ABSTRACT
OBJECTIVE@#To investigate the preparation of decellularized small intestinal submucosa (dSIS) sponge scaffolds with chelated strontium (Sr) ions at different pH values, and to select the appropriate pH values for synthesizing Sr/dSIS scaffolds using the physicochemical properties and biocompatibility of the scaffolds as evaluation indexes.@*METHODS@#(1) Sr/dSIS scaffolds preparation and grouping: After mixing dSIS solution and strontium chloride solution in equal volumes, adjusting pH of the solution to 3, 5, 7, and 9 respectively, porous scaffolds were prepared by freeze-drying method after full reaction at 37℃, which were named Sr/dSIS-3, -5, -7, and -9 respectively, and the dSIS scaffolds were used as the control group. (2) Physicochemical property evaluation: The bulk morphology of the scaffolds was observed in each group, the microscopic morphology analyzed by scanning electron microscopy, and the porosity and pore size determined, the surface elements analyzed by energy spectroscopy, the structure of functional groups analyzed by infrared spectroscopy, the chelation rate determined by atomic spectrophotometry, the water absorption rate detected by using specific gravity method, and the compression strength evaluated by universal mechanical testing machine.(3) Biocompatibility evaluation: The cytotoxicity and proliferative effect to bone mesenchymal stem cells (BMSCs) of each group were evaluated by Calcein-AM/PI double staining method.@*RESULTS@#Scanning electron microscopy showed that the scaffolds of each group had an interconnected three-dimensional porous structure with no statistical difference in pore size and porosity. Energy spectrum analysis showed that strontium could be detected in Sr/dSIS-5, -7 and -9 groups, and strontium was uniformly distributed in the scaffolds. Functional group analysis further supported the formation of chelates in the Sr/dSIS-5, -7 and -9 groups. Chelation rate analysis showed that the Sr/dSIS-7 group had the highest strontium chelation rate, which was statistically different from the other groups (P < 0.05). The scaffolds in all the groups had good water absorption. The scaffolds in Sr/dSIS-5, -7 and -9 groups showed significantly improved mechanical properties compared with the control group (P < 0.05). The scaffolds in all the groups had good biocompatibility, and the Sr/dSIS-7 group showed the best proliferation of BMSCs.@*CONCLUSION@#When pH was 7, the Sr/dSIS scaffolds showed the highest strontium chelation rate and the best proliferation effect of BMSCs, which was the ideal pH value for the preparation of the Sr/dSIS scaffolds.
Subject(s)
Tissue Scaffolds/chemistry , Biocompatible Materials , Strontium/pharmacology , Ions , Hydrogen-Ion Concentration , Tissue Engineering/methods , PorosityABSTRACT
Objective: To analyze the morbidity and mortality trends of thyroid cancer in China from 1990 to 2019, explore the causes of the trends, and predict morbidity and mortality in the future. Methods: The morbidity and mortality data of thyroid cancer in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease database. The Joinpoint regression model was used to describe the change trends. Based on the morbidity and mortality data from 2012 to 2019, a grey model GM (1,1) was constructed to predict the trends in the next ten years. The model was tested by the posterior error method and residual test method. Results: In all populations, men and women, the AAPC values of the crude morbidity rates were 4.15% (95%CI: 3.86%-4.44%, P<0.001), 5.98% (95%CI: 5.65%-6.31%, P<0.001) and 3.23% (95%CI: 2.94%-3.53%, P<0.001) respectively, the AAPC values of age-standardized morbidity rates were 2.47% (95%CI: 2.12%-2.83%, P<0.001), 3.98% (95%CI: 3.68%-4.29%, P<0.001), 1.65% (95%CI: 1.38%-1.93%, P<0.001), the AAPC values of crude mortality rates were 2.09% (95%CI: 1.92%-2.25%, P<0.001), 3.68% (95%CI: 3.45%-3.90%, P<0.001), 0.60% (95%CI: 0.50%-0.71%, P<0.001). The age-standardized mortality rates in men showed a fluctuating trend of first decrease (1990-1994), then increase (1994-2012), and then decrease (2012-2019) (AAPC=1.35%, 95%CI: 1.16%-1.53%, P<0.001). The age-standardized mortality rate in women continuously decreased (AAPC=-1.70%, 95%CI: -1.82%- -1.58%, P<0.001). The GM (1,1) models can be used for medium and long-term predictions. The results of the residual test show that the average relative error values of all models are less than 10.00%, the prediction accuracy values are more than 80.00%, and the prediction effects are good. The results of the posterior error method show that all the prediction results are good except the qualified prediction of the age-standardized morbidity rate in men. In 2029, the crude morbidity rates would increase to 3.57/100 000, 2.78/100 000, and 4.40/100 000, respectively, and the age-standardized incidence rates would increase to 2.38/100 000, 1.89/100 000, and 2.88/100 000, respectively, the crude mortality rates would increase to 0.57/100 000, 0.62/100 000 and 0.53/100 000, and the age-standardized mortality rates would decrease to 0.33/100 000, 0.42/100 000 and 0.27/100 000 in all population, men and women in China. Conclusions: The overall, gender- specific age-standardized mortality rates showed downward trends in the last decade or so, and the prediction results showed that it might further decline. However, the crude morbidity rates, age-standardized and crude mortality rates have been on the rise, and the population aging is becoming increasingly serious in China, which requires close attention and targeted prevention and control measures.
Subject(s)
Male , Humans , Female , Morbidity , Thyroid Neoplasms/epidemiology , Aging , China/epidemiologyABSTRACT
Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the serious complications mostly occurring within 100 days after hematopoietic stem cell transplantation (HSCT). Risk factors of TA-TMA include genetic predispositions, GVHD, and infections. The pathophysiological mechanisms of TA-TMA start with endothelial injury caused by complement activation, which leads to microvascular thrombosis, and microvascular hemolysis, ultimately resulting in multi-organ dysfunction. In recent years, the development of complement inhibitors has markedly improved the prognosis of TA-TMA patients. This review will give an update on risk factors, clinical manifestations, diagnosis, and treatment of TA-TMA, so as to provide references for clinical practice.
Subject(s)
Humans , Thrombotic Microangiopathies/therapy , Prognosis , Thrombosis/etiology , Risk Factors , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
@#Objective To understand the epidemiological and etiological characteristics of influenza in Mianyang City from 2019 to 2021, so as to provide a basis for the prevention and control of influenza. Methods Influenza surveillance data in Mianyang City from 2019 to 2021 were collected and analyzed statistically. Results A total of 55 970 cases of influenza were reported in Mianyang City from 2019 to 2021, with an average annual incidence of 388.08/100 000. A total of 103 723 cases of influenza -like illness cases (ILI) were reported, with an average annual ILI% of 3.58%. The incidence, ILI% , and positive detection rates of influenza were all far higher than those in the corresponding period in 2019. The classification of the population is mainly composed of students under the age of 15. The top three reported cases were Fucheng District (20 118, 35.94%), Youxian District (6 394, 11.42%) and Jiangyou District (5 800, 10.36%). 10 126 samples of ILI were received and detected, with a positive rate of 19.53%, the positive rate of ILI samples was mainly students under 15 years old. The dominant strains of influenza viruses showed an alternating trend over the years, and A (H3) was the predominant type in 2019. Except for 2 A (H9) strains detected in 2021, the rest were all BV strains. Due to the impact of COVID-19 in 2020, the positive detection rate was low throughout the year. 43 outbreaks of ILI were reported, which were mainly occurred in winter, and most of them were in primary schools. Conclusion From 2019 to 2021, the characteristics of cases, ILI, pathogen surveillance and outbreak events of influenza in Mianyang City are basically the same, with students under 15 years of age and schools remaining the key population and sites of concern. the importance of non-pharmaceutical interventions for influenza prevention and control is further evidenced by the low incidence of influenza during the COVID-19 pandemic.
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Objective: To investigate the clinicpathological characteristics of ALK-positive anaplastic large cell lymphoma (ALCL) of the gastrointestinal tract, and to discuss its diagnosis and differential diagnosis. Methods: Five cases of gastrointestinal ALK-positive ALCL diagnosed and treated in Xijing Hospital of the Fourth Military Medical University, between 2011 and 2019 were collected. There were three male and two female patients, aged 5-42 years (mean 25 years). These patients clinically presented with fever and night sweats, weight loss, abdominal pain, abdominal mass, ulcers, bleeding, or intestinal obstruction, and underwent surgical resection of the tumors or endoscopic biopsy. The clinical manifestations, auxiliary examinations, histopathological characteristics, immunophenotypes and genetic alterations were analyzed. Results: In this cohort, one case was common type, two cases were monomorphic variant of common type, and two cases were small cell variant. The tumor cells in all cases expressed ALK, CD30, and one or more T lymphocyte markers, while all the markers of B lymphocyte and plasmacyte were negative. Clonality analysis showed that two cases had clonal T cell receptor (TCR) and immunoglobulin (Ig) gene rearrangement, one case had no clonal TCR but Ig gene rearrangement, and one case had no clonal TCR and Ig gene rearrangements. During the 4 to 67 months' follow-up, two patients died of the disease, two were alive with free of disease and one had a relapse. Conclusions: ALK-positive ALCL of the gastrointestinal tract is extremely rare, and has poor prognosis. Lymphoma originating from this site with CD30 and ALK-positive phenotypes may be considered to be ALCL; however differentiation from other tumors that had anaplastic features, expressed CD30 and or ALK, in particular, ALK positive large B-cell lymphoma is necessary.
Subject(s)
Male , Female , Humans , Lymphoma, Large-Cell, Anaplastic/pathology , Receptor Protein-Tyrosine Kinases/genetics , Anaplastic Lymphoma Kinase , Gastrointestinal Tract/pathology , Lymphoma, Large B-Cell, Diffuse/geneticsABSTRACT
Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.
Subject(s)
Animals , Mice , Female , Humans , Uterine Cervical Neoplasms/radiotherapy , bcl-2-Associated X Protein/genetics , Mice, Nude , Proto-Oncogene Proteins c-bcl-2/genetics , Apoptosis , MicroRNAs/genetics , Cell Proliferation , Cell Line, TumorABSTRACT
Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.
Subject(s)
Animals , Mice , Female , Humans , Uterine Cervical Neoplasms/radiotherapy , bcl-2-Associated X Protein/genetics , Mice, Nude , Proto-Oncogene Proteins c-bcl-2/genetics , Apoptosis , MicroRNAs/genetics , Cell Proliferation , Cell Line, TumorABSTRACT
Objective:To summarize the precision fluid management of patients with severe blast injury in the emergency intensive care unit, so as to help patients smoothly pass through the dangerous period and recover smoothly.Methods:Based on the experience of fluid management in 6 patients admitted to the Second Affiliated Hospital Zhejiang University School of Medicine in the tanker truck explosion on 14 June, 2020. The main measures included: fluid volume management and dynamic adjustment; assessment of intake, output and urine volume, and dynamic adjustment of infusion volume and speed; monitoring of pulmonary oxygenation and timely adjustment of fluid resuscitation strategies; monitoring indexes and providing nursing care strategies for fluid management.Results:Finally, among 6 patients with severe blast injury, 5 patients were discharged from the hospital with follow-up treatment after they suffered from the shock and infection phases and refined fluid management, 1 patient died due to severe injury and ineffective rescue.Conclusions:Adopting individualized, phased, and refined liquid management strategy has clinical significance for patients with severe blast injury to smoothly pass the risk period.
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(3S)-Linalool synthase (LIS) is a key enzyme involved in the monoterpene biosynthetic pathway. Based on our previous transcriptome study, the expression level of LIS gene was exceedingly related to glycyrrhizic acid (GA) biosynthesis. Therefore, we used hairy root culturing to further investigate the effect of LIS on the GA biosynthesis. A LIS gene (GenBank accession number: MZ169552) was cloned from Glycyrrhiza uralensis. The plant binary overexpression vector pCA-LIS was constructed by gene fusion. G. uralensis hairy roots overexpressing LIS were induced by the Agrobacterium rhizogenes ATCC15834. The expression levels of LIS were analyzed by real-time quantitative PCR (RT-qPCR) and the contents of GA in hairy root lines were determined by UPLC. It was found that in the hairy root lines overexpressing LIS, the expression levels of LIS were significantly higher than that in the wild type, while the contents of GA were remarkably lower than those in the wild type and negative control. These findings indicate that the expression level of LIS is negatively correlated with the accumulation of GA. In this study, LIS was cloned from G. uralensis for the first time and the negative regulatory effect of LIS on GA biosynthesis was confirmed by reverse genetics. This work provides support for further improvement of the molecular regulatory network of GA biosynthesis in G. uralensis.
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@#In recent years, with the continuous improvement of computer science and technology, artificial intelligence(AI)technology based on deep learning(DL)has developed rapidly and attracted wide attention all over the world. Great progress has been made in the research and application of AI in the medical field. In the field of optometry, AI can assist the diagnosis of myopia, strabismus, amblyopia and other diseases, and has achieved good results in the screening and early diagnosis of keratoconus as well as in the prevention and correction of myopia. Nevertheless, there are some limitations and great challenges in the application of AI in optometry, including clinical and technical challenges, interpretability of algorithmic results, medical legal issues and so on. This paper reviews the application, limitation and prospect of AI in the field of optometry.
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Objective To study the acromial angle morphologic type and measurement analysis based on CT 3D reconstruction. Methods Totally 278 cases of adult CT three-dimensional reconstruction of the shoulder morphological data were collected, and the measurement data of the different types was analyzed, its statistical significance was clarified, and the morphological characteristics to division the type of acromial angle were summarized, its diagnosis and treatment under the acromion impingement of guiding significance were discussed. Results The acromial angle was divided into three types (C shaped acromial angle, L shaped acromial angle, and double angle shaped acromial angle). Among them, L type was the most, accounting for 48. 56%, followed by C type, and double angle type was the least. In comparison of the breadth of the acromion and the length of the acromion, L type was significantly longer than C type (P<0. 05). The thickness of acromion at a point of the double angle shaped acromial angle was greater than that of the other two type (P<0. 05). In the comparison of ∠a, the double-angle type was greater than the C type(P<0.05), and the C type was greater than the L type(P<0.05). Conclusion There are significant differences in the classification and anatomical parameters of acromial angle, and the differences are statistically significant. It has certain guiding significance to the etiology and clinical diagnosis and treatment of subacromial impingement syndrome.
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Objective:To explore the potential targets and pathways of steroid alkaloids<italic> </italic>from<italic> Solanum</italic> <italic>nigrum</italic> (SASN) in the treatment of non-small cell lung cancer (NSCLC) and analyze the possible mechanism. Method:The active SASN against NSCLC were searched from literature. Then potential targets of SASN were screened through SwissTargetPrediction and PharmMapper, and those of NSCLC through GeneCards. Venny was employed to yield the common targets of the two, and Cytoscape to construct the 'medicinal-component-disease-target' network. Metascape was applied to enrich the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the common targets, and STRING was used to generate the protein-protein interaction (PPI) network, followed by screening of key targets by Cytoscape. Finally, Western blot was used to verify the effects of the medicinal on key targets. Result:A total of 6 active SASN were screened out: solasonine, solamargine, solasodine, solanocapsine, solanidine, and <italic>N</italic>-methylsolasodine, which had 96 potential anti-NSCLC targets. These targets mainly involved the pathways in cancer, proteoglycans in cancer, and Forkhead box protein O (FoxO) pathway. PPI network analysis demonstrated 15 key anti-NSCLC targets of SASN, such as mitogen-activated protein kinase (MAPK)1, MAPK8, MAPK14, protein kinase B (Akt1), signal transducer and activator of transcription 3 (STAT3), and proto-oncogene tyrosine protein kinase (SRC). Meanwhile, Western blot results showed that SASN could significantly down-regulate the expression of the key proteins Akt1, SRC, and STAT3. Conclusion:We predicted the potential targets and pathways of SASN against NSCLC and obtained 15 key targets, from which we selected three key proteins for validation. The validation results were consistent with the prediction results. This paper is expected to lay a scientific basis for the subsequent in-depth study of the mechanisms of SASN against NSCLC.
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Objective:To investigate the neuroprotective effect of Danggui Shaoyaosan (DSS) in a rat model of amyloid-<italic>β</italic>-peptide<sub>1-42</sub> (A<italic>β</italic><sub>1-42</sub>)-induced Alzheimer's disease (AD) as well as its regulatory effect on NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific protease-1 (Caspase-1) signaling pathway. Method:The AD animal model was established via intracerebral injection of A<italic>β</italic><sub>1-42</sub> and treated with different concentrations of DSS after the division of rats into the sham operation group, model group, as well as the high-, medium-, and low-dose DSS groups. Morris water maze test was conducted to determine the learning and memory abilities of rats. The morphology and function of neurons were detected by hematoxylin-eosin (HE) staining and Golgi staining, followed by immunofluorescence co-localization of NLRP3 inflammasome activation. The mRNA expression levels of interleukin (IL)-1<italic>β</italic> and IL-18 were measured by Real-time polymerase chain reaction (Real-time PCR), and the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β </italic>were assayed by Western blot. Result:Compared with the sham operation group, the model group exhibited significantly decreased learning and memory abilities (<italic>P</italic><0.01), impaired neuronal morphology and function, up-regulated IL-1<italic>β</italic> and IL-18 mRNA expression, enhanced NLRP3 inflammasome activation, and elevated NLRP3, Caspase-1, and IL-1<italic>β</italic> protein expression (<italic>P</italic><0.01). Compared with the model group, DSS at both medium and high doses remarkably improved the learning and memory abilities of AD rats (<italic>P</italic><0.05, <italic>P</italic><0.01), restored neuronal morphology and function, down-regulated the mRNA expression levels of inflammatory factors IL-1<italic>β</italic> and IL-18, reduced the activation of NLRP3 inflammasomes, and lowered the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β</italic> (<italic>P</italic><0.01). Conclusion:DSS inhibits inflammasome activation and neuroinflammatory response possibly by regulating the NLRP3/Caspase-1 signaling pathway, thus exerting the neuroprotective effect.
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Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan
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OBJECTIVE@#To analyze the prognostic factors affecting the failure of transvaginal repair of vesicovaginal fistula (VVF).@*METHODS@#A retrospective nested case-control study was conducted. A total of 15 patients who underwent unsuccessful transvaginal vesicovaginal fistula repair in the Department of Urology, Peking University First Hospital from January 2014 to December 2020 were enrolled as the case group. A total of 60 patients receiving transvaginal vesicovaginal fistula repair by the same surgeon within the same time range, were selected as the control group. The age, body mass index (BMI), etiology of vesicovaginal fistula, associated genitourinary malformation, frequency of repair, characteristics of fistula, surgical procedure, postoperative recovery and other factors were compared between the case group and the control group, and the influencing factors of failure were analyzed.@*RESULTS@#The BMI of the case group was (26.3±3.9) kg/m2, the diameter of vaginal fistula was (1.5±0.8) cm, and the operative time of transvaginal repair was (111.8±19.8) min. The proportion of the patients with genitourinary malformations was 4/15, the proportion of the patients with multiple vaginal repairs was 13/15, the proportion of the patients with concurrent ureteral reimplantation was 6/15, and the proportion of the patients with postoperative fever was 5/15. In the control group, the BMI was (23.9±3.0) kg/m2, the diameter of vaginal fistula was (0.8±0.5) cm, the operative time of transvaginal repair was (99.9±19.7) min, the rate of associated genitourinary malformation was 2/60, the rate of multiple transvaginal repair was 18/60, the rate of concurrent ureteral reimplantation was 5/60, and no postoperative fever was found. Compared with the control group, the case group had higher BMI (P=0.013), bigger vaginal fistula (P=0.002), longer time of operation (P=0.027), higher proportion of genitourinary malformations (P=0.013), higher proportion of repeated transvaginal repair (P < 0.001), higher proportion of ureter reimplantation (P=0.006), and higher proportion of postoperative fever (P < 0.001). Multivariate analysis showed that fistula diameter ≥1 cm (OR=10.45, 95%CI=1.90-57.56, P=0.007) and repeated transvaginal repair (OR=16.97, 95%CI=3.17-90.91, P=0.001) were independent prognostic factors for VVF failure in transvaginal repair.@*CONCLUSION@#Fistula diameter ≥1 cm and repeated transvaginal repair are independent prognostic factors of failure in transvaginal repair.
Subject(s)
Female , Humans , Case-Control Studies , Gynecologic Surgical Procedures , Prognosis , Retrospective Studies , Treatment Outcome , Vesicovaginal Fistula/surgeryABSTRACT
OBJECTIVE@#To evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP).@*METHODS@#From January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D'Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated.@*RESULTS@#In total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 μg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462, P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group.@*CONCLUSION@#RARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.
Subject(s)
Aged , Humans , Male , Prostatectomy , Prostatic Neoplasms/surgery , Recovery of Function , Robotics , Treatment Outcome , Urinary Incontinence/etiologyABSTRACT
Objective::Based on gene array technology, gene set enrichment analysis (GSEA) and immune infiltration analysis were performed on chip data of intracranial aneurysm (IA) mRNA expression profile, in order to provide theoretical basis for understanding the formation mechanism of IA. Method::The GSE75436 raw data were obtained from the gene expression omnibus (GEO). GSEA of biological process (BP) in gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) signaling pathways were analyzed for gene expression profile by R software. The CIBERSORT deconvolution method was used to analyze the infiltration ratio of 22 types of immune cells in the expression profile. And COREMINE database was used to predict traditional Chinese medicines (TCMs), which were significant correlation with the enrichment result. Result::The GSEA results showed that the changes in gene expression of IA samples mainly involved in the regulation of cytokines, activation and differentiation of leukocyte, inflammatory immune response and other processes. The infiltration matrix analysis of immune cells showed that mast cells resting and neutrophils were significantly reduced in IA samples. The comparison of paired samples showed that mast cells and natural killer cells (NK cells) were significantly activated in the IA samples of the same individual, while neutrophils and T cells CD4 naive were significantly reduced. Through COREMINE prediction, it was found that Stephaniae Tetrandrae Radix was correlated with the activation of granulocytes, Sapindi Mukorossi Semen and Pistaciae Chinensis Cortex were correlated with the activation of neutrophils, Trichosanthis Semen, Paeoniae Radix Alba and Ligustri Lucidi Fructus were correlated with the cytotoxicity mediated by NK cells. Conclusion::Activation of mast cells and NK cells are closely associated with the occurrence and development of IA. The inflammatory immune processes and pathways such as nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway and cytotoxicity mediated by NK cells may be important factors in the pathogenesis of IA, and TCMs such as Stephaniae Tetrandrae Radix may be the potential molecular drug sources.
ABSTRACT
The application of artificial intelligence in medicine has gradually received attention along with its development. Many studies have shown that machine learning has a wide range of applications in stomatology, especially in the clinical diagnosis and treatment of maxillofacial cysts and tumors. This article reviews the application of machine learning in maxillofacial cyst and tumor to provide a new method for the diagnosis of oral and maxillofacial diseases.
Subject(s)
Humans , Artificial Intelligence , Cysts/diagnosis , Machine Learning , Oral MedicineABSTRACT
OBJECTIVE@#To explore risk factors of urinary incontinence (UI) and influences of UI on quality of life in female medical staff from Beijing.@*METHODS@#One hundred and forty-six female medical personnel were included in the present study through the convenient sampling method in Peking University First Hospital. The questionnaires contained the following information: demographic information, daily urination condition, the severity of UI [international consultation on incontinence questionnaire short form (ICI-Q-SF)], and the influences of UI on quality of life (QOL). We excluded the subjects who were in pregnancy or had urinary infection, neurogenic bladder, or urethral stricture. We used SPSS 21.0 software (IBM Corp, Armonk, NY) for statistical analysis. The Kolmogorov-Smirnov test determined the normality of the continuous variables. Means and standard deviation presented continuous variables in normality. Median and range presented continuous variables without normality. Frequency and percentile were used to present categorical or ranked variables.@*RESULTS@#There were 63 out of 146 (43.2%) female medical staff suffering from UI. The mean age and body mass index of the whole study cohort were (39.4±9.9) years and (22.3±3.4) kg/m2. The median delivery times of all the subjects were 1 time (range: 0-3 times). Fifty out of 146 (34.2%) subjects had transvaginal delivery history. Chronic constipation was diagnosed in 32 subjects (21.9%). No significant difference in daytime micturition and nocturia times were found between the UI and non-UI subjects. According to the multivariate analysis, chronic constipation (OR=4.95, 95%CI=1.81-13.53, P=0.002) and transvaginal delivery history (OR=3.50, 95%CI=1.49-8.21, P=0.004) were independent risk factors for UI. The non-UI subjects had superior quality of life than the UI subjects in terms of incontinence quality of life (I-QOL) total scores and all sub-scores of avoidance and limiting behaviors, psychosocial impacts, and social embarrassment (P<0.001). In addition, avoidance and limiting behaviors (r=-0.449, P<0.001), psychosocial impacts (r=-0.538, P<0.001), and social embarrassment (r=-0.454, P<0.001) of the 63 UI subjects were equally influenced by the incontinence symptom.@*CONCLUSION@#UI is not uncommon in female medical staff. The quality of life of medical faculty is influenced by UI in terms of avoidance and limiting behaviors, psychosocial impacts, and social embarrassment. Chronic constipation and transvaginal delivery history were independent risk factors for UI.
Subject(s)
Adult , Female , Humans , Middle Aged , Pregnancy , Medical Staff , Quality of Life , Risk Factors , Surveys and Questionnaires , Urinary IncontinenceABSTRACT
Endothelial dysfunction is a major risk factor for vascular complication. Nitric oxide (NO),the most important product of endothelial cells,lays a key role in regulating vasomotor as an endogenous vasodilatation factor. NO is produced by endothelial NO synthase (eNOS) on its substrate L-arginine. Arginase,which metabolizes L-arginine to urea and ornithine,competes directly with eNOS for L-arginine leading to the decrease of NO production. This paper reviews the basic role of arginase, the development of arginase inhibitors and its effects on diabetic vascular complications.