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Mechanical metamaterials with multi-level dynamic crushing effects (MM-MLs) are designed in this study through coordinate transformation and mirror arrays. The mechanical effects of the diameter and length ratio of the struts and connecting rods, the Euler angles, and the cell numbers on the mechanical properties are investigated separately. MM-ML can exhibit significant two-level platform stress, and the local cells in the first platform stress stage undergo rotational motion, while the second platform stress stage mainly involves collapse compression and bending. Although increasing the length of the connecting rods can increase the range of Poisson's ratio, it will reduce the level of platform stress and energy absorption. Increasing the Euler angle will reduce the strain interval of the first platform stress and can improve the energy absorption capacity. In addition, increasing the cell number while maintaining a constant relative density can effectively enhance energy absorption. MM-ML has significant parameter controllability, can achieve different platform stress regions, different ranges of Poisson's ratios, and energy absorption requirements according to the application scenario, and can demonstrate functional diversity compared to existing research. The design scheme can provide ideas for adaptive crushing protection requirements.
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KEY MESSAGE: Editing ZmGA20ox3 can achieve the effect similar to applying Cycocel, which can reduce maize plant height and enhance stress resistance. Drought stress, a major plant abiotic stress, is capable of suppressing crop yield performance severely. However, the trade-off between crop drought tolerance and yield performance turns out to be significantly challenging in drought-resistant crop breeding. Several phytohormones [e.g., gibberellin (GA)] have been reported to play a certain role in plant drought response, which also take on critical significance in plant growth and development. In this study, the loss-of-function mutations of GA biosynthesis enzyme ZmGA20ox3 were produced using the CRISPR-Cas9 system in maize. As indicated by the result of 2-year field trials, the above-mentioned mutants displayed semi-dwarfing phenotype with the decrease of GA1, and almost no yield loss was generated compared with wild-type (WT) plants. Interestingly, as revealed by the transcriptome analysis, differential expressed genes (DEGs) were notably enriched in abiotic stress progresses, and biochemical tests indicated the significantly increased ABA, JA, and DIMBOA levels in mutants, suggesting that ZmGA20ox3 may take on vital significance in stress response in maize. The in-depth analysis suggested that the loss function of ZmGA20ox3 can enhance drought tolerance in maize seedling, reduce Anthesis-Silking Interval (ASI) delay while decreasing the yield loss significantly in the field under drought conditions. The results of this study supported that regulating ZmGA20ox3 can improve plant height while enhancing drought resistance in maize, thus serving as a novel method for drought-resistant genetic improvement in maize.
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Resistencia a la Sequía , Edición Génica , Zea mays/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fitomejoramiento , Sequías , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genéticaRESUMEN
Arsenic is an identified carcinogen for humans.In this study, chronic exposure of human hepatocyte L-02 to low-doses of inorganic arsenic caused cell malignant proliferation. Meanwhile, compared with normal L-02 cells, arsenic-transformed malignant cells, L-02-As displayed more ROS and significantly higher Cyclin D1 expression as well as aerobic glycolysis. Moreover, Akt activation is followed by the upregulation of Cyclin D1 and HK2 expression in L-02-As cells, since inhibition of Akt activity by Ly294002 attenuated the colony formation in soft agar and decreased the levels of Cyclin D1 and HK2. In addition, scavenging of ROS by NAC resulted in a decreased expression of phospho-Akt, HK2 and Cyclin D1, and attenuates the ability of anchorage-independent growth ofL-02-As cells, suggested that ROS mediated the Akt activation in L-02-As cells. In summary, our results demonstrated that ROS contributes to the malignant phenotype of arsenic-transformed human hepatocyte L-02-As via the activation of Akt pathway.
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Arsénico , Ciclina D1 , Humanos , Ciclina D1/metabolismo , Arsénico/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proliferación CelularRESUMEN
The interplay between band topology and magnetism plays a central role in achieving exotic physical phenomena and innovative spintronics applications. While prior works have mainly focused on ferromagnetic matter, little is known about the manipulation of band topology in antiferromagnets. Here, we report the emergence of a two-dimensional (2D) antiferromagnetic topological insulator (AFM TIs) by proximity coupling a 2D TI and a normal AFM insulator, and remarkably realize it in a concrete example of the KCuSe/NaMnBi heterobilayer. The first-principles calculations show that a band gap as large as 63.8 meV can be opened up by spin-orbit coupling, revealing the possible application even at room temperature. The size of the band gap depends on the separation between KCuSe and NaMnBi QLs, which can be switched experimentally by applying external strain. Moreover, the heterobilayer presents an integer topological invariant with a value of Z2 = 1 and a pair of gapless edge states. The findings not only broaden the range of 2D AFM topological quantum materials, but could also inspire more research in van der Waals heterobilayers for topological spintronics.
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BACKGROUND: Comminuted patellar fractures are not rare, and the ideal treatment method remains controversial. The present study was conducted to evaluate effects and compare complications of two different methods used to treat comminuted patellar fractures. METHODS: From March 2010 to August 2016, 102 cases of 34-C2 or 34-C3 comminuted patellar fractures were treated at our hospital, wherein patients received two different treatments: titanium cable tension band with cerclage method (group A) and intrafragmentary screws with X-shaped plating technique (group B). At follow-ups, articular step-off, range of motion (ROM), Lysholm scores, time of union, and complications were recorded and analyzed. Radiographic and clinical data as well as rate of complications were statistically analyzed. RESULTS: In total, 87 patients were included in the final analysis (n = 47 in group A and n = 40 in group B). No significant differences were noted in terms of cost of implant, age, gender, rate of 34-C3 fractures, rate of layered inferior pole fractures, postoperative articular step-off and union time. At 2-year follow-up, average Lysholm scores, ROM and rate of complications were (89.0 ± 4.5), (122°±12°) and (27.7%) in group A and (90.2 ± 3.9), (124°±11°) and (17.5%) in group B, respectively, with no significant differences (p > 0.05). The mean time of surgery in group B was shorter than that in group A with significant difference (p < 0.05). CONCLUSIONS: Treatment using the intrafragmentary screws and plate method for amenable comminuted patellar fractures achieved similar complication rate and favorable functional outcomes at the 2-year follow-up, which was comparable to the titanium cable tension band with cerclage method. Thus, the intrafragmentary screws and plate method is effective, safe and convenient for 34-C2/C3 comminuted patellar fractures, especially appropriate for patients with layered fragments.
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Fracturas Conminutas , Rótula , Tornillos Óseos , Hilos Ortopédicos , Fijación Interna de Fracturas , Curación de Fractura , Fracturas Conminutas/diagnóstico por imagen , Fracturas Conminutas/cirugía , Humanos , Rótula/diagnóstico por imagen , Rótula/cirugía , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: RNF213 rare variant-p.R4810K (rs112735431) was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. Considering the allelic heterogeneity, we performed target exome sequencing of RNF213 with the aim to identify the rare variants spectrum and their association with ICASO in a Chinese population and further to explore whether the rare variants carrier patients present specific clinical phenotype. METHODS: Target exome sequencing of RNF213 was performed in 250 ICASO patients using FastTarget sequencing technology. Various filtering process were used to select the candidate variants. Control individuals were obtain from 1000 Genome Project (208 Chinese samples) and GeneSky in-house database (1007 samples). Gene-based association analyses were conducted to identify the association between RNF213 rare variants and ICASO. The clinical characteristics of rare variant carriers and non-carriers were compared using Chi-squared test or Fisher's exact test. RESULTS: After filtration, 18 rare variants were identified in 39 patients. Gene-based association test showed that rare variants of RNF213 were significantly associated with ICASO (Minor allele frequency < 0.05, WSS p = 4.88 × 10- 10; SKAT p = 9.68 × 10- 6; SKAT-O p = 3.42 × 10- 9). There were no significant clinical characteristic differences other than the diagnosis age which was older in the carriers than the non-carriers (60.5 ± 6.2 vs 57.3 ± 8.9 years old, p = 0.028). CONCLUSION: Rare variants of RNF213 are associated with ICASO in Chinese. However, there are limited genetic diagnosis values of the gene due to no specific phenotypic presentation in the carriers and non carrier patients.
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Adenosina Trifosfatasas/genética , Pueblo Asiatico/genética , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ubiquitina-Proteína Ligasas/genética , Insuficiencia Vertebrobasilar/genética , Adulto , Anciano , Estudios de Casos y Controles , China , Exoma , Femenino , Pruebas Genéticas , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Análisis de Secuencia de ADN/métodosRESUMEN
BACKGROUND Currently, proton pump inhibitors (PPIs) are the first-line treatment for ulcers resulting from endoscopic submucosal dissection (ESD). Vonoprazan is a new oral potassium-competitive acid blocker (P-CAB). The aim of this systematic review and meta-analysis was to compare the efficacy, safety, and tolerance of vonoprazan with PPIs in the treatment of peptic ulcers resulting from ESD. MATERIAL AND METHODS Published results of randomized clinical trials (RCTs) comparing vonoprazan with PPIs in the treatment of ulcers resulting from ESD were identified up to March 2018. The main clinical endpoints evaluated were healing rate and adverse events. The meta-analysis included quality assessment of the studies, statistical analysis of endpoints, and sensitivity analysis using Revman version 5.3 meta-analysis software. RESULTS Systematic literature review identified seven published studies that included 548 patients. Five studies were published as full-text manuscripts, and two studies were published as abstracts. Meta-analysis of the vonoprazan treatment, compared with PPI treatment, for ESD showed that the pooled relative risk (RR) of healing rate was 0.64 (95% CI, 0.33-1.22) for the 4-week study group and 0.98 (95% CI, 0.84-1.15) for the 8-week study group. The RR for adverse events was 0.65 (95% CI, 0.31-1.38) (P>0.05). No statistical evidence of publication bias was found. CONCLUSIONS The findings of the systematic review and meta-analysis showed that the efficacy of vonoprazan was comparable with PPIs for the treatment of peptic ulcers following ESD. Further studies are required to support the safety and efficacy of vonoprazan compared with different types of PPIs.
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Úlcera Péptica/tratamiento farmacológico , Inhibidores de la Bomba de Protones/farmacología , Pirroles/farmacología , Sulfonamidas/farmacología , Resección Endoscópica de la Mucosa/métodos , Humanos , Complicaciones Posoperatorias , Neoplasias Gástricas , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
BACKGROUND: Persistent left superior vena cava (PLSVC) is a common vena cava malformation, and drains blood into the right atrium via the dilated coronary sinus in most cases. It is usually asymptomatic and detected incidentally during invasive procedures or imaging. Whether the hemodialysis catheters can be placed in PLSVC is still controversial now (Stylianou et al. Hemodial Int 11:42-45, 2007). CASE PRESENTATION: Here we report a rare case of catheterization through PLSVC in an end-stage renal disease (ESRD) male patient whose PLSVC connected with pulmonary vein with insufficient blood flow eventually. Among the other 28 cases included in the literature review, 16 cases were non-tunneled catheter and 12 cases were cuffed, tunneled catheter and most of them could provide adequate blood flow. CONCLUSION: PLSVC is a rare malformation and mostly asymptotic, we believe that PLSVC drains blood into the right atrium with enough inner diameter and blood flow can serve as an alternative site for conventional dialysis access. However, the feasibility of hemodialysis catheterization through it and measures to avoid serious complications are still needed to be discussed.
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Cateterismo Venoso Central/métodos , Fallo Renal Crónico/terapia , Venas Pulmonares/diagnóstico por imagen , Diálisis Renal , Malformaciones Vasculares , Vena Cava Superior , Hemodinámica , Humanos , Procesamiento de Imagen Asistido por Computador , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Diálisis Renal/instrumentación , Diálisis Renal/métodos , Tomografía Computarizada por Rayos X/métodos , Malformaciones Vasculares/complicaciones , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/fisiopatología , Vena Cava Superior/anomalías , Vena Cava Superior/diagnóstico por imagenRESUMEN
Effective shielding area is a crucial indicator for the evaluation of the infrared smoke-obscuring effectiveness on the battlefield. The conventional methods for assessing the shielding area of the smoke screen are time-consuming and labor intensive, in addition to lacking precision. Therefore, an efficient and convincing technique for testing the effective shielding area of the smoke screen has great potential benefits in the smoke screen applications in the field trial. In this study, a thermal infrared sensor with a mid-wavelength infrared (MWIR) range of 3 to 5 μm was first used to capture the target scene images through clear as well as obscuring smoke, at regular intervals. The background subtraction in motion detection was then applied to obtain the contour of the smoke cloud at each frame. The smoke transmittance at each pixel within the smoke contour was interpolated based on the data that was collected from the image. Finally, the smoke effective shielding area was calculated, based on the accumulation of the effective shielding pixel points. One advantage of this approach is that it utilizes only one thermal infrared sensor without any other additional equipment in the field trial, which significantly contributes to the efficiency and its convenience. Experiments have been carried out to demonstrate that this approach can determine the effective shielding area of the field infrared smoke both practically and efficiently.
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The physicochemical properties of steel slag were investigated using SEM and IR, and it was found that free calcium oxide and free magnesium oxide in steel slag produce calcium hydroxide when in contact with water, leading to volume expansion. Thus, the expansion rate of steel slag itself was first investigated, and it was found that the volume expansion of steel slag was more obvious in seven days after water immersion. Then, the cement dosages of 5% and 6% of the steel slag expansion rate and cement-stabilized gravel volume changes between the intrinsic link were further explored after the study found that the cement bonding effect can be partially inhibited due to the volume of expansion caused by the steel slag, so it can be seen that increasing the dosage of cement can reduce the volume expansion of steel slag cement-stabilized gravel with the same dosage of steel slag. Finally, a prediction model of the expansion rate of steel slag cement-stabilized gravel based on the BP (back propagation) neural network was established, which was verified to be a reliable basis for predicting the expansion rate of steel slag cement-stabilized aggregates and improving the accuracy of the proportioning design.
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An efficient method for the synthesis of a self-supporting carbon framework (denoted Gra-GC-MoSe2) is proposed with a triple-gradient structure-in sodiophilic sites, pore volume, and electrical conductivity-which facilitates the highly efficient regulation of Na deposition. In situ and ex situ measurements, together with theoretical calculations, reveal that the gradient distribution of Se heteroatoms in MoSe2, and its derivatives tailor the sodiophilicity, while the gradient distribution of porous nanostructures homogenizes the Na+ diffusion. Therefore, Na deposition occurs from the bottom to the top of the Gra-GC-MoSe2 framework without dendrite formation. In addition, the gradient in electrical conductivity ensures the stripping process does not lead to dead Na. As a result, a Gra-GC-MoSe2 modified Na anode (Na@Gra-GC-MoSe2) shows impressive cycling stability with a high average Coulombic efficiency in an asymmetric cell. In symmetric cells, it also exhibits a long cycling life of 2000 h with a low polarization voltage and works stably even under a large capacity of 10 mAh cm-2. Moreover, a Na@Gra-GC-MoSe2|| Na3V2(PO4)3 full cell delivers a high energy density with an excellent cycling performance.
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Chinese liquor is a world-famous beverage with a long history. Base liquor, a product of liquor brewing, significantly affects the flavor and quality of commercial liquor. In this study, a machine learning method consisting of a deep residual network (ResNet)18 backbone with a light gradient boosting machine (LightGBM) classifier (ResNet-GBM) is proposed for the quality identification of base liquor and commercial liquor using multidimensional signals from an electronic nose (E-Nose). Ablation experiments are conducted to analyze the contribution of the framework's components. Five evaluation metrics (accuracy, sensitivity, precision, F1 score, and kappa score) are used to verify the performance of the proposed method, and six other frameworks (support vector machine (SVM), random forest (RF), k-nearest neighbor (KNN), extreme gradient boosting (XGBoost), multidimensional scaling-support vector machine (MDS-SVM), and back-propagation neural network (BPNN)) on three datasets (base liquor, commercial liquor, and mixed base and commercial liquor datasets). The experimental results demonstrate that the proposed ResNet-GBM model achieves the best performance for identifying base liquor and commercial liquors with different qualities. The proposed framework has the highest F1 score for the identification of commercial liquor in the mixed dataset due to the contribution of similar microconstituents from the base liquor. The proposed method can be used for the quality control of Chinese liquor and promotes the practical application of E-nose devices.
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Weyl semimetals (WSMs) have attracted great attentions that provide intriguing platforms for exploring fundamental physical phenomena and future topotronics applications. Despite the fact that numerous WSMs are achieved, WSMs with long-distance distribution of Weyl points (WPs) in given material candidates remain elusive. Here, the emergence of intrinsic ferromagnetic WSMs in BaCrSe2 with the nontrivial nature explicitly confirmed by the Chern number and Fermi arc surface states analysis is theoretically demonstrated. Remarkably, unlike previous WSMs for which opposite chirality WPs are located very close to each other, the WPs of BaCrSe2 host a long-distance distribution, as much as half of the reciprocal space vector, suggesting that the WPs are highly robust and difficult to be annihilated by perturbations. The presented results not only advance the general understanding of magnetic WSMs but also put forward potential applications in topotronics.
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Polyimide (PI) is widely deployed in space missions due to its good radiation resistance and durability. The influences from radiation and harsh temperatures should be carefully evaluated during the long-term service life. In the current work, the coupled thermal and radiation effects on the mechanical properties of PI samples were quantitatively investigated via experiments. At first, various PI specimens were prepared, and electron irradiation tests were conducted with different fluences. Then, both uniaxial tensile tests at room temperature and the dynamic mechanical analysis at varied temperatures of PI specimens with and without electron irradiation were performed. After that, uniaxial tensile tests at low and high temperatures were performed. The fracture surface of the PI film was observed using a scanning electron microscope, and its surface topography was measured using atomic force microscopy. In the meantime, the Fourier-transform infrared spectrum tests were conducted to check for chemical changes. In conclusion, the tensile tests showed that electron irradiation has a negligible effect during the linear stretching period but significantly impacts the hardening stage and elongation at break. Moreover, electron irradiation slightly influences the thermal properties of PI according to the differential scanning calorimetry results. However, both high and low temperatures dramatically affect the elastic modulus and elongation at break of PI.
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BACKGROUND AND AIMS: The efficacy and underlying mechanisms of exclusive enteral nutrition (EEN) in adult patients with Crohn's disease (CD) remain controversial. This study aimed to evaluate the role of EEN in adult patients with CD and to explore the mechanisms from the perspective of immunoregulation. METHODS: This is a prospective, open-label pilot study. Active patients with CD were enrolled and prescribed an amino-acid-rich elemental diet for 12 weeks. Dynamic changes in immune cells, including neutrophils, monocytes, T cells and B cells, were detected by flow cytometry. Plasma cytokines were evaluated by ELISA. RESULTS: Twenty adult patients with CD were enrolled. Among them, 1 discontinued treatment due to poor compliance, and 19 patients were included for final analysis. Clinical remission was achieved in 47.37% (9/19), 63.16% (12/19), and 73.68% (14/19) patients at weeks 4, 8, and 12, respectively. Endoscopic remission and transmural healing were achieved in 52.63% (10/19) and 15.79% (3/19) patients at week 12. Notably, there was no significant difference in clinical remission between week 4 and week 8 (p = 0.33) or week 12 (p = 0.09). Furthermore, we observed a rapid reconstitution of immunologic homeostasis as early as week 4. At week 4, both the frequency and activation of neutrophils and monocytes were decreased after EEN therapy. Significant decreases in Th17 cells and naïve B cells, increases in memory B cells, and regulatory B cells were also detected. These changes remained stable at weeks 8 and 12. CONCLUSIONS: EEN with an amino-acid-rich elemental diet orchestrated immunological balances and induces clinical remission in adult CD patients as early as week 4, suggesting a 4-week EEN therapy may be feasible and practicable in clinical practice.
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Enfermedad de Crohn , Adulto , Humanos , Enfermedad de Crohn/terapia , Nutrición Enteral , Estudios Prospectivos , Proyectos Piloto , Inducción de RemisiónRESUMEN
Purpose: Considering high risk of imported epidemic in port cities, it is necessary to estimate COVID-19 vaccine acceptability and to promote vaccination coverage of high-risk occupations. Methods: A cross-sectional survey was carried out among the occupations in Yantai city, China, using an online questionnaire service platform. Targeted strategies were developed based on the survey results. In addition, periodic monitoring of the vaccination rate was provided in order to evaluate the effectiveness of the strategies. Results: A total of 2231 (73.22%) of 3047 participants were willing to accept the vaccine, while 2.53% refused and 24.25% were not sure. Frontline port workers (133/152, 87.50%) and healthcare workers (999/1155, 86.49%) had higher intentions to accept, while public places and commercial service staff (584/1011, 57.76%) had the lowest. The reasons for refusal and hesitation were mainly "doubt of safety or effectiveness" (661/816, 81.00%) and "hearing previous news about vaccines" (455/816, 55.76%). Multilevel strategies such as adequate organizations, health education and promotion, and easy access to vaccination were promoted by local authorities in collaboration with schools, hospitals, enterprises and institutions. The study showed a significant increase in vaccination rate among these occupations after the implementation of these strategies (p<0.001), reaching 87.96%. Conclusion: COVID-19 vaccine acceptability among high-risk occupations was unsatisfactory before the stage of emergency vaccination. An advanced understanding of vaccine attitudes and acceptance can aid in the development of focused immunization promotion programs. It is worth emphasizing that wide strategies with the strong support and enthusiastic cooperation of the government and the industry executive can contribute to increasing occupations' acceptance of the ongoing COVID-19 immunization project.
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Background: Genetic factors play important roles in the development of intracranial aneurysm (IA). Rare RNF213 variants have been identified as being susceptible to Moyamoya disease (MMD), non-MMD intracranial artery stenosis/occlusion disease, and other vascular disorders. This study aimed to investigate the association between rare RNF213 variants and the risk of IA in a Chinese population. Methods: We recruited 174 patients with IA for RNF213 target exome sequencing. Information on the control subjects was obtained from the 1,000 Genome Project and GeneSky in-house database. After prioritizing rare RNF213 variants, the filtered variants were confirmed by Sanger sequencing. Gene-based association analyses were performed to identify the association between variants and the disease using burden and variance component methods; that is, the weighted-sum statistic (WSS) and the sequence kernel association test (SKAT), respectively. The Student's t-test, Chi-squared test, and Fisher's exact test were used to compare the clinical characteristics between carriers and non-carriers of the RNF213 variants. Results: After filtering, there were 14 RNF213 variants in 18 patients with IA, which were significantly associated with the disease after the gene-based association tests [minor allele frequency (MAF) <0.01, WSS P value 5.08×10-9; SKAT P value 2.96×10-6; SKAT-O P value 3.56×10-8]. Significant difference was not obtained between the carriers and non-carriers of the RNF213 variants in terms of the clinical characteristics. Conclusions: Rare RNF213 variants were associated with sporadic IA in a Chinese population. Our findings suggest that these rare RNF213 variants might have potentially important roles in IA. However, more comprehensive studies need to be conducted to confirm this association and causality.
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Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease caused by intracranial aneurysm (IA) rupture. Lysyl oxidase (LOX) family genes (LOX-like [LOXL] 1-4) have roles in collagen cross-linking in the extracellular matrix (ECM) and may be associated with IA rupture. We aimed to explore the association between LOX polymorphisms and the risk of aSAH. Methods: This case-control study included 2 cohorts: 133 single ruptured and 115 unruptured IA patients, and 65 multiple ruptured and 71 unruptured IA patients. Genotyping of 27 single nucleotide polymorphisms (SNPs) in LOX was performed. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of the SNPs of LOX and the risk of aSAH. Results: LOX rs1800449 and LOXL4 rs3793692 were positively associated with the risk of single IA rupture in the recessive model (OR =5.66, 2.06; 95% CI =1.22-26.24, 1.11-3.82, respectively) and LOX rs10519694 demonstrated a protective effect on single IA rupture (dominant model: OR =0.42, 95% CI =0.21-0.83; recessive model: OR =0.16, 95% CI =0.04-0.65; additive model: OR =0.46, 95% CI =0.28-0.78). LOXL1 rs2165241, LOXL2 rs1063582, and LOXL3 rs17010021 showed risk effects on multiple IAs rupture. LOXL3 rs17010022 showed a protective effect on multiple IAs ruptures (dominant model: OR =0.41, 95% CI =0.21-0.82; additive model: OR =0.51, 95% CI =0.30-0.85). Conclusions: LOX and LOXL4 may be susceptibility genes for single IA rupture, whereas LOXL1-3 may have a role in susceptibility to multiple IAs ruptures in the Chinese population, suggesting that LOX family genes may be associated with aSAH.
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BACKGROUND: Ustekinumab is effective in treating Crohn's disease (CD) and ulcerative colitis (UC). However, the loss of response (LOR) to ustekinumab and the efficacy of dose escalation have not been systematically explored. METHODS: Databases were searched for eligible studies from inception through July 2021. Summary estimates were pooled, and subgroup analyses were performed to explore heterogeneity. RESULTS: We included 14 studies (CD: 13; UC: 1). In CD patients, the annual risk of LOR to ustekinumab and dose escalation among primary responders was 21% (95% confidence interval [CI] 12-31%, 1530 person-years, n = 9) per person-year and 25% (95% CI 12-32%, 657 person-years, n = 5) per person-year respectively. Clinical response was regained in 58% (95% CI 49-67%, 279 patients, n = 8) of secondary non-responders after dose escalation (interval reduction or intravenous reinduction). In UC patients, no studies provided data on LOR, but only one study showed that 35% (100/284) of patients underwent dose escalation (or sham dose adjustment), leading to an annual risk of dose escalation of 18% per person-year. After dose escalation, 58% (14/24) of the patients regained symptomatic remission. CONCLUSIONS: Primary responders with CD experienced LOR to ustekinumab at a risk of 21% per person-year and required dose escalation at a risk of 25% per person-year. Fifty-eight per cent of secondary non-responders with CD may benefit from dose escalation. LOR has not been well characterized in patients with UC.