Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model / 中华儿科杂志

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

Effect of Salvia miltiorrhiza on retinopathy

OBJECTIVE@#To explore the effect of Salvia miltiorrhiza on diabetic retinopathy (DR).@*METHODS@#Diabetic mice of natural incidence type with monogenic inheritance were selected. Alloxan was injected into the caudal vein of mice once to induce DR. The structural changes of retina tissue in normal mice, DR mice and mice with high, medium and low dose of Salvia miltiorrhiza injection were observed under microscope. Then the blood glucose concentration and malonaldehyde (MDA) content were detected.@*RESULTS@#There were some microaneurysms in retina of DR group, number of gangliocyte was decreased significantly, and cells were sparse and in disorder. After modeling, the blood glucose level of high-dose Salvia miltiorrhiza group (SM III group) was significantly different from DR group (P<0.01). Till the tenth week, the blood glucose level of all SM groups was decreased significantly compared with DR group (P<0.01). The effective rates of three SM groups were 93.8%, 76.4% and 50.3%, respectively. After ten weeks, MDA content of DR group was significantly higher than those of the normal control group and SM group (P<0.01), and medium and low dose SM groups had significantly higher MDA than that of normal control group (P<0.01).@*CONCLUSIONS@#Salvia miltiorrhiza had certain protective effect on DR mice through the blood-ocular barrier.

Clinical characteristics of congenital nystagmus / 中华实验眼科杂志

Background Congenital nystagmus is a common disease threatening visual function.The clinical description of congenital nystagmus is still not enough now. Objective The aim of this study was to report the motor and sensory characteristics of congenital nystagmus. Methods A retrospective clinical case analysis was designed.The clinical data of 376 patients with congenital nystagmus were collected.These patients were diagnosed in Henan Eye Institute from January,2005 to August,2011.The clinical characteristics of patients,including age,pedigree analysis,nystagmus classification,ocular alignment,visual acuity,refractive error,stereoacuity and oscillopia,was summarized.Informed consent from all patients and custodian were obtained. Results The age distribution of most patients was ＞5-10 years and ＞ 15-20 years,with the percentage 24.73％ and 24.20％,respectively.Of 376 patients,sensory defect nystagmus was 172 cases,and that of motor sensory defect was 204 cases.The most common inheritance pattern was autosomal dominant.Conjugate uniplanar horizontal oscillations were found in 73.94％patients,and strabismus was found in 66.36％ in this study.Sensory defected subjects did not show a statistically significantly higher strabismus incidence when compared with the idiopaths (x2 =3.048,P =0.081 ).The binocular distance vision in all the subjects was declined in comparison with normal eyes,the best corrected vision was 0.27 ±0.11 and 0.50± 0.13 in sensory defected nystagmus and idiopaths nystagmus respectively,showing a significant difference( t =16.495,P =0.000 ).The incidence of refractive error in this study was 77.62％.Incidence of astigmatism(75.17％ ) was higher than that of myopia and hyperopia ( 39.03％ and 36.12％ ).No significant difference was seen in refractive error incidence between the sensory defected and the idiopaths (x2 =1.337,P =0.248).Patients of 65.18％ displayed non-stereoacuity or very gross acuity levels (3000) in this study,and the patients with idiopathic nystagmus showed better stereoacuity level in comparison with sensory defected ones (x2 =7.058,P =0.008 ).Five of 313 patients existed experienced oscilopla under binocular viewing conditions.Conclusions Autosomal dominant inheritance is the most common pattern of congenital nystagmus.Conjugate uniplanar horizontal oscillation is thought to be a common type of nystagmus.Incidence of strabismus is higher,and visual acuity and stereoaeuity are worse in congenital nystagmus than in common population.Oscillopia is seldom found in congenital nystagmus.

Surgery and visual function restoration for congenital idiopathic nystagmus with or without strabismus / 中华实验眼科杂志

Background The surgery for congenital idiopathic nystagmus has make great progression recent year,but the influence of surgery on visual function is closely concerned.Objective This work was to study the surgeries for congenital idiopathic nystagmus with or without strabismus and explore the effect of horizontal rectus muscle surgery on the visual function and ocular movement in congenital idiopathic nystagmus.Methods This was a case-observational study.Sixty cases with idiopathic congenital nystagmus were enrolled assigned to four groups as follows:The patients of group Ⅰ appeared the head postures of less than 15 ° and heterotropia less than 15△underwent extraocular proprioceptiou resection,and those of group Ⅱ presented with the head postures of less than 20° and heterotropia more than 15△ underwent extraocular proprioception resection and stabismus surgery.In the group Ⅲ,the patients had the head postures of more than 15° and heterotropia less than 15△ underwent Park's surgery and part of them underwent extraocular proprioception resection) and the cases in group Ⅳ were selected with the head postures of more than15° and heterotropia more than 15△ underwent Park' s surgery and strabismus surgery ( part of them underwent extraocular proprioception resection).Baseline and follow-up evaluations included the best distance and near corrected visual acuity,head posture,ocular movement and Titmus stereotest.The examination results were compared between before and after operation.Results One year after operation,monocular and binocular distance visual acuity improved significantly in all four groups ( monocular:t =6.00,8.94,11.76,16.41,P =0.00 ; binocular:t=4.81,P=0.01 ; t =6.27,4.25,4.18,P =0.00 ),but monocular and binocular near visual acuity improved significantly only in groups Ⅲ and Ⅳ after operation compared with before operation ( monocular:t=2.91,P=0.01 ; t =5.32,P =0.00 ; binocular:t =3.36,t =4.30,P =0.00 ).The compensatory head posture from 39 subjects was disappeared after operation,showing an evident difference between before and after surgery ( group Ⅲ:t =29.90,P=0.00;group Ⅳ:t=16.91,P=0.00).Strabismus were corrected rightly for 24 patients and undercorrection for 2 patients.( group Ⅱ:t =29.15,P =0.00 ; group Ⅳ:t =36.79,P =0.00 ).The binocular visual function of 23 cases with the age below 12 years were improved throughout the follow up duration ( t =12.06,P =0.00).Conclusions Park' s surgery,extraocular proprioception resection and strabismus corrective operation can improve the visual function and head posture in congenital idiopathic nystagmus patients.

Target-specific cytotoxic activity of recombinant fusion toxin C-CPE-ETA' against CLDN-3,4-overexpressing ovarian cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to explore the possibility of creating a toxin, C-CPE-ETA', by fusing C-terminal high affinity binding domain of CPE (C-CPE) with a truncated form of Pseudomonas aeruginosa exotoxin A (ETA') and to examine whether C-CPE-ETA' could specifically target CLDN-3, 4 molecule and the targeted toxin was cytotoxic against CLDN-3,4-overexpressing ovarian cancer.</p><p><b>METHODS</b>CLDN-3 and CLDN-4 expressions were analyzed at the mRNA level in three ovarian cancer cell lines and epithelial ovarian cancer tissues from 20 patients. After transforming an expression plasmid of C-CPE-ETA' into E. coli BL21 (DE3) plysS strain, the recombinant protein was purified using His-Bind resin chromatography column and analyzed by Western blot and Coomassie blue staining. The specific binding, proapoptotic and cytolytic activities were evaluated by flow cytometry, fluorescence microscopy with the JC-1 probe and MTT assay in CLDN-3,4-overexpressing ovarian cancer cells.</p><p><b>RESULTS</b>Quantitive RT-PCR results showed there existed high levels of CLDN-3 and CLDN-4 in ovarian cancer cells, CAOV3, OVCAR3 and SKOV3. Moreover, high expressions of CLDN-3 and CLDN-4 were observed in 90.0% (18/20) and 60.0% (12/20) of ovarian cancer tissues, with an expression level 10-fold higher than that in the normal ovarian tissue. A 58 000 recombinant protein C-CPE-ETA' was demonstrated by Western blot and Coomassie blue staining. Purified and recombinant C-CPE-ETA' was bound with high affinity to CLDN-3,4-overexpressing ovarian cancer cells, CAOV3, OVCAR3 and SKOV3 cells. C-CPE-ETA' was strongly proapoptotic and cytotoxic towards the CLDN-3,4-overexpressing ovarian cancer cells. The concentration of IC(50) was 7.364 ng/ml for CAOV3 cells, 8.110 ng/ml for OVCAR3 cells and 22.340 ng/ml for SKOV3 cells, respectively. However, control CLDN-3,4-deficient cell line HUVEC was not susceptible to the recombinant C-CPE-ETA' at a concentration up to 10 µg/ml.</p><p><b>CONCLUSIONS</b>The C-CPE-ETA' protein exhibits remarkably specific cytotoxicity for CLDN-3,4-overexpressing ovarian cancer cells. Its therapeutic potential warrants further development for ovarian cancer molecular targeted therapy.</p>

Association of EGFR expression with angiogenesis and chemoresistance in ovarian carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To clarify the association of EGFR expression with angiogenesis and chemoresistance in ovarian cancer.</p><p><b>METHODS</b>Immunohistochemical PV-6000 staining was used to detect the expression of EGFR, LRP protein and MVD in 102 ovarian tumor specimens.</p><p><b>RESULTS</b>EGFR, LRP positive rates and MVD in borderline and malignant ovarian specimens were significantly higher than those in the normal and benign ones (P < 0.01). EGFR positive expression rate in stage III-IV carcinoma tissues, poor differentiation and with ascites was higher than that in stage I-II carcinomas of well differentiation and without ascites (P < 0.05). MVD was related to histological grade, residual tumor and ascites, LRP positive expression had no correlation with the clinicopathologic parameters (P > 0.05). The effective rate of chemotherapy in patients with EGFR and LRP-positive expression were 57.1% and 53.7%, respectively, significantly lower than that in cases with EGFR and LRP-negative expression (85.0% and 90.9%, P < 0.05). In the 64 cases with complete data, the three-year survival rate was 53.0%. The survival time was shorter in the cases with EGFR and LRP-positive expression, poor differentiation, ascites and chemoresistance (P < 0.01), and only LRP-positive expression and chemotherapeutic effect were independently related to survival time (P < 0.05). There was a correlation between EGFR and MVD (r = 0.548, P < 0.01), EGFR and LRP positive expression (P = 0.020).</p><p><b>CONCLUSION</b>The expression of EGFR in ovarian cancer is related to angiogenesis and chemoresistance. EGFR and LRP-positive expression are related to chemoresistance, and detection of the two proteins may be helpful in guiding chemotherapy choice for ovarian cancer. LRP-positive expression and chemotherapeutic effect may be independent prognostic factors.</p>

Expression of mesothelin mRNA and protein in ovarian carcinomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of mesothelin (MESO) mRNA and protein and its significance in ovarian carcinomas.</p><p><b>METHODS</b>Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to detect the expression level of MESO mRNA and protein, respectively, in 124 samples of ovarian tumor and normal tissues, including 84 epithelial ovarian carcinomas, 12 borderline ovarian tumors, 16 benign ovarian tumors and 12 normal ovarian tissues.</p><p><b>RESULTS</b>The expression of MESO mRNA and protein in epithelial ovarian carcinomas (1.4005 +/- 0.4646, 2.7857 +/- 2.2712) and borderline ovarian tumors (1.0650 +/- 0.3100, 2.9167 +/- 2.391) were significantly higher than that in benign ovarian tumors (0.6463 +/- 0.2419, 1.2500 +/- 1.6125) and normal ovarian tissues (0.6439 +/- 0.2729, 0.9167 +/- 1.2401) (P < 0.05), and also significantly higher in serous cystadenocarcinoma (1.5255 +/- 0.4151, 3.3036 +/- 2.6141) and endometrioid carcinoma (1.5250 +/- 0.5419, 3.0000 +/- 2.3094) than that in mucinous cystadenocarcinoma (1.0675 +/- 0.3149, 1.0556 +/- 1.9242) (P < 0.05). The expression of MESO mRNA and protein in stages II and IV carcinomas (1.5100 +/- 0.4142, 3.6087 +/- 3.3959) was significantly higher than that in stages I and II carcinomas (1.1190 +/- 0.4909, 1.7895 +/- 2.6320; P < 0.05), and also significantly higher in grade 3 carcinomas than that in grade 1 and 2 ones (P < 0.05), but was not correlate with age or serum CA125 of the patients (P > 0.05).</p><p><b>CONCLUSION</b>The results of this study demonstrated that the expression of MESO mRNA and protein is increased in ovarian carcinomas and borderline ovarian tumors, and MESO may play a role in the adhesion and dissemination of ovarian carcinomas.</p>

Analysis of the expression of matrix metaUoproteinase and tissue inhibitor of metalloproteinase in gestational trophoblastic diseases / 中华全科医师杂志

Objective To explore the relationship between the expression of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) in gestational trophoblastie diseases and its invasiveness.Methods The expression and distribution of MMP-7,MMP-9,TIMP-1 and TIMP-2 were determined by immunohistochemistry PV-6000 in 49 cases of hydatidiform mole (eight of them with malignant transformation),six cases of invasive hydatidiform mole,two cases of choriocarcinoma and 18 cases with normal villi in early pregnancy.Results The expression of MMP-7,MMP-9,TIMP-2 and MMP- 9/TIMP-1 was significantly higher in choriocareinoma,invasive mole and malignant transformed mole than that in normal villi in early pregnancy and non-malignant transformed mole (F=10.950,7.760,7.304, 3.442;P