Lung cancer (LC) is the malignant tumor with the highest incidence in the world, and treatment methods include surgery, radiotherapy, chemotherapy, and immunotherapy. Cancer pain is a common symptom in patients with LC, and the clinical treatment is to relieve it with analgesics. Acupuncture can relieve cancer pain. This study aims to systematically study the efficacy and safety of acupuncture combined with analgesics on cancer pain in patients with LC.From the beginning to April 2021, search Medline, Embase, Cochrane Central Controlled Trials Register , China National Knowledge Infrastructure (CNKI), Wanfang Database, China Biomedical Literature Database (CBM), and Chinese Science Journal Database (VIP database). Search the international clinical trial registration platform and the Chinese clinical trial registration platform to find ongoing or unpublished trials. The main outcome indicator is the total effective rate of analgesia, and the secondary outcome indicator is pain intensity score and adverse reactions. The RevMan 5.4 software will be used for statistical analysis.This study will provide the latest evidence for acupuncture combined with analgesics to relieve LC pain.The conclusion of this study is to evaluate the effectiveness and safety of acupuncture combined with analgesics in alleviating LC pain.INPLASY202150051 Smoking is almost one of the important factors in the development of LC. The current main treatments for LC include surgery, chemotherapy, radiotherapy, and targeted therapy, etc. Patients with LC reported a series of physical and psychological social symptoms, including coughing, dyspnea, pain, and anxiety. Pain is one of the most serious symptoms of LC patients and seriously affect the patient's quality of life. The cause of LC pain is related to the location of the tumor, the spread and metastasis of the tumor, and the treatment plan.,8 Regarding LC pain, the current main treatment is the use of analgesics, but studies have shown that opioids can cause hypogonadism, inhibit the hypothalamic-pituitary-adrenal axis, and have an impact on bone health. Patients with significant pain are more likely to use alternative therapies such as massage, acupuncture, herbal medicine, and hyperthermia.Primary bronchial lung cancer, also known as lung cancer (LC), ranks second in absolute incidence globally and in developing countries, and is the most common cause of cancer death in the world. A large number of studies have shown that acupuncture can be effective for patients with pain symptoms in cancer patients. The main mechanism of action is to activate the pain modulation system in the body, regulate the human nerve-endocrine-immune system, activate the production, and release of endogenous opioids, and at the same time promote the reduction of substance P and the increase of β-EP content, to achieve the purpose of alleviating cancer pain. In addition, related studies have shown that acupuncture can reduce postoperative opioid consumption and improve postoperative analgesia.As a traditional treatment method, acupuncture has been used clinically, and it may be a better choice for the treatment of LC pain.In recent years, some research data have shown that acupuncture can relieve cancer pain. Although some existing studies have shown that acupuncture combined with analgesics can improve LC pain, there is a lack of relevant comprehensive evaluation. Therefore, we decided to conduct this study to further evaluate the efficacy and safety of acupuncture combined with analgesics in patients with LC pain and provide clinical evidence.2The aim of this study was to evaluate the efficacy and safety of acupuncture combined with analgesics on LC pain, and provide the latest evidence of evidence-based medicine for the clinical treatment of LC pain.33.1https://inplasy.com/inplasy-2021-5-0051/). This protocol will be reported in accordance with the Preferred Reporting Project (PRISMA-P) Statement Guidelines for Systematic Reviews and Meta-Analysis Agreements.The review scheme of this study has been registered on the INPLASY website  of acupuncture combined with analgesics in the treatment of LC pain, whether blinded or unblinded.3.2.2All the patients included in the study were diagnosed LC pain, regardless of age, sex, race, and course of disease.3.2.3The treatment plan is acupuncture combined with analgesics. Acupuncture treatment includes all types, such as electric acupuncture, fire acupuncture, warm acupuncture, body acupuncture, and so on.3.2.4Conventional analgesic treatment.3.2.5The main outcome measure was the total effective rate of analgesia . The secondary outcome indicators were pain intensity score and adverse reactions.3.31.RCTs comparing 2 different types of needle knife;2.Non-randomized controlled trials;3.Duplicated data;4.Invalid outcome indexes.3.4The English databases include PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases include China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database (VIP), China Biomedical Literature (CBM). From the establishment of the database to April, 2021, the key words include “acupuncture,” “body acupuncture,” “electro-acupuncture,” “warm acupuncture,” “auricular acupuncture,” “fire needling,” “analgesics,” “lung cancer,” “pain.” In addition, we will also retrieve ongoing or unpublished trials from the International Clinical Trial Registration Platform and Chinese Clinical Trial Registry Platform. PubMed's search strategy is shown in Table 3.53.5.1The literature search results were independently completed by 2 examiners according to the inclusion criteria. Import all the documents searched in the database into EndNote X9 to exclude duplicate documents. Exclude obviously unqualified articles by reading the title and abstract, then read the full text of the remaining articles, and discuss the final included documents in groups. When there is a difference in the results of the literature screening, it will be discussed and resolved with the third examiner. The selection process will be shown in the PRISMA flow chart Fig. .3.5.2The 2 researchers used predesigned tables to collect data, collect the following information: study data , subject details , research methods , intervention measures in the treatment group and the control group, acupuncture therapy, result measurement . Any differences in the data collection process will be resolved through discussion by a third researcher. If the above data in the article is incomplete, we will contact the author to supplement it.3.6 It includes the following 7 domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias. Each domain includes a judgment of low, high, and unclear risk of bias according to information provided by authors. Disagreements between reviewers will be resolved through discussion with a third reviewer.Two reviewers will use Cochrane collaborative tools to evaluate the quality of the literature.3.73.7.1For continuous data, will be used mean difference (MD) as the effect indicator with 95% confidence interval, and dichotomous data will be calculated as risk ratio (RR) or odds ratio (OR) as the effect index with 95% confidence interval. If the studies are with no statistical homogeneity, the fixed-effect model can be used for analysis; if the studies are with significant statistical heterogeneity, random-effects model analysis will be used. The Review Manager (RevMan) V.5.3 software will be used for statistical analysis.3.7.2χ2 test was used to estimates the degree of heterogeneity. When I2 < 40%, it indicates that no significant statistical heterogeneity. When 40% < I2 < 75%, it indicates that there is statistics heterogeneity, and the source of heterogeneity needs to be further analyzed. When I2 > 75%, it indicates that there is statistics heterogeneity between the studies.3.7.3Subgroup analysis will be performed if there have heterogeneity between the study results, following items will be considered: type of acupuncture, cancer stage, sex, and age.3.7.4We will eliminate the “high-risk” low-quality articles for sensitivity analysis to judge the robustness of the results.3.7.5Two researchers used the Recommendation, Evaluation, Development, and Evaluation system to independently evaluate the quality of evidence for each result, which system divides the level of evidence into 4 levels: high, medium, low, and very low.3.7.6When >10 trials were included in this study, the funnel chart was used to judge the report bias. I3.8The study does not involve the personal information of participants, so no ethical approval is required, and the research will be published in a peer-reviewed journal or related journal meeting.4 this disease has almost become the most widespread and the highest mortality disease in the world. Tumor invasion makes LC pain the most common symptom of patients, which seriously affects the quality of life of patients.,6 At present, common clinical treatments for LC include surgery, chemotherapy, radiotherapy, and targeted therapy, but opioid analgesics are still used for LC pain. Opioids have a good analgesic effect, but their adverse reactions and dependence have always been a problem that has not been effectively solved, and cancer patients are easily tolerated by analgesics. Acupuncture as a traditional Chinese medical technique is widely used in modern clinical practice. A large number of research reports have shown that acupuncture can effectively relieve pain. Its main mechanism is to stimulate the central nervous system to regulate inflammation and significantly reduce the expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6.LC is a global health burden. Due to the limited conditions for lung cancer screening,So far, although some RCTs have shown that acupuncture therapy combined with analgesics is effective for LC pain, there is no systematic review. Therefore, this study conducted a systematic review and meta-analysis of acupuncture combined with analgesics in the treatment of LC pain, aiming to provide the latest evidence for the treatment of LC pain and guide clinical decision-making.Conceptualization: Renqing kuang, Guojiang xiong.Data curation: Yun Zhao, Wei Lv, Jiawang Jiang.Formal analysis: Guojiang Xiong, Wei Lv.Methodology: Guojiang xiong, Yun Zhao.Software: Wei Lv, Yun Zhao.Supervision: Guojiang xiong, Wei Lv.Writing – original draft: Renqing Kuang, Jiawang Jiang, Min Yu.Writing – review & editing: Renqing Kuang, Jiawang Jiang.


ABCA4-related STGD1 from the PRPH2/RDS-related PSPD and to compare the performance with that of retinal specialists. (2) Methods: We trained a convolutional neural network (CNN) using 729 FAF images from normal patients or patients with inherited retinal diseases (IRDs). Transfer learning was then used to update the weights of a ResNet50V2 used to classify the 370 FAF images into STGD1 and PSPD. Retina specialists evaluated the same dataset. The performance of the CNN and that of retina specialists were compared in terms of accuracy, sensitivity, and precision. (3) Results: The CNN accuracy on the test dataset of 111 images was 0.882. The AUROC was 0.890, the precision was 0.883 and the sensitivity was 0.883. The accuracy for retina experts averaged 0.816, whereas for retina fellows it averaged 0.724. (4) Conclusions: This proof-of-concept study demonstrates that, even with small databases, a pretrained CNN is able to distinguish between STGD1 and PSPD with good accuracy.(1) Background: Recessive Stargardt disease (STGD1) and multifocal pattern dystrophy simulating Stargardt disease  share phenotypic similitudes, leading to a difficult clinical diagnosis. Our aim was to assess whether a deep learning classifier pretrained on fundus autofluorescence (FAF) images can assist in distinguishing  ABCA4) gene encodes for a membrane-associated protein located in the outer segment (OS) disc membranes of rod and cone photoreceptors [ABCA4 gene are a known cause for recessive Stargardt disease (STGD1). STGD1 follows an autosomal recessive pattern of inheritance, with usual disease onset in the second decade of life. Nevertheless, albeit rare, late-onset forms of STGD1 do exist [The adenosine triphosphate-binding cassette, subfamily A, member 4  is an autosomal-dominant inherited retinal disease, caused by a te STGD1 . Pseudo-te STGD1 .ABCA4-associated disease [ABCA4-positive patients, but the qFAF levels were also elevated in eyes with a PRPH2/RDS mutation [Fundus autofluorescence (FAF) is an in vivo imaging method for the metabolic mapping of lipofuscin accumulation in the retina ,9,10. St disease ,10,11,12mutation . TherefoDespite the overlap between STGD1 and PSPD, the natural history is different, with only mild vision loss until the advanced stages of the disease for PSPD patients, and hence a better prognosis than STGD1 patients, making a correct diagnosis essential in these patients.ABCA4-related STGD1 from PSPD caused by mutations in PRPH2/RDS, and to compare these findings with the grading of retinal specialists.Deep learning approaches require large volumes of high-quality training data, which may be difficult in the case of rare inherited retinal diseases having undergone genetic screening. Moreover, the pretrained networks used in the current literature undergo transfer learning using the ImageNet dataset, containing color photography. Thus, our objective was to consider whether a deep learning classifier, pretrained using various FAF images, can assist in distinguishing ABCA4 mutation and associated STGD1 at various stages of progression OR (2) a confirmed PRPH2/RDS-associated disease with a PSPD phenotype. Genetic diagnosis was established by high-speed sequencing of genes involved in hereditary diseases on HiSe. Of note, only 1 pathogenic ABCA4 variant was required for STGD1 patients to be included. This retrospective study was conducted in accordance with the tenets of the Declaration of Helsinki. Written consent was waived due to the retrospective nature of the study.Patients retrospectively included in this study had (1) a confirmed We used macula-centered fundus autofluorescence retinal images from genetically confirmed eyes with STGD1 or PSPD, in the Department of Ophthalmology of Créteil, France. FAF images had been obtained in the Ophthalmology outpatient clinic in the Department of Ophthalmology in Créteil between April 2007 and April 2020, using Spectralis HRA + OCT . High-resolution (1536 × 1536 pixels), 30° × 30°, as well as 55° × 55° field-of-view images, centered on the fovea, with a minimum averaging of 30 frames, were extracted. One FAF image/eye/year of each patient was extracted. All images were deidentified, and all personal data  were removed. FAF images were not cropped but were resized to 224 × 224 pixels to meet the network specifications, with the fovea at the center, and were labeled as either STGD1 or PSPD, according to the specific mutation obtained following genetic testing.A two-class classification system (STGD1 and PSPD) was implemented. The images were then partitioned into three sets using the function train_test_split of scikit-learn: the training set (60% of the images), the validation set (10% of the images), and the test set (30% of the images). The assignment of the images towards the training, the validation, and the testing sets was performed randomly. The training, validation and test data were strictly separated to prevent correlations. The images of patients used for training the deep learning classifier were not used to test it.ABCA4 mutation) or PSPD (PRPH2/RDS mutation).We used ResNet50V2 to perform the classification task. We pretrained the ResNet50V2 model using 729 FAF images from patients with either normal FAF (73 images) or IRDs without genetic confirmation (656 images). The loss function used was cross-entropy. The model was optimized using the Adam Optimization Algorithm . The RedGraders evaluated the FAF images to distinguish between STDG1 and PSPD based on typical features. For STGD1, typical features were considered to be the presence of hyperautofluorescent flecks, presence/absence of hypoautofluorescent areas of atrophy, and presence of peripapillary sparing. For PSPD, the typical features were considered to be central hypoautofluorescent lesion with jagged border, butterfly-shaped hyperautofluorescent lesions in the macula, and absence/presence of peripapillary sparing ,8,13.The graders were masked to the mutation, to the grades from previous retinal imaging, and to all clinical data. Four graders  evaluated each FAF image independently. The same metrics  were computed for human grading. The expert grader’s performance was compared to the deep learning classifier’s performance.In this study, we included 304 FAF images from 80 eyes of 40 patients with genetically confirmed STGD1  and 66 images from 18 eyes of nine patients with PSPD . Using a pretrained classifier on FAF images, we obtained an overall accuracy of 0.882 on the test dataset of 111 images. The AUROC was 0.89. The test loss was 0.413. The precision was 0.883. The recall (sensitivity) was 0.883. The F1-score was 0.884. Of the 91 STGD1 FAF images, 88 were correctly classified. The sensitivity for STGD1 was 0.967, while the specificity was 0.50. The positive predictive value was 0.897 and the negative predictive value was 0.769 for STGD1.Of the 20 PSPD FAF images, 10 were correctly classified. Conversely, the sensitivity for PSPD was 0.5, with a specificity of 0.967. The positive predictive value was 0.769 and the negative predictive value was 0.897 for PSPD. The results on the training, validation, and test sets are presented in The retina specialists consisted of two retina experts (E.S. and O.Z.) and two retina fellows (D.S. and P.D.). The diagnostic accuracy for retina experts averaged 0.816, whereas for retina fellows it averaged 0.724. The sensitivity for the detection of STGD1 on FAF imaging was higher than for PSPD detection, both for retina experts and for retinal fellows . In terms of specificity, it was higher for PSPD compared to STGD1 for both retina experts and for retinal fellows. The interclass correlation (ICC) between the four human graders was 0.242. The evaluation of retina specialists’ performances in distinguishing, using FAF images, STGD1 from PSPD, is summarized in In this study, we evaluated the performance of a deep learning classifier in distinguishing between STGD1 and PSPD on FAF, and we compared the results with those of retina specialists with varying levels of expertise. The ground truth consisted of STGD1 and PSPD with a genetic molecular diagnosis. The human graders were masked to the mutation, to the grades from previous retinal imaging, and to all clinical data.The accuracy of the DL model was non-inferior to that of the retina experts (accuracy: 0.88 versus 0.816), as shown in There are several reasons for these low values of sensitivity and specificity. Both STGD1 and PSPD have a phenotypic similarity in multimodal imaging, including FAF. While the model correctly relies on pixels within the area of atrophy and flecks, the similarity between the two images, and the inconsistency of differentiating features , may be misleading for the DL model, as for the clinician. An important point is that, on 30° × 30° FAF images, the presence of the optic disc and the subsequent (when present) peripapillary sparing was inconstant, which may help further explain the model’s performance.PRPH2-associated PSPD, qFAF was shown to be lower in patients with PSPD compared to STGD1 [Furthermore, the class imbalance may also have contributed to the difference between the specificity and sensitivity of each class. Moreover, functional testing, such as full-field ERG in PSPD, is often normal , but higto STGD1 ,16. As gGiven the inherently small databases, and in order to improve the classification accuracy, ResNet50V2 was pretrained with various FAF images to learn how to extract features specific to FAF. Despite our limited database (304 FAF images of STGD1 and 66 images of PSPD) and the class imbalance, the pretrained ResNet50V2 obtained a good accuracy of 0.88. Other approaches may have been implemented in order to deal with the small sample size. In practice, it takes hundreds of thousands of images to optimize the innumerable parameters of a CNN. We pretrained ResNet50V2 using 729 FAF images from patients with either normal FAF (73 images) or other IRDs without genetic confirmation (656 images). Pretraining the CNN with a larger sample size could have led to a better performance of the model. We performed data augmentation only on the training set within the Keras framework. Although data generation of the input database has been previously performed in a study classifying diabetic retinopathy using OCT Angiography , as it mIf both age-related macular degeneration and diabetic retinopathy are retinal diseases where, due to the high incidence and prevalence, large-scale, publicly available databases exist, predominantly consisting of color fundus photography and/or OCT images, this is not true for IRDs. In IRDs, deep learning applications are developing, but are still at an early stage due to the rarity of these diseases. Our group recently focused on the applications of DL to classify IRDs using FAF, obtaining excellent accuracies when distinguishing STGD1, retinitis pigmentosa, BD and healthy controls , as wellABCA4 for STGD1 and PRPH2 for PSPD), a genetic molecular diagnosis for all included eyes was essential. These databases would be extremely useful, even more so when dealing with rare, orphan diseases. Therefore, the ultimate and best solution for increasing the accuracy of our model would be multi-institutional collaborations. Another limitation is the fact that we included various stages of STGD1, with various degrees of overlap with PRPH2. To date, no reference databases of FAF imaging are available. Finally, while the image size was reduced to fit CNN requirements, the FAF images were not cropped, leading to a variability within the database with regard to the visualization of the optic disc and peripapillary sparing, which may have additionally impacted the results.This study has several limitations, of which the main is the small dataset. Given that STGD1 and PSPD, while presenting a phenotypic overlap on FAF imaging, are consequent to mutations in different genes (Last but not least, it is important to keep in mind that the comparison of a deep learning classifier and retina specialists to distinguish STGD1 from PSPD relies solely on the features in a single FAF image. In a clinical setting, a diagnosis by a physician is made with the consideration of other clinical parameters such as the age of the patient, time of onset, family history and a battery of other imaging and functional tests. The high number of graders, leading to a greater difficulty to reach agreement, as well as the phenotypic similarity between STGD1 and PSPD, may explain the fair agreement between the different human readers. This highlights the relevance of the CNN in detecting these phenotypically similar diseases, which present diagnostic challenges to the clinician and are solely based on FAF imaging. Larger studies with larger datasets and, ideally, a multimodal approach, are needed before implementation in a clinical setting.Our results show the efficiency of training a CNN with transfer learning, generating a stable classification performance despite the small dataset. Therefore, pretraining the model with the same type of imaging may prove useful when it is difficult to amass image data, such as in cases of rare genetic diseases.This proof-of-concept study demonstrates that a DL-based distinction between STGD1 and PSPD is possible using FAF images, with a good accuracy, sensitivity, and specificity compared to retinal experts relying solely on FAF images.


Catalytic transfer hydrogenolysis (CTH) displays high energy and atom efficiency. We have studied a series novel solid catalysts for CTH of glycerol. In this work, detailed studies have been conducted on energy optimization, tech-economic analysis, and environmental impact for both processes. The key finding is that relatively less energy demands and capital investment are required for CTH process. CO2 emission per production of propylene glycol is much lower in the case of transfer hydrogenolysis. The outcome of this study could provide useful information for process design and implementation of novel hydrogenolysis technologies for other energy and environmental applications.Hydrogenolysis of glycerol to propylene glycol represents one of the most promising technologies for biomass conversion to chemicals. However, conventional hydrogenolysis processes are often carried out under harsh H Actually, this process is still heavily dependent on the use of fossil-derived H2, with cost-ineffective investment on H2 compression, recycling, and manufacture of process equipment. (2 (“green H2”) can now be produced from other feedstocks, e.g., electrolysis of water. But one should note that most hydrogenation plants have to be established adjacent to H2 source or pipelines, which could unfavorably increase operational and constructional cost for biorefineries. In addition, potential safety risk is another important factor hindering industrial implementation of this technology. Advanced aqueous phase hydrogenolysis technologies with low-carbon emission are highly demanded for future development of bio-refineries.Aqueous phase hydrogenolysis of bio-oxygenates provides a most promising technology for the production of various megaton chemicals from renewable feedstocks. . In thisuipment. . It is t2 make CTH processes more energy and atom efficient compared with CHDO processes. Extensive research efforts have been devoted to develop active and selective solid catalyst materials with bifunctional natures for both H2 generation and hydrogenolysis reactions. Pt-based (oC) and pressures (inert <2 MPa), with remarkable atom efficiency for the synthesis of PG as the main product , which takes use of renewable H-donors in liquid medium, is considered as one of the most economically and environmentally beneficial technique to substitute conventional hydrogenolysis processes CHDO, . Jin et. Much miPt-based , Cu-basePt-based , and Pd-Pt-based  catalyst product . ExperimHowever, to our best knowledge, limited studies on energy, economic, and environmental assessment (E3A) have been carried out to evaluate the overall impact of CTH processes particularly for the production of PG from glycerol . This st2 compression contributes to overall economic improvement has been conducted. 3) Environmental analysis has also been carried out to estimate the CO2 emission and water discharge for both processes, respectively. Finally, both advantages and disadvantages for CTH of glycerol have been quantitatively discussed for future design of next-generation bio-refineries.However, to our best knowledge, no relevant reports have been published on comparative studies of energy, economy, and environmental assessment for both CHDO and CTH of glycerol. Therefore, in this work, we reported a detailed and comparative study on CHDO and CTH of glycerol to PG. Specifically, 1) energy consumptions for glycerol pretreatment, hydrogenolysis reactors, and separation/purification sections have been compared for both CHDO and CTH. Heat exchange network has also been optimized. 2) Economic analysis on how reduction of H4, H2, and CO2. Redlich-Kwong and NRTL models were adopted for simulation. Redlich-Kwong model was used to determine gas composition, while NRTL method was used to describe liquid phase , propanol (PrOH), ethylene glycol (EG), acetol, cycloheptane, methanol (MeOH), ethanol (EtOH), acetic acid, CHid phase . Since rid phase .Redlich-Kwong and NRTL models are only suitable for polar and gas-liquid phase systems. Tech-Economic analysis has been focused on utilities and capital investment. There are many empirical parameters which may generate large errors. However, those errors are acceptable for engineering design.2 catalyst were used for simulation of CHDO process  and fed to the reactor , MeOH/PrOH separation (T102), acetol purification (T103), azerotropic separation (T104), and PG purification units (T105). Cycloheptane is used as azerotropic agent and recovered from T104 and T105 , together with recycling water, is pumped into reactor (R201 in 2 and CO2 from reaction mixture. EtOH and water are recycled into the reactor in Alcohol + Water Recycle Column (T202), in which the raw material could be saved. After being separated in Acetol + acetic acid/PG + EG Separation Column (T203), Acetol is purified in Acetol Purification Column (T204), while PG is purified in azeotropic distillation system including Azeotropic Distillation Column (T205) and PG Purification Column (T206). R201 in . The reaReaction parameters such as temperatures, pressures, and catalyst loading have been studied experimentally in our laboratory, as already reported previously . ConversRstoic model was applied for the hydrogenolysis reactor. In separation and purification section, the main unit operations are fractionation and azeotropic distillation; thus, the RadFrac model was used. This model could be used for accurate calculation of each column . PropertE,i is the capital cost of each process corresponding to actual capacity Q, Cbasic indicates the capital cost with the base case capacity, α is the cost scale factor, and f is a comprehensive adjustment factor   which ist factor . Q/Qbasiterature . DetailsThe capital cost summary of CHDO and CTH scheme is shown in 2, the effluent discharge, the organic compounds, and equivalent greenhouse gas emissions in CHDO and CTH process. The quantitative analysis is reported according to million $ production , CO2 catalyst in literature. As a result, the operating conditions for Ni/Cu/TiO2 catalyst in CHDO of glycerol cannot be optimized in this work. Such optimization would not be reliable without kinetic data under different temperatures and pressures from experimental studies. Therefore, the operating conditions Ni/Cu/TiO2 catalyst.Prior to detailed comparative studies for both CHDO and CTH processes, it is important to set up the reference operating conditions for systematic investigation. Despite extensive studies on CHDO processes, there is lack of experimental kinetic data for the leading Ni/Cu/TiO2 is recycled and compressed in this scheme (V101). To simplify the scheme, we have reduced the purification part for H2 recycling for the convenience of further cost estimation. It is also critical that, for CHDO process, we already found that recycling water is not economically viable as the cost for H2 purification. Those preliminary calculations showed that H2O recirculation and H2 purification are not expedient from the technological point of view, and therefore, they are excluded from the technological schemes.It is important to mention that H2 compression unit is not required, as there is no external H2 added in CTH of glycerol. However, glycerol should be fed with EtOH (H-donor) as feedstock into the reactor. Glycerol/EtOH/H2O (69.7/24.8/0.5 M ratio) is pumped into reactor  is recycled back with fresh feedstock with Glycerol/EtOH/H2O stream. The remaining unreacted alcohols can be used as H-donor for fresh feedstocks. For CTH process, dehydration of glycerol leads to the formation of acetol, while dehydrogenation of EtOH eventually generates acetic acid as the final product. Acetol and acetic acid are separated from PG and EG in T203, while acetol could be further obtained in T204 with 99.95% purity. Similar to CHDO scheme, PG and EG are separated using azeotropic distillation sequence .Different from CHDO process, CTH of glycerol is composed of relatively simpler scheme. H R201 in  for CTH 2 cycling and product separation units are completely different from the conventional one. Therefore, we were motivated to further study the advantages and possible disadvantages of CTH technology for glycerol conversion in the following sections.Based on description presented above, it is clear that, for CTH of glycerol, H2 generation from EtOH as H-donor leads to the formation of acetic acid in the reaction medium, while conversion of glycerol undergoes dehydration and hydrogenolysis steps, forming acetol and PG as intermediate and final products, respectively.Prior to detailed investigation on the influence of process parameters on productivity and energy/capital costs, we first compared the product flow rate and composition for CHDO and CTH processes. The mass flow rates for PG, EG, acetol, and PrOH are 893.4 kg/h, 89.3 kg/h, 14.1 kg/h, and 12.3 kg/h, respectively, while CTH of glycerol leads to 606.3 kg/h, 42. kg/h, and 116.6 kg/h for those products. The product distribution   for the 4 and CO2 as by-products. As a result, the overall product mass flow rates for PG and acetol are much lower than that at 200°C.The influence of temperature on product distribution and product mass flow rate is presented in We also studied the influence of glycerol concentration on the amount of total recycled water for CTH scheme. It is found from In this part of work, simulation of glycerol concentration effect on CHDO process could not be conducted due to lack of kinetic data in literature. It would be very useful to compare the concentration effect for both schemes, providing more critical insights into the sustainability of CHDO and CTH processes. Therefore, 20wt% glycerol concentration was still used for further comparison of two schemes to ensure consistency in processing capability of the two technologies.It is also important to mention that the water generated in both CHDO and CTH meets the environment regulation for discharge. Therefore, CTH processes with much lower water demand is more favorable for lowering the overall cost of water treatment.2 with high H2/glycerol ratio (10), for CHDO processes, utilization of stoichiometric liquid H-donors exhibits much better overall atom economics.1) Higher atom efficiency for value-added PG and acetol products. Considering the use of external pressurized H2) Lower water input. Based on Based on the comparison shown above, it is clear that CTH process displays the following advantages:The interesting results in In the following sections, we will further discuss the energy demands for CHDO and CTH processes, which provide important evaluation for the economics and profit analysis.Glycerol concentration will influence the reaction kinetics as well as separation cost. This is because glycerol concentration will influence the amount of recirculating water as well as the heat duty for each of the downstream separation column. In this section, energy requirement for CHDO and CTH under identical glycerol concentration will be compared prior to detailed investigation on how glycerol concentration in the feed affect energy cost for CTH scheme. The amount of water (solvent) used in this system under different glycerol concentration varies significantly from 20wt% to 40wt%, as already seen in oC). Detailed information on product composition has already been shown in The effect of reaction temperature on the energy input for pretreatment and reaction sections, as well as separating and purification sections was also studied in the following sections. It is found in We have selected 20wt% glycerol concentration and 200°C as the reference condition for further process analysis. Energy analysis was conducted to reveal the energy consumption for each unit operation in both CHDO and CTH processes. Specifically, For separating and purification sections, we have found that energy requirements for CHDO and CTH schemes are again different from each other. In CHDO process, water, MeOH, and PrOH were obtained from the overhead of T101 column, while the mixture from the bottom of this column contained PG, EG, acetol, and small amounts of water (4wt%). Water has been obtained from the bottom of T102 and recycled back to the mixer in the pretreatment and reaction section, with MeOH/PrOH obtained from overhead of T102. Acetol of 92wt% purity can be produced from T103 as one of the co-products from CHDO process. PG and EG are separated in T104 with cycloheptane as azeotropic agent. EG of 99.97wt% purity can be obtained from T104, while PG of 99.92wt% can be produced from T105. Clearly, the heat duty for T101 is the highest compared with other columns in CHDO scheme. The azeotropic unit consisting of T104 and T105 demands a total energy input of 8,044 kW.2 (7wt%), CH4 (9wt%), CO2 (79.8wt%), and MeOH (3wt%) from the product mixture. Alcohol and water mixture was produced from the top of T202 and recycled back to the mixer in hydrogenolysis unit.Since the product distribution for CTH is different from that of CHDO, the separating and purification scheme for CTH varies significantly. In particular, T201 separates light gases such as Hvia azeotorpic distillation, in T205 and T206 columns. It can be seen that alcohol and water recycle unit (T202) demands significantly high energy input in CTH scheme, while for CHDO process, separating water/MeOH/PrOH from product mixture needs remarkably high energy input (T201). The overall energy requirement for purification of acetol, PG, and EG is relatively lower in CTH process compared with CHDO scheme. As a result, the energy requirement for purification unit is 49,597 kW and 42,491 kW for CHDO and CTH, respectively. Considering the advantages of milder operation temperatures and pressures in CTH process, the total energy for the proposed process is 17% lower than CHDO scheme.Acetol and acetic acid were separated from PG and EG in T203, while purified acetol of 99.9wt% as the highly valuable co-product can be obtained from bottom of T204. Acetic acid of 97wt% purity (containing 0.2wt% acetol and ∼2.8wt% water as impurities) was produced from the top of T204. Similar to CHDO process, PG and EG were also separated 2 compressor at all, while in CHDO scheme, H2 compressor is a critical unit to recycle excess H2 back to the reaction unit.Based on the detailed analysis shown above, we further conducted techno-economic analysis for CHDO and the proposed CTH process, with regard to energy consumption and product distribution. The total number of equipment is summarized in Detailed capital investment for CHDO and CTH processes is compared in 2, the maintenance and safety cost will also be much lower compared with CHDO process. This is because that, in CTH scheme, reactor is conducted under much milder temperature and pressure. As a result, H2 compressor is not needed, with reduced operation cost.It is important to point out that, since CTH process does not involve use of pressurized H2 tank and compressor.In addition, CTH process produces other co-products including acetol, acetic acid, and EG; therefore, three additional storage tanks are needed. However, the overall cost for the three tanks is obviously lower than HDetailed cost assignment for different unit operations in CTH process is presented in According to our detailed simulation on CHDO and CTH processes, the sale revenue for both processes is listed in The novelty of transfer technologies has been demonstrated in numerous previous work . However2. Actually, H2 is industrially derived from fossil fuels using coal or natural gas as the starting material. Therefore, the environmental impact from fossil-H2 generation is also included in this assessment. The leaving materials are mainly consisting of the oxygenate products and waste gases, such as PG, PrOH, EG, acetol, MeOH, and CO2. Differently, the entering materials for CTH process . The leaving materials in CTH scheme also include PG, acetol, and EG, similar to CHDO process  has been achieved.In this work, we have conducted detailed analysis for both conventional hydrogenolysis (CHDO) and catalytic transfer hydrogenolysis (CTH) of glycerol processes. Process scheme for both processes has been discussed with respect to energy consumption, productivity, and product distribution. The key finding in this part is that total energy input for CTH of glycerol is approximately 83% of CHDO process. Detailed economic analysis has demonstrated a total reduction of 7% for total investment in CTH scheme, owing to simplification of HThis work has clearly demonstrated the advantages of transfer hydrogenolysis of glycerol to propylene glycol over PtFe-based catalysts. This work will be useful for future process development and implementation of transfer hydrogenolysis technologies in next-generation bio-refineries. The advantages of CTH compared with CHDO are shown in Additional information on process schemes, equipment design, economic analysis, and heat transfer optimization are available in supporting information.


Dactylorhiza maculata (L.) Soó (family Orchidaceae) is used to treat gastritis, colic, gastrointestinal tract, and bladder diseases. This study aimed to investigate the properties and characteristics of the in vitro Dactylorhiza maculata extract. The recommended parameters for producing Dactylorhiza maculata extract were determined: temperature 60 °C, process duration 60 min, hydro module 1:10. It is recommended to carry out the extraction using an aqueous ethyl alcohol solution with a mass fraction of the parent substance of 70%. It was found that such biologically active substances as rutin, quercetin, 3,3′,4′,5,5′,7-hexahydroxyflavonone, 3,3′,4′,5,5′,7-hexahydroxyflavonone-3-O-glycoside, gallic acid, and ferulic acid were dominant in Dactylorhiza maculata. A high phosphorus content was noted (2410.8 mg/kg dry matter). The studied Dactylorhizamaculata samples contained a large number of organic acids and water-soluble vitamins. The tested extracts were safe in terms of the content of heavy metals, pesticides, aflatoxin B1, and radionuclides, as well as pathogenic and opportunistic microorganisms; the content was significantly lower than the threshold limit values. The studied complex of biologically active substances from Dactylorhiza maculata extract samples had antimicrobial properties. It was found that the antioxidant activity of the samples was 217.89 ± 10.89 mg AA/g (AA—ascorbic acid). The high content of bioactive substances and the antimicrobial and antioxidant properties of Dactylorhizamaculata extract samples determine the application potential of this plant as a substitute for growth stimulants and feed antibiotics in the production of feed additives, aiming to increase the physiological and immune status of livestock and poultry.The medicinal plant  Gastrointestinal diseases from various causes present a considerable problem for the livestock industry, as they lead to low productivity and the death of young animals . Some ofAmong the many medicines used to preserve the livestock and treat diseases of the gastrointestinal tract, course and feed antibiotics are most often used; however, their prolonged and unconsidered use reduces the body’s resistance to fungal and staphylococcal infections, and disrupts the processes of digestion and metabolism, as a result of which it decreases live weight gain and the quality of livestock products, including the fact that meat raw materials may contain residual amounts of antibiotic agents . In addiCurrently, the number of studies on the use of medicinal plants in the treatment and prevention of a wide range of diseases in humans and animals has increased worldwide , includiThe use of plant components as feed additives that can increase livestock productivity, stimulate reproduction, and improve the consumer properties of products is relevant and promising. Such components of the livestock diet, called “phytogenic feed additives” (phytogenics), have been widely used since the year 2000, primarily in pig and poultry farming. Interest in them is associated with the restriction on using certain synthetic growth promoters (antibiotic growth promoters) in EU countries . The maiThe main effects of phytogenics are increased food intake, stimulation of digestion and growth, reduced incidence of diarrhea, improved feed efficiency and productivity, and ultimately increased production profitability (Commission implementation regulation (EC) No. 131/2012).The search for new effective phytogenic additives is a promising and relevant area of animal husbandry, especially considering modern international requirements for product safety .Cotinus coggygria, Lunaria rediviva, Sarothamnus scoparius, Eryngium maritimum, Goodyera repens, Corallorhiza trifida, Listera cordata, Dactylorhizamaculata, Platanthera chlorantha, P. bifolia, etc., of the Kaliningrad region, which is characterized by a mild climate and landscape diversity. [A promising raw material for the production of biologically active substances of antimicrobial action from which to create feed additives is medicinal plants, such as versity. .Orchidaceae genus are used in traditional medicine. Their chemical components and pharmacology have been studied for the past 15 years. Dactylorhiza maculata has not undergone detailed pharmacological studies. A wide range of chemical compounds has been identified in this plant, including alkaloids, bibenzyl derivatives, flavonoids, phenanthrenes, and terpenoids, which have recently been isolated from this species. These plants’ extracts and metabolites, especially those obtained from flowers and leaves, have valuable pharmacological properties. Their diuretic, antirheumatic, anti-inflammatory, anticarcinogenic, hypoglycemic, antimicrobial, anticonvulsant, relaxing, neuroprotective, and antiviral effects are particularly interesting [Many plants of the eresting ,12.Dactylorhizamaculata is mainly found in the northern and central regions of the non-chernozem zone. The biomass of the medicinal plant contains mainly rutin, quercetin, ferulic acid, hexahydroxyflavonone, and gallic acid. In addition, the composition of the medicinal plant includes essential oils and bitter substances [Dactylorhizamaculata is used as a general tonic in folk medicine, and has anti-inflammatory and enveloping properties [It is known that bstances ,14. ThisOver the past decades, increased anthropogenic activity, rapid industrialization, and modern agricultural practices have led to increased environmental pollution with heavy metals, which has increased the toxicity of plants, including non-endemic ones. Large areas of land are already contaminated with heavy metals due to the use of pesticides, fertilizers, household and compost waste, as well as due to the emissions of heavy metals by metallurgical facilities, and mines containing metals. Although many heavy metals are found naturally in the Earth’s crust at various levels, the problem arises when they are released into the environment in excess by natural and/or anthropogenic activities and, through the air and water, enter and accumulate in plants .Dactylorhizamaculata extract . For the first time, rational values of the parameters of the BAS isolation process from Dactylorhiza maculata, which is widespread in the territory of the Russian region of the Baltics, were determined. The content of heavy metals and toxicological properties were determined, and the antimicrobial and antioxidant activities of the Dactylorhiza maculata extracts were proved; the obtained data allowed the consideration of Dactylorhiza maculata as a possible part of feed additive formulations aiming to increase the physiological and immune status of livestock and poultry.This study aimed to investigate the properties and characteristics of the in vitro Dactylorhizamaculata extracts enriched with BAS were selected. The extraction temperature, duration, and hydro module  were chosen as the primary technological parameters that affect the yield of the plant extract of biologically active substances [In this study, the conditions for the production process of bstances .Dactylorhizamaculata extracts was considered. It was found that the highest extract yield is obtained when using ethanol with a concentration of 70%. The results of optimizing the technological parameters for producing a Dactylorhizamaculata extract enriched with BAS using 70% ethanol as an extractant are presented in At the preliminary stage of the study, the possibility of using different solvents  at different concentrations to obtain Dactylorhizamaculata extract samples by preparative chromatography are shown in Preparative chromatography was used to isolate individual compounds from the mixture in the pure form . The resDactylorhiza maculata extracts are presented in The results of determining the qualitative and quantitative composition of BAS from Dactylorhiza maculata extracts are presented in The results of evaluating the antimicrobial activity of Dactylorhiza maculata extract samples had antimicrobial properties against the tested strains .The studied The content of toxic elements is presented in Dactylorhiza maculata BAS complex extract samples was within the acceptable limits [The content of heavy metals, pesticides, aflatoxin B1, and radionuclides in the e limits ,16.Dactylorhiza maculata extract samples was 217.89 ± 10.89 mg AA/g, which indicates the high antioxidant characteristics of the obtained extracts.The antioxidant activity of the Dactylorhiza maculata BAS complex extract samples showed their high microbiological reliability .The results of studying the microbiological safety indicators of the obtained p < 0.05) were found in the yield of the extract, with an extraction duration of at least 60 min. With this extraction duration (≥60 min), no statistically significant differences were found at the ratio of the hydro module at 1:1, 1:2 and 1:5, 1:10, 1:20, but significant differences were established between 1:(2 maximum) and 1:(5 minimum). A statistically significant difference was found at an extraction temperature up to 40 °C and not less than 60 °C (p = 0.879−0.921). The recommended parameters for producing a plant extract from Dactylorhizamaculata were a temperature of 60 °C, a process duration of 60 min, and a hydro-module of 1:10. The yield of the plant extract, in this case, was 9.07%. Under these conditions, the extraction of biologically active substances was the most complete  [The extraction process was carried out at different temperatures for a duration from 10 min to 360 min . No stat of 70%) .O-glycoside, gallic acid, and ferulic acid were isolated from fractions of Dactylorhizamaculata extract in the system with methylene chloride:methanol at 4:1 by preparative HPLC. HPLC was carried out using a column with phenyl end-capping and modified with nitrile and octyl groups, sorbent size 2.5 μm, pores 25 nm, inner diameter 2.5 mm, length 150 mm. The eluent was composed of phosphate buffer (pH 8.8) and 30% acetonitrile, with a flow rate of 1 mL/min, and a chromatography time of 30 min. The collection of individual substances was carried out automatically using a fraction collector [Rutin, quercetin, 3,3′,4′,5,5′,7-hexahydroxyflavonone-3-ollector .Dactylorhizamaculata extract (O-glycoside (13.04 mg/100 g), 3,3′,4′,5,5′,7-hexahydroxyflavonone (12.58 mg/100 g), quercetin (11.07 mg/100 g) and rutin (8.52 mg/100 g).The  extract  showed hDactylorhizamaculata growing on the Kaliningrad region and the Belarus territory, it was found that in vitro Dactylorhizamaculata of the Kaliningrad region contains 13% more flavonoids than the Belarusian one [When comparing the BAS of the sian one .Dactylorhiza maculata extracts are planned to be used for producing feed additives for livestock, studying their toxicological and microbiological safety indicators was of interest [As interest . It is kDactylorhiza maculata, show that these extracts have a low content of such metals as mercury, cadmium, lead, and arsenic.Empirical data obtained in the course of studying the quantitative content of heavy metals, in plant extracts of the BAS complex from Dactylorhiza maculata did not exceed 0.0001 mg/kg. The cadmium and lead content were within the normal range and was less than 0.002 mg/kg for each indicator. It was experimentally established that the arsenic content in plant extracts did not exceed 0.08 mg/kg.Thus, mercury content in the studied samples of plant extracts of the BAS complex isolated from Dactylorhiza maculata contained copper and zinc compounds, but all indicators were within the normal range. The sum of α-, β-, and γ-isomers of hexachlorocyclohexane in the samples under study did not exceed 0.001 mg/kg, and the content of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane and its metabolites did not exceed 0.007 mg/kg. It was also shown that the studied plant extracts of the BAS complex were within the normal range in terms of the content of aflatoxin B1 and radionuclides. Dactylorhiza maculata extracts were distinguished by high microbiological reliability .The BAS complex extracts isolated from The Dactylorhiza maculata extract samples obtained in the territory of central Russia was 217.89 ± 10.89 mg AA/g, which indicates their high antioxidant properties.The antioxidant activity of the Dactylorhiza maculata growing in Romania [D. maculata ethanol extract (ethanol content 70%) contained the highest amount of isoquercitrin (518.6 ± 3.7 μg/g), followed by quercitrin (474.6 ± 4.34 μg/g). Ferulic acid, para-coumaric acid, caffeic acid, and kaempferol were also identified, but at a lower concentration  in Dactylorhiza maculata extract from a toxicological and microbiological point of view, which makes it possible to recommend their use as ingredients in the formulation of feed additives for livestock [The results of these studies indicate the safety of the obtained samples of the ivestock .Dactylorhiza maculata (L.) Soó (family Orchidaceae) extract were used as objects of research. The raw material for the extracts was the medicinal plant Dactylorhizamaculata, collected in August 2020 in the Kaliningrad region. The biomaterial of the species was confirmed by A. Pungin, the head of the herbarium of the Institute of Living Systems of the IKBFU (protocol No. 16/2020). The aerial parts of mature plants  were collected. The ratio of shoots/leaves/flowers in the harvested biomass was, on average, 4:2:1 for each medicinal plant. Extracts were produced from the collected biomaterial of the medicinal plant.Samples of Dactylorhiza maculata extracts; detection was carried out using a diode array detector in the range detection of 180 nm–900 nm, the flow rate of the eluent in all cases was 1 mL/min. The preparative isolation of Dactylorhiza maculata hydroxyflavones was carried out by HPLC, using an amine phase column with phenyl end-capping, sorbent size 2.5 μm, pores 25 nm, inner diameter 2.5 mm, length 150 mm. The conditions were: eluent phosphate buffer, pH 8.8, 30% acetonitrile, flow rate 1 mL/min, chromatography time 60 min. The collection of individual substances was carried out automatically using a fraction collector [HPLC method  according to GPM.1.2.1.2.0005.15  was applied to study the chemical composition of O-glycoside , 3-hydroxyflavone , 5-hydroxyflavone , 7,8-dihydroxyflavone , apigenin , gallic acid , hyperoside , disulfuretin , quercetin , kaempferol , luteolin , ruthin , sulfurein , sulfuretin , and ferulic acid  were purchased from Fluka/Sigma-Aldrich . The values of the standard samples for BAS were used to construct calibration curves, which were used to determine the number of components.3,3′,4′,5,5′,7–hexahydroxyflavonone , 3,3′,4′,5,5′,7-hexahydroxyflavonone-3-The method for the mercury content determination is based on the destruction of the analyzed sample by a mixture of nitric and sulfuric acids, precipitation of mercury with copper iodide, and subsequent colorimetric determination in the form of copper tetraiodomercuroate, by comparison with a standard scale .The method for determining cadmium is based on the dry mineralization (ashing) of a sample using nitric acid as an auxiliary agent, and quantitative determination of cadmium by polarography in alternating current mode .The method for arsenic determination is based on measuring the color intensity of a solution of a complex compound of arsenic with silver diethyldithiocarbamate in chloroform. The method for the determination of copper and zinc is based on the dry mineralization (ashing) of a sample using nitric acid as an auxiliary agent, and quantitative determination of copper (zinc) by polarography, in alternating current mode .Dactylorhiza maculata extract was determined using the enzyme immunoassay [The presence of aflatoxin B1 in the unoassay . Organocunoassay . The preunoassay .Listeria are determined by inoculation on a selective medium and the presence of colonial growth with growth characteristics. S. aureus was detected and quantified by inoculation on agar selective diagnostic media, counting the number of characteristic colonies (when determining the S. aureus number), confirming the attribution of the isolated characteristic colonies to S. aureus by biochemical signs [The method for the determination of mesophilic aerobic and facultative anaerobic microorganisms is based on inoculation of the product and/or dilutions of the weighed product portion into a liquid nutrient medium, the incubation of inoculates, accounting for visible signs of microorganism growth, if necessary, the subculture of culture liquid on agar nutrient media to confirm the growth of microorganisms, and finally, counting their numbers using the table. Coliform bacteria are determined by inoculation on agar selective diagnostic media; toxin-forming anaerobes are determined by inoculating a certain amount of the product or its dilutions into a liquid selective medium, isolating characteristic colonies and confirming their attribution using biochemical tests. Pathogenic microorganisms of the genus al signs .Dactylorhiza maculata extract samples against the growth of opportunistic and pathogenic test strains was determined by two methods: the diffusion method (on a solid nutrient medium) and a method based on measuring the optical density (in a liquid nutrient medium) [Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Proteus vulgaris ATCC 63, Candida albicans EMTK 34, Leuconostoc mesenteroides EMTK 1865), acquired from the State Collection of Pathogenic Microorganisms and Cell Cultures .Antimicrobial activity of the in vitro  medium) . MedicalThe bacterial lawns of test strains were produced on agar nutrient media, and simultaneously, BAS complex extract samples were placed on the lawn. A paper disc with a nutrient medium was used as a control, and a disc with antibiotic rifampicin (from a standard kit) was used as a reference drug. Petri dishes were incubated at a temperature corresponding to the optimal growth temperature of each test strain for 24 ± 0.5 h. The results were accounted by the presence and size (in mm) of the transparent zone showing the absence of microorganism growth around the disc .All standard media were purchased from Khimreaktivsnab, Ufa, Russia.18H12N5O6, M = 394.33). The reaction of the interaction of antioxidants with the DPPH radical proceeds according to the scheme [The antioxidant activity of plant extracts was determined by their ability to reduce the 2,2-diphenyl-1-picrylhydrazyl radical  used in this study were purchased from Fluka/Sigma-Aldrich .p < 0.05).Each experiment was repeated three times, and the data are expressed as means ± standard deviation. Data processing was carried out via the standard methods of mathematical statistics. Post hoc analysis (Tukey test) was undertaken to identify samples that were significantly different from each other. The equality of the variances of the extracted samples was checked using the Levene test. The data were subjected to analysis of variance (ANOVA) using Statistica 10.0 . Differences between means were considered significant when the confidence interval was below 5%  for the production of feed additives is relevant to improving regional economies and improving the quality of life and the nation’s health, by providing ecologically clean livestock products. The flavonoids, which are of interest for the production of feed additives for livestock that are an alternative to antibiotics, have been identified among Dactylorhizamaculata BAS.Plant-based feed additives are now widely used to treat and prevent many diseases of livestock and poultry. A limiting factor in introducing domestic medicinal plants into the production of feed additives is the lack of information on the chemical composition of medicinal plant raw materials, and poor knowledge of the medicinal properties of plant preparations . The useDactylorhiza maculata properties offers new opportunities for further research aimed at developing technologies for obtaining plant material in a short time, year-round, regardless of weather conditions; the possibility of producing planting material for species that are difficult to reproduce; reproduction of hybrid forms of plants with preservation of valuable properties; improvement of planting material; the possibility of automating the in vitro reproduction process, and ensuring the genetic homogeneity of the resulting plants.This study of


No significant differences were found for the MCS. Conclusions: HRQoL was significantly lower in patients with endometriomas or DIE compared to controls. If confirmed, these results may have important implications for prevention, clinical practice, and intervention.Endometriosis is a disabling disease that may significantly compromise a woman’s social relationships, sexuality, and mental health. Considering the impact of endometriomas and deep infiltrating endometriosis (DIE) on quality of life and the limited number of papers on this topic, the objective of this study was to assess health-related quality of life (HRQoL) in adult Spanish women with the condition. A case-control study was conducted on a group of 99 patients with ovarian endometriomas or DIE and 157 controls. Women underwent physical and gynecological examinations, and they completed health questionnaires including the Short Form-12v2 (SF-12v2), a survey for HRQoL. Eight scales and two component summary scores  and Mental (MCS), respectively) were calculated. Women with endometriomas or DIE had significantly worse PCS: 47.7 ± 9.7 vs. 56.1 ± 5.9, respectively ( Endometriosis is defined as a benign and proliferative chronic disease characterized by endometrial glands and stroma outside the uterus, frequently in the peritoneal spaces . A prevaIn recent years, there has been growing interest in incorporating the assessment of health-related quality of life (HRQoL) in the clinical studies and routine clinical management of diseases, including endometriosis. Several studies have addressed the association between quality of life and endometriosis ,20,21,22To the best of our knowledge, no previous study has evaluated the relationships between HRQoL and presence of endometriomas or DIE after controlling for confounding factors in adult Spanish women. We sought to assess whether endometriomas or DIE have a significant impact on HRQoL in adult women. We hypothesized that women with endometriosis would have worse HRQoL scores than controls.n = 99) were women attending the hospital’s Endometriosis Unit. Endometriosis diagnoses were established by clinical history and confirmed by transvaginal ultrasound (TVUS) as having endometriomas (n = 79) or DIE (n = 20) [n = 157). Women who were pregnant, undergoing oncological treatment, or had genitourinary prolapse were excluded from the study. Women attending the outpatient clinic at the hospital were recruited for the study by gynecologists. More than 95% of them agreed to participate and signing a informed consent form, with refusal mostly linked to a lack of time to complete the questionnaires. This study was approved by the Ethics Review Board of the University of Murcia on 3 October 2013. Moreover, this article follows the STROBE guidelines for reporting observational studies [We conducted a case-control study between September 2014 and May 2015 in a tertiary hospital from Murcia Region (Spain). Cases ((n = 20) ,25. Cont studies .® and 4–9 MHz transducer, General Electric Healthcare, Fairfield, CT, USA) at a scheduled clinical visit. For ultrasound examinations, the methods described by Abrao et al. for DIE cases [Women completed health questionnaires, were asked about gynecological history, and underwent a gynecological examination including TVUS (Voluson E-8IE cases  and GuerIE cases  were folIE cases . Height The Short Form (SF)-12v2 Health Survey is a validated short version of the SF-36v2 generic questionnaire that encompasses 12 items evaluating physical and mental health from the participant’s point of view  ,29,30. Tt tests, and differences between groups on categorical variables were compared with Pearson’s χ2. An analysis of covariance was used to calculate adjusted crude (0–100) and norm-based scales, as well as component summary differences between cases and controls, while taking relevant covariates into account. A multiple logistic regression model was used to explore associations between cases and controls, as well as norm-based scales and summary measure score with a cut-off of above/below 50 using odds ratios (ORs) and 95% CI. The model was adjusted for the following potential sources of confounding: age, educational level, marital status, infertility problems, and current occupation. based on previous publications, we decided that it would be adequate to detect a difference of at least 3 points (with an SD of about 7 points) in the global scores (PCS or MCS) between cases and controls for sample size calculation. If we accepted a risk of 0.05 and a statistical power of 80% to detect differences, if there were any, we would have needed 90 women in each group for a total of 180. All tests were two-tailed with a 0.05 significance level. All analyses were conducted using IBM SPSS 25.0 .We reported categorical variables as frequencies, and we reported valid percentages and continuous variables as mean/median and standard deviations. Group differences in continuous variables were analyzed using unpaired Student’s For the entire population, controls were younger and showed a higher educational level than cases, and there were also differences regarding marital status and current occupation .A comparison of the norm-based scales and summary measure scores of the SF-12v2 between cases and controls is presented in p < 0.05). For example, women with endometriosis (compared to controls) were 2.65 (1.48–4.75) or 2.33 (1.29–4.22) times more likely to have vitality or social functioning scores <50, respectively. However, when considering the MCS and its scales, only vitality, social functioning, and mental health remained significantly associated after multivariate adjustment. Nevertheless, no significant crude or adjusted associations were found with the MCS. For women with only endometriomas (n = 79), a sensitivity analysis was conducted, and it showed similar results compared to the total cases.The crude and adjusted OR and the 95% CI for the norm-based scales and summary measure scores of SF-12v2 between cases and controls were also calculated while taking a cut-off of 50 to indicate better or worse mental or physical health than the mean US population. Women with endometriosis were 8.36 times (95% CI: 4.06–17.2) more likely than controls to have PCS scores <50. The strength of this relationship remained significant when the analysis was conducted for the PCS subscales , with ORs ranging between 3.4 and 6.5  and the PCS of the SF-12v2 questionnaire in patients with endometriosis compared to controls. This fact suggests that endometriosis may play an important role in these women’s quality of life. Moreover, to our knowledge, no previous study has assessed associations between the HRQoL and presence of endometriomas or DIE in adult Spanish women.Several studies have evaluated HRQoL in women with endometriosis, and the presence of an impaired quality of life in this condition has been established. However, most of these studies assessed changes in HRQoL after randomized clinical trials—with surgery or drugs—or pre- and post-operative interventions in women with endometriomas or DIE ,34,35,36n = 931), HRQoL was significantly reduced in all eight scores, as well as both summary components, compared to norm-based scores from the general US population [Many validated questionaries, such as the WHOQOL-BREF quality of life questionnaire  and the pulation . The sampulation . Recentlpulation . In a crpulation  reportedOur results were moderately consistent with previous studies that showed similar findings. In our study, HRQoL was diminished in seven of the eight health scales and the PCS in cases compared to controls. Moreover, women with endometriosis presented values of around 45 for some of the scales , indicating a moderate influence of the disease on those aspects of HRQoL. Likewise, cases also showed values of around 45 for a few scales of the MCS . It is worth mentioning that the general health and emotional role scores were about 42, denoting a potentially large effect on HRQoL ,32.In our current study, MCS scores were relatively low (<50), mainly for cases (mean = 43.8). However, no significant differences between cases and controls were observed. In this regard, our results were not consistent with most of the previous studies ,17,21,22On the other hand, longitudinal studies would be necessary to confirm the potential causal assumptions reported here and to allow for the assessment of the effects of disease progression and related symptoms on women’s HRQoL. Endometriosis is a chronic disease that, in most patients, can only be “controlled” . A treatOn the basis of our findings, we may recommend a multidisciplinary approach to endometriosis care . A patieOur study was subject to limitations that we would be remiss not to point out. In case-control designs, selection and measurement bias must always be taken into account. Nevertheless, controls were women attending the same hospital in the same period who were from the same population from which the endometriosis cases came. The misclassification of disease status may have occurred, but, if present, it would have contributed to an underestimation of the true magnitude of associations.In conclusion, our findings support the hypothesis that HRQoL is significantly impaired in adult Spanish patients with endometriomas and DIE compared to controls. If confirmed, these results may have important implications for prevention, clinical practice, and intervention in women with this disease.


Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has additional benefits compared to other ARBs remains unclear.p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis . They also had lower risk of dementia diagnosis with IS as a competing risk  and with all-cause mortality as a competing risk . In addition, the telmisartan users had a lower risk of any IS  during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data.Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population. Chi-Hung Liu and co-workers study associations between antihypertensive medication prescriptions and dementia risk in people with type 2 diabetes. The drug of choice for antihypertensive treatment, and its association with dementia in patients with both type 2 diabetes mellitus (T2DM) and hypertension, is a valid question worthy of further investigations.Angiotensin receptor blockers (ARBs) modulate the renin–angiotensin–aldosterone system and potentially associate with cognitive preservation, but internal comparisons of the cognitive protective effects of different ARBs have not previously been performed.Telmisartan is the only ARB that, at a clinical dose, has agonistic effects on peroxisome proliferator-activated receptor γ (PPAR-γ), which maintains insulin sensitivity, reduces insulin resistance, and potentially has a protective impact on dementia.Using the electronic health records of the National Health Insurance Research Database of Taiwan between 1997 and 2013, we studied whether telmisartan was associated with a lower incidence of dementia compared to other ARBs in patients with T2DM and hypertension.Using telmisartan was associated with a lower risk of dementia diagnosis compared to using non-telmisartan ARBs (2.19% versus 3.20%).Telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any ischemic stroke events in an East-Asian population.Further work will be needed to investigate the observed association, owing to the limitations inherent in this observational study. Hypertension (HTN) is a major risk factor for stroke and dementia ,2. StrokAdequate HTN control has been shown to lower the risk of dementia ,9. In adThis nationwide cohort study included all patients registered in the National Health Insurance Research Database (NHIRD), which contains claims data from the National Health Insurance (NHI) program in Taiwan. International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used for the registration of all diagnoses, and the NHIRD is routinely monitored. Patients with T2DM were initially identified using the ICD-9-CM 250.XX diagnostic code between 1 January 1997 and 31 December 2013 ,28. StroWe used a “pseudo-placebo” comparison group rather than an active comparator design. We divided the eligible patients into 2 groups based on the ARB they received during the 6-month exposure window after the index date: telmisartan or non-telmisartan ARBs. We extracted data on medications from outpatient claims data or pharmacy refills for chronic illnesses. The patients were defined as being ARB users if telmisartan or another ARB was prescribed continuously for 6 months (or more) at outpatient visits or as pharmacy refills. We excluded patients from the non-telmisartan ARB group if they had taken telmisartan for even 1 day during the 6-month exposure period, to ensure there was consistent use of the study drugs in the 2 groups. In addition, to assess adherence to the medication, we calculated the medication possession ratio as the number of days that the medication was prescribed divided by the number of days during the 6-month time period after the index date. An ARB medication possession ratio ≥ 80% was required for the patients in both study groups. Blood sugar and BP levels were not available in the NHIRD, and therefore we adjusted for the types and average numbers of oral antidiabetic drugs (OADs) and antihypertensive medications to mitigate the bias related to different levels of blood sugar and BP . Cohort The covariates were age, sex, comorbidities , other antihypertensive medications , insulin, OADs , and other medications . We extracted the patients’ baseline characteristics from the database, and obtained their medical records before the index date to track any history of major comorbidities. The comorbidities were defined if the patients had at least 1 inpatient diagnosis or 2 outpatient diagnoses of a given disease in the previous year. We used the NHI’s catastrophic illness certificate database to identify a history of malignancy or dialysis. Previous MI and stroke were identified by any inpatient diagnosis before the index date, which was tracked up to 1997. Validation studies of the diagnostic codes for these events and comorbidities have been performed previously  33]. Pa. Pa33]. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease (AD) and the occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The diagnostic codes for dementia were recorded by a neurologist and/or a psychiatrist at a minimum of 2 outpatient visits or 1 inpatient hospitalization  35]. Th. Th35]. We used propensity score matching (PSM) to balance the distribution of baseline characteristics, and the number of OADs and antihypertensive drug classes used, between the study groups. The propensity score indicated the predicted probability of being in the telmisartan group, given the values of the selected covariates. The covariates used to calculate the propensity score included the variables listed in p < 0.05. Except for the additional analysis considering all-cause mortality as a competing risk, the other statistical analyses in this study were predefined.It is noted that this study did not have a formal prespecified analysis plan. As for the time-to-event outcomes , we used a Cox proportional hazard model to compare the risks between the study groups. We used the Fine and Gray subdistribution hazard model, which considered IS as a competing risk, to compare the time-to-dementia outcome between the 2 groups. We considered the study group (telmisartan versus non-telmisartan ARBs) as the only explanatory variable in the survival analyses. In addition, we conducted another post hoc analysis considering all-cause mortality during follow-up as a competing risk. Finally, we conducted subgroup analyses for dementia diagnosis based on 13 prespecified subgroup variables, including age, sex, CAD, CKD, chronic obstructive pulmonary disease, dyslipidemia, AF, number of antihypertensive agents, insulin use, aspirin use, pioglitazone use, statin use, and chronic benzodiazepine use. We used SAS version 9.4  to perform all statistical analyses. Statistical significance was set at Between 1 January 1997 and 31 December 2013, a total of 2,166,944 patients with a diagnosis of T2DM were recorded in the NHIRD. A total of 1,314,598 patients, including those who had missing information  and those who did not have a history of HTN , were excluded. Then, 111,879 patients who did not receive any ARB and 306,601 patients who had an ARB medication possession ratio < 80% were further excluded. In addition, patients who were aged < 50 years at enrollment  and those with a history of heart failure , previous stroke , previous traumatic brain injury , and dementia at enrollment  were also excluded. In total, 65,511 patients with T2DM and HTN were confirmed as eligible for analysis within the study based on the inclusion/exclusion criteria .Before PSM, there were 2,284 patients in the telmisartan group and 63,227 patients in the non-telmisartan ARB group. The patients in the telmisartan group were younger; had a higher prevalence of dyslipidemia, CAD, and chronic obstructive pulmonary disease; and had higher Charlson Comorbidity Index scores. The patients in the telmisartan group also had a lower prevalence of CKD, lower average number of antidiabetic drugs, and a shorter follow-up duration . After Pp = 0.030; p = 0.022; p = 0.029; The follow-up duration between the index date and the first outcome exposure was similar between the 2 groups  after PSM . The prip = 0.008; p = 0.207; p = 0.966), and AD  were not significantly different between the 2 groups at the end of the follow-up period Click here for additional data file.S1 Figp < 0.05. CI, confidence interval; HR, hazard ratio.Statistical significance for the interaction of subgroup analyses was set at (TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.


Uveal melanoma (UVM) is the leading cause of eye-related mortality worldwide. This study aimed to explore the expression and prognostic value of matrix metalloproteinases (MMPs) in UVM.Gene expression levels were obtained from the Gene Expression Omnibus (GEO) and Oncomine databases. Functional and pathway enrichment analyses were performed using the Metascape database. GeneMANIA was then applied to construct a protein-protein interaction network and identify the hub genes. Moreover, overall survival (OS) and disease-free survival (DFS) analysis for the hub genes was performed using the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Furthermore, TRRUST was used to predict the targets of the MMPs.MMP1, MMP9, MMP10, MMP11, MMP13, MMP14, and MMP17 were upregulated in UVM tissues compared to normal tissues. A protein-protein interaction (PPI) network was constructed and the top 50 hub genes were identified. The functions of MMPs and their neighboring proteins are mainly associated with ECM-receptor interaction, proteoglycans in cancer, the IL-17 signaling pathway, and microRNAs in cancer. Among the MMPs, MMP1/2/9/11/14/15/16/17/24 played significant roles in the progression of UVM from stage 3 to stage 4. We also found that the expression of MMP1, MMP2, MMP9, and MMP16 positively correlated with OS and DFS in patients with UVM. Additionally, 18 transcription factors associated with nine MMPs were identified.Our results revealed that the transcriptional levels of The results of this study may provide potential biomarkers and targets for UVM. However, further studies are required to confirm these results. Uveal melanoma (UVM) is the most common primary malignant tumor of the eye in adults . It ofteTo date, 26 MMPs have been investigated, most of which are present in the human proteome . MMPs caIn recent years, studies have shown that MMPs expression is associated with the occurrence and development of a variety of tumors. These molecules are important in the growth and invasion of malignant tumors and their expression has an important impact on the prognosis of patients –16 . HowIn recent years, with the development of high-throughput technology, gene chips and gene sequencing have become necessary and efficient methods for studying tumor diseases. In the era of big data, much genomic, epigenomic, and transcriptomic data are available in online databases. However, effective data mining remains lacking. This study used bioinformatic methods to detect the expression and mutation of the core MMPs, aiming to screen the genes closely related to the occurrence, development, and prognosis of UVM through clinical big data. We aimed to provide a reference for the clinical treatment of UVM, by establishing a theoretical basis for the research and development of targeted therapies for this malignancy.Since all the data were retrieved from the online databases, we assumed that all written informed consent had been already obtained.https://www.malacards.org) is an integrated database of human maladies and their annotations, modeled on the architecture and richness of the popular GeneCards database of human genes [MalaCards (an genes . In thiswww.oncomine.org) is a classic cancer sample database. It is a cancer microarray database and integrated data mining platform which aims to promote the discovery of genome-wide expression analysis [p-value were as follows: fold change, 1.5; p value, 0.01; gene rank, 10%; data type, mRNA.ONCOMINE  is currently the largest cancer gene information database that is comprehensive in many cancer types and multi-omics data [http://www.cbioportal.org/) [TCGA  . Mutatiohttp://metascape.org/gp/index.html#/main/step1) is a public online analysis database used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses [p value cutoff, 0.01; minimum enrichment, 1.5.Metascape  is an online prediction website that provides information on protein-DNA, protein-protein, and genetic interactions, reactions, pathways, and protein domains of related genes [GeneMANIA (ed genes . In our http://gepia2.cancer-pku.cn/#index) is an indispensable and highly cited database for gene expression analysis [Based on tumor and normal samples from the TCGA and GTEx databases, GEPIA 2  is an effective website for online analysis and mining of cancer data, mainly based on the relevant cancer data in the TCGA database [p < 0.05.UALCAN (database . In thishttps://www.grnpedia.org/trrust/) is a curated database of human and mouse transcriptional regulatory networks that contains information derived from 11,237 published articles [TRRUST (articles . In our http://timer.cistrome.org/) is a comprehensive resource for systematical analysis of immune infiltrations across diverse cancers [TIMER  functions for these genes were primarily endodermal cell differentiation, negative regulation of membrane protein ectodomain proteolysis, response to wounding, ovulation cycle, negative regulation of defense response, response to cAMP, and regulation of multi-organism processes. The cellular components (CC) related to these genes were mainly collagen-containing extracellular matrix, tertiary granules, blood microparticles, and endoplasmic reticulum lumen. The identified molecular functions (MF) related to these genes were metalloendopeptidase activity, serine-type peptidase activity, carbohydrate binding, collagen binding, metalloaminopeptidase activity, calcium ion binding, sulfur compound binding, cytokine activity, and growth factor binding Fig. .Fig. 2PThe top eight KEGG pathways for MMP family members and their neighboring genes are shown in Fig. MMP16 (43%) had the highest genetic variation rate, while MMP1 (1.3%) had the lowest. MMP2, MMP9, MMP11, MMP14, MMP15, MMP17, and MMP24 were altered in 8, 6, 6, 6, 4, 6, and 10% of the patients with UVM, respectively , while there was a significant difference in DFS   Fig. A. MMP16 MMP16 4% had theMMP16 4% had theHPX (hemopexin), CTB-96E2.2, PRG4 (proteoglycan 4), VTN (vitronectin), and ASTL . Figure Moreover, a gene-gene interaction (GGI) network of 23 MMPs was constructed and analyzed using the GeneMANIA database  and OS in patients, which was almost consistent with the results presented above. Moreover, there were significant associations between certain MMPs  and DFS.We also used the GEPIA dataset to compare the mRNA expression of MMPs to the OS and DFS of patients with UVM. DFS and OS curves are presented in Figs. MMP1, MMP2, MMP9 and MMP16 expression levels may be exploited as potential biomarkers for the prediction of the survival of patients with UVM.Taken together, these results showed that MMP1, MMP2, MMP9, MMP11, MMP14, MMP15, MMP16, MMP17, and MMP24 were included in TRRUST. We found that 18 transcription factors  were associated with the regulation of MMPs , which contains a potential transmembrane domain, indicating that it is expressed on the cellular surface.The protein encoded by MMP14 expression is associated with poor prognosis and might serve as a marker of progression in muscle-invasive bladder cancer and colorectal cancer [MMP14 expression can inhibit the invasion and metastasis of breast cancer and gastric cancer cells [MMP14 was found to be upregulated in UVM, and high expression indicated shorter DFS, but it was not associated with OS in patients with UVM.Studies have reported that high l cancer , 46. Lower cells , 48. In MMP14, the protein encoded by MMP15 is also a member of the MT-MMP. MMP15, also known as MT2-MMP, was first extracted from a human lung cDNA library.Like MMP15 is highly expressed in bladder cancer and contributes to inflammation and angiogenesis in cancer cells [MMP15 is significantly higher in tumors with a higher level of aggressiveness and malignancy [MMP15 was not found to be upregulated in UVM and the expression of MMP15 was not associated with OS or DFS in patients with UVM.It is composed of 669 amino acids encoded in 3530 bp of the gene. Proteins in this family are associated with the breakdown of the extracellular matrix in various diseases. er cells . MMP15 ier cells . The expMMT16 was once referred to as MT-MMP2 and is has been renamed as MT-MMP3 or MMP16.MMP24 is an important paralog of the MMP16 gene. Some studies have indicated that high expression of MMP16 is associated with the proliferation, migration, and invasion of cutaneous squamous cell carcinoma cells [MMP16 could inhibit cell proliferation and invasion in chordoma cells [MMP16 have been found to be associated with different types of diseases [MMP16 was found to be upregulated in UVM, and high expression was associated with shorter OS and DFS.MMP16 is activated when cleaved by other proteinases. Degradation of extracellular and microRNAs in cancer is an important pathway related to MMP16. ma cells , while kma cells . Moreovediseases , 53. In MMP17 is a protein-coding gene that is associated with diseases such as breast cancer [MMP17 has been associated with different physiological and pathological processes, the mechanisms underlying these processes remain unknown. In our study, MMP17 was not found to be upregulated in UVM and the expression of MMP17 was not associated with OS and shorter DFS in UVM.t cancer , colon ct cancer , and heat cancer . While tMMP16 is an important paralog of this gene.The MMP24 protein is associated with the breakdown of the extracellular matrix in disease processes and normal physiological processes. The proteins cadherin 2 and MMP2 are substrates of this protease. MMP24 was not found to be upregulated in UVM and the expression of MMP24 was not associated with overall survival and shorter disease-free survival in uveal melanoma patients. However, MMP24 play a significant role in the progression from stage 3 to stage 4 for UVM patients.In the present study, we comprehensively assessed the expression and prognostic value of 26 MMPs in UVM. In our study, To date, our study is the first bioinformatic analysis to explore the association between UVM and all the members of the matrix metalloproteinase family. However, there are some limitations in our study. First, due to the limitation of conditions, there is no relevant experimental verification in our study. At the appropriate time in the future, we will carry out related experiments. Second, due to the lack of clinical data on UVM in relevant databases, such as TCGA, we could not find sufficient data for an effective analysis.MMP1/9/10/11/13/14/17 are obviously upregulated in UVM and may play an important role in its occurrence and progression. MMP 1/2/9/11/14/15/16/17/24 could be used as molecular markers to elucidate the stages of UVM. In addition, abnormal expression of MMP1/2/9/11/16 was found to be related to OS in UVM, and MMP1/2/9/11/14/16 were found to be associated with DFS. Moreover, the expression of MMP1, MMP2, MMP9, and MMP16 was positively correlated with OS and DFS. We also found that most MMPs correlated with the infiltration of immune cells. Overall, our results revealed that MMP1 and MMP9 may serve as potential prognostic biomarkers and as therapeutic targets for UVM. However, further studies are needed to confirm our results and assess the clinical utility of MMPs.In conclusion, the current study suggests that the transcription levels of