Objective:To analyze the clinical phenotypes and genotypes of a family with posterior segment microphthalmia-retinoschisis and drusen syndrome.Methods:A pedigree investigation study was conducted.A family with four members across two generations treated at Shenzhen Eye Hospital in July 2021 was enrolled.Detailed ophthalmic examinations, including best corrected visual acuity (BCVA), intraocular pressure, slit-lamp microscopy, color fundus photography, optical coherence tomography (OCT), anterior segment OCT, fundus fluorescein angiography (FFA), and visual field tests were performed in the four members.Peripheral venous blood samples were collected from members for whole exome sequencing and data analysis.The pathogenicity of novel variant sites was assessed according to the ACMG guidelines.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shenzhen Eye Hospital (No.22KYPJ018).Written informed consent was obtained from each subject or the guardian.Results:The proband is a 14-year-old female with high hyperopia since childhood, BCVA of + 9.75 DS-0.75 DC×150°=0.9 and + 11.75 DS-1.25 DC×30°=0.7, corneal transverse diameters of 12.1 and 12.2 mm, anterior chamber depths of 2.56 and 2.92 mm, lens thicknesses of 3.92 and 3.94 mm, and axial lengths of 17.47 and 17.01 mm in the right and left eyes, respectively.Fundus photography revealed diffuse yellow-white drusen-like lesions with unclear borders in the mid-peripheral retina, while OCT showed retinoschisis in the inner nuclear layer and homogeneous mound-like elevations with hyperreflective dense spots under the retinal pigment epithelium.FFA demonstrated diffuse punctate transilllumination of the mid-peripheral retina in both eyes, and visual field tests revealed a general decrease in visual acuity.The proband's 8-year-old brother exhibited similar signs to the proband.The consanguineously married parents were phenotypically normal.Whole exome sequencing identified compound heterozygous mutations in the membrane frizzled-related protein ( MFRP) gene in the proband and her brother, c.1150_1151insC (p.His384Profs*8) in exon 5 and c. 498_499insC (p.Asn167Glnfs*34) in exon 10.The father carried the c. 498_499insC mutation, while the mother carried the c.1150_1151insC mutation.Both were frameshift mutations predicted to alter gene function.These novel mutations had not been reported in the ESP, 1 000 Genomes (Phase 3), or ExAC databases, indicating they are novel variants.The variants co-segregated with the disease and both were classified as pathogenic according to ACMG guidelines.Based on the clinical and genetic findings, the family was diagnosed with posterior segment microphthalmia-retinoschisis and drusen syndrome, inherited in an autosomal recessive manner. Conclusions:The MFRP gene mutations c. 1150_1151insC and c. 498_499insC are the pathogenic variants for the posterior segment microphthalmia-retinoschisis and drusen syndrome in this family, and these compound heterozygous mutations are reported for the first time.

Objective:To observe the clinical effect of prolonged photodynamic therapy (PDT) irradiation time combined with intravitreal injection of ranibizumab in the treatment of circumscribed choroidal hemangioma (CCH).Methods:A retrospective clinical study. From March 2012 to March 2018, 51 eyes of 51 patients diagnosed in Shenzhen Eye Hospital were included in the study. Among the patients, the tumor of 36 eyes were located in macular area, of 15 eyes were located outside macular area (near center or around optic disc). All patients underwent BCVA, color fundus photography, FFA, ocular B-scan ultrasonography and OCT examinations. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. OCT showed 48 eyes with macular serous retinal detachment. of 36 eyes with tumor located in macular area, the logMAR BCVA was 0.05±0.05, the tumor thickness was 4.5± 2.2 mm, the diameter of tumor was 9.7±3.6 mm. Of 15 eyes with tumor located outside macular area, the logMAR BCVA was 0.32±0.15, the tumor thickness was 3.8±1.4 mm, the diameter of tumor was 7.7± 1.9 mm. PDT was performed for all eyes with the irradiation time of 123 s. After 48 h, all patients received intravitreal injections of 0.5 mg ranibizumab (0.05 ml). At 1, 3 and 6 months after treatment, the same equipment and methods before treatment were used for related examination. BCVA, subretinal effusion (SRF), tumor leakage and size changes were observed. BCVA, tumor thickness and diameter before and after treatment were compared by t test. Results:At 6 months after treatment, the tumor was becoming smaller without scar formation. FFA showed that the blood vessels in the tumor were sparse compared with those before treatment, and the fluorescence leakage domain was reduced. OCT showed 43 eyes of macular serous detachment were treated after the combined treatment. The logMAR BCVA were 0.16±0.15 and 0.55±0.21 of the eyes with tumor located in or outside macular area, respectively. The difference of logMAR BCVA between before and after treatment was significant ( t=-2.511, -2.676; P=0.036, 0.040). Both the tumor thickness ( t=3.416, 3.055; P=0.011, 0.028) and diameter ( t=4.385, 4.171; P=0.002, 0.009) of CCH patients were significantly reduced compared with that before treatment. Conclusion:The tumor of CCH can be reduced by prolonged PDT irradiation time combined with intravitreal injection of ranibizumab.

Objective: To investigate the expression of lncRNA01296 in esophageal cancer (EC) tissues and its effect on the proliferation and migration of EC TE-2 cells. Methods:Atotal of 36 pairs of esophageal cancer tissues and corresponding para-cancerous tissues were collected from EC patients admitted to the Department of Thoracic Surgery,Affiliated Hospital of Chengde Medical College from January 2017 to September 2018. The human normal esophageal epithelial (HEEC) cells and human esophageal cancer cell lines ECA109, TE-1 and TE-2 were cultured. qPCR was used to detect the mRNAexpressions of lincRNA01296, SNRPA(small nuclear ribonucleoproteinA) and NGF (nerve growth factor) in EC tissues and cells. Recombinant lentiviral interference vectoror control vector were used to transfect EC cell lines, as sh-lncRNA01296#1,#2 and Mock groups. WB was used to detect the protein expressions of SNRPAand NGF in transfected cells. MTS assay was used to detect cell proliferation, and Transwell assays were used to detect cell invasion and migration of TE-2 cells after transfection. Results: The mRNAexpressions of lncRNA01296, SNRPAand NGF were significantly increased in esophageal cancer tissues and cell lines (all P<0.01), and these expressions in poorly differentiated TE-2 cells were higher than those in highly differentiated ECA109 and TE-1 cells (all P<0.05). The mRNAexpressions of lncRNA01296 and NGF in sh-lncRNA01296#1 and sh-lncRNA01296#2 groups were significantly lower than those in Mock group (all P<0.01), while the mRNAexpression of SNRPAshowed no statistical difference among three groups (P>0.05). The protein expressions of lncRNA01296 and NGF in sh-lncRNA01296#1 and sh-lncRNA01296#2 groups were significantly lower than those in Mock group (all P<0.01). The relative proliferation ability of cells in sh-lncRNA01296#1 and shlncRNA01296#2 groups was significantly lower than that of Mock group at 48 and 72 h after transfection (P<0.05 or P<0.01). The number of invasive cells was (72.0±6.3), (36.6±4.3) and (33.9±3.7) in Mock, sh-lncRNA01296#1 and sh-lncRNA01296#2 groups, respectively; and the number of migrated cells was (85.2±9.9), (47.5±8.1) and (43.8±6.5), respectively, indicating that the numbers of invasive and migrated cells in sh-lncRNA01296#1 and sh-lncRNA01296#2 groups were significantly less than those in Mock group(all P<0.01). Conclusion: lncRNA01296 can up-regulate SNRPAexpression to promote NGF-mediated proliferation and metastasis of EC cells, which may provide new target for the diagnosis and treatment of esophagealcancer.

Objective To analyze the risk factors of early acute kidney injury (AKI) after liver transplantation from donation after cardiac death(DCD) donor liver. Methods Clinical data of 184 donors and recipients undergoing liver transplantation from DCD donor liver were retrospectively analyzed. According to the incidence of early AKI, all participants were divided into the AKI and non-AKI groups. The patients in the AKI group were subject to AKI staging. Baseline data, preoperative, intraoperative and postoperative related parameters were statistically compared between two groups. The cumulative survival rate and clinical prognosis of patients in non-AKI group and AKI group with different staging were statistically analyzed by Kaplan-Meier curve analysis. Results Among 184 patients, 68 cases (37.0%) presented with early AKI after liver transplantation including 31 stage 1 AKI, 26 stage 2 AKI and 11 stage 3 AKI, mainly occurring within postoperative 3 d. Univariate analysis revealed that preoperative levels of albumin <35 g/L, preoperative levels of serum sodium ≤137 mmol/L, operation time>7.5 h, intraoperative hemorrhage volume>3 000 mL, intraoperative red cell infusion volume>15 U and intraoperative urine amount ≤100 mL/h were the risk factors of early AKI after liver transplantation (all P<0.05). Multi-variate Logistic regression analysis demonstrated that intraoperative red cell infusion >15 U was an independent risk factor of early AKI after liver transplantation [odds ratio(OR) 1.061, 95% confidence interval(CI)1.008-1.118,P=0.024].Result of Kaplan-Meier survival curve suggested that the cumulative survival rate was gradually reduced along with the aggravation of AKI with statistical significance (all P<0.05). Conclusions The incidence of early AKI following liver transplantation is relatively high. The severity of early AKI is intimately correlated with the short- and long-term prognosis of the recipients. A large quantity of intraoperative red blood cell infusion is an independent risk factor of AKI.

Objective To investigate evaluation role of IP-10 level in urine of kidney transplant recipients when using rabbit anti-human T-lymphocyte immunoglobulin to treat acute cellular rejection.Methods A total of 40 patients who underwent renal transplantation and had been diagnosed as acute cellular rejection according to the results of histopathological examination were randomly divided them into IP-10 group (n =20) and serum creatinine group (Scr group,n =20).Urinary IP-10 and Scr levels were measured in time and patients then were treated with ATG,of which the doses and duration were adjusted according to IP-10 or Scr levels.We compared the total and daily ATG dosages,ATG administration period,side effects of ATG such as incidence of severe platelet and neutropenia,acute rejection during first 3 months and infection rates during first 1 year.Result The number of ATG duration is 5.35 ± 1.93 for IP-10 group versus 6.70 ± 1.75 for Scr group.We used a daily dose of 2.50 ± 0.57 mg/(kg·d) for IP-10 group and 2.77 ± 0.74 mg/(kg· d) for Scr group,a total dose of 13.40 ± 6.59 mg/kg for IP-10 group and 18.25 ± 7.35 mg/kg for Scr group.There was significance between the two group in above three outcomes (P ＜ 0.05).There was no significance in incidences of severe thrombocytopenia and neutropenia,incidences of acute rejection during first 3 months,incidences of infection during first 1 year between the two group (P ＞ 0.05).Conclusion Urine IP-10 test is effective and reliable indicators which can guide ATG usage in patients with acute rejection and reduce the ATG cost.

Objective To summarize the clinical efficacy of renal transplantation from donors of donation after brain death (DBD) complicated with acute kidney injury (AKI). Methods Fifty-nine DBD donors successfully undergoing renal transplantation were recruited in this investigation. According to the Scr level upon admission of intensive care unit (ICU), DBD donors were divided into the AKI group (n=14) and control group (n=45). A total of 101 recipients were assigned into the AKI group (n=23) and control group (n=78) correspondingly. The organ donation conditions of 59 donors were summarized. Main parameters of the donors before organ procurement were statistically compared between two groups. Postoperative kidney function, hospitalization condition and clinical outcomes of the recipients were statistically compared between two groups. Results Among 59 donors, 14 cases (24%) suffered from AKI. Two donors received continuous renal replacement therapy during organ maintenance. Compared with the donors in the control group, the APACHE Ⅱ score of the donors was significantly higher (P<0.05), the incidence of central diabetes insipidus was considerably higher (P<0.01), the Scr levels at admission of ICU and before organ procurement were significantly higher (both P<0.01) and the amount of urine at 24 h before organ procurement was dramatically less in the AKI group (P<0.01).Compared with the recipients in the control group, the Scr levels at postoperative 2 and 3 d were significantly higher (both P<0.05), the length of hospital stay was considerably longer (P<0.01) and the hospitalization expanse was significantly higher in the AKI group (P<0.05). No statistical significance was observed in the postoperative delayed recovery of renal graft function, incidence of acute rejection, infection and rehabilitation dialysis in the recipients between two groups (all P>0.05). At 3 months after transplantation, the recipients in two groups were discharged and the graft survival rate was 100%. Conclusions For renal transplantation from DBD donors complicated with AKI, active measures should be taken to maintain the organ and relieve the AKI, which yields similar clinical efficacy to renal transplantation from non-AKI donors and widens the origin of kidney graft.

OBJECTIVETo investigate the clinical value of three-dimensional (3D) laparoscopic cholecystectomy in the treatment of complicated gallstone disease.

METHODSFrom March 2014 to March 2015, 46 patients underwent cholecystectomy for complicated gallstone disease under 3D laparoscopy (3D group) and 43 received 2D laparoscopic cholecystectomy (2D group). The surgical data including the operative time, intraoperative blood loss, the rate of conversion to open laparotomy, recovery time of postoperative bowel motion and hospital stay were compared between the 2 groups.

RESULTSLaparoscopic cholecystectomy was successfully completed in 43 patients in 3D group and in 39 patients in 2D group, and the rates of conversion to open laparotomy were similar between the two groups (P>0.05). The median operation time was significantly shorter in 3D group than in 2D group (50.5∓15.2 vs 65.4∓18.1 min, P<0.05), and the median volume of intraoperative blood loss was significantly smaller in 3D group (34.1∓13.6 vs 44.5∓22.3 mL, P>0.05). No significant differences were found in the recovery time of postoperative bowel motion and postoperative hospital stays between the two groups (P>0.05).

CONCLUSION3D laparoscopy, which provides three-dimensional vision with a good sense of depth to allow precise surgical manipulation, can shorten the operation time and reduce the rate of conversion to open laparotomy for patients undergoing 3D laparoscopic cholecystectomy for complicated gallstone disease.

Blood Loss, Surgical ; Cholecystectomy, Laparoscopic ; methods ; Gallstones ; surgery ; Humans ; Imaging, Three-Dimensional ; Length of Stay ; Operative Time

Objective To explore the characteristics and effects of interventional therapy of transplant renal artery rupture of donation after citizens death (DCD).Method Among 28 cases of DCD renal transplantations (from February 2012 to December 2013),the transplant renal artery rupture occurred in 4 cases.Vascular complications were treated with the guide wires to place stents in the pseudoaneurysms or bleeding period.Result Pseudoaneurysms occurred in 2 cases,and they were successfully discharged after interventional treatment.In the rest two patients,the artery residual ruptured and bled after the nephrectomy,and they recovered after interventional treatment to stop bleeding.Conclusion For kidney transplant recipients,the DCD postoperative infection is risky.Some transplant kidneys have local infection and erosion of renal artery,which causes arterial hemorrhage.The interventional treatment of transplant renal artery pseudoaneurysms and rupture bleeding has the advantages of small trauma and instant effect,and can be used as an alternative treatment of open surgery.

OBJECTIVEPotention drug-targets on anti-neuropathy of stroke were summarized, and it will provide materials for developing innovation components traditional Chinese medicine on anti-cerebral infarction neuropathy.

METHODThis article had done a series of researching work about neurovascular unit which includes three kinds of cells: neuron, gliacyte,brain microvascular endothelial cell, then signal mechanism of cell death or apoptosis of each section of stroke neuropathy was analysised by the historical documents.

RESULTThere are five important pathways: inflammatory factor-MMPs pathway- Caspases, Ca2+ -mitochondrial pathway-Caspases, Ca2+ -Phospholipase-PI-3K/AK pathway, Ca2+ -radical-MAPK pathway, Ca2+ -NO-protease pathway, among all the nodes, Caspases, Ca2+, NO were the most important ones.

CONCLUSIONDeveloping the multi-mechanism and multilevel of traditional chinese medicine under the guidance of the theories of network pharmacology and neurovascular unit will play an important role in studying the key links of signal-network of stroke neuropathy.

Calcium ; metabolism ; Caspases ; metabolism ; Cerebral Infarction ; metabolism ; prevention & control ; Drug Delivery Systems ; methods ; Humans ; MAP Kinase Signaling System ; Matrix Metalloproteinases ; metabolism ; Medicine, Chinese Traditional ; methods ; Models, Biological ; Pharmacology ; methods ; Phosphatidylinositol 3-Kinases ; metabolism ; Polyneuropathies ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction

OBJECTIVETo solve the difficult in the active compounds screening from traditional Chinese medicines (TCM).

METHODAccording to preliminary lab results and related literature, systematic analysis of the high-throughput technology was made.

RESULTTechnologies of rapid preparation, high-throughput screening and biochip, together with the thought of drug target network, will contribute to TCM research on active ingredients screening, toxic components exclusion and molecular mechanisms. They are key technologies and ideas for modernization of TCM and research of TCM network pharmacology.

CONCLUSIONHigh throughput technology and network pharmacology-related technologies will provide new ideas and key methods for active compounds screening from TCM.

Drug Delivery Systems ; methods ; Drug Evaluation, Preclinical ; methods ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; Humans ; Medicine, Chinese Traditional ; Pharmacology ; methods ; Technology, Pharmaceutical ; methods