[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.

[Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant].

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

[Comparison of corneal power assessment methods after small incision lenticule extraction].

Objective: To compare the accuracy of different corneal curvature parameters in assessing the corneal refractive status and tracking corneal power changes after small incision lenticule extraction (SMILE). Methods: This prospective cross-sectional study tracked and recorded total corneal curvature parameters measured by different instruments before and three months after SMILE for myopia. These parameters, including total keratometry (TK) from the IOLMaster 700, total corneal refractive power (TCRP) from the Pentacam AXL, real keratometry (RK) from the CASIA 2, and corrected parameters calculated using the Haigis, Shammas, and Maloney methods, were compared with data obtained using the clinical history method (CHM). Surgically induced changes in TK, TCRP, and RK were analyzed and compared with those in spherical equivalent on the corneal plane (ΔSEco). Results: The study included 40 eyes (40 participants). After SMILE, the difference was smallest between TK [(0.08±0.38) D] and CHM values (P>0.05). However, TCRP, RK, KHaigis, KShammas, and KMaloney were significantly different from CHM data (P<0.05). The width of the 95% limits of agreement of TK (1.49 D) was narrowest, followed by that of RK (1.57 D). Pearson analysis showed that each parameter had a good correlation with CHM data. The differences between the changes in TK, TCRP and RK caused by surgery and ΔSEco were (0.03±0.39) D, (0.17±0.43) D, and (-0.19±0.46) D, respectively. The width of the 95% limits of agreement of ΔTK (1.54 D) was narrowest, and the correlation coefficient of ΔTK (0.951) was highest. Conclusion: The parameter TK of the IOLMaster 700 can provide accurate and objective corneal power evaluation after SMILE.

[Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma].

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.

[Screening and preliminary validation of biomarkers in sputum-negative pulmonary tuberculosis based on positron emission tomography/computed tomography and transcriptomics].

Objective: To screen and perform preliminary clinical validation of biomarkers of activity based on positron emission tomography/computed tomography (PET-CT) and transcriptomics in sputum-negative pulmonary tuberculosis lesion tissue. Methods: Nine patients with sputum-negative pulmonary tuberculosis treated surgically at the Shanghai Public Health Clinical Center for Thoracic Surgery from January 1, 2017 to December 31, 2019 were retrospectively collected as the discovery group, including four males and five females, aged 20-57 years (mean 36 years). All of the patients underwent PET-CT scanning before surgery, and the resected specimens were postoperatively classified according to preoperative PET-CT. The resected specimens were divided into areas with increased fluorodeoxyglucose (FDG) metabolism (SUVmax>3) and areas with normal FDG metabolism (SUVmax ≤ 3) according to the preoperative PET-CT performance. After sample processing, total RNA was extracted from the tissues of different regions, and then whole gene transcriptome sequencing was performed. Bioinformatics analysis of the two sets of data was performed to discover the expression profiles of the differences in whole gene transcriptome data between the two regions and to screen for candidate biomarkers. Eighty patients with sputum-negative pulmonary tuberculosis admitted to Shanghai Public Health Clinical Center from January 1, 2019 to January 1, 2021 were retrospectively collected as the validation group, including 37 males and 43 females, aged 20-62 years, with an average age of 39 years. The validation group was divided into a group with increased SUV (n=40) and a group without lesions on CT imaging (n=40). Enzyme-linked immunosorbent assay (ELISA) was used to determine the protein levels of candidate biomarkers in the peripheral plasma of patients. The effect of biomarkers was assessed using subject operating characteristic (ROC) curves. Student's t-test was used to determine whether the difference in protein levels between the two groups was statistically significant. Results: Bioinformatics analysis revealed that the expression levels of C1QB, CCL19, CCL5 and HLA-DMB correlated with the metabolic activity of sputum-negative tuberculosis lesion tissue. Further screening and validation by the validation group confirmed that the difference in C1QB protein levels in the peripheral plasma of patients was statistically significant between the group with increased SUV and the group without lesions on CT imaging [(3.55±0.34) mg/L vs. (2.75±0.21) mg/L, t=4.12, P<0.001]. And the ROC curve showed that the area under the curve for C1QB protein levels was 0.731, which had potential clinical value. Conclusion: The C1QB protein level can be used to assess the activity of lesions in patients with sputum-negative tuberculosis and is a potential biomarker.

[Thought of corneal collagen cross-linking combined with excimer laser ablation for irregular corneas in keratoconus].

The concept of diagnosis and treatment of keratoconus is constantly updated. Today, we are not only concerned with how to delay the progress of the disease, but also with the preservation of useful vision for patients as well as improvement of visual quality. With the precise and individualized application of excimer laser and femtosecond laser technology in ophthalmology, corneal cross-linking combined with excimer laser ablation for the irregular cornea has become a new strategy for keratoconus. However, questions have been raised and caused ophthalmologists' thinking. Are patients with keratoconus who have progressively thinned corneas suitable for excimer laser ablation? Which is better when the combined strategy is applied, simultaneous or sequential surgery? Based on the research data from home and abroad, we comprehensively sort out various treatment methods for the focus issues. It is hoped that this article can provide guidance for the rational selection of an optimal clinical solution to keratoconus. (Chin J Ophthalmol, 2021, 57:251-253).

[Regulation of bFGF and TGF-ß2 in human scleral fibroblasts by the lumican gene mutation associated with myopia].

Objective: To investigate the regulation of basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-ß2 in human scleral fibroblasts (HSFs) by the adenovirus-mediated Lumican gene mutation, and to illustrate the effect of this mutation on myopia. Methods: Experimental study. The HSFs were isolated and cultured from human scleral tissues. The 3rd to 5th generation HSFs were transduced with Lumican mutant (c.596T>C) adenovirus, Lumican wild-type adenovirus, and defective adenovirus as the mutant group, wild group, and negative control group, respectively. Untransduced HSFs were defined as control group. The operation was conducted three times in each group. The expression levels of Lumican, bFGF and TGF-ß2 were detected by qPCR. Statistical analysis of gene expression differences between groups was performed by fold changes. The differences were analyzed by one way ANOVA combined with LSD-t test. Results: The expressions of Lumican in the mutant group and the wild group were 103.146-fold and 398.646-fold increased compared to the control group with significant difference (t=-16.641, -21.729; P<0.05). There was no statistical difference between the negative control group and the control group (t=1.689, P>0.05). The expressions of bFGF and TGF-ß2 in the mutant group were 2.812-fold and 2.346-fold increased compared to the control group with significant difference, and higher than the other groups (t=-3.921, -4.851; P<0.05). There was no significant difference among the wild group, negative control group and control group (P>0.05). Conclusions: The Lumican mutation (c.596T>C) increased the expressions of bFGF and TGF-ß2 in HSFs. It indicates that the Lumican mutation (c.596T>C) may change the metabolism of extracellular matrix in the sclera by regulating bFGF and TGF-ß2 to participate in scleral remodeling during the process of myopia. (Chin J Ophthalmol, 2021, 57:277-283).

Deep small RNA-Seq reveals microRNAs expression profiles in lactating mammary gland of 2 sheep breeds with different milk performance.

Micro ribonucleic acid (miRNA) is a type of noncoding RNA, and it has been revealed to play important roles in the activity of the mammary gland (MG) in some species. However, the function of miRNAs in MG of sheep is poorly understood. In the study, Gansu Alpine Merino (GAM; n = 9) and Small-tailed Han sheep (STH; n = 9) with different milk production traits were investigated. Microstructures and the expression profile of miRNAs of MG tissues at peak lactation were studied. Mature alveolar lumens of MG in appearance were larger in STH than GAM. The expression levels of CSN2 and the content of rough endoplasmic reticulum were also higher in STH ewes than GAM ewes. A total of 124 mature miRNAs were expressed, and 18 of these were differentially expressed between the 2 breeds. The KEGG analysis results showed that the targeted genes of differentially expressed miRNAs were mainly involved in some metabolic pathways and signaling pathways related to MG development, milk protein, and fat synthesis. The findings in the study can improve our understanding of the roles of miRNAs in the development and lactation of MG in sheep.

[Consideration of surgeons participating in 2019 coronavirus disease emergency medical rescue].

As a newly epidemic, 2019 coronavirus disease (COVID-19) with a concentrated outbreak poses a great challenge to medical treatment. The severe and critical patients are complex complicatied with the psychological problems, and the medical staff are overworked and under tremendous psychological pressure. The surgeon participated in emergency medical rescue could provide professional treatment for the patients combined with surgical diseases, as well as specialized training for the non-surgeon crew, to reduce surgical-related mortality. With the advantages of good team consciousness, strong aseptic concept and good psychological quality, the surgeons can quickly adapt to and carry out rescue work under the premise of good self-protection. Surgeons need to develop critical care management concepts and focus on the critical care support equipment. Some suggestions are put forward for the standardized training of resident surgeons to cultivate compound talents. It is hoped that this article can lead to the thinking of how to participate in the emergency medical rescue of infectious diseases among surgeons and provide some enlightenment for future surgical education.

[Assessment of corneal biomechanical changes after small incision lenticule extraction with Pentacam and Corvis ST].

Objective: To investigate the application value of Pentacam combined with Corvis ST in evaluation of the changes of corneal biomechanics after femtosecond laser small incision lenticule extraction (SMILE) in Chinese myopia with an irregular cornea. Methods: The clinical records for 104 eyes of 57 patients who received SMILE in the Refractive Center of Beijing Tongren Hospital during January 2018 and May 2018 were collected. According to the keratoconus severity index (KSI), they were divided into two groups: regular corneal group (KSI<15%) and irregular corneal group (KSI: 15% to 25%). In both groups, the anterior corneal surface radius curvature was>7.25 mm (K<46.50 diopters), the posterior corneal surface radius curvature was>5.90 mm, the thinnest pachymetry was>490 µm, and best corrected visual acuity was ≥1.0. The vision, refraction, and corneal biomechanics before and after SMILE were assessed. The Topographic and Biomechanics Index (TBI) was analyzed by Pentacam combined with Corvis ST. Results: Before SMILE, the Corvis Biomechanical Index (CBI), TBI, and Belin/Ambrósio Deviation Normalized Index (BADD) of the irregular corneal group were significantly higher (t=-2.17, -6.78, -4.37, P<0.05) than the regular corneal group, while the stiffness parameter (SPA1) was significantly lower (t=2.58, P=0.011) compared to the regular corneal group (P<0.05). In the irregular group, the TBI was (0.28±0.2); the maximum value was 0.03, and the minimum value was 0.43. The CBI was (0.09±0.21); the maximum value was 0.00, and the minimum value was 0.54. The BADD was (1.33±0.47); the maximum value was 0.42, and the minimum value was 2.26. In the regular group, the TBI was (0.05±0.08); the maximum value was 0.00, and the minimum value was 0.20. The CBI was (0.01±0.03); the maximum value was 0.00, and the minimum value was 0.17. The BADD was (0.92±0.46); the maximum value was 0.00, and the minimum value was 1.64. There was no significant difference between two groups in age (t=0.20, P=0.508), central corneal thickness (t=1.64, P=0.104), biomechanical corrected IOP (t=0.73, P=0.468), max inverse radius (t=-0.24, P=0.815), spherical equivalent (t=-0.97, P=0.335), and best corrected visual acuity (t=0.21, P=0.833). After SMILE, the deformation amplitude in the irregular group was significantly higher at 1 month and 3 months (t=-3.13, -3.09, P<0.05). The irregular group had a significantly higher deformation amplitude ratio at 1 week, 1 month, and 1 year (t=-2.72, -3.39, -2.51, P<0.05). The SPA1 in the irregular group was significantly lower than the regular group at 1 week, 1 month, and 3 months (t=2.11, 2.73, 3.70, P=0.335, 0.010,<0.001). The changes of deformation amplitude (t=0.50, -1.10, -0.73, 2.12, P>0.05), max inverse radius (t=-1.52, -1.41, 0.01, -0.79, P>0.05), and SPA1(t=0.89, 0.90, 1.12, 0.90, P>0.05) after SMILE were similar between the irregular and regular groups, except that at 1 month after SIMILE, the deformation amplitude ratio changed more significantly in the irregular group (t=-3.01, P=0.003). Conclusions: The changes of corneal biomechanics in the groups of regular cornea and irregular cornea were stable with no significant difference during 1 year of post-SMILE. The diagnosis based on the corneal topography and corneal biomechanics is of certain significance for the screening of early keratoconus before keratorefractive surgery. (Chin J Ophthalmol, 2020, 56:103-109).

[Study on the status of low vision among students of Beijing in 2017].

Objective: The purpose of this study was to describe the status quo and related factors on low vision (LV) among students of Beijing. Methods: All the students in Beijing were included as the subjects of interest, based on the reference of the Chinese National Survey on Students' Constitution and Health. Results: The overall rate of LV among students in Beijing was 58.6% in 2017, with 61.6% in females, higher than 55.9% in males. LV also appeared higher in urban than in rural areas. The rates of LV appeared as 46.8%, 78.0%, 89.0%, 71.0%, in students from primary, middle, high or vocational high schools, respectively. Rates on light, moderate or severe LV were 8.4%, 17.8% and 32.5%, respectively. Conclusions: The overall rate of LV among students in Beijing was considered high. Students in preschool, in 4-6 grades and the 2(nd) grade of middle schools, were at the key stages of developing vision-related problems. Factors as heavy load on homework, lack of outdoor activities and 'limit of vision space' as well as incorrect reading behavior during puberty, need to be of concern.

[Differential expression of small leucine-rich proteoglycans gene in Lumican transgenic mouse cornea].

Objective: To investigate the differential expression of small leucine-rich proteoglycans at mRNA level in Lumican transgenic mouse cornea with Real-time Quantitative PCR Detecting System. Methods: Experimental research. Ten Lumican transgenic mice (5 male and 5 female) were chosen as experimental group and 10 wild mice (5 male and 5 female) were chosen as control group. All the mice were killed and enucleated both eyes at eight weeks of age. Gene expression levels of Lumican, Decorin, Biglycan, Keratocan, Fibromodulin in the excised corneas were analyzed by real-time quantitative polymerase chain reaction (RT-Q-PCR) using Real-time Quantitative PCR Detecting System. Differential expression within each group were analysed by fold changes and independent t-test. Results: There were statistic different expression level of Lumican, Decorin, Biglycan and Keratocan mRNA between experimental and control group. The expression level of Lumican RNA was found to be 1.497-fold increased relative to the control (t=4.34, P<0.05) , while Decorin, Biglycan, Keratocan were 0.648-fold (t=-9.98, P<0.05) , 0.522-fold (t=-7.74,P<0.05), 0.323-fold (t=-95.94, P<0.05)decreased in transgenic mice. Fibromodulin mRNA up regulated 1.193-fold in transgenic mice without statistic difference (t=1.66, P>0.05). Conclusions: Lumican gene mutation(cDNA 569T>C) results in abnormal SLRP expression in transgenic mouse cornea at mRNA level, which may indicate that this mutation changes the structure of Lumican and impairs the function of regulating SLRP expression. Also, Lumican gene mutation leads to amio acid exchanging(L199P), which may hinder Lumican from binding to collagens and result in abnormal expression of SLRP at mRNA level. (Chin J Ophthalmol, 2018, 54:911-917).

[Clinical and genetic analysis of eleven pediatric patients with Alagille syndrome].

Objective: To explore the clinical and molecular genetic features of patients with Alagille syndrome (AS). Methods: The clinical data of eleven pediatric patients, who were suspected to have AS at the Department of Pediatrics in the First Affiliated Hospital of Jinan University from August 2010 to March 2017, were collected and analyzed. Genomic DNA was extracted from peripheral blood leukocytes of the patients and their parents. For 5 patients collected before March 2006, all JAG1 exons and their flanking sequences were directly sequenced. For the remaining 6 patients, high-throughput gene capture technology, chromosomal microarray analysis (CMA) and whole-genome copy-number variant(CNV) analysis were utilized, when necessary, to explore the genetic causes. Results: All patients had cholestasis. However, the γ-glutamyl transpeptidase (GGT) levels in one patient were normal. Nine patients had posterior embryotoxon and facial malformations. Eight patients displayed heart defects. Seven patients presented with vertebral anomalies and among them, 1 patient had sacralization of the cubitus and radius. The condition of nine patients tended to be stabilized on follow-up, but 1 patient died of liver failure in late infancy and 1 got worse. Seven JAG1 variants were detected in 9 out of the 11 AS patients, with c.1977G>A (p.Trp659*) and c.1106_1107delCC (p.Pro369fs) being two novel variants. Two heterozygous interstitial deletions of 3.0 Mb and 9.24 Mb in size, respectively, in chromosome 20 were discovered in the remaining 2 patients. Both deletions involved the entire JAG1 gene. De novo origin was unveiled for the detected variants in 7 patients and interstitial deletions in two. Although the mother of 2 patients carried the relevant variant, she did not demonstrate any clinical features of AS. Conclusions: With cholestasis, posterior embryotoxon, facial malformations, heart defects and vertebral anomalies being the major manifestations, AS demonstrated variable clinical expressivities and incomplete penetrance. This study identified a total of 7 JAG1 variants as well as 2 interstitial deletions involving this gene, and among them, the variants c.1977G>A (p.Trp659* ) and c.1106_1107delCC (p.Pro369fs) as well as the 9.24 Mb chromosomal interstitial deletion had not been reported previously.

[Factors influencing survival and recurrence and potential significance of postoperative radiotherapy and adjuvant chemotherapy for stage â ¢A-N2 non-small cell lung cancer].

Objective: To investigate the survival, recurrence patterns and risk factors in patients with stage ⅢA-N2 NSCLC treated with curative surgery and adjuvant chemotherapy and to explore the significance of postoperative radiation therapy. Methods: The clinical data of 290 patients with pathologically diagnosed stage ⅢA-N2 NSCLC after curative resection and adjuvant chemotherapy from January 2010 to December 2014 at our department were retrospectively analyzed. The survival and recurrence patterns were observed, and the factors affecting locoregional recurrence were analyzed. Results: The median survival time was 31.5 months. The 1-, 3-and 5-year survival rates were 88.3%, 46.0% and 33.2%, respectively. The median locoregional control time was 38.5 months. The 1-, 3-and 5-year locoregional control rates were 78.6%, 55.2% and 41.0%, respectively. The median distant metastasis-free survival was 26.8 months. The 1-, 3-and 5-year distant metastasis-free survival rates were 76.4%, 45.5% and 39.5%, respectively. The median progression-free survival was 19.1 months. The 1-, 3-and 5-year progression-free survival rates were 64.1%, 32.5% and 23.8%, respectively. Univariate analysis showed that clinical N status, histological type, pathological T stage, operation mode, the number of positive N2 lymph nodes and the number of positive N2 lymph node stations had a significant influence on overall survival; clinical N status, histological type, the number of positive N2 lymph nodes and the number of positive N2 lymph node stations had a significant influence on locoregional control. Multivariate analysis demonstrated that the number of N2 positive lymph nodes (P= 0.017) was an independent factor for overall survival of stage ⅢA-N2 patients; the number of N2 positive lymph nodes (P=0.009) and histological type (P=0.005) were independent factors for locoregional recurrence. For left-sided lung cancer, the lymph node station failure sites were mostly in 2R, 4R, 5, 6 and 7, and the contralateral mediastinum was frequently involved. For right-sided lung cancer, the lymph node station failure sites were mostly in 2R, 4R, 7, 10R and surgical stump. Conclusions: Clinical N2, squamous cell carcinoma, positive N2 nodes of more than 3 and multiple positive N2 stations are poor prognostic factors for locoregional recurrence. Locoregional recurrence of left lung cancer frequently involves the contralateral mediastinum, while that of the right lung cancer usually locates in the ipsilateral mediastinum.

[Changes of ocular biological parameters and Lumican expression in the monocularly deprivation myopic model of mutant Lumican transgenic mice].

Objective: To investigate ocular changes in the monocularly deprivation myopic model of mutant Lumican transgenic mice. Comparing influences on biological parameters and sclera development between Lumican transgenic and form deprivation mice, and to prepare for further study of pathogenesis of pathological myopia (PM). Methods: Experimental research. Lumican transgenic mice and wild mice were monocularly lid-sutured at ten days after birth. All eyes were divided into 6 groups, group A(32 eyes): control eyes in transgenic mice; group B(34 eyes): sutured eyes in transgenic mice; group C(34 eyes): fellow eyes in transgenic mice; group D(28 eyes): control eyes in wild mice; group E(32 eyes): sutured eyes in wild mice; group F(32 eyes): fellow eyes in wild mice. Refraction was measured by streak retinoscopye and axial length was measured by vernier caliper at 8 weeks (56 days) after birth. Lumican expression was detected by quantitative real-time PCR in all groups. Results: The refraction in group B and group E were (-0.38±1.10) D and (0.14±1.26)D respectively, which were significantly different compared with contralateral groups and normal control groups (F=9.525, 10.067; P<0.01). The mean axial length were also increased in group B ((3.28 ± 0.07)mm and group E (3.24 ± 0.09)mm, (F=7.183, 6.671; P<0.05). Expression level of Lumican mRNA in sclera was increased in group B, which was significantly different from group A and group C (F= 6.262; P<0.05). The expression of Lumican mRNA was increased in group B and C when compared with group E and F (t=4.772, 2.218, P<0.05). Conclusions: Form-deprivation in mutant Lumican transgenic mice causes myopic changes in deprived eyes. The gene expression level of Lumican in sclera of transgenic mice is significantly increased compared with contralateral eyes or that of wild group. Lumican mutation may effect the development of PM, and the interaction of genetic and environmental factors may lead to development of PM. (Chin J Ophthalmol, 2016, 52: 850-855).

[Advocating standardization and customization of corneal refractive surgery in Chinese domestic situation].

With the improvement and application of excimer laser and femtosecond laser equipment in clinical ophthalmology, the diversified strategies for corneal refractive surgery candidates have been provided. Based on the trend of " all-laser treatment", it is very necessary to take the domestic situation into consideration when a standard and customized choice is made according to the indications of each specific surgical type. The characteristics and limitations of various surgeries are elucidated and commented here in order to provide some reasonable treatment options for refractive surgery. (Chin J Ophthalmol, 2016, 52: 481-485).

An analysis of the intervention effect of perioperative evidence-based nursing on orthopedic trauma patients' vagal reflex.

OBJECTIVE: to discuss the application value of evidence-based nursing (EBN) on orthopedic trauma patients' perioperative vagus reflex intervention effect. PATIENTS AND METHODS: Eighty-six patients were selected, who were hospitalized in orthopedics department of our hospital because of trauma from March, 2013 to March, 2014. Then, they were divided into the control group (n = 41 cases) and the treatment group (n = 45 cases) according to random number table after obtaining the consent of the Hospital Ethics Committee and the informed consent of the patients as well as their relatives. Control group patients were treated with conventional nursing before, during and after operation, and treatment group patients were treated with EBN. Then, the incidence of vagal reflex on the two groups of patients was compared. HRV frequency domain was applied to analyze the differences of autonomic nervous function changes on the two groups of patients, and ELISA test was taken to detect the differences of the concentration change of serum TNF-alpha and IL-6. RESULTS: The prevalence of vagal reflex on patients in treatment group was significantly lower than that in the control group, with statistically significant difference (p < 0.05); low frequency (LF) and high frequency (HF) on patients from both groups decreased after treatment while LF/HF increased, and LF and HF on patients of the treatment group decreased more significantly and LF/HF increased more significantly than those of the control group, with statistically significant difference (p < 0.05); the concentration of TNF-alpha and IL-6 on both groups of patients after nursing also decreased, and the treatment group decreased more significantly, with statistically significant difference (p < 0.05). CONCLUSIONS: EBN could reduce the prevalence of vagal reflex to some extent on perioperative orthopedic trauma patients. It might be because EBN could improve vagal tone and reduce the concentration of TNF-alfa and IL-6.

8-Chloro-methyl-5-(2,5-dioxooxolan-3-yl)-3,3a,4,5-tetra-hydro-1H-naphtho-[1,2-c]furan-1,3-dione.

The title compound, C17H13ClO6, is an asymmetric alicyclic dianhydride containing a chloro-methyl-substituted tetra-hydro-naphthalene moiety. The cyclo-hexene ring in the tetra-hydro-naphthalene moiety exhibits an envelope conformation with the tertiary C atom as the flap The dihedral angle between the two anhydride rings is 79.96 (6)°, while those between the benzene ring and the non-fused and fused anhydride rings are 71.03 (5) and 42.57 (7)°, respectively. In the crystal, mol-ecules are connected by weak C-H⋯O inter-actions, forming a three-dimensional supramolecular structure.