Objective:To investigate the related risk factors of surgical appendectomy after endoscopic retrograde appendicitis therapy (ERAT) in children.Methods:From September 2019 to November 2023 at the Children's Hospital Affiliated to Shandong University,the data from all related children with appendectomy after ERAT were analyzed. The general situation and main clinical manifestations of the children were collected. According to the effect of ERAT,the patients were divided into transfer to surgical group and appendicitis recurrence group by the reasons and time of transfer to surgical treatment. The indexes such as ERAT and reoperation process and pathological types of appendix after operation were collected,and the clinical experience was summarized.Results:Among the 242 children who underwent ERAT,32 cases underwent appendectomy again,including 19 males and 13 females,with an average age of（9.16±2.77）years,and the reoperation rate was 13.2%. The clinical manifestation was abdominal pain (32 cases,100.0%),mainly right lower abdominal pain (28 cases,87.5%),and the main duration was less than 3 months (30 cases,93.8%). Abdominal ultrasound or CT before ERAT mainly indicated appendicitis (11 cases,34.4%) and appendicitis complicated with appendiceal calculus (11 cases,34.4%). There were 9 children in transferred to surgical group,of which 5 cases were transferred to surgery because of ERAT intubation failure,and 4 cases were transferred to surgery because of appendix perforation or abscess. Postoperative pathology showed acute suppurative appendicitis in 5 cases and acute gangrenous appendicitis in 4 cases. There were 23 children in appendicitis recurrence group,whose abdominal pain was relieved after ERAT,but their symptoms were repeated after discharge. After clinical evaluation,they were diagnosed as recurrent appendicitis and underwent surgical appendectomy. Most of them were reoperated within 6 months after ERAT (21 cases,91.3%).Postoperative pathology was mainly chronic appendicitis (10 cases,43.5%).Conclusion:Acute suppurative appendicitis and acute gangrenous appendicitis are prone to catheterization or endoscopic failure during ERAT,and there is a high risk of surgical transfer. ERAT may relieve the symptoms of chronic appendicitis in children. If the symptoms are repeated,surgery is still needed to remove the appendix.

Objective:To observe the expression and significance of Jagged1 in fibrovascular membranes of proliferative diabetic retinopathy (PDR).Methods:Sixty preretinal fibrovascular membrane specimens collected from fifty-seven patients (60 eyes) with PDR during vitrectomy in The Affiliated Hospital of Qingdao University from July 2014 to July 2015 were set as the PDR group.The patients were divided into the injection group (30 cases, 32 eyes) and non-injection group (27 cases, 28 eyes) according to whether they received anti-vascular endothelial factor drug intravitreally before surgery.Ranibizumab injections were administered to the patients in the injection group intravitreally 2-7 days before surgery.Eighteen macular epiretinal membrane specimens obtained from 18 non-diabetic patients were served as the control group.Hematoxylin-eosin staining was applied to observe the structural festures of specimers. The immunohistochemical staining was used to detect the expression levels of Jagged1, Delta-like 4(Dll4) and Notch1 in the injection and non-injection groups, and the real-time fluorescent quantitative polymerase chain reaction was performed to detect the relative expression levels of Jagged1, Dll4 and Notch1 mRNA in the three groups.Pearson linear correlation analysis was used to evaluate the relationships between the expression of Jagged1 mRNA and both Dll4 mRNA or Notch1 mRNA in the PDR fibrovascular membranes.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The Affiliated Hospital of Qingdao University (No.QYFYWZLL25645). Written informed consent was obtained from each patient.Results:The neovascularization was found in fibrovascular membranes of PDR with a light microscope, and the lumen of the new blood vessels in the injection group was narrow, but relatively dilated in the non-injection group.There was no neovascularization found in the macular epiretinal membranes.The immunohistochemical staining revealed that there was the positive expression of Jagged1, Dll4 and Notch1 proteins in all PDR membranes, mainly located in the vascular endothelium during neovascularization.The absorbance values of Jagged1, Dll4 and Notch1 proteins were 6.25±1.82, 6.87±1.89 and 5.12±2.14 respectively in the non-injection group, which were all higher than 1.46±0.37, 1.55±0.24 and 1.32±0.53 respectively in the injection group, showing statistically significant differences ( t=5.168, P=0.014; t=6.012, P=0.008; t=3.453, P=0.030). There were statistically significant differences in Jagged1, Dll4 and Notch1 mRNA relative expression levels among the three groups ( F=77.337, 62.305, 51.869; all at P<0.01). The relative expression levels of Jagged1, Dll4 and Notch1 mRNA in the fibrovascular membranes with PDR were significantly higher than those of control macular epiretinal membranes, and the relative expression levels of Jagged1, Dll4 and Notch1 mRNA of the injection group were significantly lower than those of the non-injection group (all at P<0.05). The expression level of Jagged1 mRNA was positively correlated with expression levels of both Dll4 and Notch1 mRNA ( r=0.925, 0.950; both at P<0.05). Conclusions:There is a high expression of Jagged1 in the vascular endothelium of fibrovascular membranes with PDR and the Jagged1 expression is positively correlated with the expression of Dll4 and Notch1.The effect of Jagged1 on the neovascularization in PDR may be related to Dll4 and Notch1.

Objective:To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS).Methods:This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration.Results:(1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant ( P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups ( P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion:The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

Objective:To observe and investigate the effect of HIF-2α in the process of neovascularization of proliferative diabetic retinopathy (PDR).Methods:Retrospective clinical study. From July 2014 to July 2015, 60 eyes of 57 PDR patients diagnosed in Ophthalmology Department of Affiliated Hospital of Qingdao University were included in the study. Twenty-eight eyes of 27 patients received intravitreal injections of 0.5 mg ranibizumab (0.05 ml) at 2-7 days before surgery (ranibizumab group) and other 32 eyes of 30 patients did not (group without ranibizumab). Eighteen eyes of 18 patients with epiretinal membranes were included as controls. Pathological specimens of PDR fibrovascular membrane and premacular membrane were obtained during vitrectomy. The immunohistochemical staining and real-time PCR (RT-PCR) were used to detecting the expression of HIF-2α, Dll4 and VEGF. Kruskal-wallis test was used to compare the expression differences of correlation factors between groups. Spearman correlation analysis was used to analyze the relationship between the two variables.Results:The immunohistochemical staining revealed that there were positive expression of HIF-2α, Dll4 and VEGF in all PDR membranes, regardless of the injection of the ranibizumab. The levels of HIF-2α, Dll4 and VEGF protein in the group without ranibizumab were higher than those of the ranibizumab group ( t=4.36, 6.01, 4.82; P=0.000, 0.008, 0.016). RT-PCR showed that the differences of the mRNA expression of HIF-2α, Dll4 and VEGF were all statistically significant among the PDR patients and controls ( H=18.81,19.60, 20.50; P=0.000, 0.000, 0.000). The expression of HIF-2α, Dll4 and VEGF in the PDR membranes was higher than that of epiretinal membranes from non-diabetic patients. In the PDR patients,the expression of HIF-2α, Dll4 and VEGF of the group without ranibizumab was higher than that of the ranibizumab group. The spearman correlation analysis showed that the expression of mRNA between HIF-2α and Dll4, HIF-2α and VEGF were both significantly correlated ( r=0.95, 0.87; P<0.05). Conclusions:The expression of HIF-2α in the PDR membranes was higher than that of the controls. It is positively correlated with the expression of the DLL4 and VEGF.

Objective By analyzing the clinical manifestations and pathologic features of Erdheim-Chester's disease (ECD) to improve the recognition of the disease.Methods The clinical characteristics,diagnosis and treatment of a young male with ECD were reported and the related literature was reviewed.Results A previously healthy young male patient with bilateral exophthalmos,blurred vision of right eye,polyuria and hypertension without obvious causes for nine months were admitted into our hospital.He developed low back pain two months ago.Thoracic vertebra Magnetic resonance imaging (MRI) showed multiple nodules extending from the 2th-7th thoracic vertebrae intra-medullary.MRI of the brain showed multiple masseswith abnormal intensities within the retro-ocular intraconal muscle cone,sellar and cavernous sinus,maxillary sinus.Biopsy specimens from the right orbital lesion demonstrated proliferation of fibrous connective tissue and fat tissue infiltrating with lymphocytes,plasma cells,eosinophils,foam cells,spindle cells,and multinucleated giant cells accompanied by fat necrosis.Immunohistochemistry showed infiltrated lymphocytes stained positive for CD68,CD20,CD3,LCA and negative for CD1a,S-100 protein and langerin.The clinical symptoms of exophthalmos and low back pain relieved after treated with methylprednisolone and interferon-α.Conclusion Understanding the characteristics of ECD can help to make the correct diagnosis and treatment.

Objective To observe the influence of human umbilical cord mesenchymal stem cells (hUCMSC) transplanted into the tail vein of diabetic rats on apoptosis of retinal neurons and the retinal expression level of glial fibrillary acidic protein (GFAP).Methods Seventy clean male Sprague-Dawley rats were randomly divided into the normal control group (group A),diabetes mellitus (DM) only group (group B),DM + balanced salt solution (BSS) group (group C),DM + hUCMSC group (group D),with 10 rats in each group.DM rats were induced by intraperitoneal injection of streptozotocin.Apoptosis of retinal cells was assayed by dUTP nick end labeling.Immunohistochemistry and Western blot was performed to detect the retinal expressions of GFAP in rats.Results Compared with group A,large numbers of apoptotic cells could be found in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) of group B and group C,however the apoptotic cells in group D were significantly reduced than group B and C.The expression of GFAP was mainly located in the retinal GCL and retinal nerve fibre layer (RNFL) in group A,throughout the inner plexiform layer (IPL) in group B and C,only distributed in RNFL and GCL in group D.It was obvious that the expression of GFAP in group B and C was higher than group A.Compared with group B and C,the expression of GFAP in group D was significantly reduced.The difference of GFAP expression among the 4 groups was significant (F=79.635,P＜0.05).Conclusion hUCMSC could inhibit the apoptosis of retinal cells and activation of glial cells in early DM rats.

Objective To observe the effect of macular retinal thickness (CMT) on the long-term visual prognosis after intravitreal injection of Conbercept combined with retinal laser photocoagulation for macular edema (ME) secondary to branch retinal vein occlusion (BRVO).Methods A retrospective non randomized controlled study.Forty-one patients (41 eyes) of ischemic BRVO secondary ME were included in the study.Among them,there were 23 males (23 eyes) and 18 females (18 eyes).The average age was (56.49±8.94) years.The best corrected visual acuity (BCVA) and optical coherence tomography were performed.The mean logMAR BCVA was 0.82±0.41,and the mean CMT was (512.61 ± 185.32) μrn.According to the CMT reduction value at 1 month after treatment,the eyes were divided into no response group and response group,each has 15 patients of 15 eyes and 26 patients of 26 eyes respectively.The age and sex composition of the two groups were not statistically significant (t=-0.298,-1.708;P=0.767,0.096),and the difference of frequency of injection was statistically significant (t=3.589,P=0.010),and there was no statistical difference between the patients with logMAR BCVA and CMT (t=2.056,-1.876;P=0.460,0.070).The average follow-up was 8 months.The logMAR BCVA on 6 months after treatment was defined as long term vision.The changes of long term vision and CMT on 1 and 6 months of two groups after treatment were observed.Pearson correlation analysis showed that the correlation between long-term vision and age,logMAR BCVA before treatment,CMT before treatment,frequency of injection,and CMT value decreased 1 month after treatment.The correlation of long-term visual acuity with age,sex,logMAR BCVA before treatment,CMT before treatment,number of drugs before treatment,CMT reduction at 1 month after treatment,integrity of ellipsoid band and integrity of external membrane (ELM) were analyzed by multiple regression analysis.Results On 1 month after treatment,the CMT of the eyes was lower than that before treatment (231.48± 177.99) μm,and the average integrity of ELM and ellipsoid were 0.56±0.50 and 0.41 ±0.50 respectively.On 6 months after treatment,the average logMAR BVCA of the eyes was 0.48 ± 0.34.The results of Pearson correlation analysis showed that the long-term vision was positively correlated with the logMAR BCVA before treatment and the number of CMT reduction and the number of drug injection at 1 month after treatment (P＜0.05);there was no correlation with age and CMT before treatment (P＞0.05).The results of multiple regression analysis showed that the long-term vision was associated with logMAR BVCA before treatment,CMT reduction,ELM integrity,and the number of times of injection (P＜0.05),and no correlation with age,sex,CMT before treatment and the integrity of the ellipsoid (P＞0.05).On the 6 months after treatment,the logMAR BCVA in the non-response group and the response group were 0.86±0.23 and 0.26±0.14,and the average CMT was respectively (398.93±104.87) and (255.15 ± 55.18) μrn,and the average injection times were respectively (2.53 ± 1.46) and (1.31 ± 0.74) times.The average logMAR BCVA,CMT and injection times of the two groups were statistically significant (t=10.293,5.773,3.589;P=0.000,0.000,0.001).No complications related to drug or intravitreal injection occurred in all patients.Conclusion The long-term vision of ME secondary to BRVO after intravitreal injection of Conbercept combined with retinal laser photocoagulation was associated with the decrease of CMT and the integrity of the ELM after 1 month of treatment,no correlation was found between CMT and ellipsoid integrity before treatment.

Diabetic retinopathy is a serious complication of diabetes and is the leading cause of blindness in people with diabetes.At present,there are many views on the pathogenesis of diabetic retinopathy,including the changes of retinal microenvironment caused by high glucose,the formation of advanced glycation end products,oxidative stress injury,inflammatory reaction and angiogenesis factor.These mechanisms produce a common pathway that leads to retinal degeneration and microvascular injury in the retina.In recent years,cell regeneration therapy plays an increasingly important role in the process of repairing diseases.Different types of stem cells have neurological and vascular protection for the retina,but the focus of the target is different.It has been reported that stem cells can regulate the retinal microenvironment and protect the retinal nerve cells by paracrine production,and can also reduce immune damage through potential immunoregulation,and can also differentiate into damaged cells by regenerative function.Combined with the above characteristics,stem cells show the potential for the repair of diabetic retinopathy,this stem cell-based regenerative therapy for clinical application provides a pre-based evident.However,in the process of stem cell transplantation,homogeneity of stem cells,cell delivery,effective homing and transplantation to damaged tissue is still a problem of cell therapy.

Objective To observe the effect of Delta-like ligand 4 (Dll-4) on the pathological structure of retina in early diabetic rats (DM) and its relationship with vascular endothelial growth receptor-2 (VEGFR-2).Methods A total of 70 male Sprague-Dawley rats were randomly divided into normal group and DM group,with 10 and 60 rats in each group,respectively.The rats of DM group was induced by intraperitoneal injection of streptozotocin to established DM model.The rats with blood glucose recovery and death were excluded,and the final 60 rats were included in the statistics.Rats in the normal group were injected with an equal volume of citric acid-sodium citrate buffer.Rats in the DM group were divided into DM 1 month (DM lm) group,DM 2 months (DM 2m) group,DM 3 months (DM 3m) group and DM 3m + Anti group,DM 3m + phosphate buffer solution (PBS) group by random number table method,and 10 rats in each group.In the DM 3m+Anti group,4 μl ofantiDll-4 polyclonal antibody was injected into the vitreous cavity,and the antibody concentration was 0.25 mg/ml.The DM 3m+PBS group was intravitreally injected with an equal volume of PBS.Five days after the injection,the rats were sacrificed.Rats in the DM 3m group and the normal group were not treated,and were sacrificed 3 months after the model was established.The structure and microvascular changes of the retina were observed by hematoxylin-eosin staining,and the total thickness of the retina was measured.The expression of Dll-4 and VEGFR-2 in the retina was detected by immunohistochemistry and fluorescence quantitative polymerase chain reaction (PCR).One-way analysis of variance was used to compare the expression of Dll-4 and VEGFR-2 in the retina of each group.The least significant difference t test was used to compare the two groups.Results Light microscopy showed that the retinal ganglion cells layer in the DM 3m group were obviously edematous,the inner and outer nuclear layers were thinner,the number of cells was reduced,the arrangement was disordered,the edema of outer plexiform layer was obvious,and the microvessels were abnormally dilated.In the DM 3m+Anti group,the edema of outer plexiform layer was lessened than that of the DM 3m group,and the other layers were not significantly different from the DM 3m group.Compared with the normal group,the total retinal thickness of the DM 3m group,the DM 3m+Anti group and the DM 3m+PBS group increased (t=5.596,3.290,4.286;P=0.000,0.008,0.002).Immunohistochemical staining showed that a small amount of Dl14 was positively expressed in the retinal ganglion cell layer of the normal group;a small amount of VEGFR-2 was positively expressed in the ganglion cell layer and the inner and outer nuclear layers.The positive expression of Dll-4 and VEGFR-2 in retinal vascular endothelial cells of DM 3m group increased significantly.The expression of Dll-4 was significantly decreased in the retinal layers and vascular endothelial cells ofDM 3m+Anti group,while the expression of VEGFR-2 was significantly increased.There was no significant difference between the positive expression of Dll4 and VEGFR-2 in the DM 3m+PBS group and the DM 3m group.The results of real-time PCR showed that the relative expression of Dll-4 and VEGFR-2 mRNA in the DM 3m group was significantly higher than that in the normal group (t=6.705,20.871;P＜0.05).Compared with DM 3m group,the relative expression of Dll-4 mRNA in DM 3m+Anti group decreased,and the relative expression of VEGFR-2 mRNA increased (t=2.681,3.639;P＜0.05).The relative expressions of Dll-4 and VEGFR-2 mRNA in the DM 3m+PBS group and DM 3m group were not statistically significant (t=0.513,0.657;P＜0.05).Conclusions The expression of Dll-4 in retinal vascular endothelial cells is gradually increased during the early retinopathy of DM rats.The expression of Dll-4 is inhibited,the expression of VEGFR-2 is up-regulated,and the plexus edema is alleviated.

Objective To observe the efficacy of intravitreal injection of ranibizumab (IVR) for different patterns of optical coherence tomography (OCT) of diabetic macular edema and the relationship between integrity of ellipsoidal zone and visual acuity outcomes.Methods Eighty-five IVR treated eyes were enrolled.The examination of BCVA was according to Early Treatment Diabetic Retinopathy Study,and the results were recorded as logarithm of the minimum angle of resolution (logMAR).Frequency-domain OCT was used to measure the central foveal thickness (CFT) and the integrity of ellipsoidal zone.All eyes were classified as diffuse macular edema (DRT group,31 eyes),cystoid macular edema (CME group,29 eyes),and serous retinal detachment (SRD group,25 eyes).All the patients were treated with intravitreal injection of 0.05 ml (0.5 mg) ranibizumab.The mean follow-up time was (9.21+3.56) months after IVR treatment.The changes of BCVA and CFT in 3 groups were compared and analyzed after 3,6 and 12 months.According to visual acuity at different ranges,the relationship between integrity of ellipsoidal zone and BCVA was analyzed.Results Compared with the average logMAR BCVA before treatment,except for 12 months after treatment in group SRD (t=2.104,P=0.053),the average logMAR BCVA after IVR at 3 months,6 months and 12 months improved in DRT group (t=7.847,6.771,6.426;P=0.000,0.000,0.000),CME group (t=8.560,6.680,5.082;P=0.000,0.000,0.000) and SRD group (t=5.161,3.968,2.104;P=0.000,0.001,0.053).The average logMAR BCVA of the DRT group was lesser than that in CME and SRD group after 12 months treatment (t=-2.043,-3.434;P=0.030,0.001).The average CFT after IVR at 3 months,6 months and 12 months reduced significantly in DRT group (t=12.746,10.687,9.425;P=0.000,0.000,0.000),CME group (t=13.400,11.460,10.169;P=0.000,0.000,0.000),and SRD group (t=1 1.755,10.100,9.173;P=0.000,0.000,0.000).After 12 months of treatment,the average CFT of the SRD group was thicker than that in DRT group and CME group (t=-3.251,-1.227;P=0.003,0.025);there was significant difference in the integrity of ellipsoidal zone among 3 groups (x2=1.267,P=0.531).The results showed that there were significant differences in the integrity of ellipsoidal zone with different ranges of BCVA before and after 12 months treatment (x2=20.145,41.035;P=0.000,0.000).Conclusions IVR could significantly improve the visual acuity of different patterns of DME,reduced the CFT,and had the best efficacy in the DRT group.There was relationship between the integrity of ellipsoidal zone and the visual acuity outcomes.