[Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer].

Objective: To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods: In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results: In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions: In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

[The expression and significance of protease activated receptor 2 in ovarian epithelial carcinoma].

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P=0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival (P<0.05). The progression-free survival (P=0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P<0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/ß-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P=0.029) and glycolysis related pathway (P=0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/ß-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.

[Relationship between carotid atherosclerotic plaque characteristics in magnetic resonance imaging and perioperative hemodynamic instability].

Objective: To analyze the relationship between carotid atherosclerotic plaque characteristics in magnetic resonance imaging (MRI) and perioperative hemodynamic instability in patients with severe carotid artery stenosis undergoing carotid artery stenting (CAS). Methods: A total of 89 patients with carotid artery stenosis who underwent CAS treatment at Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University from January 1, 2017, to December 31, 2021, were prospectively included. Among them, 74 were male and 15 were female, with an age range of 43 to 87 years (mean age: 67.8±8.2 years). Preoperative examinations included carotid artery MRI vessel wall imaging to analyze the existence of large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture in carotid artery plaques. Plaques without the above-mentioned risk factors were defined as stable plaque group (34 cases), while those with such risk factors were defined as vulnerable plaque group (55 cases). The number of risk factors present in each plaque was also calculated. Intraoperative changes in blood pressure and heart rate were recorded, and the use of dopamine postoperatively was noted. Using the risk factors that the plaque has as independent variables and the clinical outcomes as dependent variables, the RR values were calculated, and the differences in clinical outcomes of patients with different risk factors were compared. Results: The incidence rates of hypotension and bradycardia were higher in patients with vulnerable plaques than those with stable plaques (60.0% (33/55) vs 14.7%(5/34) and 38.2%(21/55) vs 14.7%(5/34), respectively; both P<0.05). Based on MRI imaging features, the large LRNC was present in 45 cases, with RR values for hypotension and bradycardia of 3.15 (1.69-5.87) and 2.20 (1.07-4.53), respectively; IPH was present in 37 cases, with RR values for hypotension and bradycardia of 2.70 (1.61-4.55) and 2.25 (1.15-4.39), respectively; and fibrous cap rupture was present in 29 cases, with RR values for hypotension and bradycardia of 1.50 (0.94-2.40) and 1.29 (0.67-2.49), respectively. The higher the number of risk factors in vulnerable plaques, the higher the incidence of intraoperative blood pressure and heart rate decrease: when the number of risk factors ranged from 0 to 3, the incidence of blood pressure decrease was 14.7% (5/34), 9/18, 11/18, and 13/19, respectively (P<0.001), and the incidence of heart rate decrease was 14.7% (5/34), 6/18, 7/18, and 8/19, respectively (P=0.022). There was no significant difference in the number of cases of dopamine use between the two groups (P>0.05). Conclusion: Patients with a higher number of risk factors for vulnerable carotid plaques, as indicated by carotid artery MRI vessel wall imaging, are at a higher risk of experiencing blood pressure and heart rate decrease during CAS surgery.

[Analysis of distribution characteristics and influencing factors of chord µ in young myopia].

Objective: To explore and analyze the distribution characteristics of chord µ related parameters, as well as the pupil center's relative position to the coaxial corneal light reflex on the corneal surface, and the influencing factors in young myopia. Methods: This was a cross-sectional study. A total of 761 myopic patients (761 eyes) were collected from March 2021 to December 2021 in the Refractive Surgery Center of Tianjin Eye Hospital, including 388 males and 373 females, with an average age of (24±6) years. The relationship between age, sex, diopter, anterior and posterior corneal surface parameters, and chord µ related parameters was analyzed, including the x and y absolute values of the pupil center, chord µ length, and angle. The normality of the data was tested using the Kolmogorov-Smirnov test, and the influencing factors of chord µ were analyzed through Pearson and Spearman correlation analysis. Results: The equivalent spherical degree and chord µ length were (-5.47±1.66) D and (0.178±0.095) mm, respectively. The chord µ length followed an approximately normal distribution. The chord µ length of 266 eyes (35%) was distributed in the range of 0.120 to 0.200 mm, while the chord µ length of 479 eyes (63%) was<0.200 mm, and the chord µ length of 620 eyes (81%) was<0.260 mm. The chord µ angle distribution accounted for the largest proportion in the superior nasal quadrant (45.6%), followed by the superior temporal quadrant (34.3%), the inferior temporal quadrant (10.1%), and the inferior nasal quadrant (10.0%). High myopia (r=0.11, P=0.002) and high astigmatism (r=0.08, P=0.023) were associated with an increase in chord µ length. The higher the degree of myopia, the smaller the chord µ angle (r=-0.09, P=0.019). The larger the ISV (r=0.09, P=0.017), IVA (r=0.08, P=0.025), and IHD (r=0.08, P=0.039) on the anterior surface of the cornea, the longer the chord µ length. The higher the astigmatism of the posterior corneal surface, the greater the absolute value of the Y coordinate of the pupil center (r=0.07, P=0.044), and the longer the chord µ length (r=0.08, P=0.035), and the smaller the chord µ angle (r=-0.08, P=0.032). Conclusions: The chord µ length of young myopic individuals in China followed an approximately normal distribution, with the majority located in the superior nasal and superior temporal quadrants. High myopia, high astigmatism, and irregular corneal shape are the main factors related to an increase in chord µ length.

[Urine metabolomics study of hepatocellular carcinoma].

Objective: To investigate the urinary small molecular metabolites and their metabolic characteristics of patients with hepatocellular carcinoma (HCC). Methods: High throughput ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to detect the small molecular metabolites in urine of healthy control (n=10), patients with hepatic hemangioma (n=10) and patients with HCC (n=10). The orthogonal projections to latent structures-discriminant analysis (OPLS-DA), hierarchical cluster analysis of multivariate analysis and univariate analysis were used to analyze the differential metabolites of the three groups. Results: The metabolic profiles of the three groups showed that the total of 381 differential metabolites were identified and divided into 96 up-regulated metabolites and 285 down-regulated metabolites. There were 55 urinary metabolites specifically related to HCC. Twenty-one of them were significantly up-regulated, including Acetyl-DL-Leucine, Ala Asp, HoPhe-Gly-OH, while 34 were significantly down-regulated, including Selenocystathionine, Met Trp Met Cys, Valsartan acid and so on. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differential metabolites were mainly enriched in glutamine/glutamate metabolism, lysine biosynthesis, tricarboxylic acid cycle and purine metabolism. Conclusions: The occurrence of HCC is accompanied by the abnormalities of multiple metabolites and metabolic pathways. The analysis of the characteristic metabolic profile of urine in patients with HCC is helpful to find metabolic markers and potential therapeutic targets for liver cancer.

[Comparison of application effects of colonoscopy, fecal immunochemical test and a novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population].

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.

Changes in ocular biomechanics after treatment for active Graves' orbitopathy.

PURPOSE: To evaluate the changes in ocular biomechanical properties in active moderate-to-severe Graves' orbitopathy (GO) after intravenous glucocorticoids (IVGCs), and to clarify correlations between clinical findings and ocular biomechanical properties. METHODS: A prospective study. A total of 20 consecutive GO patients and 20 age- and sex-matched healthy control subjects were included. GO was diagnosed on the basis of the recommendation by the European Group on Graves' Orbitopathy (EUGOGO), and disease activity was assessed by the clinical activity score (CAS). Patients were assigned to receive once weekly IVGCs (0.5 g, then 0.25 g, 6 weeks each). All participants received a full ophthalmic examination and biomechanical evaluation was performed with dynamic Scheimpflug analyzer (Corvis ST) at baseline and 12th weeks after therapy. RESULTS: The biomechanically corrected intraocular pressure (bIOP) in GO patients was significantly higher than that in healthy subjects. In contrast, the whole eye movement (WEM) in GO patients was significantly lower than in healthy subjects after adjusting for bIOP. The CAS, NOSPECS score, and exophthalmos were significantly positively correlated with the bIOP and negatively correlated with the WEM after adjusting for bIOP, CCT and age. The WEM significantly increased, whereas bIOP significantly decreased after IVGCs (P < 0.001, P = 0.001 respectively). The overall response rate at the 12th week was 85% (17 of 20). CONCLUSIONS: The changes of ocular biomechanical properties measured by Corvis ST were an objective indicator of inflammatory activity and severity of GO. Combining CAS and ocular biomechanical properties could better evaluate the therapeutic outcome of active moderate-to-severe GO.

Glycation sites and bioactivity of lactose-glycated caseinate hydrolysate in lipopolysaccharide-injured IEC-6 cells.

During the thermal processing of milk, Maillard reactions occur between proteins and lactose to generate glycated proteins. In this study, a lactose-glycated caseinate was hydrolyzed by trypsin. The obtained glycated caseinate (GCN) hydrolysate had a lactose content of 10.8 g/kg of protein. We identified its glycation sites and then assessed it for its protective effect against lipopolysaccharide-induced barrier injury using a rat intestinal epithelial cell line (IEC-6 cells) as a cell model and unglycated caseinate (CN) hydrolysate as a reference. Results from our liquid chromatography-mass spectrometry analysis of the GCN hydrolysate verified that lactose glycation occurred at the Lys residues in 3 casein components (αS1-casein, ß-casein, and κ-casein), and this resulted in the formation of 5 peptides with the following amino acid sequences: EMPFPKYPKYPVEPF, HIQKEDVPSE, GSENSEKTTMPL, NQDKTEIPT, and EGIHAQQKEPM. The results from cell experiments showed that the 2 hydrolysates could promote cell growth and decrease lactate dehydrogenase release in the lipopolysaccharide-injured cells; more importantly, they could partially protect the damaged barrier function of the cells by increasing trans-epithelial electrical resistance, decreasing epithelial permeability, and upregulating the expression of the 3 tight junction proteins zonula occludens-1, occludin, and claudin-1. However, compared with CN hydrolysate, GCN hydrolysate showed lower efficacy in protecting against cellular barrier dysfunction. We propose that the different chemical characteristics of the CN hydrolysate and the GCN hydrolysate (i.e., amino acid loss and lactose conjugation) contributed to the lower barrier-protective efficacy of the GCN hydrolysate. During dairy processing, protein glycation of the Maillard type might have a non-negligible, unfavorable effect on dairy proteins, in view of the resulting protein glycation we found and the critical function of proteins for maintaining the integrity of the intestinal barrier.

[Effect of RNF152 on NO induced apoptosis of colon cancer cells].

Objective: To investigate the role and mechanism of ring finger protein 152 (RNF152) in the development of colitis-associated colon cancer (CAC). Methods: CAC was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Three different stages of mice during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment was set up as well. The expression of RNF152 in mouse colon tissues was measured by real-time quantitative polymerase chain reaction (RT-qPCR). The effects of RNF152 overexpression on apoptosis and nitric oxide (NO) induced apoptosis was examined by flow cytometry. The expressions of Bcl-2 and Bcl-XL were detected by western blot. Results: CAC was effectively induced by AOM and DSS in C57BL/6 mice. The tumor incidence rate of AD3 group was 100%. The whole genome expression microarray data from mouse AOM-DSS model indicated that the mRNA level of RNF152 was gradually decreased during the development of colon cancer. The RT-qPCR results showed that RNF152 mRNA level in AD3 was 1.23±0.18, higher than 0.52±0.08 in negative control (P<0.01). Flow cytometry analysis showed that overexpression of RNF152 increased the apoptosis of RKO cells (P<0.01). The apoptotic rate of RKO-RNF152 cells treated with NO donor DETA NONOate was (31.2±3.1)%, higher than (14.2±2.1)% in RKO-PCDB cells (P<0.001). Overexpression of RNF152 significantly decreased the protein expressions of Bcl-XL and Bcl-2. Conclusion: Downregulation of RNF152 may facilitate the development of CAC by inhibiting the cell apoptosis.

[Incidence of unintended pregnancy within 2 years after delivery and its influencing factors in China].

Objective: To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China. Methods: Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women's socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis. Results: A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95%CI: 4.5%－6.1%) and 13.1% (95%CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions: In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

Anti-aging gene Klotho ameliorates diabetic nephropathy in mice by inhibiting FGF2 signaling pathway.

The aim of this study was to observe the expression of Klotho in renal tissues of mice with diabetic ne¬phropathy (DN), and to further explore the effect of Klotho on DN in mice and its mechanism. The 10-week-old mice in this experiment were divided into three groups: heterozygous db/+ mouse group (db/+ group, n=20), homozygous db/db mouse group (db/db group, n=20) and homozygous db/db mice + Klotho group (db/db + Klotho group, n=20). Firstly, Western blotting and immunohistochemical staining were applied to detect the protein expression of Klotho in the renal tissues of diabetic and non-diabetic mice of different ages. Finally, the protein expressions of fibroblast growth factor 2 (FGF2) and E-cadherin in the renal tissues of mice in each group were examined by Western blotting. The protein expression level of Klotho in the renal tissues of mice aged 10 and 16 weeks in the db/db group was remarkably lower than that in yhedb/+ group. In addition, it was found that db/db + Klotho group exhibited a prominently lower degree of interstitial fi¬brosis and content of Collagen I and Collagen III in the renal tissues than db/db group. Furthermore, it was revealed that the overexpression of Klotho could significantly repress the protein expression level of FGF2 but elevate that of E-cadherin in the renal tissues of DN mice. Klotho protein may ameliorate the renal injury and fibrosis in diabetic mice by inhibiting FGF2, so it is expected to become a targeted drug for DN.

[Preliminary evaluation of a virtual reality dental simulation system on training of caries identification ability].

OBJECTIVE: To develop a software based on "UniDental" system which is a virtual reality dental simulation system and applied to undergraduate majoring in stomatology to improve the ability of identifying caries. METHODS: A software was developed applying to identify virtual dental caries based on UniDental system. In the software, a virtual dental caries model was designed and carious tissue was separated to 3 layers by the depth. The stiffness was the same within each layer which was increasing gradually layer by layer. The roughness was also the same within each layer which was decreasing gradually layer by layer. Sixty-four participants in pre-clinical stage of the class of 2014 majoring in stomatology from Peking University School of Stomatology were trained with the software. During the training, the students should probe on the virtual dental carious tissue layer by layer and feel the difference of vertical stiffness and horizontal roughness of each layer by using a handpiece with realistic force feedback. After training, a questionnaire survey was conducted to evaluate the software including a score of 1-5 for haptic fidelity of stiffness and roughness and their relevant gradient and benefit of improving the ability of identifying caries, choosing the preferred training method. The data were statistically analyzed using Kruskal-Wallis test. RESULTS: The median of subjective evaluation scores of the proposed metrics were all "4", demonstrating that the software operated above medium fidelity. The stiffness scores of all 3 layers were statistically significant (P < 0.05) on the stiffness gradient score. The roughness scores of the 1st and 2nd layers were statistically significant (P < 0.05) on the roughness gradient score. The training was helpful to improve the ability of identifying caries (median was 4). The scores of all 3 layers stiffness and relevant gradient were statistically significant (P < 0.05) on the score of benefit of improving the ability of identifying caries. 90.4% of the participants preferred the traditional extracted teeth training method. CONCLUSION: The virtual reality dental simulation system was helpful to improve students' ability of identifying caries. It couldn't replace the traditional extracted teeth training method by now, it should be used as a supplement to the traditional training method.

[Prevalence and predictors of intraplaque hemorrhage in stroke patients with intracranial atherosclerosis].

Objective: To investigate the prevalence and predictors of intraplaque hemorrhage (IPH) in ischemic stroke patients with intracranial atherosclerosis. Methods: Ischemic stroke patients with intracranial atherosclerosis who were consecutively admitted to Beijing Tsinghua Changgung Hospital from January 2017 to April 2018 were retrospectively analyzed. High-resolution magnetic resonance vessel wall imaging was used to assess atherosclerotic plaque characteristics of intracranial artery. Possible variables correlated with IPH were compared between IPH and no-IPH groups, as well as in symptomatic IPH and no symptomatic IPH groups. Logistic regression analysis was used to determine the predictors of all IPH and symptomatic IPH in intracranial artery. Results: A total of 276 ischemic stroke patients with intracranial atherosclerosis were included, of which, 41.3% (114/276) were IPH-postive, and 28.1%(32/114) of them were symptomatic. In multivariate regression analysis, maximum wall thickness was independently associated with the presence of all IPH and symptomatic IPH (OR=2.15, 95%CI: (1.42-3.24) and OR=3.46, 95%CI: (1.94-6.17), respectively). Conclusion: The prevalence of IPH in ischemic stroke patients with intracranial atherosclerosis is much higher than expected. Moreover, atherosclerosis plaque burden is independently associated with IPH, but it is non-specific in identifying symptomatic IPH.

[A cohort study on the association between resting heart rate and the risk of new-onset heart failure].

Objective: To prospectively explore the relationship between resting heart rate (RHR) and risk of new-onset heart failure. Methods: It was a prospective cohort study. People who attended the physical examination of Kailuan Group Company in 2006 and with complete electrocardiography (ECG) recordings were eligible for this study. A total of 88 879 participants aged 18 years old or more who were free of arrhythmia, a prior history of heart failure and were not treated with ß-blocker were included. Participants were divided into 5 groups according to the quintiles of RHR at baseline (Q(1) group, 40-60 beats/minutes (n=18 168) ; Q(2) group, 67-70 beats/minutes (n=18 970) ; Q(3) group, 71-74 beats/minutes (n=13 583) ; Q(4) group, 75-80 beats/minutes (n=22 739) ; and Q(5) group,>80 beats/minutes (n=15 419) ) .The general clinical data and laboratory test results were collected. The outcome was the first occurrence of heart failure at the end of follow-up (December 31, 2016) .We used Cox regression model to examine the association between RHR and the risk of new-onset heart failure. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: Among the included patients 68 411 participants were male, mean age was (51.0±12.3) years old, and RHR was (74±10) beats/minutes. Statistically significant differences among the RHR quintiles were found for the following variables: age, gender, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, body mass index, the level of high-sensitivity C-reactive protein, education status, physical activity, smoking status, drinking status, history of diabetes, history of hypertension and history of use antihypertensive drugs (all P<0.01) . Higher RHR was linked with higher prevalence of diabetes, hypertension history, and higher systolic blood pressure, diastolic blood pressure and FBG levels (all P<0.01). After a mean follow-up of 9.5 years, the incidence of new-onset heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.60%(290/18 168), 1.36%(258/18 970), 1.80%(245/13 583), 1.76%(400/22 739) and 2.35%(362/15 419),respectively (P<0.01) . The person-year incidence of heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.7, 1.5, 1.9, 1.9 and 2.6 per 1 000 person-years respectively. Compared with the Q(2) group, multivariate analysis with adjustment for major traditional cardiovascular risk factors showed that HRs of Q(3),Q(4),and Q(5) group were 1.23 (95%CI 1.03-1.48, P<0.05) , 1.19 (95%CI 1.01-1.41, P<0.05) , 1.39 (95%CI 1.18-1.65, P<0.01) , respectively. In the absence of hypertension, diabetes, smoking and acute myocardial infarction, the Cox regression model showed that compared with Q(2) group, the HR of new-onset heart failure in Q(5) group was 1.58 (95%CI 1.02-2.45, P<0.05) . Conclusion: Increased RHR is associated with increased risk of new-onset heart failure in this cohort.

[Analysis of related factors affecting evolution of recent small subcortical infarcts with cerebral small vessel disease].

Objective: To explore related factors affecting evolution of recent small subcortical infarct (RSSI) with small-artery occlusion. Methods: A total of 96 RSSI patients with RSSI were admitted from Shanghai Tongji Hospital between January 2015 and December 2018. The age of patients containing 60 men was 64.5 (58-73) years, and MRI follow-up time was 11.6 (6.3-11.8) months. Clinical information of patients, images data at baseline head MRI and evolution outcomes at follow-up MRI were collected. All patients were divided into cavitation group (lacunes) and no cavitation group (white matter hyperintensities (WMH) and disappearance) to analyze related factors. Results: Fifty-nine cases (61.5%) developed to cavities, 32 cases (33.3%) were focal WMH, and 5 cases (5.2%) disappeared.In the univariate analysis, RSSI maximum diameter on the DWI or T(2)WI sequence of cavitation group was significantly higher than non-cavitation group, but male proportion was lower (11.6 (9.9-16.6) vs 8.6 (6.9-13.0) mm, 11.8 (9.7-16.2) vs 8.8 (6.7-13.1) mm, 54.2% vs 75.7%, all P<0.05). In Logistic regression analysis,the maximum diameter on DWI sequence was an independent predictor of cavity formation (P=0.022,OR=1.138).When conducting quantitative analysis of infarct diameter and taking infarct maximum diameter ≤10 mm group as reference, the cavitation risk of maximum diameter>15 mm group was about 7.5 times higher (P=0.010, OR=7.464). The maximum diameter of 10-15 mm lost predictive value for cavity formation (P=0.129, OR=2.444). Conclusions: About 61.5% of RSSI develop to cavitation and 38.5% to WMH or disappear. The RSSI showing larger diameter on DWI has a greater possibility of cavitation.

[A preliminary study on resting-state functional magnetic resonance imaging of brain after anterior cruciate ligament preservation reconstruction with autologous tendon].

Objective: To preliminarily study on the possible mechanism of cerebral cortical dysfunction pattern after anterior cruciate ligament (ACL) preservation reconstruction with autologous tendon through resting-state functional magnetic resonance imaging (fMRI). Methods: From June 2015 to February 2019, 18 patients (10 males and 8 females with an average age of (36±10) years) with left anterior cruciate ligament rupture and treated with arthroscopic preservation reconstruction with autologous tendon were enrolled in this study, and 17 comparable healthy controls were included in Tongji Hospital of Tongji University. fMRI was performed after the postoperative period (2 to 12 weeks). The fMRI data were preprocessed by SPM8 software package and RESTplus software. The amplitude of low-frequency fluctuation (ALFF) and the fractional amplitude of low-frequency fluctuation (fALFF) in those two groups were calculated. Two-sample t-test was performed on ALFF and fALFF of the two groups, and multiple test corrections were performed by using AlphaSim. These methods were used for contrast studies on the characteristic activities of the brain dysfunction. Results: Compared with those in the control, ALFF in the central cingulate gyrus (cingulum_mid_bilateral), involving the auxiliary movement zone (supp_motor_ area) were significantly higher in the patients (P<0.01 before correction, P<0.05 after AlphaSim correction). The fALFF in activation cluster 1 was significantly higher in the right central gyrus (postcentral_R), the right lower lobule (parietal_inf_R), and the right upper margin (supramarginal_R) in the patients than that in the normal control group, respectively (P<0.01 before correction, P<0.05 after AlphaSim correction); the fALFF in activation cluster 2 in the right central cingulate gyrus (cingulum_mid_R), involving the right auxiliary movement zone (supp_motor_area_R) was significantly higher in the patients than that in the normal control group, respectively (P<0.01 before correction, P<0.05 after AlphaSim correction). Conclusion: The patients' cerebrum cortical function associated with the kinesthesis and their regulations are abnormally changed after anterior cruciate ligament preservation reconstruction with autologous tendon.

[Reduction of the atlantoaxial dislocation associated with basilar invagination through single-stage posterior approach: using Xuanwu occipital-cervical reduction surgical suite].

Objective: To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital-cervical fusion system in single stage. Methods: Thirty-seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital, Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3±12.3)years (range: 18-69 yars). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital-cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI),the distance of odontoid tip above Chamberlain line,clivus-canal angle (CCA) and the length of syrinx were collected.The preoperative and postoperative JOA score and radiological measurements were compared by paired t-test. Results: The mean JOA score of the patients increased from 10.5 to 14.4 at the one-year follow-up(t=14.3,P=0.00).Complete reduction of AAD and BI was achieved in 34 patients.The mean clivus-canal angle improved from 118.0 degrees preoperative to 143.7 degrees postoperative(t=6.2,P=0.00). Shrinkage of the syrinx was observed 1 week after surgery in 24 patients, and 6 months in 31 patients. Twenty-eight patients achieved bone fusion 6 months after surgery. All the patients achieved bone fusion 12 months after surgery. One-side vertebral artery occlusion was diagnosed in 1 case postoperatively for transient dizziness, and relieved in 2 weeks. Two patients developed moderate neck pain after surgery, and relieved in 1 month. No implant failure, spacer subsidence or infection was observed. Conclusions: The treatment of AAD associated with BI using Xuanwu occipital-cervical fusion system from posterior approach in single stage is effective and safe. Cage implantation intraarticularly and fixation with cantilever technique achieve complete reduction in most cases.

[Association between resting heart rate trajectory pattern and risk of cardiovascular and cerebrovascular diseases].

Objective: To examine whether the long-term resting heart rate (RHR) pattern can predict the risk of cardiovascular and cerebrovascular diseases (CVDs). Methods: This prospective cohort study included 63 040 participants who took part in the health examination in 2006 and one of the health examinations on 2008 or 2010 and were free of myocardial infarction, stroke, arrhythmia, cancer and not treated with ß-recepter blocker. The outcomes were the first occurrence of myocardial infarction and stroke during the follow up ended on December 31, 2015. RHRs were measured in 2006, 2008, and 2010. We used latent mixture modeling SAS Proc procedure to identify RHR trajectories. We identified 4 distinct RHR trajectory patterns based on the data derived from 2006 and on the pattern change during 2006 to 2010 (low-stable, moderate-stable, moderate-increasing, elevated-decreasing). Collected the general clinical data of the patients. Cox regression model was used to determine the association between RHR trajectory patterns and the risk of CVDs during follow up. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: There were statistical significance among the 4 distinct RHR trajectory patterns on the following variables: age, gender, smoking status, drinking status, physical activity, education status, history of use antihypertensive drugs, history of hypertension,history of diabetes, body mass index, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, and the level of high-sensitivity C-reactive protein (all P<0.01). The moderate-increasing pattern experienced the highest risk of developing stroke and CVDs among all 4 patterns. The cumulative incidence of cerebral infarction, cerebral hemorrhage and CVDs in the order of low-stable trajectory, moderate-stable trajectory and moderate-increasing trajectory. The cumulative incidences of cerebral infarction, cerebral hemorrhage and CVDs in elevated-decreasing trajectory group were significantly lower than those in moderate-increasing trajectory group, but higher than those in moderate-stable trajectory group. Compared to the low-stable pattern, adjusted HR was 1.3 (95%CI 1.0-1.6) for the moderate-increasing pattern after adjustment for potential confounders. Conclusion: Our study finds that individuals with moderate-increasing RHR trajectory pattern are associated with higher risk of cardiovascular and CVDs.

Cross-Kerr effect in a parity-time symmetric optomechanical system.

The cross-Kerr effects between the cavity and the mechanical oscillator in a parity-time symmetric optomechanical system are investigated. It is found that in the double-passive case there appears an asymmetric optomechanically induced transparency (OMIT) spectrum which is composed of a broad absorption peak located around the resonant point and a absorption line at the frequency position mainly determined by the Kerr interaction. The distinctive asymmetry induced by the cross-Kerr coupling is precisely demonstrated by the analytic findings. In the passive-active case, the resonance peaks in the OMIT spectrum are increased with the weak tunnel coupling, which is contrary to that in the double-passive case. When the tunnel coupling is increased up in the strong coupling region, the broad absorption peak and the absorption line in the OMIT spectrum are sequentially changed into the amplification ones, and the central amplification dip is split into two parts due to the normal mode splitting induced by the strong tunnel coupling. This can be used to realize a switching from absorption to amplification by only adjusting the tunnel interaction.

Liver injury induced by clomiphene citrate: A case report and literature reviews.

WHAT IS KNOWN AND OBJECTIVE: Clomiphene citrate is used to cause ovulation in females and to increase semen production in males. Clomiphene citrate is well tolerated in most patients and rarely induces liver injury. We report a case of liver injury which is associated with administration of clomiphene citrate in a male patient. CASE SUMMARY: A 31-year-old man who was treated by clomiphene citrate for 5 days was transferred to our emergency room with reddish-brown urine and upper abdominal pain. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were elevated. Based on the subsequent examination, he was diagnosed with liver injury and cholecystitis. The levels of AST and ALT returned to normal range after discontinuation of clomiphene citrate and symptomatic treatment. WHAT IS NEW AND CONCLUSION: The mechanism of liver injury caused by clomiphene citrate is still unclear. Polymorphism of CYP2D6 may have had an effect. Liver function tests should be performed when there is upper abdominal pain after administration of clomiphene citrate.