Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis.

AIM: To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40% ≤ LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. RESULTS: Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. CONCLUSION: LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

[Literature data mining on the current research status of uveitis in China].

Objective: To analyze the current research status of uveitis in China. Methods: It was a bibliometric analysis study. Using search formulas covering uveitis and its multiple subtypes, uveitis-related literature in English with publication dates from 2013 to 2022 was retrieved in Web of Science core databases through certain search strategies. This study used the latent Dirichlet allocation (LDA) algorithm to build topic models and analyzed the trends of research topics in recent years. Bibliometric analysis was used to analyze and visualize the bibliometric indicators (e.g., number of publications, citations, and H-index) of the included literature using tools such as VOSviewer software. Results: Over the past decade, China has published 1 657 papers on uveitis, ranking second globally. However, there is still room for improvement in terms of the H-index (58) and citation (12.28 per publication). Countries such as the USA (43.04%) and the United Kingdom (62.54%) were engaged in more international collaboration. We identified ten optimal LDA topics for uveitis literature in China such as immunotherapy, Behçet's disease, and Vogt-Koyanagi-Harada syndrome. Research on uveitis in China was mostly published in Ocular Immunology and Inflammation (92). Conclusions: China has made remarkable progress in uveitis research. Nonetheless, there is still untapped potential to enhance our global academic influence. It is encouraged to promote international collaborations, harness our expertise in areas like Behçet's disease and VKH syndrome, and publish our scientific achievements in high-impact journals.

Multibreed genomic prediction using summary statistics and a breed-origin-of-alleles approach.

Because of an increasing interest in crossbreeding between dairy breeds in dairy cattle herds, farmers are requesting breeding values for crossbred animals. However, genomically enhanced breeding values are difficult to predict in crossbred populations because the genetic make-up of crossbred individuals is unlikely to follow the same pattern as for purebreds. Furthermore, sharing genotype and phenotype information between breed populations are not always possible, which means that genetic merit (GM) for crossbred animals may be predicted without the information needed from some pure breeds, resulting in low prediction accuracy. This simulation study investigated the consequences of using summary statistics from single-breed genomic predictions for some or all pure breeds in two- and three-breed rotational crosses, rather than their raw data. A genomic prediction model taking into account the breed-origin of alleles (BOA) was considered. Because of a high genomic correlation between the breeds simulated (0.62-0.87), the prediction accuracies using the BOA approach were similar to a joint model, assuming homogeneous SNP effects for these breeds. Having a reference population with summary statistics available from all pure breeds and full phenotype and genotype information from crossbreds yielded almost as high prediction accuracies (0.720-0.768) as having a reference population with full information from all pure breeds and crossbreds (0.753-0.789). Lacking information from the pure breeds yielded much lower prediction accuracies (0.590-0.676). Furthermore, including crossbred animals in a combined reference population also benefitted prediction accuracies in the purebred animals, especially for the smallest breed population.

Age-dependent genetic and environmental variance of semen quality in Nordic Holstein bulls.

The aim of this study was to estimate genetic and environmental parameters, across bull's age, for semen quality traits including pre- and postcryopreservation semen concentration, sperm motility, and sperm viability as well as ejaculate volume and number of doses per ejaculate. A data set on 96,595 ejaculates from 2,831 Nordic Holstein bulls collected between 2006 and 2019 was used. Genetic and environmental parameters were estimated using a random regression model and applying the average-information REML approach. Spline functions were chosen to fit the additive genetic and permanent environmental effects across bull's age, and the optimal number of knots was chosen using cross validation. Residual variance heterogeneity was assumed in different bull age classes. The estimated repeatabilities of semen quality traits ranged from 0.16 to 0.85 across different ages of bulls. The estimated heritabilities of semen quality traits ranged from 0.02 to 0.56 across different ages of bulls. The results indicate possibilities for genetic improvement of semen quality traits through selective breeding.

[Effect of closed extension tube on preventing airway leakage during artificial airway clearance].

Objective: To explore the role of closed extension tube in preventing airway leakage during artificial airway clearance. Methods: The test lung was connected with a ventilator for mechanical ventilation. The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O(1 cmH2O=0.098 kPa), respectively. The circuit was connected with an open extension tube or a closed extension tube. The ventilator was set with different pressure parameters to observe the changes of airway pressure and tidal volume during airway clearance. Results: (1) The pressure parameters were set as 16/5, 20/6, 24/7, 28/8, 32/9 and 36/10 cmH2O, and the airway pressures (in cmH2O) of circuit connected with open extension tube were (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12)and(35.65±0.31)/(9.72±0.07), respectively.Under the same ventilator pressure parameters, the airway pressures (in cmH2O) of circuit connected with close extension tube were (16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively. The airway pressure of circuit connected with open extension tube was lower than that connected with closed extension tube(P<0.05);with the increase of the pressure setting of the ventilator, the difference of the airway pressure between the two extended tubes gradually increased. When the maximum inspiratory pressure of the ventilator was set 36 cmH2O, the difference reached 1.69 cmH2O. (2) The airway pressures (in cmH2O) dropped from (15.94±0.27)/(4.81±0.04), (20.09±0.23)/(6.05±0.16), (23.89±0.41)/(6.94±0.06), (27.90±0.22)/(7.71±0.18), (31.92±0.13)/(8.74±0.12), (35.65±0.31)/(9.72±0.07) to (13.42±0.4)/(3.15±0.14), (16.81±0.6)/(4.30±0.14), (20.22±0.5)/(5.48±0.45), (23.73±1.4)/(6.25±0.22), (24.78±0.7)/(7.13±0.21), (20.83±0.4)/(6.61±0.19)when the suction port of the open extension tube was opened (P<0.05);and the tidal volume (in L) also decreased from 0.328±0.004, 0.580±0.012, 0.621±0.003, 0.626±0.003, 0.615±0.003, 0.603±0.002 to 0.272±0.008, 0.416±0.051, 0.487±0.047, 0.396±0.116, 0.507±0.022, 0.508±0.079, respectively (P<0.05). The decrease of airway pressure and tidal volume gradually increased with the increase of ventilator setting pressure. When the ventilator setting parameter was 36/10 cmH2O, the decrease of airway inspiratory pressure was (14.82±0.51) cmH2O and the maximum reduction of tidal volume was (0.164±0.021)L. (3)The airway pressure (in cmH2O) was increased to(15.70±0.23)/(4.80±0.33), (19.01±0.81)/(5.71±0.34), (22.27±0.62)/(6.85±0.44), (25.35±2.09)/(7.94±0.16), (28.38±0.46)/(8.96±0.23), (33.34±0.71)/(9.71±0.25) when the suction tube was inserted from the suction port of the open extension tube in the open state, and the tidal volume (in L) was increased to 0.340±0.016, 0.563±0.020, 0.571±0.030, 0.556±0.026, 0.514±0.021, 0.512±0.031 as well.The airway pressure and tidal volume of the ventilation circuit were higher than those in the open state, but still lower than those in the closed state. Compared with the closed state of the suction port, the maximum pressure drop and tidal volume decrease were (3.53±0.46) cmH2O and (0.101±0.011) L, respectively. (4) The pressure of the ventilator was set between 16/5 cmH2O to 36/10 cmH2O. The airway pressure (in cmH2O) was decreased from (16.26±0.04)/(4.85±0.04), (20.74±0.15)/(6.42±0.11), (25.09±0.31)/(7.10±0.13), (29.38±0.24)/(8.17±0.09), (33.80±0.16)/(9.02±0.17), (37.89±0.19)/(9.83±0.07) to(16.36±0.06)/(4.85±0.04), (20.54±0.26)/(6.44±0.12), (24.36±0.24)/(7.01±0.33), (28.69±0.25)/(8.07±0.08), (32.97±0.33)/(8.93±0.09), (37.34±0.29)/(9.75±0.08), respectively during the insertion of the suction tube from the suction port of the closed extension tube, and the tidal volume (in L) was decreased from0.361±0.005, 0.592±0.003, 0.631±0.001, 0.642±0.007, 0.633±0.007, 0.626±0.08 to 0.335±0.005, 0.588±0.008, 0.631±0.002, 0.638±0.004, 0.628±0.004, 0.618±0.005.The maximum pressure change of the ventilation circuit was (0.83±0.27) cm H2O and the maximum tidal volume change was (0.008±0.006)L. The changes of airway pressure and tidal volume were significantly lower than those of ventilation circuit connected with open extension tube under the same pressure parameters. Conclusion: The connection of closed extension tube in mechanical ventilation circuit can reduce the airway leakage during artificial airway clearance, which is worthy of clinical recommendation.

[A case report of congenital osteogenesis imperfacta with corneal ectasia].

An 8-year-old male patient was admitted to ophthalmology for bilateral progressive blurred vision for 5 years. He had a history of multiple spontaneous fractures. Ocular examination revealed best-corrected visual acuity (BCVA) of 0.5 in the right eye and 0.6 in the left eye. Slitlamp examination showed bilateral blue sclerae, thining of the entire cornea and corneal ectasia. General physical examination demonstrated multi-site ligamentous laxity. The diagnosis of osteogenesis imperfacta was made. The patient was advised to wear rigid gas permeable contact lens with large diameter and stabilized peripheral curve, and the BCVA achieved 0.8 for both eyes.

[Detection of the spontaneous blinking pattern of dry eye patients using the machine learning method].

Objective: To establish a method to record the spontaneous blink pattern with a machine learning model, and to clarify the spontaneous blink pattern in patients with dry eye. Methods: It was a cross-setional study.We selected 357 dry eye patients (102 males and 255 females), aged (46.2±13.3) years, who visited corneal specialist clinics of Beijing Tongren Eye Center in 2019, as the dry eye group. The control group enrolled 152 normal controls, including 32 males and 120 females, aged (48.1±13.9) years. All participants completed the Ocular Surface Disease Index questionnaire, blink video capture, lipid layer thickness measurement, tear break-up time measurement, corneal fluorescein staining, and Schirmer Ⅱ test. Based on the assembled model built using UNet image segmentation algorithm and ResNet image classification algorithm, single frames of the blink video were analyzed, and then the palpebral opening height of each frame was obtained in order to establish a spontaneous blink wave. Finally, the characteristics of spontaneous blinks in dry eye patients were analyzed based on different types of complete blinks (types A, B and C) and partial blinks (types Ⅰ, Ⅱ and Ⅲ). Independent sample t test and Wilcoxon rank-sum test were used to judge if there was significant difference between the dry eye group and the normal group. Results: The accuracy of the segmentation model and the classification model was 96.3% and 96.0%, respectively, and the consistency with the manual analysis was 97.9%. In dry eye patients, the number of blinks was 30 (18, 42)/min, which was higher than that in normal controls [20 (9, 46)/min] (U=18 132.50, P=0.002). The number of complete blinks in dry eye cases was significantly lower than that in normal controls [6 (3, 24)/min vs. 12 (3,33)/min; U=12 361.00, P=0.016], and the number of partial blinks was significantly higher than that in normal controls [15 (6, 27)/min vs. 3 (0, 10)/min; U=22 839.00, P<0.001]. In complete blinks, the proportion of type A blinks in dry eye patients was significantly higher than that in normal controls [53.7% (2 796/5 177) vs. 39.3% (633/1 698); χ²=101.83, P<0.001]; in partial blinks, the proportion of type Ⅱ blinks in dry eye patients was significantly higher than that in normal controls [36.0%(2 334/6 477) vs. 29.6%(126/426); χ²=6.99, P=0.007]. The average interblink interval of dry eye patients was 1.2 s, which was not significantly different from that of normal controls (1.1 s; U=15 230.00, P=0.093). The eyelid closed phase of dry eye patients was 0.8 s, which was significantly shorter than that of normal controls (1.3 s; U=16 291.50, P=0.006). There were no significant differences in eyelid closing phase, early opening phase and late opening phase between the two groups (all P>0.05). Conclusions: In dry eye patients, the number of partial blinks increased, the number of complete blinks decreased, and the duration of eyelid closed phase shortened significantly. The main blink patterns of dry eye patients included type Ⅱ partial blinks with a reduced closure amplitude and type A complete blinks with a shortened closure time.

Genetic parameters for rectal temperature, respiration rate, and drooling score in Holstein cattle and their relationships with various fertility, production, body conformation, and health traits.

Genetic selection for improved climatic resilience is paramount to increase the long-term sustainability of high-producing dairy cattle, especially in face of climate change. Various physiological indicators, such as rectal temperature (RT), respiration rate score (RR), and drooling score (DS), can be used to genetically identify animals with more effective coping mechanisms in response to heat stress events. In this study, we investigated genetic parameters for RT, RR (score from 1-3), and DS (score from 1-3). Furthermore, we assessed the genetic relationship among these indicators and other economically important traits for the dairy cattle industry. After data editing, 59,265 (RT), 30,290 (RR), and 30,421 (DS) records from 13,592 lactating Holstein cows were used for the analyses. Variance components were estimated based on a multiple-trait repeatability animal model. The heritability ± standard error estimate for RT, RR, and DS was 0.06 ± 0.01, 0.04 ± 0.01, and 0.02 ± 0.01, respectively, whereas their repeatability was 0.19, 0.14, and 0.14, respectively. Moderate genetic correlations of RR with RT and DS (0.26 ± 0.11 and 0.25 ± 0.16) and nonsignificant correlation between RT and DS (-0.11 ± 0.14) were observed. Furthermore, the approximate genetic correlations between RT, RR, and DS with 12 production, 29 conformation, 5 fertility and reproduction, 5 health, and 9 longevity-indicator traits were assessed. In general, the approximate genetic correlations calculated were low to moderate. In summary, 3 physiological indicators of heat stress response were measured in a large number of animals and shown to be lowly heritable. There is a value in developing a selection index including all the 3 indicators to improve heat tolerance in dairy cattle. All the unfavorable genetic relationships observed between heat tolerance and other economically important traits can be accounted for in a selection index to enable improved climatic resilience while also maintaining or increasing productivity in Holstein cattle.

[Efficacy analysis of retroperitoneal laparoscopic selective renal artery branch occlusion and nephron sparing surgery for ≥ T1b stage renal carcinoma].

Objective: To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b. Methods: From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery. Results: Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m2. The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),both P<0.05]. Conclusion: Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease leading to visual impairment. Its pathogenic mechanisms remain poorly understood. Our purpose was to investigate the distinctive protein and metabolic profiles of sweat in patients with VKH disease. In the present study, proteomics and metabolomics analysis was performed on 60 sweat samples (30 VKH patients and 30 normal controls) using liquid chromatography tandem mass spectrometry. Parallel reaction monitoring (PRM) analysis was used to validate the results of our omics analysis. In total, we were able to detect 716 proteins and 175 metabolites. Among them, 116 proteins (99 decreased and 17 increased) were observed to be significantly different in VKH patients when compared to controls. Twenty-one differentially expressed metabolites were identified in VKH patients, of which 18 included choline, L-tryptophan, betaine and L-serine were reduced, while the rest were increased. Our multi-omics strategy reveals an important role for the amino acid metabolic pathway in the pathogenesis of VKH disease. Significant differences in proteins and metabolites were identified in the sweat of VKH patients and, to some extent, an aberrant amino acid metabolism pathway may be a pathogenic factor in the pathogenesis of VKH disease.

[Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia].

The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.

[Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia].

The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.

[Pulmonary rehabilitation guidelines in the principle of 4S for patients infected with 2019 novel coronavirus (2019-nCoV)].

A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.

[Pulmonary rehabilitation guidelines in the principle of 4S for patients infected with 2019 novel coronavirus (2019-nCoV)].

A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.

[In vivo confocal microscopic characteristics of limbal stem cell deficiency].

Objective: To investigate the cellular changes and quantitative analysis of basal cell density (BCD) and corneal epithelial thickness (CET) in limbal stem cell deficiency (LSCD) by in vivo confocal microscopy (IVCM). Methods: Prospective case-control study. A total of 35 eyes of 23 patients diagnosed with LSCD and 25 eyes from normal subjects were included in this study. Based on slit-lamp presentation and the global consensus on classification, the LSCD patients were classified into LSCD Ⅰ, LSCD Ⅱ and LSCD Ⅲ. Confocal images of the central cornea, and the superior, inferior, nasal and temporal limbus were inspected by IVCM. Morphologic characteristics of LSCD were summarized. The BCD and CET in all locations were measured. ANVOA or Kruskal-Wallis test was used for analysis when appropriate. A receiver operating characteristic was used to detect the diagnosis efficiency of BCD and CET. Results: The characteristics in the corneal epithelium of LSCD on IVCM included nested corneal epithelial cells, goblet cells with hyper-reflective spots, irregular basal cells and decreasing subbasal nerve density. The mean BCD of the LSCD group was (8 976±1 096) cells/mm2 in the central cornea. Compared to the control group, the BCD in the central cornea, superior, inferior, nasal and temporal limbus decreased by 30.2%, 26.0%, 28.7%, 29.3% and 30.2%, respectively (all P<0.007). The CET in the central cornea was (47.3±8.1) µm. The CET in the central cornea, superior, inferior, nasal and temporal limbus decreased by 27.9%, 23.7%, 20.6%, 26.9% and 23.1%, respectively, compared to the control group (all P<0.007). There was a decline of BCD and CET in more serious LSCD. Additionally, the decline of BCD and CET was shown in the unaffected region. The receiver operating characteristic showed the diagnosis efficiency of BCD in the corneal center and limbus (0.931 and 0.916) was superior to CET (0.853 and 0.817). Conclusions: There was a series of characteristic cellular changes in LSCD on IVCM. Both BCD and CET decreased significantly in LSCD. The BCD had higher diagnostic efficiency for LSCD.(Chin J Ophthalmol, 2020, 56:447-455).

[Efficacy and safety of alirocumab versus ezetimibe in high cardiovascular risk Chinese patients with hyperlipidemia: ODYSSEY EAST Study-Chinese sub-population analysis].

Objective: To compare the efficacy and safety profile of alirocumab (PCSK9 inhibitor) versus ezetimibe on top of maximally tolerated statin dose in high cardiovascular risk Chinese patients with hyperlipidemia. Methods: The ODYSSEY EAST study was a randomized, double-blinded, double dummy, active-control, parallel group, multi-centers clinical trial, the Chinese sub-population included 456 patients with hyperlipidemia and high cardiovascular risk on maximally tolerated statin dose. Patients were randomized (2∶1) to receive the subcutaneous injection of alirocumab (75 mg Q2W; with dose up titration to 150 mg Q2W at week 12 if low-density lipoprotein cholesterol (LDL-C) was ≥1.81 mmol/L at week 8) or the oral administration of ezetimibe (10 mg daily) for 24 weeks. The primary endpoint was percentage change in calculated LDL-C from baseline to week 24. Key secondary efficacy endpoints included percentage change from baseline to week 12 or 24 in LDL-C (week 12) and other lipid parameters, including apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), TC, lipoprotein(a) (Lp(a)), HDL-C, fasting triglycerides (TG), and Apo A1, and the proportion of patients reaching LDL-C<1.81 mmol/L at week 24. Safety profile of therapeutic drugs was also assessed during the treatment period. Results: The mean age of 456 Chinese patients was (59.5±10.9) years, 341(74.8%) patients were male, 303 patients (66.4%) in alirocumab group and 153 patients (33.5%) in ezetimibe group. Demographic characteristics, disease characteristics, and lipid parameters at baseline were similar between the two groups. LDL-C was reduced more from baseline to week 12 and 24 in alirocumab group versus ezetimibe group, the difference of their least-squares mean (standard error) percent change were(-35.2±2.2)% and (-36.9±2.5)% (both P<0.001). At 12 weeks, alirocumab had significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-40.3±2.8)%, (-27.7±1.8)%, (-19.6±1.5)% and (-27.7±1.9)%, respectively (all P<0.001). At 24 weeks, the percent of patients who reached LDL-C<1.81 mmol/L and LDL-C<1.42 mmol/L was significantly higher in alirocumab group (85.3% and 70.5%) than in ezetimibe group (42.2% and 17.0%, both P<0.001), and alirocumab use was also associated with significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-37.2±2.8)%, (-29.1±2.0)%, (-21.6±1.6)% and (-29.6±2.2)%, respectively (all P<0.001). The incidence of treatment related adverse events was similar between the two treatment groups (223/302 patients (73.8%) in alirocumab group and 109/153 patients (71.2%) in ezetimibe group). Respiratory infection, urinary infection, dizziness and local injection-site reactions were the most frequently reported adverse events. Conclusions: In high cardiovascular risk patients with hyperlipidemia from China on maximally tolerated statin dose, the reduction of LDL-C induced by alirocumab is more significant than that induced by ezetimibe. Both treatments were generally safe during the observation period of study.

Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.

Genome-wide association study identifies loci linked to serum electrolyte traits in Chinese Holstein cattle.

We aimed to identify QTL for serum electrolyte traits by performing a GWAS of calcium, chloride, sodium, potassium and magnesium ion concentrations in Chinese Holstein cattle. We detected five SNPs that had significant associations with calcium ion concentrations and identified GATA2 from Bos taurus chromosome (BTA)22 as having the highest significance. Among the genes with significant results, we speculate that TMEM123 might be related to calcium channel proteins according to the functions of the TMEM family.

Transcriptome analysis of the endometrium from Chinese Erhualian sows that differ in calcium ion concentration and litter size.

Embryonic survival rate, an important factor in the fecundity of sows, is affected by endometrium-secreting histotroph. A higher concentration of calcium ion has been observed in the uterus of highly prolific Erhualian sows (EH) compared with those of less prolific (EL) sows. This suggests that EH sows have better establishment and maintenance of pregnancies, thus increasing embryonic survival rate during the peri-implantation period. To understand the mechanisms of how the endometrium-secreting histotroph affects embryonic survival rate during the Erhualian peri-implantation period, the expression patterns of endometrial mRNA in the EH and EL sows on day 12 of gestation were analyzed using RNA sequencing technology. A total of 164 differentially expressed genes (DEGs) were identified (Padj  < 0.05, |log2 (FC)| ≥ 1), including 46 upregulated and 118 downregulated genes in EH compared to EL. Gene Ontology enrichment indicated that a subset of DEGs was involved in calcium ion binding and cell adhesion. Solute carrier family 8 member A3 and solute carrier family 24 member 4, identified as upregulated genes (Padj  < 0.05) in EH, were considered key candidate genes expressed in the endometrium affecting embryonic survival rate during the peri-implantation period. The results improve understanding of the genetic mechanism underlying the variation in litter size of Erhualian pigs during the peri-implantation period.

Genetic analysis of skinfold thickness and its association with body condition score and milk production traits in Chinese Holstein population.

The skin has many important roles in dairy cattle, and skinfold thickness could be used as an indicator of body fat deposition. The objectives of this study were to estimate genetic parameters of skinfold thickness and to explore its association with body condition score (BCS) and milk production traits in a Chinese Holstein population. Skinfold thicknesses over the neck (STN) and the last rib (STR), BCS, and test-day records of milk production traits were available for 6,416 lactating Holstein cows in the summers of 2015 and 2016 in Beijing, China. Multi-trait animal models were used to estimate variance and covariance components using the DMU software. The average STN was 7.15 ± 1.28 mm, and the average STR was 11.76 ± 1.95 mm (mean ± standard deviation). Estimated heritability was 0.13 ± 0.03 for STN and 0.26 ± 0.04 for STR. We detected a high genetic correlation (0.79 ± 0.08; heritability ± standard error) between STN and STR. Genetic correlations between skinfold thickness and BCS were low to moderate: 0.18 between STR and BCS, and 0.33 between STN and BCS. Genetic correlations between skinfold thickness and milk yield, milk fat percentage, and milk protein percentage were negligible, ranging from -0.02 to 0.15. Collectively, skinfold thickness is characterized as a trait with moderate heritability. Skinfold thickness is sensitive to changes in body condition or fat deposition across parities and lactation stages in milking cows, and we confirmed the complementary nature of skinfold thickness and BCS genetically as well as phenotypically by comparing their changing trends throughout lactation and across lactations. The use of skinfold thickness, together with BCS, can assist in the monitoring of changes in body fat deposition to achieve higher management precision.