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1.
Nature ; 599(7883): 57-61, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732870

RESUMO

A central goal of condensed-matter physics is to understand how the diverse electronic and optical properties of crystalline materials emerge from the wavelike motion of electrons through periodically arranged atoms. However, more than 90 years after Bloch derived the functional forms of electronic waves in crystals1 (now known as Bloch wavefunctions), rapid scattering processes have so far prevented their direct experimental reconstruction. In high-order sideband generation2-9, electrons and holes generated in semiconductors by a near-infrared laser are accelerated to a high kinetic energy by a strong terahertz field, and recollide to emit near-infrared sidebands before they are scattered. Here we reconstruct the Bloch wavefunctions of two types of hole in gallium arsenide at wavelengths much longer than the spacing between atoms by experimentally measuring sideband polarizations and introducing an elegant theory that ties those polarizations to quantum interference between different recollision pathways. These Bloch wavefunctions are compactly visualized on the surface of a sphere. High-order sideband generation can, in principle, be observed from any direct-gap semiconductor or insulator. We thus expect that the method introduced here can be used to reconstruct low-energy Bloch wavefunctions in many of these materials, enabling important insights into the origin and engineering of the electronic and optical properties of condensed matter.

2.
Plant Biol (Stuttg) ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748691

RESUMO

Seed ageing has an important effect on germination and productivity. During natural ageing, seed vigour decreases rapidly but, to date, the molecular mechanisms underlying this decrease have not been fully elucidated. Using omics, some of the details regarding seed vigour decline during natural ageing might be elucidated through integrated analysis. Safflower seed germination and physio-biochemical changes during natural ageing (stored for 4, 16 and 28 months) were determined. Proteome and lipidome profiling during natural seed ageing was performed, and the differentially expressed proteins and lipid metabolite species analysed. The surface and internal structures of cotyledons were observed. An integrating analysis of the proteome and lipidome was also carried out. Natural seed ageing significantly decreased safflower seed germination and vigour. 4,184 proteins and 1,193 lipids were quantified, both of which show huge differences among the different naturally aged seeds. The surface of the cotyledons collapsed and cracked, and the oil bodies become looser during natural ageing. The total content of DAG and PA increased, while the content of TAG and PL (PC, PE, PS, PI and PL) significantly decreased during seeds ageing. Two lipase genes (HH-026818-RA and HH-025320) likely participated in this degradation of lipids. We conclude that the enzymes that participate in glycerolipid metabolism and fatty acid degradation probably lead to the degradation of oil bodies (TAG) and membrane lipids (PC, PE, PS, PI, PG) and, ultimately, destroy the structure, causing a decline in seed vigour during natural seed ageing.

3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(11): 969-976, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34823297

RESUMO

Objective: To investigate the safety of definitive surgery for chronic radiation intestinal injury. Methods: A descriptive case series study was performed. Clinical data of 105 patients who were diagnosed as chronic radiation intestinal injury, had complete data and received definitive surgery (the radiation-induced intestinal segment and digestive tract reconstruction) at Department of Gastrointestinal Surgery of Beijing Tsinghua Changgung Hospital from June 2016 to May 2020 were retrospectively analyzed. There were 30 males (28.6%) and 75 females (71.4%) with the median age of 58 years (P25, P75: 52, 64 years). Patients who had tumor recurrence or refused surgical treatment were excluded. According to the preoperative evaluation and clinical manifestations, to select the resection range. Outcome parameters: (1) preoperative evaluation (nutrition risk assessment and status of obstruction or fistula); (2) clinical manifestations and treatment strategies; (3) details of surgical parameters; (4) postoperative complications, and Clavien-Dindo classification III to V was defined as main moderate-severe complication. Results: (1) Preoperative evaluation: Eighty-eight patients (83.8%) developed symptoms of chronic radiation intestinal injury more than 1 year after the end of radiotherapy. Ninety-eight patients (93.3%) had preoperative NRS-2002 score ≥3, 74 patients (70.5%) received preoperative parenteral nutritional support, and the median time of nutritional support was 10.5 (7.0, 16.0) days. Sixteen patients (15.2%) received small intestinal decompression tube implantation due to severe obstruction. (2) Clinical manifestations and treatment strategies: Among 105 patients, 87 (82.9%) presented with obstruction and received definitive resection of the radiation-induced intestinal segment plus one-stage digestive tract reconstruction; 18 (17.1%) presented with intestinal fistula and all of them received definitive resection of the radiation-induced intestinal segment, intestinal fistula plus one-stage digestive tract reconstruction. Among above 18 patients with fistula, 3 patients with ileorectal stump fistula received pedicled pelvic closure of greater omentum at the same time; 4 patients had ileal vesical fistula, of whom 2 patients received cystectomy and bladder repair due to preoperative nephrostomy decompression, and the other 2 patients received transection of the small intestine proximal and distal to the fistula and anastomosis of the intestinal loop without fistula resection, intestinal fistula or bladder fistula repair. (3) The details of surgical parameters: Median operative time and intraoperative blood loss was 230 (180, 300) minutes and 50 (20, 50) ml respectively. Ninety-two patients (92/105, 87.6%) underwent ileocolonic anastomosis, and anastomosis on the hepatic flexure or splenic flexure colon were performed in 88 (83.8%) and 4 (3.8%) patients respectively. Ileoileal anastomosis was performed in 13 patients (12.4%). The anastomotic site of 92 patients (87.6%) was strictly located in the contralateral quadrant of the radiation field, and the anastomotic site of 13 patients (12.4%) was far from the radiation field. Nine patients (8.6%) had more than one anastomosis, 5 patients (4.8%) had less than 180 cm of residual small intestine, 7 patients (6.7%) underwent retrograde intestinal permutation, 4 patients (3.8%) underwent abdominal wall reconstruction surgery due to abdominal wall defects, and 87 patients (82.9%) had severe abdominal pelvic adhesions (grade 3-4 adhesions). Intraoperative complications occurred in 3 patients (2.9%), which were found in time and handled properly. The median postoperative hospital stay was 13.0 (12.0, 24.5) days, and all the patients had resumed oral feeding upon discharge. (4) Postoperative complications: Fourteen patients (13.3%) had 18 major complications (grade III to V). The incidence of postoperative anastomotic leakage was 5.7% (6/105), and the incidence of anastomotic leakage for ileocolon anastomosis and ileoileal anastomosis was 2.2% (2/92) and 4/13, respectively (χ(2)=17.29, P<0.001). The incidence of postoperative anastomotic leakage of intestinal fistula and intestinal obstruction was 3/18 and 3.4% (3/87), respectively (χ(2)=4.84, P=0.028). The mortality at 30 days after operation was 1.0% (1/105), after abdominal infection and septic shock caused by postoperative anastomotic leakage resulting in multiple organ failure. Conclusion: For chronic radiation intestinal injury patients with obstruction or fistula, definitive surgical treatment is feasible and safe with acceptable major complications.


Assuntos
Fístula Anastomótica , Lesões por Radiação , Anastomose Cirúrgica , Feminino , Humanos , Intestinos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos
4.
Phys Med Biol ; 66(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34757945

RESUMO

Purpose.We have previously reported an artificial intelligence (AI) agent that automatically generates intensity-modulated radiation therapy (IMRT) plans via fluence map prediction, by-passing inverse planning. This AI agent achieved clinically comparable quality for prostate cases, but its performance on head-and-neck patients leaves room for improvement. This study aims to collect insights of the deep-learning-based (DL-based) fluence map prediction model by systematically analyzing its prediction errors.Methods.From the modeling perspective, the DL model's output is the fluence maps of IMRT plans. However, from the clinical planning perspective, the plan quality evaluation should be based on the clinical dosimetric criteria such as dose-volume histograms. To account for the complex and non-intuitive relationships between fluence map prediction errors and the corresponding dose distribution changes, we propose a novel error analysis approach that systematically examines plan dosimetric changes that are induced by varying amounts of fluence prediction errors. We investigated four decomposition modes of model prediction errors. The two spatial domain decompositions are based on fluence intensity and fluence gradient. The two frequency domain decompositions are based on Fourier-space banded frequency rings and Fourier-space truncated low-frequency disks. The decomposed error was analyzed for its impact on the resulting plans' dosimetric metrics. The analysis was conducted on 15 test cases spared from the 200 training and 16 validation cases used to train the model.Results.Most planning target volume metrics were significantly correlated with most error decompositions. The Fourier space disk radii had the largest Spearman's coefficients. The low-frequency region within a disk of ∼20% Fourier space contained most of errors that impact overall plan quality.Conclusions.This study demonstrates the feasibility of using fluence map prediction error analysis to understand the AI agent's performance. Such insights will help fine-tune the DL models in architecture design and loss function selection.

5.
Phys Med Biol ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34808605

RESUMO

OBJECTIVE: To design a deep transfer learning framework for modeling fluence map predictions for stereotactic body radiation therapy (SBRT) of adrenal cancer and similar sites that usually have a small number of cases. APPROACH: We developed a transfer learning framework for adrenal SBRT planning that leverages knowledge in a pancreas SBRT planning model. Treatment plans from the two sites had different dose prescriptions and beam settings but both prioritized gastrointestinal sparing. A base framework was first trained with 100 pancreas cases. This framework consists of two convolutional neural networks (CNN), which predict individual beam doses (BD-CNN) and fluence maps (FM-CNN) sequentially for 9-beam intensity-modulated radiation therapy (IMRT) plans. Forty-five adrenal plans were split into training/validation/test sets with the ratio of 20/10/15. The base BD-CNN was re-trained with transfer learning using 5/10/15/20 adrenal training cases to produce multiple candidate adrenal BD-CNN models. The base FM-CNN was directly used for adrenal cases. The deep learning (DL) plans were evaluated by several clinically relevant dosimetric endpoints, producing a percentage score relative to the clinical plans. MAIN RESULTS: Transfer learning significantly reduced the number of training cases and training time needed to train such a DL framework. The adrenal transfer learning model trained with 5/10/15/20 cases achieved validation plan scores of 85.4/91.2/90.7/89.4, suggesting that model performance saturated with 10 training cases. Meanwhile, a model using all 20 adrenal training cases without transfer learning only scored 80.5. For the final test set, the 5/10/15/20-case models achieved scores of 73.5/75.3/78.9/83.3. SIGNIFICANCE: It is feasible to use deep transfer learning to train an IMRT fluence prediction framework. This technique could adapt to different dose prescriptions and beam configurations. This framework potentially enables DL modeling for clinical sites that have a limited dataset, either due to few cases or due to rapid technology evolution.

6.
Plant Dis ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34735279

RESUMO

Botryosphaeria dothidea is a latent pathogen with global importance to woody plant health, which causes serious tree trunk cankers on Chinese hickory. To date, only one Illumina short-read-based genome assembly of strain CK16 is available for host Chinese hickory. To address this problem, we reported a near telomere-to-telomere genome assembly of strain BDLA16-7 (46.05 Mb, N50 3.87 Mb) using Oxford Nanopore Sequencing Technology. Our genome assembly was consisted of 15 contigs, of which, 3 were assembled into chromosomal level and the maximum contig length was 6.19 Mb. The assembly contained 7.96% repeats and 12,815 protein-coding genes (10,274 genes were functional annotated). We also identified 3,642 pathogen-host interaction (PHI) genes, 250 carbohydrateactive enzymes (CAZymes), 252 cytochrome P450 enzymes (CYPs), 752 putative secreted proteins and 63 secondary metabolite biosynthesis gene clusters (SMBGCs). The BUSCO completeness of genome assembly and predicted genes was 99.34% and 97.50%, respectively, at fungal level (n=758). The almost chromosomal-level and well-annotated genome assembly will provide a valuable genetic resource for understanding of the infection mechanisms of B. dothidea in future.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34736841

RESUMO

AIMS: The EMPOWER-Lung 1 trial showed that cemiplimab significantly prolongs the duration of progression-free survival and overall survival in advanced non-small cell lung cancer (NSCLC) patients with at least 50% programmed cell death receptor ligand-1 (PD-L1) positivity, yet the financial burden may limit its use. The aim of the present study was to evaluate the cost-effectiveness of cemiplimab versus chemotherapy in a US setting. MATERIALS AND METHODS: A Markov model, with three mutually exclusive health states, was used to compare the expected health outcomes and cost of cemiplimab with chemotherapy. Survival data and transition probabilities were collected from the EMPOWER-Lung 1 trial. Utility values and costs are publicly available from open sources. One-way and probabilistic sensitivity analyses were conducted in both the whole population and subgroups to test the robustness of the parameters and structure. RESULTS: Treatment of NSCLC with cemiplimab yielded an extra 1.07 quality-adjusted life years (QALYs) at an additional cost of $98 211 compared with chemotherapy, associated with an incremental cost-effectiveness ratio of $91 891/QALY and an incremental net health benefit of 0.087 QALYs at a willingness to pay threshold of $100 000/QALY. The probabilistic sensitivity analysis indicated that cemiplimab provided an 83.2% probability of being cost-effective. One-way sensitivity analysis suggested that the price of cemiplimab was the chief driver in this model. A subgroup analysis showed that cemiplimab was the preferred incremental net health benefit in more than half of the subgroups, including patients with squamous type disease and metastases. CONCLUSIONS: Cemiplimab is a cost-effective option in the first-line treatment of NSCLC in patients who are at least 50% PD-L1 positive from an American perspective.

8.
Biomed Phys Eng Express ; 8(1)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34731837

RESUMO

Deep learning algorithms for radiation therapy treatment planning automation require large patient datasets and complex architectures that often take hundreds of hours to train. Some of these algorithms require constant dose updating (such as with reinforcement learning) and may take days. When these algorithms rely on commerical treatment planning systems to perform dose calculations, the data pipeline becomes the bottleneck of the entire algorithm's efficiency. Further, uniformly accurate distributions are not always needed for the training and approximations can be introduced to speed up the process without affecting the outcome. These approximations not only speed up the calculation process, but allow for custom algorithms to be written specifically for the purposes of use in AI/ML applications where the dose and fluence must be calculated a multitude of times for a multitude of different situations. Here we present and investigate the effect of introducing matrix sparsity through kernel truncation on the dose calculation for the purposes of fluence optimzation within these AI/ML algorithms. The basis for this algorithm relies on voxel discrimination in which numerous voxels are pruned from the computationally expensive part of the calculation. This results in a significant reduction in computation time and storage. Comparing our dose calculation against calculations in both a water phantom and patient anatomy in Eclipse without heterogenity corrections produced gamma index passing rates around 99% for individual and composite beams with uniform fluence and around 98% for beams with a modulated fluence. The resulting sparsity introduces a reduction in computational time and space proportional to the square of the sparsity tolerance with a potential decrease in cost greater than 10 times that of a dense calculation allowing not only for faster caluclations but for calculations that a dense algorithm could not perform on the same system.

9.
Phys Rev Lett ; 127(15): 152702, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34678013

RESUMO

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.

10.
Int J Radiat Oncol Biol Phys ; 111(3S): e91, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701997

RESUMO

PURPOSE/OBJECTIVE(S): Artificial intelligence (AI) driven tools have been maturing in automating the radiation treatment planning process. To prepare for clinical deployment of these tools, it is essential to understand their robustness in clinical scenarios. This study works to fill the existing gap between research initiated and clinically ready AI tools by investigating a clinical assessment approach based on phantom design and planning complexity simulation. The hypothesis is that AI tool assessment program provides more clinically relevant and comprehensive evaluations beyond typical model validation studies. MATERIALS/METHODS: A cylindrical digital phantom was designed in the treatment planning system with an axial diameter of 30 cm and length of 18 cm. The phantom contains key structures involved in pancreas SBRT including the PTV25Gy, PTV33Gy, C-loop, stomach, bowel and liver with their base shape and volume representing the average of 100 clinical SBRT patients. Phantom cases were synthesized to mimic real-life anatomical variations and overlaps through displacement, expansion, and rotation of PTVs and OARs. This study involved a total of 32 simulated cases to test a broad range of planning scenarios. A previously developed deep learning based automatic planning tool was assessed in this study. This AI tool is composed of two deep neural networks (NNs) which predict beam dose and fluence maps sequentially. The goal of treatment planning was to deliver 25 Gy to PTV25 and 33 Gy to PTV33 in 5 fractions via simultaneous integral boost (SIB) while limiting luminal OAR max dose to below 29 Gy. The AI-plan's quality was analyzed against the clinical evaluation criteria, which include PTV V100%, luminal OAR max dose using Dmax and D0.03cc. The passing rate of key clinical criteria were collected to quantify overall robustness. RESULTS: For all scenarios, the mean PTV25 V25Gy of the AI plans was 96.7% while mean PTV33 V33 Gy was 82.2%. Large variation (16.3%) in PTV33 V33 Gy was observed due to anatomical variations, i.e., proximity of luminal structures to PTV33. Mean max dose was 28.55, 27.68, and 24.63 Gy for the C-loop, bowel and stomach respectively. Using D0.03cc as a surrogate for max dose, the value was 28.03, 27.12, and 23.84 Gy for the same respective structures. A max dose constraint of 29 Gy was achieved for 81.3% cases for the C-loop and stomach, and 78.1% for the bowel. Using D0.03cc as a surrogate for max dose, the passing rate was 90.6% for the C-loop and 81.3% for both the bowel and stomach. CONCLUSION: The results showed promising robustness of AI planning tool for pancreas SBRT, providing important evidence of its readiness for clinical implementation. The established approach could guide the robustness testing and other clinical assessments of AI based treatment planning tools in general, which is an important component for safe clinical implementation.

11.
Int J Radiat Oncol Biol Phys ; 111(3S): e94, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34702003

RESUMO

PURPOSE/OBJECTIVE(S): With many deep learning (DL) models being developed for clinical applications, it is important to understand their behavior and clinical consequence. This study aims to collect insights of the relationship between fluence map prediction error and its dosimetric impacts in a DL-based AI agent for H&N IMRT planning. MATERIALS/METHODS: An AI agent has been implemented to generate IMRT plans via fluence map prediction, bypassing inverse optimization. While the prostate IMRT plans generated by the agent were comparable to clinical plans in quality, the application into H&N patients exhibited large variations in the plan quality due to higher anatomy complexity. As the DL model's output is fluence maps of an IMRT plan, standard error analyses were focused on the differences between the predicted and ground truth fluence maps, i.e., prediction error. However, the ultimate plan evaluation is based on clinical criteria such as DVHs and dose distributions. Therefore, the AI agent's performance in clinics is subjected to complex and non-intuitive relationships between fluence map prediction error and corresponding dose distribution changes, and warrants thorough investigation. In this study, a series of tests were designed to collect insights of the impact of DL model performance on plan's dosimetric quality. The fluence map prediction error was analyzed for its dosimetric effects using five error decomposition modes:1) ground truth fluence intensity bands in 5 threshold levels, 2) predicted fluence intensity bands in 5 threshold levels, 3) ground truth fluence gradient bands (high and low), 4) Fourier space bands (frequency bands) in 8 threshold levels, and 5) Fourier space circles (below certain frequency) in 8 threshold levels. The DL model was trained with 216 cases and tested with 15 additional cases. PTV and OAR dosimetric metrics were analyzed by Spearman's rank tests (P = 0.05). RESULTS: Most PTV-related metrics were significantly correlated with the error components. Among the different decomposition modes, the Fourier space circle radii have large Spearman's coefficients with PTV metrics, suggesting that they were best able to extract error components that reveal plan quality impacts. The low-frequency error within a Fourier space circle of radius = 32 pixels (20% of Fourier space) had the most significant impact on overall plan quality and PTV heterogeneity. CONCLUSION: The fluence map prediction error analysis is critical to evaluate the AI agent performance. Such insight will help with fine-tuning the DL models in architecture design and loss function selection.

12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(5): 891-895, 2021 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-34650290

RESUMO

OBJECTIVE: To bring forward an arthroscopic classification of the popliteal hiatus of the lateral meniscus (PHLM) tears and to assess the effects of arthroscopic all-inside repair with suture hook in management of such injuries. METHODS: This study involved 146 patients who underwent arthroscopic operation because of PHLM tears from April 2014 to October 2017, eliminating the patients who had discoid lateral meniscus. There were 81 males and 65 females, with 54 left knees and 92 right knees. The average ages were (34.7±3.7) years. Among the selected participants, there were 107 patients with anterior cruciate ligament (ACL) injuries, 39 patients with medial collateral ligament (MCL) injuries, and 48 patients with medial meniscus tears. The average preoperative Lysholm and International Knee Documentation Committee (IKDC) scores were 57.7±9.2 and 54.1±8.9, respectively. The arthroscopic classification was based on the extent and degree of PHLM tears and using the arthroscopic all-inside repair with suture hook for such injuries. For the patients associated with ACL injuries, the ipsilateral autograft hamstring tendons use as the reconstruction graft for single bundle ACL reconstructions. The suture anchors were used for treatment of MCL Ⅲ injuries, and the arthroscopic all-inside repair for medial meniscus tears. RESULTS: A total of 146 PHLM tears in 146 patients were divided into type Ⅰ (tears not involved in popliteus tendon incisura; n=86, 58.9%), type Ⅱ (tears involved in popliteomeniscal fascicles; n=36, 24.7%), and type Ⅲ (tears involved in popliteus tendon incisura; n=24, 16.4%). For type Ⅰ, there were three subtypes, including type Ⅰa: longitudinal tear (n=53, 61.6%), type Ⅰb: horizontal tear (n=27, 31.4%), and type Ⅰc: radial tear (n=6, 7.0%). For type Ⅱ, there were also three subtypes, including type Ⅱa: anterosuperior popliteomeniscal fascicle tear (n=5, 13.9%), type Ⅱb: posterosuperior popliteomeniscal fascicle tear (n=20, 55.6%), and type Ⅱc: both tears (n=11, 30.6%). For type Ⅲ, there were two subtypes, including type Ⅲa: horizontal tear (n=9, 37.5%), type Ⅲb: radial tear (n=15, 62.5%). In the follow-up for an average of 15.3±2.6 months, all the patients had done well with significantly improved Lysholm (84.6±14.3) and IKDC (83.2±12.8) scores at the end of the last follow-up relative to preoperative scores (P > 0.01). CONCLUSION: We propose that it is possible to classify lateral meniscus tears at the popliteal hiatus region for three types, which can summarize the injury characteristics of this area. The arthroscopic all-inside repair with suture hook for the PHLM tears can avoid stitching to popliteal tendon or narrowing popliteal hiatus and have satisfactory clinical results.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Lesões do Menisco Tibial , Adulto , Lesões do Ligamento Cruzado Anterior/cirurgia , Artroscopia , Feminino , Humanos , Masculino , Meniscos Tibiais/cirurgia , Lesões do Menisco Tibial/cirurgia
13.
Lett Appl Microbiol ; 73(6): 770-778, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34597432

RESUMO

An engineered Pichia pastoris GS115 with a FIP-glu gene was mutated using ultraviolet (UV) radiation, and a high-throughput screening method was established for screening of high-yield strains. Meanwhile, a preliminary study was conducted to determine the bioactivity of the rFIP-glu. Based on OD600 value and the mortality of engineered P. pastoris GS115, the best UV irradiation time was determined. Bradford method and SDS-PAGE method were employed to analyze the concentration and yield of rFIP-glu. Melanoma B16 cells were employed to evaluate the biological activities of rFIP-glu in vitro. Results showed that the protein yield of the best mutant #4-336 screened from 3680 mutant strains increased from 242 to 469 µg ml-1 . In vitro assays of biological activity indicated that rFIP-glu had significant toxicity and possessed the ability to affect melanin content and enhance tyrosinase activity in B16 cells. In conclusion, an effective high-throughput screening approach was established for screening mutant strains. The screened mutant possesses a good ability to enhance the production of rFIP-glu, and recombinant proteins display a better biological activity on melanoma B16 cells. The engineered P. pastoris mutant seems promising as a potential source for industrial production of rFIP-glu and should be a candidate industrial strain for further study.


Assuntos
Pichia , Saccharomycetales , Proteínas Fúngicas/genética , Pichia/genética , Proteínas Recombinantes/genética
14.
Osteoporos Int ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519833

RESUMO

Exogenous melatonin inhibited the senescence of preosteoblast cells in type 1 diabetic (T1D) mice and those cultured in high glucose (HG) by multiple regulations. Exogenous melatonin had a protective effect on diabetic osteoporosis, which may depend on the inhibition of senescence. INTRODUCTION: Senescence is thought to play an important role in the pathophysiological mechanisms underlying diabetic bone loss. Increasing evidence has shown that melatonin exerts anti-senescence effects. In this study, we investigated whether melatonin can inhibit senescence and prevent diabetic bone loss. METHODS: C57BL/6 mice received a single intraperitoneal injection of 160 mg/kg streptozotocin, followed by the oral administration of melatonin or vehicle for 2 months. Then, tissues were harvested and subsequently examined. MC3T3-E1 cells were cultured under HG conditions for 7 days and then treated with melatonin or not for 24 h. Sirt1-specific siRNAs and MT1- or MT2-specific shRNA plasmids were transfected into MC3T3-E1 cells for mechanistic study. RESULTS: The total protein extracted from mouse femurs revealed that melatonin prevented senescence in T1D mice. The micro-CT results indicated that melatonin prevented bone loss in T1D mice. Cellular experiments indicated that melatonin administration prevented HG-induced senescence, whereas knockdown of the melatonin receptors MT1 or MT2 abolished these effects. Sirt1 expression was upregulated by melatonin administration but significantly reduced after MT1 or MT2 was knocked down. Knockdown of Sirt1 blocked the anti-senescence effects of melatonin. Additionally, melatonin promoted the expression of CDK2, CDK4, and CyclinD1, while knockdown of MT1 or MT2 abolished these effects. Furthermore, melatonin increased the expression of the polycomb repressive complex (PRC), but knockdown of MT1 or MT2 abolished these effects. Furthermore, melatonin increased the protein levels of Sirt1, PRC1/2 complex-, and cell cycle-related proteins. CONCLUSION: This work shows that melatonin protects against T1D-induced bone loss, probably by inhibiting senescence. Targeting senescence in the investigation of diabetic osteoporosis may lead to novel discoveries.

15.
J Postgrad Med ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34528516

RESUMO

Drug-induced hemolytic anemia (DIHA) is a rare complication of drug therapy and usually underdiagnosed. Cefoperazone/sulbactam is a compound prepared from the third generation of cephalosporin and ß-lactamase inhibitor. There are limited data of DIHA induced from cefoperazone/sulbactam. A 93-year-old female patient, who had an operation on the biliary tract 3 months ago, was admitted to our hospital with an abdominal infection. After cefoperazone/sulbactam was given as anti-infection treatment, the patient developed hemolytic anemia on the third day. Cefoperazone/sulbactam was discontinued and replaced with meropenem. Subsequently the level of red blood cells, hemoglobin, and hematocrit returned to normal. Clinicians should pay attention to monitoring the possible adverse reactions during the use of cefoperazone/sulbactam and should be aware of the occurrence of DIHA, so as to give timely treatment.

16.
IEEE Trans Cybern ; PP2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546939

RESUMO

Pattern recognition is significantly challenging in real-world scenarios by the variability of visual statistics. Therefore, most existing algorithms relying on the independent identically distributed assumption of training and test data suffer from the poor generalization capability of inference on unseen testing datasets. Although numerous studies, including domain discriminator or domain-invariant feature learning, are proposed to alleviate this problem, the data-driven property and lack of interpretation of their principle throw researchers and developers off. Consequently, this dilemma incurs us to rethink the essence of networks' generalization. An observation that visual patterns cannot be discriminative after style transfer inspires us to take careful consideration of the importance of style features and content features. Does the style information related to the domain bias? How to effectively disentangle content and style features across domains? In this article, we first investigate the effect of feature normalization on domain adaptation. Based on it, we propose a novel normalization module to adaptively leverage the propagated information through each channel and batch of features called disentangling batch instance normalization (D-BIN). In this module, we explicitly explore domain-specific and domain-invariant feature disentanglement. We maneuver contrastive learning to encourage images with the same semantics from different domains to have similar content representations while having dissimilar style representations. Furthermore, we construct both self-form and dual-form regularizers for preserving the mutual information (MI) between feature representations of the normalization layer in order to compensate for the loss of discriminative information and effectively match the distributions across domains. D-BIN and the constrained term can be simply plugged into state-of-the-art (SOTA) networks to improve their performance. In the end, experiments, including domain adaptation and generalization, conducted on different datasets have proven their effectiveness.

17.
Zhonghua Fu Chan Ke Za Zhi ; 56(8): 537-544, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34420285

RESUMO

Objective: To investigate the safety, efficacy and application indication of intra-operative cell salvage (IOCS) in cesarean section. Methods: A total of 1 265 pregnant women who received IOCS blood transfusion during cesarean section in 11 tertiary A hospitals from August 2016 to January 2019 were collected and divided into <1 500 ml group (796 cases) and ≥1 500 ml group (469 cases) according to the amount of blood loss during cesarean section. The general clinical data, ultrasonic imaging data, perinatal and puerperium indicators were analyzed retrospectively. The risk factors of intraoperative blood loss ≥1 500 mL using IOCS transfusion were analyzed by logistic multivariate regression. Results: (1) A total of 848 001 ml of blood was recovered and a total of 418 649 ml of blood was transfused in 1 265 pregnant women who received IOCS transfusions, which was equivalent to 23 258 U red blood cell suspension, greatly saving medical resources. The intraoperative blood loss in <1 500 ml group and ≥1 500 ml group was 800 ml (300-1 453 ml) and 2 335 ml (1 500-20 000 ml), respectively. No amniotic fluid embolism, severe adverse reactions, shock and death occurred in the two groups. (3) Multivariate regression analysis showed that age ≥35 years (OR=1.5, 95%CI: 1.1-1.9), prenatal hemoglobin level <110 g/L (OR=1.7, 95%CI: 1.3-2.2), history of uterine surgery (OR=1.8, 95%CI: 1.3-2.6), placenta previa (OR=1.9, 95%CI: 1.1-3.1), placenta accreta (OR=2.6, 95%CI: 1.8-3.9), blood pool in the placenta (OR=1.6, 95%CI: 1.1-2.3), abnormal posterior placenta muscle wall (OR=1.8, 95%CI: 1.2-2.6), placenta projecting to the anterior uterine wall (OR=3.0, 95%CI: 1.3-7.0) were risk factors for blood loss ≥1 500 ml in obstetric transfusion using IOCS technique, with statistical significance (all P<0.05). Conclusion: IOCS is safe and effective in cesarean section, which could save the medical resources and reduces medical expenses, however, it is necessary to strictly master the application indication.


Assuntos
Placenta Acreta , Placenta Prévia , Adulto , Perda Sanguínea Cirúrgica , Cesárea , Feminino , Humanos , Gravidez , Estudos Retrospectivos
18.
Zhonghua Yi Xue Za Zhi ; 101(28): 2223-2227, 2021 Jul 27.
Artigo em Chinês | MEDLINE | ID: mdl-34333935

RESUMO

Objective: To explore the association of systemic immune-inflammation index (SII) with protein-energy wasting (PEW) and prognosis in maintenance hemodialysis (MHD) patients. Methods: A multicenter cohort study was conducted in 11 hemodialysis centers of Guizhou province from July to September 2019. The patients were divided into the PEW group and non-PEW group. After 12 months of follow-up, death was the endpoint event. Multivariate logistic regression analysis was used to assess the independent risk factors of PEW in MHD patients. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of SII for PEW, and the optimal cut-off value of SII was calculated. The Kaplan-Meier method was used to draw the survival curve, and log-rank test was employed to compare the difference of survival rate between the two groups. Results: A total of 859 patients were included [540 males and 319 females, aged (54±15) years], and there were 220 cases (25.6%) and 639 cases (74.4%) in PEW and non-PEW groups, respectively. SII was higher in the PEW group than that of the non-PEW group [600 (440, 915) vs 475 (353, 633), P<0.01]. Multivariate logistic regression analysis showed that SII was an independent predictor for PEW (OR=1.001, 95%CI: 1.000-1.002, P=0.02). ROC curve analysis showed that the area under the curve for SII to predict PEW in MHD patients was 0.725 (95%CI: 0.683-0.766), with the sensitivity and specificity of 69% and 70%, respectively. All patients were followed up for 12 months, and 45 died (with a mortality rate of 5.24%). Patients were divided into SII>520 group and SII≤520 group according to the optimal cut-off value, and subsequent Kaplan-Meier survival analysis showed that the 1-year cumulative survival rate of the SII>520 group (92.3%) was lower than that of SII≤520 group (97.1%) (χ2log-rank=9.707, P=0.002). Further subgroup analysis revealed that, in PEW patients with MHD, the 1-year cumulative survival rate of the SII>520 group (88.5%) was also lower than that of SII≤520 group (92.3%) (χ2log-rank=7.226, P=0.007). Conclusion: SII is an independent risk factor for PEW in MHD patients, and the higher the SII level, the lower the long-term survival rate and the prognosis.


Assuntos
Inflamação , Diálise Renal , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
19.
Fa Yi Xue Za Zhi ; 37(3): 351-357, 2021 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34379904

RESUMO

Abstract: Objective To study the correlation between the abdominal wall subcutaneous fat thickness and heart weight, so as to provide reference for prediction methods of normal range of heart weight that is suitable for autopsy in China. Methods The forensic pathology autopsy cases accepted by Center for Medicolegal Expertise of Sun Yat-sen University from 1998 to 2017 were collected. Then the exclusion criteria were determined, and according to them the total case group was selected, and the 6 disease groups and the normal group were further selected from the total case group. The rank sum test was used to compare the heart weight of the normal group and the disease groups to determine the influence of diseases on heart weight. Then the Spearman rank correlation analysis of abdominal wall subcutaneous fat thickness and heart weight in different genders and different ages in the total case group and the normal group was conducted to get the correlation coefficient (rs). Results In the total case group, correlation between abdominal wall subcutaneous fat thickness and heart weight was shown in males of all ages (P<0.05); while in females, the correlation had no statistical significance (P>0.05) in 15-<20 age and 50-<60 age, but was statistically significant (P<0.05) in other age groups. For the males in the normal group, rs was respectively 0.411, 0.541 and 0.683 in the 15-<40 age, the 40-<60 age, and the ≥60 age. For the females, rs was respectively 0.249 and 0.317 in the 15-<40 age and the 40-<60 age. The correlation in the ≥60 age had no statistical significance(P>0.05). Conclusion In the general population and the normal population, abdominal wall subcutaneous fat thickness is correlated with the heart weight of males. It is of significance to include the abdominal wall subcutaneous fat thickness in the prediction of normal range of heart weight for males in China.


Assuntos
Parede Abdominal , Parede Abdominal/diagnóstico por imagem , China , Feminino , Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Gordura Subcutânea/diagnóstico por imagem
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