressive disease(PD):(11%),Disease control rate(DCR):(89%).The ORR of 2 patients with SDH gene mutation,SDHB and SDHD respectively,was 100%.Median overall survival time(OS)was 16.3 months(IQR:11.3～21.8 months).Median progression-free survival(PFS)was 16.3 months(IQR:9.8～20.8 months).There were 2 patients with adverse events grade≥3/4,all of which were hypertension.Conclusions Anlotinib monotherapy and combined therapy have preliminary efficacy and manageable safety in the treatment of advanced pheochromocytoma/paraganglioma.

Objective To investigate the diagnostic value of blood homocysteine,ankle -brachial index and brachial -ankle pulse wave velocity in elderly patients with coronary heart disease (CHD).Methods 97 patients with routine coronary angiography were classified into CHD group (65 cases)and non -CHD group (32 cases) according to the results of coronary angiography.There were 24 cases with single -vessel disease in 65 CHD cases, 21 cases with double -vessel disease and 20 patients with multivessel disease of CHD.Basic clinical parameters,age, gender,TC,TG,LDL -C,HDL -C,etc and blood HCY,ABI,baPWV levels were compared among groups.Results The age of double -vessel disease group,multivessel disease group was significantly higher than that in single -vessel disease group(t =3.721,3.927,all P <0.05).HCY,ABI,baPWV in CHD group were (18.29 ±2.73)μmol/L, (0.97 ±0.16),(16.38 ±1.27)m/s,which had statistically significant differences compared with non -CHD group (HCY:t =5.701,P <0.01;ABI:t =6.138,P <0.01;baPWV:t =15.132,P <0.01 ).There were no significant differences between single -vessel disease group and non -CHD group on the ABI(all P >0.05),and the ABI of multi -vessel disease,double vessel disease group were significantly lower than that of non -CHD group (all P <0.01).HCY,baPWV of CHD group were significantly higher than non -CHD group(all P <0.01 ),double vessel disease,HCY multivessel disease group,ABI,baPWV average water with single -vessel disease group were signifi-cantly different(all P <0.01 ).With the increase of coronary lesions involved,the blood HCY,baPWV showed an increasing trend and ABI showed an decreasing trend.Conclusion Combined detection of HCY,baPWV and ABI has great value in early detection and early intervention of CHD in the elderly.

AIM: To explore the molecular mechanisms of SC58125 on apoptosis in HepG2 cells. METHODS: Cell culture, ELISA, flow cytometry, RT-PCR, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to clarify the effect of SC58125 on apoptosis in HepG2 cells and related molecular mechanisms. RESULTS: SC58125 induced apoptosis in HepG2 cells in a concentration-dependent manner, which was accompanied by inhibition of NF-?B, activation of caspase-3, decrease of bcl-2 mRNA and increase of p53 mRNA. However, no significant changes were found in the DNA binding of AP-1. CONCLUSION: SC58125 induces apoptosis in HepG2 cells, which may be related to the inhibition of NF-?B, activation of caspase-3, decrease of bcl-2 mRNA and increase of p53 mRNA.

AIM: To clarify the effect of SC58125 on cell proliferation and apoptosis in HepG-2 cells and explore the molecular mechanisms. METHODS: Cell culture, MTT, TUNEL, DNA ladder, flow cytometry and Western blot analysis were employed in the present study. RESULTS: SC58125 inhibited the growth of HepG-2 cells and induced the apoptosis. Furthermore, it arrested G_0/G_1 phase and inhibited S phase in HepG-2 cells. Depressed expression of P33 cdk2 ,P34 cdc2 ,cyclin B_1,cyclin E ,Mpm-2,Rb ,PCNA proteins were found in HepG-2 cells treated with SC58125. CONCLUSION: SC58125 inhibits cell proliferation and induces apoptosis, which may be related to the altered low protein levels of P33 cdk2 ,P34 cdc2 ,cyclin B_1,cyclin E ,Mpm-2,Rb,PCNA