OBJECTIVE: To explore the clinical features and genetic etiology of a child with Hoyeraal-Hreidarsson syndrome (HHS). METHODS: A child with HHS diagnosed at the Affiliated Hospital of Jining Medical University due to "developmental delay and anaemia" on April 27, 2024 was selected as the study subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Whole-exome sequencing was carried out, and candidate variant was verified by Sanger sequencing of his family members and bioinformatics analysis using CASAVA v1.8.2. The pathogenicity of the candidate variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by the American College of Medical Genetics and Genomics (ACMG). Relevant literature on HHS cases reported in China was reviewed to analyze the clinical and genetic characteristics. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-10-C003). RESULTS: The child, a 7-month-old boy, had mainly manifested with growth retardation, developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency and bone marrow failure. Routine blood test indicated pancytopenia. The immunological workup showed reduction of B cells, NK cells and immunoglobulins. Cranial MRI demonstrated the volume of bilateral cerebellar hemispheres and brainstem and corpus callosum was small. Whole-exome sequencing revealed that he has harbored a hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene. Sanger sequencing showed that his mother and two sisters have carried the same variant. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PM1+PM4+PS4_Supporting+PM2_Supporting). Four relevant literature were retrieved, which has involved 8 HHS cases. Together with the patient from this study, they have consisted of 8 males and 1 females. The most common symptoms of the 9 patients were blood system abnormalities and developmental delay. All patients had shown cerebellar dysplasia and anemia/erythrocytopenia. Among them, 3 cases have harbored TINF2 gene variants, and 6 cases had harbored DKC1 gene variants. The c.103_105del variant has not been reported in China previously. CONCLUSION The hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene probably underlay the disease in this child. Above finding has expanded the mutational and phenotypic spectra of the DKC1 gene, and has facilitated early diagnosis of HHS in this child.
Humans ; Infant ; Male ; Cell Cycle Proteins/genetics* ; Dyskeratosis Congenita/genetics* ; Exome Sequencing ; Fetal Growth Retardation/genetics* ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Mutation ; Nuclear Proteins/genetics* ; X-Linked Intellectual Disability/genetics*

Objective : To estimate the risk threshold of route index（RI）and mosq-ovitrap index（MOI）based on Breteau index（BI）,as supplements for dengue fever risk monitoring in specific habitats. Methods : Two towns and two streets were selected from nine towns（streets）in Jiashan County,and then one village（community）was selected from each of them as a Aedes albopictus monitoring site. The BI,RI and MOI were employed at the same time and area from April to October in the year 2018. Linear regression models were built with RI,MOI and BI to calculate the dengue risk threshold of RI and MOI according to BI. Results : The linear regression model of BI（X）and RI（Y）was Y=0.145+0.662X（P<0.05）,of BI（X）and MOI（Y）was Y=3.423+0.524X（P<0.05）. If BI=5（having risk of transmission of dengue fever）,then RI=3.455（95%CI：1.717-5.198）,MOI=6.043（95%CI：-0.327-12.417）. If BI=10（having risk of outbreak）,then RI=6.765（95%CI：5.018-8.518）,MOI=8.663（95%CI：2.260-15.071）. If BI=20（having risk of epidemic）,then RI=13.385（95%CI：11.326-15.453）,MOI=13.903（95%CI：6.352-21.461）. Conclusion The dengue fever risk threshold of RI estimated by BI had a narrow 95%CI and could be applied for dengue fever risk assessment,while the risk threshold of MOI had a wide 95%CI and the application value needed further study.

Objective: To observe the effect of internal limiting membrane peeling and transplantation on vision-related quality of life in refractory macular hole. Methods: A retrospective clinical study. Thirty patients (30 eyes) with refractory macular hole diagnosed in Ophthalmology Department of The First Affiliated Hospital of Nanjing Medical University from January to December 2016 were included in this study. There were 13 males (13 eyes) and 17 females (17 eyes), with the mean age of 57.3±6.9 years. There were 15 patients(15 eyes) with large macular diameter, 12 patients (12 eyes) with high myopia macular hole, and 3 patients (3 eyes) with secondary traumatic macular hole. The BCVA examination was performed using the Snellen visual acuity chart, which was converted into logMAR visual acuity. OCT was performed to measure the macular retinal thickness (CRT), base diameter and minimum diameter of macular hole. Then, the macular hole index(MHI) was calculated. The logMAR BCVA was 1.52±0.30, MHI was 0.51±0.19. The Chinese version of visual-related quality of life scale-25 (CVRQoL-25) was used to evaluate the vision-related quality of life of patients. The CVRQoL-25 score was 57.60±7.13. All patients underwent 23G vitrectomy combined with inner limited membrane peeling and autologous ILM transplantation. The follow-up was at least 3 months after surgery. The changes of BCVA, MHI, CRT and CVRQoL-25 score before and after surgery were comparatively analyzed. Paired t test was performed to compare the measurement data before and after surgery, and Spearman rank correlation analysis was used for the correlation analysis among the parameters. Results: At 3 months after surgery, the hole closure was detected in 28 eyes (93.3%), not detected in 2 eyes (6.7%). The logMAR BCVA was 1.16±0.33, CRT was 161.00±15.26, and CVRQoL-25 scores was 70.83±9.77. Compared with before surgery, the BCVA (t=4.386, P=0.000) and CVRQoL-25 score (t=-5.991, P=0.000) after surgery were improved. Spearman rank correlation analysis showed that CVRQoL-25 score was negatively correlated with preoperative and postoperative logMAR BCVA (r=−0.536, −0.796; P=0.002, 0.000); positively correlated with preoperative MHI (r=0.421, P=0.020) and postoperative CRT (r=0.589, P=0.001). Conclusion Internal limiting membrane peeling and transplantation for refractory macular hole can significantly improve the vision-related quality of life and visual acuity, while achieved a high hole closure rate (93.3%).

Objective To explore the effect of the position of the biliary stents on the short?term and long?term effects of the patients with low malignant obstructive jaundice after treatment.Methods Seventy?eight patients with low?grade malignant obstructive jaundice diagnosed in Jiangyin Hospital Affiliated to Medical College of Southeast University who underwent biliary stenting were enrolled as the study object.According to the placement of the biliary stents,the stents were divided into the spanning group and the non?crossing group.The baseline data and related serological indexes were recorded,and the changes of jaundice between the two groups were compared by repeated measurements.All patients were followed up for 48 weeks.Multivariate Cox regression analysis was applied on the risk factors that might affect the prognosis of patients, and the degree of influence of various factors on the prognosis of patients was further evaluated.Results Repeated measures analysis showed that the biochemical indicators of the spanning group and the non?crossing group showed a significant downward trend and the difference was statistically significant (TBil: Fintra?group＝9.392,Pintra?group＝0.000; DBil: Fintra?group＝7.581,Pintra?group＝0.001).Among them,the total bilirubin (TBil) (Preoperative: (318.69±101.13) μmol／L,1 week after surgery: (135.98 ±63.61) μmol／L,2 weeks after surgery: (60.21±24.81) μmol／L) was lower than the non?crossing group preoperative: (309.07±109.97) μmol／L,1 week after surgery: (158.87±66.92) μmol／L,2 weeks after surgery: (75.91 ± 20.46) μmol／L), and the difference was statistically significant ( Finter?group ＝3.362, Pinter?group＝0.041).The direct bilirubin ( DBil) ( Preoperative: (171.93 ± 73.01) μmol／L,1 week after surgery: (90.38± 57.33) μmol／L,2 weeks after surgery:(36.64± 18.95) μmol／L) was lower than the non?crossing group ( Preoperative: ( 174.53 ± 82.74) μmol／L,1 week after surgery: ( 107.85 ± 49.07) μmol／L,2 weeks after surgery: ( 37.87 ± 14.55 ) μmol／L.The difference was statistically significant (Finter?group＝6.284,Pinter?group＝0.003).There was an interaction between the treatment regimen and treatment time (1 week after surgery and 2 weeks after surgery) (TBil: Finteraction＝12.262,Pinteraction＝0.000; DBil:Finteraction＝10.254,Pinteraction＝0.000).The results of the multi factor Cox proportional hazard model of the spanning group and the non?crossing group showed that the ALP, DBil, TBil and lymphatic metastasis of malignant tumor were the two independent risk factors that affect the prognosis.However, the pancreatic cancer,ALT and age in the spanning group across the ampulla also have a certain effect on the prognosis of the patients.Conclusion The effect of the placement of biliary stents across the Vater ampullary was more obvious in the short term on the decline of bilirubin.But in the long term,there was no significant difference in the prognosis of patients with biliary stenting position.ALP,TBil,DBil,and disease classification were all important risk factors affecting the prognosis of two groups of patients

Background and Purpose: With the rapid development of minimally invasive technique, robotic surgery is widely used in the gynecological surgery. This study aimed to compare the clinical data of roboticassisted laparoscopy and laparotomy in the treatment of early ovarian cancer. Methods: A total of 22 patients with early ovarian cancer receiving stage Ⅰ operation between Jan. 2015 and Dec. 2016 in Jilin Province Tumor Hospital were randomly divided into two groups: 8 patients received robotic-assisted surgery (robotic-assisted laparoscopic group), 14 patients received laparotomy (laparotomy group). Results: All patients underwent successful operation without changing surgical approach. The operation time in robotic-assisted laparoscopic group was longer than that in laparotomy group [(194.50±10.90) min vs (178.71±10.58) min, P＜0.05]. Blood loss volume [(60.10±8.88) mL vs (73.71±12.99) mL], 24 hours postoperative drainage volumes of robotic-assisted laparoscopic group were less than those in laparotomy group [(96.88±10.21) mL vs (108.00±11.43) mL, P＜0.05]. Others had no statistical significance (P＞0.05). Conclusion: In the clinical treatment of early ovarian cancer, there is no difference between robotic-assisted laparoscopic operation and laparotomy. Robotic-assisted laparoscopic operation is worthy of clinical promotion and application.

Background Choroidal neovascularization (CNV) is one of the primary causes leading to visual damage in many fundus diseases.Many evidences indicate that macrophage activation and monocyte chemoattractant protein-1 (MCP-1) play important roles in CNV.However, the dynamic expression of macrophage and MCP-1 in the initial stage of CNV is not clear.Objective This study was to investigate the dynamic changes of F4/80 and MCP-1 expressions in retina-choroid tissue with experimental CNV.Methods Laser-induced CNV models were monocularly established in 105 SPF 8-week-old male wild type C57BL/6 mice.The mice were sacrificed at 6,12,24, 48 and 72 hours after photocoagulation, respectively, and the retina-choroid tissue sections and choroidal flatmounts were prepared.The histopathological examination was carried out to observe the changes of morphology and structure as well as inflammatory response in CNV.The expression and distribution of F4/80 and MCP-1 protein in retinachoroid were detected by double immunofluorescence technique.The expression and distribution of F4/80 in choroid were examined by immunofluorescence.The relative expression levels of F4/80 mRNA and the content of MCP-1 protein in RPE-choroid complex were assayed using real-time quantitative PCR and ELISA,respectively.The use and care of the mice complied with the Regulation for the Administration of Affair Concerning Experimental Animals by Ethic Committee of Experimental Animals of Nanjing Medical University.Results The rupture of Bruch membrane, RPE, outer nuclear layer and choroid was exhibited under the optical microscope 6 hours after photocoagulation.Infiltration of inflammatory cells and tissue edema were seen as the lapse of photocoagulation time, and proliferation of vascular endothelial cells was found 72 hours after photocoagulation.F4/80 was expressed in photocoagulation area 6 hours later, and MCP-1 was expressed around the area.With the lapse of photocoagulation time,the expression intensity of MCP-1 weakened and that of F4/80 enhanced.The contents of MCP-1 protein in RPE-choroid complex were (31.25±4.73), (276.31 ±4.20), (331.95 ±5.86), (221.24±4.42), (179.89 ± 4.10) and (130.80 ± 5.90) pg/mg in the normal control group, photocoagulation 6-, 12-, 24-, 48-and 72-hour groups, respectively,with a significant difference among the groups (F=1 416.46 ,P＜0.01).The contents of MCP-1 protein peaked at 12 hours after photocoagulation and then gradually declined.The expression levels of MCP-1 protein in different time groups were higher than those in the normal control group (all at P＜0.01).A significant difference in F4/80 mRNA expression in RPE-choroid complex was also found among the groups (F =762.72, P＜0.01, and a gradually raising tendency was seen over time, showing evidently increase in comparison with the normal control group (all at P＜0.01).Conclusions Inflammatory response occurs in the early stage of experimental CNV.MCP-1 responds to the CNV at early stage,and the accumulation and activation of macrophage play an important role in the development of CNV.

Objectives To investigate the clinical profile and prognosis of hemophagocytic syndrome (HPS). Methods A retrospective study was carried out to analyze the clinical features and laboratory findings in 28 children with HPS. Fisher's exact probability method and Logistic multivariate regression were used to explore the prognostic risk factors.. Results HPS was clinically characterized by prolonged fever (100%), hepatomegaly (64.29%),and other minor features including respiratory symptoms (53.57%), splenomegaly (50%), hydrops of multiple serous cavity (42.86%), lymphadenectasis (32.14%), jaundice (17.85%), skin rash (14.29%), central nervous system involvement (14.29%), and alimentary tract hemorrhage (10.71%). Labo-ratory data showed that 1iver dysfunction, pancytopenia, coagulation abnormalities, disseminated intravascular coagulation, hy-pertriglyceridemia, decreased number of natural killer cells and hyponatremia were prominent. The etiological analysis indicated that infection associated hemophagocytic syndrome was most common (60.71%), in which EB virus associated HPS was pre-dominant, accounting for 64.71%. Significant difference was observed in the difference of albumin,blood urea nitrogen and acti-vated partial thromboplastin time between death and survival cases (P<0.05). The Logistic regression multivariate analysis showed that hypoalbuminemia was an independent prognostic factor. Conclusions There are various underlying diseases and clinical manifestations for HPS. The lower level of serum albumin is an independent prognostic factor. A prompt diagnosis and treatment is very important for HPS prognosis due to the rapid progression and high mortality.

This report presented a male patient aged 69 years,who was admitted into our hospital for fever,hemoptysis and chest pain.Chest X-Ray showed shadows on the right lung and pleural thickening.The effect of broad spectrum antibiotic therapy was poor.With the disease progressed,pleural effusion appeared on the right side.Blood culture showed methicillin-resistant staphylococcus aureus.Pleural effusion tests indicated pyothorax,but the effects of closed chest drainage and sensitive antibiotic therapy were poor.After disentangling with open thoracic exploration,the right middle lobe was resected and the right lung lobe pathology showed Wegener granulomatosis.His blood antineutrophil cytoplasmic autoantibodies was negative.The paranasal sinus CT scan and renal function showed no abnormalities.The definitive diagnosis was pulmonary limited Wegener granulomatosis.

Objective To investigate the CT and MRI findings of primary hepatic neuroendocrine carcinomas.Methods Imaging findings of 6 patients with pathologically confirmed hepatic neuroendocrine carcinomas were retrospectively analyzed.Four patients underwent plain CT and contrast enhanced CT examinations.The other 2 patients underwent plain MRI and contrast enhanced MRI.Results One out of the 6 cases manifested multicentric tumor which appeared as one large tumor surrounded with multiple small nodules peripherally,and the tumors of the other 5 cases were solitary.On plain CT images,all lesions were well-defined and hypoattenuating with central areas of even lower density except punctuate calcifications at tumor periphery in 1 case.On pre-contrast MRI,the cases manifested heterogeneous low signal intensity on T1 wI and slightly high intensity on T2 WI.On dynamic contrast enhanced CT and MRI,Tumors manifested slight to mild enhancement in arterial phase,slight enhancement in portal venous phase or delayed phase with no enhancement in the center,accompanied by dislocation of surrounding vessels.There Was no lymphadenopathy in peritoneal cavity and retroperitoniurm. Conclusion CT and MRI scanning can demonstrate specific features of primary hepatic neuroendocrine carcinoma,which may help the diagnosis and differential diagnosis of the tumor.