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Objective:To observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR).Methods:A retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed.Results:The time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, prethreshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes.Conclusions:The lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.
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Objective:To compare the thickness of the macular ganglion cell inner plexiform layer (mGCIPL) in patients with a history of laser photocoagulation (LP) versus intravitreal injection of ranibizumab (IVR) for retinopathy of prematurity (ROP).Methods:A retrospective clinical study. From June 2020 to January 2021, 70 eyes of 35 children with a history of surgery for ROP in Shenzhen Eye Hospital were included in the study. Among them, 18 males had 36 eyes, and 17 females had 34 eyes. The average age was 5.54±1.04 years. There were 18 patients (36 eyes) in LP group and 17 patients (34 eyes) in IVR group. There was no significant difference in age ( t=-1.956), sexual composition ratio ( χ2=0.030), birth gestational age ( t=-1.316) and birth weight ( t=-1.060) between the two groups ( P=0.059, 0.862, 0.197, 0.297). All the eyes underwent the examination of optical coherence tomography (OCT). An elliptical region of 14.13 mm 2 centered on macular fovea was scanned according to the macular cube 512×128 model of the Cirrus HD-OCT 5000. The software was used to automatically divide macular fovea into six sectors (superior, inferior, temporal-superior, temporal-inferior, nasal-superior and nasal-inferior) and the average and minimum thickness of mGCIPL. t test was used to compared mGCIPL thickness between two groups using independent samples. Pearson correlation analysis was used to evaluate the correlation between mGCIPL thickness and age, birth gestational age, birth weight. Results:Patients in IVR group had significantly decreased mGCIPL thickness than that in LP group in the six sectors (superior, inferior, temporal-superior, temporal-inferior, nasal-superior and nasal-inferior) and the average and minimum ( t=6.484, 6.719, 7.682, 7.697, 5.151, 5.008, 7.148, 6.581; P<0.05). The thickness of mGCIPL was not significantly correlated with age, birth gestational age, birth weight ( P>0.05). Conclusion:The thickness of mGCIPL in patients with IVR treatment history is thinner than that in LP treatment.
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Objective:Kallmann syndrome(KS) is a complex genetic disease characterized by congenital hypogonadotropic hypogonadism and anosmia. More than 20 genes have been reported to be associated with KS. Herein, we explore potential genetic aberration in 3 KS patients using the whole-exome sequencing. The potentially pathogenic variants filtered were validated by Sanger sequencing.Methods:Genomic DNA was extracted from the peripheral blood of 3 patients with KS and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants identified using whole-exome sequencing. The function of the mutation sites were analyzed with bioinformatics software.Results:The proband 1 was a 25 years old male, characterized by lower gonadotropin gonad hypofunction, early grey hair and bilateral sensorineural hearing loss. A heterozygous mutation c. 475C>T(p.R159W) of SOX10 gene was detected in the proband 1. His mother, sister and cousin who had KS phenotype were also found carrying this mutation, showing an autosomal dominant inheritance. The proband 2 was a 15-year-old male with hypogonadotropic hypogonadism and unilateral renal agenesis. The proband was hemizygous for c. 844delC(p.R282Vfs*28) of ANOS1 gene, his mother was heterozygous for the mutation, which was consistent with the X-linked recessive inheritance. The proband 3 was a 21 years old female, characterized by hypogonadotropic hypogonadism and anosmia. A heterozygous missense mutation c. 149G>A(p.R50Q) was detected in FGF17 gene. The mutation p. R50Q was predicted to be pathogenic by the SIFT and PolyPhen2 programs, and has not been reported in HGDM database yet, which considered to be a novel mutation.Conclusion:KS is a clinically and genetically heterogeneous disease. In this study, ANOS1 c. 844delC, SOX10 c. 475C>T and FGF17 c. 149G>A mutations were found in 3 patients with KS by whole exome sequencing, which would expand the genotypic and phenotype spectrum of KS.
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Objective:To evaluate the safety and efficacy of 27G micro-incision vitrectomy surgery (MIVS) combined with intravitreal injection of ranibizumab (IVR) in the treatment of retinopathy of prematurity (ROP) with early intervention failure.Methods:Retrospective case series was performed. Fourteen eyes (11 infants) with ROP who underwent 27G MIVS combined with IVR were included from March 2016 to January 2018 in Shenzhen Eye Hospital. Among them, there were 5 males with 7 eyes, 6 females with 7 eyes. The average gestational age of the infants was 28.12±0.90 weeks; the average birth weight was 1 023.64±200.96 g. Before the early clinical intervention, 1 infant (2 eyes) had ROP in zone Ⅰ stage 3 with plus disease, 8 infants (10 eyes) had ROP in zone Ⅱ stage 3 with plus disease, and 2 infants had ROP in aggressive posterior ROP. Six eyes underwent laser photocoagulation, while 8 eyes received laser therapy combined with IVR. Six eyes of stage 4A ROP and 8 eyes in stage 4B. Retinal detachment was detected with a mean of 10.44±9.21 weeks. At the time of surgery, the average post-conceptional age was 48.02±8.09 weeks. All the affected eyes were treated with standard sclera with three incisions 27G MIVS. During the operation, only local vitrectomy was performed to release and clear fibroascular proliferation in the optic disc, anterior macular area and pericristal area. After surgery, 10 mg/ml of ranibizumab 0.03 ml was injected into the vitreous cavity. The average follow-up time was 23.36±8.34 months. The primary objectives were the condition of retinal reset, ROP progression control and complications.Results:All patients had uneventful surgeries with an average duration of 32.86±9.35 mins. Of the 14 eyes, 12 eyes (85.71%) were controlled, 8 eyes (57.14%) had a good rearrangement of macular structure, while 4 eyes with macular traction. Two eyes had ROP progression, recurrence of retinal detachment, posterior synechia. Complicated cataract was in 1 eye. Proliferative vitreoretinopathy and retinal detachment was in 1 eye after 7 months the operation.Conclusion:27G MIVS combined with IVR is a safe and effective treatment for ROP with early clinical intervention failure.
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Two patients with primary hypertrophic osteoarthropathy (PHO) and their available healthy family members were studied.All exons of the SLCO2A1 and HPGD gene and adjacent exonintron sequences were amplified by PCR and subsequently sequenced.To assess the damaging effects of missense mutations in silico,the online database,PolyPhen-2 and SIFT were used.We identified two homozygous mutations in SLCO2A1 gene:one was c.1106G＞A (p.G369D) in exon 9,the other was c.611C＞T (p.S204L) in exon 4.No HPGD mutation was found in the affected individuals.The two mutation were predicted in silico by the bioinformatic tools.Our study further supports the role of mutations in the SLCO2A1 gene in the pathogenesis of PHO.Identification of the genotype in PHO may not only help the clinical diagnosis of PHO but also help the interpretation of genetic information for prenatal diagnosis and genetic counseling.
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Objective To observe the effect of retinal hemorrhage on the treatment of retinopathy of prematurity (ROP) by laser photocoagulation.Methods Retrospective case analysis.Screening and diagnosis of 134 eyes in 67 patients with ROP in Zone IⅡ Stage 3+ were included in the study.Among them,32 patients were male and 35 patients were female.The average birth gestational age was 27.80 ± 2.55 weeks.The average birth weight was 1060± 320 g.All children underwent binocular indirect ophthalmoscopy and RetCam Ⅲ.Of the 134 eyes,38 eyes (28％) with anterior,ridge or vitreous hemorrhage (group A);96 eyes (72％) without hemorrhage.Retinal avascular photocoagulation was performed within 72 hours after diagnosis by intravenous sedative combined with ocular surface anesthesia with 810 nm laser.Follow-up was performed at 1,4,8 and 12 weeks after treatment,and then every 6 months thereafter.The same equipment and methods before treatment were used to examine and document the regression and progression of ROP.The number of eyes with lesions after photocoagulation in the two groups was compared by x2 test.The t-test was used to compare the gestational age and birth weight.Results Among 134 eyes,lesions completely resolved in 125 eyes (93.3％),progressed in 9 eyes (6.7％).In group A,7 eyes were progressive (18.4％).In group B,2 eyes were progressive (2.1％).There was a statistically significant difference in the number of eyes with lesions after laser treatment in group A and B (x2=9.14,P=0.003).There was no significant difference in birth gestational age and birth weight (t=0.85,0.25;P=0.40,0.80).Conclusion The laser photocoagulation is safe and effective in the treatment of ROP.The preretinal,ridge or vitreous hemorrhage is related to the progression of the lesion after laser photocoagulation.
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OBJECTIVE@#To explore the eff ect of silibinin on β cells in C57BL/6J mice fed a high-fat diet and the possible mechanisms.@*METHODS@#A total of 18 male C57BL/6J mice at 3 weeks old were divided into a normal chow group (n=6), a high-fat diet group (n=6) and a high-fat diet plus silibinin group (n=6). Aft er intervention for 10 weeks, fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), alanine aminotransferase (ALT), creatinine (Cr) and blood urea nitrogen (BUN), lipid metabolism, antioxidant enzyme activities and apoptosis were evaluated. Pancreatic tissues were isolated to examine insulin-induced gene-1 (Insig-1), sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthetase (FAS) mRNA and protein expression.@*RESULTS@#Compared with the high-fat diet group, the function of insulin secretion was improved, and the level of blood glucose was decreased in the high-fat diet plus silibinin group (P0.05).@*CONCLUSION@#Silibinin can protect β cells of mice fed a high-fat diet, and this effect might be related to, at least partially, increase in its antioxidative ability through regulation of insig-1/SREBP-1c pathway. Moreover, silibinin is safe for long-term treatment.
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Animals , Male , Mice , Alanine Transaminase , Blood , Apoptosis , Blood Glucose , Blood Urea Nitrogen , Creatinine , Blood , Diet, High-Fat , Fatty Acid Synthases , Metabolism , Insulin , Blood , Insulin-Secreting Cells , Cell Biology , Lipid Metabolism , Lipids , Membrane Proteins , Metabolism , Mice, Inbred C57BL , Oxidative Stress , Silymarin , Silymarin , Pharmacology , Sterol Regulatory Element Binding Protein 1 , Metabolism , Triglycerides , BloodABSTRACT
OBJECTIVE@#To investigate the change in serum visfatin level after laparoscopic Roux-en-Y gastric bypass surgery in patients with Type 2 diabetes mellitus (T2DM) and to explore the relationship between visfatin insulin resistance and diabetes.@*METHODS@#Thirty-three patients with Type 2 diabetes were studied before and after the gastric bypass surgery. The level of fasting serum visfatin was measured by enzyme-linked immunosorbent assay. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and fasting insulin (FINS) were measured before and after the gastric bypass surgery.@*RESULTS@#Compared with before the operation, the indicators of HbA1c, FINS, and insulin resistance index (HOMA-IR) were decreased after the laparoscopic Roux-en-Y gastric bypass surgery. The body mass index (BMI) [(24.53 ± 0.62) kg/m² vs (26.71 ± 0.69) kg/m2] was decreased, with significant difference (P<0.001). The serum visfatin level [(9.79 ± 0.64) ng/mL] was significantly lower than before the operation [(38.24 ± 5.32) ng/mL], with significant difference (P<0.001).@*CONCLUSION@#Serum level of visfatin is decreased in T2DM patients who undergo gastric bypass surgry, reflecting an improvement in insulin resistance and diabetes.
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Female , Humans , Male , Middle Aged , Diabetes Mellitus, Type 2 , Blood , General Surgery , Gastric Bypass , Insulin Resistance , Laparoscopy , Nicotinamide Phosphoribosyltransferase , Blood , Postoperative PeriodABSTRACT
OBJECTIVE@#To investigate whether miR-125b regulates the osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) by modulating Smad4, a predicted target in silicon.@*METHODS@#Smad4 3'-UTR-luciferase vector was constructed and dual-luciferase reporter gene assay was employed to examine the effect of miR-125b on luciferase activity. MSCs were isolated and cultured from human bone marrow, and then transfected with miR-125b mimics followed by induction of osteogenic differentiation. qRT-PCR and Western blot were used to detect the expressions of Smad4 mRNA and protein. MSCs were induced into the osteoblasts after transfecting with Smad4 siRNA, and the effect of Smad4 downregulation on osteogenic differentiation was observed by AKP activity and RUNX2 mRNA levels.@*RESULTS@#miR-216b bound Smad4 3'-UTR and inhibited the luciferase activity (P<0.05). Smad4 mRNA and protein expressions were significantly down-regulated in the MSCs induced into osteogenic differentiation when miR-125b was overexpressed. Downregulation of Smad4 suppressed the AKP activity and RUNX2 mRNA expression, indicating that Smad4 siRNA simulated at least in part the function of miR-125b as the regulator of MSCs osteogenic differentiation.@*CONCLUSION@#miR-125b can suppress MSCs osteogenic differentiation by directly targeting Smad4.
Subject(s)
Female , Humans , Young Adult , Bone Marrow Cells , Cell Biology , Cell Differentiation , Physiology , Cells, Cultured , Core Binding Factor Alpha 1 Subunit , Genetics , Metabolism , Down-Regulation , Mesenchymal Stem Cells , Cell Biology , MicroRNAs , Physiology , Osteoblasts , Cell Biology , Osteogenesis , RNA, Messenger , Genetics , Metabolism , RNA, Small Interfering , Genetics , Smad4 Protein , Genetics , Metabolism , TransfectionABSTRACT
Objective: To investigate the effects of glucagon-like peptide-1(GLP-1)on high glucose-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and the mechanism involved. Methods: HUVECs were cultured under varying conditions for 48 h, and the cell viability was spectrophotometrically measured by MTT assay. Flow cytometry detected the ratio of cell apoptosis. Western blot detected the protein levels of p-Akt and p-eNOS, while NO assay kit detected the NO concentration. Results: Treatment of high glucose (33 mmol/L) for 48 h signiifcantly decreased the HUVECs viability and induced the apoptosis of HUVECs, concomitant with decreased Akt and eNOS phosphorylation leves and subsequent NO production. Treatment with GLP-1 (3 nmol/L) for 48 h in the high glucose group increased the HUVECs viability (P Conclusion: GLP-1 can ameliorate high glucose-induced HUVECs apoptosis, which is probably related to the up-regulation of PI3K/Akt/eNOS pathway.
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Objective To investigate the effect of erythropoietin on the proliferation,differentiation,and apoptosis of the cultured neonatal porcine islet cells in vitro.Methods Neonatal porcine islet cells were separated and pured from neonatal pigs with collagenase digestion and tissue culture,and their viability and purity were tested. The neonatal porcine islet cells were divided into a control group and an experimental group.The experimental group was treated with erythropoietin but not the control group,and the insulin secretion responsiveness induced by low and high glucose stimulation in the islet was tested after 5 days. Cells were counted and the activation of amplification was determined by MTT chromatometry. The rates of cell apoptosis were observed by ethidium bromide/acridine orange (EB/AO) of fluorescent light staining and flow cytometry,and the cell cycle was analyzed by flow cytometry. The expression of bcl-2,bax,caspase-3,glucose transporter 2 (GlUT-2),and pancreatic duodenal homeobox-1 (PDX-1) mRNA was tested by RT-PCR.Results After erythropoietin was treated in the cell culture,the neonatal porcine islet cells had normal morphology,function,and reaction of insulin secretion to the glucose stimulation. Cell count showed more cells in the experimental group than in the control group (P＜0.05). MTT chromatometry showed the optical absorbance tended to increase with time,and compared with the control group,the optical absorbance was higher in the experimental group (P＜0.05),the expression of PDX-1 mRNA was slightly up-regulated (P＜0.05). The expression of GLUT-2 mRNA had no difference in the 2 groups (P=0.34). In the experimental group,the apoptisis rate was lower than that in the control group by flow cytometry and EB/AO fluoscence staining (P＜0.01),and the expression of bcl-2 mRNA was higher. Howerer bax mRNA and caspase-3 mRNA were obviously lower than those in the control group (P＜0.01).Conclusion Erythropoietin can promote the proliferation but has no effect on the function of neonatal porcine islet cells in vitro. Erythropoietin can protect neonatal porcine islet cells from apoptosis through up-regulating bcl-2 mRNA and downreguling bax and caspase-3 mRNA.
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OBJECTIVE@#To investigate the effect and mechanism of glucagon like peptide 1(GLP-1)on the proliferation and differentiation of endothelial progenitor cells(EPCs)derived from the peripheral blood.@*METHODS@#Mononuclear cells were isolated from human peripheral blood by density gradient centrifugation. After 7 days of culture,attached cells were stimulated with different cultures of 0.2% BSA,and GLP-1(1,10,and 20 nmol/L). Laser scanning confocal microscope was used to determine the EPCs from human peripheral blood.The activity of EPCs was observed under reverse microscope. MTT was used to determine the proliferation of EPCs. The expression of KDR,Flt-1,VE-cadherin,and eNOS mRNA was detected by RT-PCR.The concentration of serum VEGF was detected by ELISA. The expression of VEGF protein was detected by immunohistochemical SP method. The EPCs cultured in GLP-1 were intervened by VEGFmAb.@*RESULTS@#EPCs was proliferated more in the GLP-1 group(1,10,and 20 nmol/L) than in the control group (P<0.05 or P<0.01). The expression of KDR,FLT-1,VE-cadherin,eNOS mRNA and VEGF protein was higher than that in the control group(P<0.05 or P<0.01). VEGFmAb(100 ng/mL)down-regulated the expression of KDR,Flt-1,VE-cadherin,and eNOS mRNA.@*CONCLUSION@#GLP-1 can promote the proliferation and differentiation of EPCs derived from the peripheral blood by up-regulating VEGF autocrine.