Objective:To explore the genetic etiology and clinical phenotype of Feingold syndrome due to chromosome 2p24.3p24.2 microdeletion.Methods:The clinical data of a child admitted to Henan Provincial People′s Hospital in November 2021 and diagnosed as Feingold syndrome type 1 (FGLDS1) associated with chromosome 2p24.3p24.2 microdeletion were collected. The clinical and genetic variation characteristics of the patient were summarized, and 10 patients with chromosome 2p microdeletion reported until November 2022 were reviewed.Results:The boy was 12 years and 5 months old. He presented with backward physical development, motor development retardation, low intelligence, special body and facial appearance, finger developmental deformity and other manifestations, accompanied by hyperactivity and aggressive behavior, impulsive irritability, self-injury and other behavior problems. The proband showed normal chromosome karyotype; the genome-wide copy number variant sequencing and trio-whole exome sequencing revealed a 2.61 Mb deletion at chromosome 2p24.3p24.2 region, and 10 genes including MYCN gene (exons 1 to 3) in the deleted region.The same deletion was not found in either of his parents. The genetic features of 11 cases (including this case) with chromosome 2p microdeletion were summarized, all of whom had insufficient haploid dosage of the MYCN gene due to chromosome 2p microdeletion, and the clinical manifestations of these 11 patients matched the clinical diagnosis of FGLDS1. Conclusion:The proband is consistent with the clinical presentation of the typical Feingold syndrome, and the haploinsufficiency of the MYCN gene due to the microdeletion of chromosome 2 is the genetic etiology of the proband.

Objective:To explore the postprandial plasma low-density lipoprotein cholesterol (LDL-C) changes by various detection methods.Methods:A total of 85 subjects admitted to the Second Xiangya Hospital of Central South University from November 2017 to May 2019 were included. Serum samples were collected from fasting and the 2 nd hour and the 4 th hour after breakfast. Serum lipid levels were measured with enzymatic assays and nuclear magnetic resonance spectroscopy (NMRS), and proprotein invertase subtilisin/kexin type 9 (PCSK9) levels were measured with enzyme-linked immunosorbent assays. The differences of blood lipid components at different time points were compared by Friedman two-way rank analysis of variance and Wilcoxon signed rank test, and the correlation between PCSK9 level and lipoprotein particles was analyzed by Spearman correlation. Results:Measured by enzymatic assays, compared with the fasting state, LDL-C decreased at the 2 nd hour and the 4 th hour after the meal (2.58[2.09, 3.12], 2.47[1.92, 3.02], 2.37[1.82, 2.80] mmol/L, P<0.001). Measured by NMRS, the concentration of LDL particles (1 086[830, 1 239], 1 083[848, 1 213], 1 061[814, 1 213] nmol/L, P=0.417) did not change significantly, and cholesterol in LDL particles were 2.13 (1.56, 2.54), 2.16 (1.68, 2.50), 2.06 (1.58, 2.50) mmol/L, respectively ( P=0.047)，and postprandial cholesterol in LDL particles in the 2 nd hour and in the 4 th hour did not change significantly compared with fasting ( P>0.05). while the concentration of large LDL particles (185.2[150.6,221.6], 173.0[144.8,220.3], 178.1[144.0,233.6] nmol/L, P=0.001), and the cholesterol level in large LDL particles (0.49[0.39, 0.57], 0.47[0.38, 0.57], 0.46[0.37, 0.58]mmol/L, P<0.001) decreased after the meal. The PCSK9 level also decreased significantly after the meal (299[233, 397], 257[208, 342], 251[215, 340] ng/ml, P<0.001). There was an independent positive correlation between the decrease of PCSK9 levels and the increase of remnant cholesterol detected by MNRS after the meal ( r=0.232, P=0.035). Conclusions:The postprandial LDL-C level measured by NMRS and enzymatic assays is not consistent. The decrease of LDL-C measured by enzymatic assays is not caused by the clearance of LDL particles, but by the redistribution of cholesterol in each LDL subfraction.

Objective To evaluate surgical treatment of chronic tibial osteomyelitis of Cierny-Mader type Ⅳ with Ilizarov technique and lesion osteotomy. Methods From January 2010 to May 2016, 39 patients with chronic tibial osteomyelitis of Cierny-Mader type Ⅳ were treated at our center. They were 33 males and 6 females, 8 to 54 years of age (average, 33.8 years). After debridement and lesion osteotomy, the tibia was fixated with Ilizarov external fixator. Bone was transported to the bone defect after corticotomy was performed on the proximal and/or distal tibial metaphyses simultaneously. Bifocal corticotomy was per-formed in 11 cases, proximal corticotomy in 21 cases, and distal corticotomy in 7 cases. The transport began 3 to 5 days after operation at a speed of 0.5 to 1.0 mm/d initially. The speed was lowered according to the bone healing and pain. Radiographic examination was done every 2 weeks to observe transporting deviation and osteogenesis in the transporting area. The transporting was adjusted whenever any abnormality was observed. The bone transporting lasted for 50 to 130 days (average, 62.4 days). Results The patients were fol-lowed up for 11 to 49 months (average, 21 months). All the soft tissue wounds healed uneventfully and there was no relapse of osteomyelitis. The bone defects in the 32 cases were reconstructed primarily. Nonunion of fracture ends happened in 5 cases and nonunion of the bone lengthening zone in 2 cases. The 7 cases of nonunion were healed after secondary bone grafting. Malalignment happened in 5 cases, 4 of which responded to timely adjustment of the external fixation and one of which had to receive secondary bone grafting after failure in adjustment of the external fixation. Ankle joint dysfunction occurred in 7 cases, 5 of which re-sponded to functional exercise and 2 of which accepted joint dysfunction because they refused surgery after unsatisfactory functional exercise. Pin tract infection of different severities occurred in 9 cases, one of which was treated by replacement of the K-wires under local anesthesia and the other 8 of which responded to rein-forced dressing change. Conclusions Chronic tibial osteomyelitis of Cierny-Mader typeⅣcan be treated by Ilizarov technique and lesion osteotomy. However, the Ilizarov technique should be improved because of the risks of multiple complications which can be reduced significantly by strengthening postoperative instruction, nursing, and regular follow-up.

Objective To measure the concentration of serum transthyretin (TTR) of patients with different stages of diabetic retinopathy (DR).Methods A total of 176 patients with diabetes mellitus were included in this study.There were 104 males and 72 females.The patients aged from 21 to 74 years,with the mean age of(56± 11) years.The diabetes duration raged from 1 to 30 years,with the mean diabetes duration of (10 ± 7) years.The HbA 1C was 5.2％-14.1％,with the mean HbA 1C of (8.6 ± 2.0)％.According to the fundus examination,58 patients had DR (33.0％),but the other 118 patients not (67.0％).For these DR patients,10 patients were in stage Ⅰ (5.7％),26 patients in stage Ⅱ (14.8％),8 patients in stage Ⅲ (4.5％),and 14 patients in stage Ⅳ (8.0％).The concentration of serum TTR was measured by enzyme-linked immunosorbentassay kit.The differences in the concentration of serum TTR between different DR stages were compared.Bivariate analysis was used to analyze the influencing factors of TTR.Results The concentrations of serum TTR of the patients without DR or with DR of stage Ⅰ to Ⅳ were (224.96±65.47),(383.68± 102.99),(247.44±63.21),(228.2 ± 45.89),(189.34± 70.12) mg/L,respectively.The difference between different DR stages was statistically significant (F=14.690,P＜ 0.001).Bivariate analysis showed that the concentration of TTR was correlation to DR (r=0.179,P=0.017).There was no correlation between the concentration of TTR and diabetes duration (r=-0.027,P=0.727),hypertension (r=0.018,P=0.810),hyperlipoidemia (r=0.101,P=0.182),and the use of insulin (r=-0.032,P=0.675).Conclusion The concentration of serum TTR was increased in early DR patients,and gradually decreased with the progression of DR.The concentration of TTR is correlated to DR.

Objective To assess the outcome of fixation of Rüedi-Allg(o)wer type Ⅱ and Ⅲ pilon fracture using multiple low-profile plates (MLPP) via multiple incisions.Methods A retrospective study was made on 21 cases of pilon fracture immobilized using MLPP via multiple incisions between July 2007 and March 2012.There were 7 cases of Rüedi-Allgower type Ⅱ and 14 type Ⅲ.Fractures were reduced and fixed based on X-ray films and CT scans for fracture line and effect area.Quality of reduction was evaluated by Burwell-Charnley radiological score.Ankle and hindfoot functions were evaluated by American Orthopedic Foot & Ankle Society ankle-hindfoot scale.Fracture types,healing rate,and wound complication incidence were recorded.Results All fractures were healed,with the excellence rate of 95％ (20/21).According to AOFAS score,the results were rated as excellent in 11 cases,good in 6,fair in 4,with the excellence rate of 81％.None suffered from wound infection,except for wound dehiscence in 1 case and traumatic arthritis in 5.Conclusion Treatment of pilon fractures by MLPP via multiple incisions can reduce wound complications,promote reduction and stabilization of fracture,and satisfy the demand of early movement and late weight bearing of the ankle.

Objective To investigate the effect of TGF-β1/SMAD signaling pathway on K562 cells growth inhibition caused by HMBA. Methods After establishing the in vitro differentiation model with HMBA on K562 cells, the MTT assay was used to detect the proliferation of K562 cells, the cell cycle profile was detected by flow cytometry, and the mRNA expression of TGF-β1, SMAD3, SMAD4 and EVI1 was measured by RT-PCR assay. Results HMBA could inhibit the proliferation and promote the differentiation of K562 cells obviously, which was time and concentration-dependent, and the 72 h corresponding IC50, was about 2 mmol/L. Within 72 h, flow cytometry assay indicated that the ration of G0-G1 phase cells was up-regulated, and the results of RT-PCR showed that relative mRNA expression of TGF-β1, SMAD3 and SMAD4 at mRNA level was increased gradually while that of EVI1 was decreased gradually. Conclusion HMBA can inhibit K562 cells proliferation through TGF-β1/SMAD signaling pathway.

Objective To evaluate the positive effects of cisplatin on sensitivity of human glioma U251 to tumor necrosis factor-related apoptosis inducing ligand and to investigate the potential mechanism. Methods The expression of green fluorescent protein (GFP) in U251 which was transfected with pAdxsi-GFP-TRAIL was observed by inverted fluorescent microscope ×400) and to ascertain the MOI. The proliferation inhibition was studied by MTT method. Morphological change was detected through inverted florescent microscope and the Hoechst33342 staining assay was used to verify whether cell apoptosis could be induced or not. The cell apoptosis was also analyzed by flow cvtometry with propidium iodide staining. Semi-quantitative RT-PCR was introduced to detect the mRNA expression of apoptosis related gene.Results The expression of TRAIL mRN A was significantly upregulated after transfection. Compared with treatment group of cisplatin and TRAIL alone, the proliferation of U2S1 was significantly inhibited in the cisplatin sensitizing TRAIL group (P < 0.05 ). Nuclear shrinkage and pyknosis fragmentation were observed by Hoechst 33342 staining assay; Apoptotic peak was detected from the results of flow cvtometry and there were significant differences between the sensitizing group and the other two groups ( P < 0.05 ) ; Moreover, the relatively high expression of TRAIL, DR5, caspaseS and down - regulated survivin genes were also observed. There was no significant changes in DR4 expression. Conclusion Cisplatin could extremely enhance the sensitivity of U251 cells to TRAIL And the potential mechanism may related to the increase of TRAIL, DRS, caspaseS genes while the reduction of surivivin gene.

Objective To investigate the reversal effect of the monomer of traditional Chinese medicine on muhidrug resistance(MDR) and its possible mechanism in K562/ADM cell line in vitro. Methods With different concentrations of baicalin, geniposide administered to K562/ADM cells, the proliferation of K562/ ADM cells was detected by the MTY assay. Expression of mdr-1 mRNA, Topo Ⅱ mRNA was measured by semi-quantitive RT-PCR. Results Thatbaicalin and geniposide could increase the sensitivity of K562/ADM cells to adriamycin, multiples of reversion were 1.95 times and 1.46 times. The proliferation of K562/ADM cells was in-hibited obviously by baicalin and geniposide, the level of mdr-1 mRNA expression was down-regulated and the Topo Ⅱ mRNA was up-regulated(P<0.01 ). Conclusion Baicalin and geniposide may reverse the multi-drag-resistance of K562/ADM cells, which was related to the down-regulation of mdr-1 expression and up-reg-ulation of Topo Ⅱ beta expression.

Objective To explore molecular mechanism of expression of vascular endothelial growth factor (VEGF) mRNA and secretion of VEGF protein in HL-60 cells induced by all-trans refinoic acid (ATRA). Methods MTr method was used to detect the proliferation of HL-60 cells induced by ATRA,cell cycle and CD11b expression in HL-60 cells were detected by flow cytometry. Expression of VEGF, c-myc, by-poxia-inducible factor(HIF)-lα, matrix metalloproteinase (MMP)-9 and MMP-2 mRNA were detected by semi-quantitative RT-PCR. VEGF protein in HL-60 cells culture supernatant was measured by ELISA before and after being induced by ATRA. Results After treatment with ATRA,the proliferation of HL-60 cells was obviously inhibited, CD11b expression increased, trend of granulocyte directional differentiation emerged, and differentiation degree was increasd(P <0. 05) ;expression level of c-my and VEGF mRNA was down-regulated (P < 0. 05), but expression level of HIF-1α mRNA was up-regulated (P < 0. 05). VEGF protein level in HL-60 cells culture supernatant was decreased by blocking the expression of MMP-9 or MMP-2(P <0. 05).Conclusion VEGF expression has positive correlation with c-myc expression,but has negative correlation with HIF-1α expression. MMP-9 and MMP-2 may be the main factors regulating VEGF secretion in HL-60 cells.

Objective To study the molecular mechanism of different sensitivities to apoptosis induced by low concentration of As2O3 in PML-RARα negative HL-60 cells and PML-RARα positive NB4 cells. Meth-ods NB4 and HL-60 cells were cultured with As2O3 for 1 to 4 days; cell proliferation were detected by MTT method; the apoptosis was detected by flow cytometry,Bcl-2,Bax and Fas mRNA were determined by RT-PCR. Results The proliferation of NB4 cells was inhibited obviously by As2O3(1.0 μmol/L)with the induction of apoptosis( P <0.05) ,which was accompanied by the down-regulation of Bcl-2 mRNA expression( P <0.05)and the ratio of Bcl-2/Bax(P <0.05), but there was no obvious variation of Bax and Fas expression( P >0.05). Inhibition of proliferation and apoptosis were not obvious in PML-RARα negative HL-60 cells induced by low concentration As2O3 ( P >0.05), and there was no obvious variation of Bcl-2, Bax, Fas mRNA expres-sion or Bcl/Bax ratio( P >0.05). Conclusion The ratio of Bcl-2/Bax is contributed to the different sensitiv-ities of PML-RARα negative HL-60 cells and positive NB4 cells induced by low concentration of As2O3.