[Efficacy and safety of Anlotinib in the treatment of advanced sarcoma].

Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.

[Association between remnant cholesterol levels and incident diabetic retinopathy in middle-aged and older patients with diabetes].

Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.

[Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study].

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

[Development and validation of a prognostic prediction model for patients with stage â to â ¢ colon cancer incorporating high-risk pathological features].

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

[Role of CT and MRI image fusion and computer assisted simulation technique in guiding type â ¢ and â £ primary pelvic sarcoma surgeries].

Objective: To explore the possible clinical benefits of CT/MRI image fusion and computer-assisted simulation techniques in guiding type Ⅲ and Ⅳ primary pelvic bone tumor surgeries. Methods: The clinic data of primary bone sarcomas patients treated at Department of Bone and Soft Tissue,Zhenghzhou University Affiliated Cancer Hospital from January 2019 to December 2021 were retrospectively analyzed. Based on whether the CT and MRI image fusion technique was utilized for tumor evaluation and surgical planning,the patients were divided into image fusion group (n=21) or control group (n=27). There were 7 male and 14 female patients included in the image fusion group, with the age of (37.0±10.4) years(range: 18 to 67 years). In the control group, there were 10 males and 17 females with the age of (39.7±15.2) years (range: 16 to 65 years). Both groups included osteosarcoma,chondrosarcoma and undifferentiated polymorphic sarcoma as the pathological diagnosis. Clinical information such as gender,age,pathological diagnosis,location of disease,and metastasis at diagnosis were collected. Surgical related information such as duration of surgery,blood loss,surgical margin,and wound complications were also obtained. Periodical follow-ups every 3 months were performed for all patients to monitor the status of local recurrence,distant metastasis,and survival information. Independent t test and χ² test were used for data comparison between groups. Results: Significant reduced duration of surgery was observed in the image fusion group in comparison with control group both in type Ⅲ and Ⅳ surgeries ((144.0±31.6)min vs. (248.2±56) min,t=-8.084, P<0.01); (173.0±42.0)min vs. (306.1±62.0)min, t=-4.518, P<0.01). Blood loss was significantly reduced in the image fusion group compared with the control group ((484.8±226.3)ml vs. (836.1±359.8)ml,t=-4.130, P<0.01). In addition, significant lower ratio of R1 margin and recurrence rates of type Ⅲ and Ⅳ surgeries were found in the image fusion group comparing with the control group (4.8%(1/21) vs. 22.2%(6/27), χ²=4.214, P=0.040; 4.8%(1/21) vs. 22.2%(6/27), χ²=4.214, P=0.040).In the image fusion group, there were 3 cases of incision infection, 1 of which underwent secondary debridement.And in thecontrol group there were 7 cases of incision infection, 3 of which underwent secondary debridement. There was no significant difference in the incidence of complications between the two groups (14.2%(3/21)vs. 25.9%(7/27), χ²=0.645, P=0.422). Up to the last follow-up, 1 patient died in the image fusion group and 2 patients died in the control group, the difference was not statistically significant (χ²=1.885, P=0.220). Conclusion: Compared with the traditional operation,the image fusion technique can significantly reduce the duration of surgery,blood loss and lower the recurrence rate by achieving better surgical margins.

Conophylline Suppresses Angiotensin II-Induced Myocardial Fibrosis In Vitro via the BMP4/JNK Pathway.

We studied the effects and mechanisms of action of conophylline in different concentrations in the original in vitro model of myocardial fibrosis (treatment of cardiac fibroblasts isolated form the hearts of newborn rats with angiotensin II). Viability, collagen content, and expression of related protein in cardiac fibroblasts were assessed using the MTT-test, Sircol assay, and Western blotting, respectively. Conophylline markedly protected the cultured cells against the development of angiotensin II-induced fibrosis, which was seen from reduced viability of fibroblasts, decreased collagen content, and down-regulation of the expression of α-smooth muscle actin (α-SMA). Conophylline did not affect the TGF-ß pathway altered by angiotensin II, but markedly decreased the level of bone morphogenetic protein-4 (BMP4) enhanced by angiotensin II and BMP4 itself. Conophylline produced no effect on phosphorylation of α-SMA and Smad homologue-1/5/8, the classic BMP4 downstream pathway elements, but reduced the level of c-Jun N-terminal kinase (JNK) elevated by BMP4. Conophylline did not inhibit the development of myocardial fibrosis in the presence of JNK activator anisomycin. Thus, conophylline inhibited angiotensin II-provoked myocardial fibrosis via the BMP4/JNK pathway.

Effective Model of Food Allergy in Mice Sensitized with Ovalbumin and Freud's Adjuvant.

To better explore the pathophysiology of FA and its therapy, we aimed to establish a simple and practicable FA model with Freund's adjuvant and introduce an easy and reliable laboratory evaluation method for assessment of inflammation in intestinal segments at different anatomical locations. BALB/c mice were sensitized with ovalbumin combined with Freund's adjuvant. Complete Freund's adjuvant was chosen for the first sensitization and two weeks later incomplete Freund's adjuvant was used for a second sensitization. Two weeks later, the sensitized mice were challenged with 50 mg ovalbumin every other day. After the 6 challenge, all mice were assessed for systemic anaphylaxis, and then sacrificed for sample collection. All sensitized mice showed anaphylactic symptoms and markedly increased levels of serum ovalbumin-specific IgE and IgG1. The activity of mast cell protease-1 (mMCPT-1) was significantly increased in the serum and interstitial fluid of the duodenum, jejunum, ileum, and colon. A successful FA model was established, of which inflammation occurred in the duodenum, jejunum, ileum, and colon. This model provides a reliable and simple tool for analysis of the mechanism of FA and methods of immunotherapy. Moreover, combined detection of ovalbumin-specific antibody and local mMCPT-1 levels could potentially be used as the major indicator for assessment of food allergy.

[miR-455 Inhibits HepG2 Cell Proliferation and Promotes Apoptosis by Targeting RhoC].

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor prognosis and high mortality. The aberrant expression or alteration of microRNAs (miRNAs) contributes to the development and progression of cancer. Studies have shown that miR-455 plays a regulatory role in the development of HCC. Therefore, in the present study, the role of miR-455 was analyzed in HepG2 cells proliferation and apoptosis using MTT and flow cytometry methods. Binding sites were predicted by bioinformatics and luciferase assay was used to verify the target relationship between miR-455 and RhoC-encoding gene RHOC. After that, the effects of miR-455 on RHOC and its product RhoC, were explored by qPCR and Western blotting. As PTEN is a key tumor suppressor gene in HCC, and Bcl-2 and Caspase 3 are important indication of apoptosis, expression levels of PTEN, Bcl2 and Caspase 3 proteins were determined in cells overexpressing RhoC. We show that miR-455 promotes HepG2 cells apoptosis and inhibits proliferation. Bioinformatics analysis and luciferase assay indicate that specific recognition sites for miR-455 are within the RhoC 3'-UTR. Luciferase activity was significantly lower in the cells co-transfected with miR-455 mimics and RhoC-WT (p < 0.01) as compared to that in control cells, pointing that RHOC gene is, indeed, targeted by miR-455. RHOC mRNA was significantly reduced after miR-455 transfection in HepG2 cells. In addition, we show that RhoC could activate the HCC cells proliferation ability and inhibit apoptosis rate (p < 0.01), and decrease expression of PTEN and Caspase 3 (p < 0.01), while upregulating levels of Bcl2. In conclusion, our study indicates that miR-455 plays a suppressive role in HCC development by targeting RhoC-encoding mRNA.

[Breakthrough of invasive fungal disease with posaconazole as primary prophylaxis after induction chemotherapy for acute myeloid leukemia].

Objective: To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML). Methods: A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared. Results: During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group (P<0.05). The difference of posaconazole group and voriconazole group was not significant (P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05]. Conclusions: Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

[Ikaros family zinc finger 1 mutation is a poor prognostic factor for adult Philadelphia chromosome positive acute lymphoblastic leukemia].

Objective: To analyze the prognostic impact of Ikaros family zinc finger 1(IKZF1) mutation on adult Philadelphia chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) patients. Methods: IKZF1 mutation was detected in 63 adult Ph1 positive ALL patients at diagnosis using capillary electrophoresis. Recruited patients were treated in our center and other three hospitals in Ningbo from January 2014 to January 2017. Clinical data were collected and retrospectively analyzed. Results: Thirty-nine (61.9%) patients were positive IKZF1 mutation in this cohort. The white blood cell (WBC) count in IKZF1 mutation group was significantly higher than that of mutation negative group [(64.6±11.3)×10(9)/L vs. (33.7±5.6)×10(9)/L, P<0.05]. Patients with WBC count over 30×10(9)/L accounted for 56.4% in IKZF1 mutation group. Complete remission (CR) rate in the IKZF1 mutation group was also lower than that of negative group after induction chemotherapy (64.1% vs. 75.0%, P>0.05). IKZF1 was a negative prognostic factor but not independent factor for survival by univariate and multivariate analyses. Patients were divided into chemotherapy and allogeneic transplantation groups. The 3-year overall survival (OS) rate and 3-year leukemia-free survival (LFS) rate in IKZF1 mutation group were significantly lower than those of negative group in both transplantation group (42.3% vs. 59.3%; 31.2% vs. 50.0%; respectively, both P<0.05) and chemotherapy group (24.8% vs. 40.0%; 19.0% vs. 34.3%; respectively, both P<0.05). Conclusion: IKZF1 mutation is a poor prognostic factor for adult Ph1 positive ALL patients.

[Genetic typing and susceptibility testing of strains from Staphylococcus aureus keratitis or conjunctivitis patients].

Objective: To study the relationship between genetic typing and the antibiotic susceptibility of staphylococcus aureus (SA) isolated from keratitis or conjunctivitis patients. Methods: Experimental study. Thirty-four (34) strains of Staphylococcus aureus were isolated from 34 cases of keratitis or conjunctivitis. The genomic DNA was extracted and amplified with PCR. With the method of multi locus sequences typing (MLST), gene fragments from 7 house-keeping genes were amplified and the products were sequenced. The results were submitted to the MLST website (www.pubmlst.org). In comparison with the allele of the corresponding gene, the allele spectrums of the strain were obtained with 7 housekeeping genes. At last, the MLST genotypes of the isolated strains were determined. With the START software, the evolutionary tree was established with UPGMA method. With the microdilution method, the MIC(90) of 13 antimicrobial agents was determined. The MIC(90) value of antimicrobial agents among different genotypes of Staphylococcus aureus was comparatively analyzed. Results: Ten (10) genotypes were obtained from 34 strains of Staphylococcus aureus. The dominant types were ST239, ST2592 and ST188. The clustering of genotyping was relatively concentrated, mainly in group Ⅰ (25 strains of SA, 83.3% of the total), and followed by group Ⅱ (5 strains of SA, 16.7%). The conjunctival isolates were distributed in the subgroup A of group Ⅰ. The cornea isolates were concentrated in subgroup B and group Ⅱ. With the exact probability method, the R×C chi square tests were used as statistic analysis method. The difference between the bacterial genotyping of two sources was statistically significant (P=0.011). Twenty-four strains of SA in group Ⅰ was sensitive to Vancomycin, Rifampicin and Amikacin (sensitivity ratio was 24/24, 20/24 and 20/24, respectively), and was generally resistant to other antibiotics. The values of MIC(90) of ciprofloxacin, ofloxacin, gatifloxacin and moxifloxacin to Staphylococcus aureus in subgroup A (0.16±0.07, 0.51±0.42, 0.31±0.14, 0.22±0.33) were significantly lower than the values in subgroup B(0.74±0.11, 0.84±0.45, 0.67±0.03, 0.68±0.26). The difference was statistically significant (P=0.004, 0.026, 0.034, 0.001). There was no significant difference between the MIC(90) values of the other 9 kinds of antibiotics in the subgroup A and in the subgroup B of Staphylococcus aureus (P value 0.047-0.561). Conclusion: The genotype of Staphylococcus aureus of corneal isolations and conjunctival isolations were different. The conjunctival isolates were distributed in the subgroup A of group Ⅰ and the corneal isolates were concentrated in subgroup B and group Ⅱ. There is a significant correlation between the MLST genotypes and antibiotic sensitivity. (Chin J Ophthalmol, 2018, 54:767-774).

[Effect of two different acellular lung matrices on α-SMA expression in A549 cells].

Objective: To explore the effect of acellular normal and fibrotic lung matrices on alpha smooth muscle actin (α-SMA) expression in human lung adenocarcinoma cell line A549. Methods: Twenty adult SD rats were randomly divided into normal group and idiopathic pulmonary fibrosis(IPF)group (n=10 each). The pulmonary fibrosis was induced by Bleomycin. Normal and fibrotic decellularized lungs were made, then sections with 500 µm thick were cut by a standard Vibratome. None scaffold was set as control group. A549 cells were seeded dropwise into different slices (normal and fibrotic scaffolds), and cultured for one week in vitro. The expression of α-SMA was measured by immunofluorescence staining and quantitative real time polymerase chain reaction (qRT-PCR). Results: In control group, the expression of α-SMA protein was positive in A549 cells by immunofluorescence staining. However, it expressed weakly both in normal and fibrotic scaffold group, and the fluorescence intensity in fibrotic scaffold group was significant lower than that in normal group (P<0.05). The relative expression amount of α-SMA mRNA in normal and fibrotic scaffold group were (0.70±0.11) and (0.55±0.12), which were significant lower than that of control group (1.28±0.21) (P<0.05). Moreover, the relative expression of α-SMA mRNA in fibrotic scaffold group was decreased compared to that in normal scaffold group (P<0.05). Conclusions: Acellular normal and fibrotic lung scaffold can downregulate the expression of α-SMA in human lung adenocarcinoma cell line A549. It may inhibit the movement of A549 cells in acellular normal and fibrotic lung matrices, especially in acellular fibrotic lung scaffold.

[Epidemiologic study of tear film lipid layer thickness measurement in the population of Taishitun Community in Beijing].

Objective: To investigate the distribution of tear film lipid layer thickness (LLT) and the relationship between symptoms and signs of dry eye and tear film LLT in the population of Taishitun Community in Beijing. Methods: A cross-sectional study. From May 2016 to August 2016, three streets of Taishitun Community were randomly selected as survey districts and 540 persons were taken as investigation subjects. Every participant completed 6 items of dry eye examinations as follows: questionnaire (Ocular Surface Disease Index, OSDI), measurement of tear film LLT, tear film break-up time (TBUT), corneal and conjunctival staining, SchirmerⅠtest and the infrared meibomian photography. According to their age, all participants were divided into four groups: junior group (<18 years old), youth group (18 to 40 years old), middle-aged group (41 to 59 years old) and the elderly group (over 60 years old). With the OSDI criteria, no dry eye symptom group (score, <12 points), mild to moderate dry eye symptom group (score, 12 to 32) and severe dry eye symptom group (score, 33-100) were included. With the statistical methods of variance analysis and multivariate Logistic regression analysis, distribution of the variables of LLT and the relationship between dry eye symptoms and LLT were studied. Results: A total of 473 residents finally participated in this study, and the response ratio was 87.6%. The values of LLT were normally distributed. The average LLT was (59.87±18.50) nm [(60.16±19.15) nm in males and (59.67±18.57) nm in females], and the comparison of LLT with different genders was not statistically significant (t=0.198, P=0.843). The tear film LLT of four different age groups had statistical significance (F=15.092, P<0.05), and increased with age [(56.10±18.33) nm in the junior group, (54.60±16.29) nm in the youth group, (60.61±19.18) nm in the middle-aged group and (73.25±14.58) nm in the elderly group]. The LLT was inversely proportional to the severity of dry eye symptoms. With a thinner LLT, the symptoms of the subjects turned severe. In the elderly with different degrees of symptoms, the LLT was significantly different (F=0.019, P<0.05), while in the youth and middle-aged groups with different degrees of symptoms, the LLT was not significantly different (F=0.096, P>0.05. F=0.538, P>0.05). In the OSDI symptom questionnaire, only blurred vision and decreased visual acuity were related to the tear film LLT (P<0.05). There was no significant correlation between the TBUT, SchirmerⅠtest result, meibomian gland loss rate and the tear film LLT (P>0.05). Conclusions: In Taishitun Community of Beijing, the values of tear film LLT had a normal distribution. The LLT was positively correlated with age, but inversely correlated with the severity of the symptoms of dry eye. There was no significant correlation between the LLT and the TBUT, SchirmerⅠtest result and meibomian gland loss rate.(Chin J Ophthalmol, 2017, 53: 495-501).

Designing a stronger interface through graded structures in amorphous/nanocrystalline ZrCu/Cu multilayered films.

Many multilayered nano-structures appear to fail due to brittle matter along the interfaces. In order to toughen them, in this study, the microstructure and interface strength of multilayered thin films consisting of amorphous ZrCu and nanocrystalline Cu (with sharp or graded interfaces) are examined and analyzed. The interface possesses a gradient nature in terms of composition, nanocrystalline phase size and volume fraction. The bending results extracted from the nano-scaled cantilever bending samples demonstrate that multilayered films with graded interfaces would have a much higher interface bending strength/strain/modulus, and an overall improvement upgrade of more than 50%. The simple graded interface design of multilayered thin films with improved mechanical properties can offer much more promising performance in structural and functional applications for MEMS or optical coating.

[The research advances of psychological disorder in patients with dry eye].

In clinical practice, dry eye disease (DED) is recognized as one of the most frequent reasons for chronic ocular surface disorder, which can cause the damage to the ocular surface and some symptoms associated with ocular discomfort and impaired visual quality. This common ocular problem is characterized by high incidence and difficulty in treatment. DED can make the visual disturbance and degrade the quality of everyday life and social activities in different levels. Some patients with DED often report psychological changes because of the symptoms of ocular discomfort. This article mainly summarizes the characteristics and mechanism of psychological disorder in patients with DED.

[Study on the evaluation of pterygium activity with in vivo confocal microscopy].

Objective: To observe the characteristics of pterygium with in vivo confocal microscopy (IVCM) and understand pterygium activity with the density of inflammatory cells, formation of new blood vessels, and the number of activated keratocytes within the stroma. Methods: A prospective case-controlled study. Thirty-six pterygia from 28 patients were analyzed in this study. A pterygium activity score was obtained by summing four scores of ocular discomfort, pterygium hyperemia, keratitis, and the presence of Fuchs patches. Among them, the low activity of pterygium (PAS score less than 3 points) appeared in 12 eyes and high activity of pterygium (PAS score ≥ 4 points) in 24 eyes. All Patients underwent pterygium IVCM quantitative analysis by observing the boundaries between the pterygium and the adjacent cornea, the density of goblet cells and dendritiform inflammatory cells and Fuchs patches. The correlation of pterygium activity between IVCM and PAS with slit lamp was analyzed with Spearman correlation analysis. Results: The presence of inflammatory cells, numerous blood vessels, and irregular boundary between the cornea and the pterygium with infiltration of hyper-reflective cells in the adjacent corneal epithelium were signs observed with IVCM associated with pterygium activity. With IVCM technique, epithelial cells, goblet cells, and dendritiform inflammatory cells of various sizes were observed within the pterygium epithelium.The active (PAS ≥4) pterygium showed irregular boundaries between the pterygium and the adjacent cornea (score, 0.84±0.51) comparing with inactive subjects (score 0.23±0.12, t=2.68, P=0.009). Fuchs patches were observed as islets of hyper-reflective polygonal cells in front of the pterygium head with blurred boundary. The score (0.75±0.25) in active group showed significant changes as compared with normal subjects (0.23±0.12, t=3.79, P=0.001). The score of dendritiform inflammatory cells, activated keratocytes, and goblet cells in active group were 2.75±0.76, 1.92±0.68, and 2.08±0.42, which were significantly higher than those in inactive group (1.25±0.55, 0.50±0.25, 1.15±0.32, P=0.035, 0.030, <0.01). There was significant positive correlation between IVCM activity and traditional slit lamp PAS. Conclusion: Quantitative analysis of dendritiform inflammatory cells, vascular proliferation and activated keratocytes of pterygium by IVCM may be a reliable evaluation method to evaluate the activity of pterygium.(Chin J Ophthalmol, 2016, 52: 755-763).

[In vivo confocal microscopy evaluation of meibomian glands in meibomian gland dysfunction patients].

OBJECTIVE: To observe the morphology, fibrosis grade and inflammatory infiltration of meibomian glands using in vivo confocal microscopy(IVCM)in meibomian gland dysfunction(MGD)patients. METHODS: A prospective case-controlled study. According to the diagnostic criteria of MGD, 20 MGD patients(20 eyes)were included in our study from August to October 2015. Fifteen normal subjects(15 eyes)were also studied. METHODS All subjects completed the questionnaire of the Ocular Surface Disease Index(OSDI), lid margin and ocular surface examination by slit lamp microscropy, tear film break-up time(TBUT)test, corneal and conjunctival staining(Oxford scale), Schirmer I test, infrared meibomian photography and IVCM. Main outcomes in IVCM included meibomian gland acinar longest diameter(MGALD), meibomian gland acinar shortest diameter(MGASD), meibomian gland acinar unit density(MGAUD), meibomian gland acinar unit area(MGAUA), meibomian gland inflammatory cell density and fibrosis degree. The parameters between the MGD group and the control group were compared using the independent samples t test. RESULTS: The OSDI score[(31.80±22.97)points], 1id margin abnormality score[(3.10±0.31)points], loss rate of meibomian glands(38.31%±19.94%)and corneal and conjunctival staining score[1.00(2.75)points]in the MGD group were obviously higher than those in the control group[(7.93±6.51)points,(0.33±0.31)points, 21.31% ± 7.70%, and 0.00(1.00)points, P=0.001, P<0.001, P=0.004, and P=0.037, respectively]. The TBUT was significantly lower in the MGD group[(3.35±2.28)s]than in the control group[(6.67±2.51)s, P<0.001]. According to Schirmer I test, there was no significant difference in the two groups(P=0.139). The mean values of MGALD[(156.80 ± 46.10)µm], MGASD[(38.75 ± 11 .72)µm], MGAUA[(10 113.84 ± 5 531.21)µm(2)], meibomian gland inflammatory cell density[(621.90 ± 405.63)cells/mm(2)]and fibrosis degree 1.50(1.00)in the MGD patients were larger than those in the control group[(67.47 ± 9.117)µm,(22.00 ± 2.95)µm,(3 102.13 ± 1111.97)µm(2),(188.80 ± 72.25)cells/mm(2), and 0.00(0.00), all P<0.001, respectively]. The mean MGAUD was lower in the MGD patients[(61.10 ± 34.97)glands/mm(2)]than in the control group[(105.07±18.58)glands/mm(2), P<0.001]. CONCLUSIONS: IVCM was pertinent to investigate the meibomian glands by detecting the irregularity of meibomian orifices, the diameter and area, and the inflammation and fibrosis levels in MGD patients. It may have a potential clinical value for the diagnosis of MGD. (Chin J Ophthalmol, 2016, 52: 649-656).

Molecular cloning and expression analysis of jasmonic acid dependent but salicylic acid independent LeWRKY1.

Various plant genes can be activated or inhibited by phytohormones under conditions of biotic and abiotic stress, especially in response to jasmonic acid (JA) and salicylic acid (SA). Interactions between JA and SA may be synergistic or antagonistic, depending on the stress condition. In this study, we cloned a full-length cDNA (LeWRKY1, GenBank accession No. FJ654265) from Lycopersicon esculentum by rapid amplification of cDNA ends. Sequence analysis showed that this gene is a group II WRKY transcription factor. Analysis of LeWRKY1 mRNA expression in various tissues by qRT-PCR showed that the highest and lowest expression occurred in the leaves and stems, respectively. In addition, LeWRKY1 expression was induced by JA and Botrytis cinerea Pers., but not by SA.