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@#Abstract: In recent years, the field of nucleic acid therapeutics has been flourishing, progressively establishing itself as the third generation of drug modalities following small molecules and antibody-based drugs. Artificial intelligence technology based on machine learning is advancing rapidly, which can significantly accelerate the development process of nucleic acid therapeutics. This review provides an overview of the foundational aspects of artificial intelligence algorithms, databases, and characterizations in the field of nucleic acid drug development. It elucidates the advances in the application of artificial intelligence in nucleic acid structural prediction, small nucleic acid drug design, and other research and development phases of nucleic acid therapeutics, aiming to offer some reference for the interdisciplinary development of artificial intelligence and nucleic acid drugs.
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Surgical treatment is the first choice for patients with aortic stenosis(AS)and hypertrophic obstructive cardiomyopathy(HOCM),this article reports a case of a high-risk surgical patient who underwent transcatheter aortic valve replacement(TAVR)after undergoing percutaneous septal embolization with microspheres(PSEM)to treat left ventricular outflow tract(LVOT)obstruction.A 77-year-old male patient was admitted due to chest tightness and shortness of breath post physical activities.Echocardiography showed signs of severe aortic valve stenosis(mean gradient:53 mmHg)and HOCM(peak LVOT gradient:93 mmHg).The risk of cardiac surgery is extremely high.Multidisciplinary decision was reached in that PSEM strategy should be performed at first to relieve LVOT obstruction,followed by TAVR to treat aortic valve stenosis.After embolization of the first septal branch with microparticles,the peak LVOT gradient decreased to 15 mmHg immediately post PSEM.TAVR was performed at 6 days post PSEM,the postoperative aortic valve pressure gradient decreased to 2 mmHg.The patient was discharged without complications.
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Objective:To analyze the diagnosis, treatment and prognosis of patients with rare malignant tumors of the temporal bone. Methods:Four cases of rare temporal bone malignant tumors in our hospital between March 2014 and December 2020 were reviewed, including two cases of chondrosarcoma, one case of fibrosarcoma and one case of endolymphatic cystic papillary adenocarcinoma. There were three males and one female, ages between 28 and 56 years at the time of surgery. Common symptoms included hearing loss, facioplegia, tinnitus, and headache. All patients underwent imaging examinations to evaluate the extent of the lesions. Tumors were removed by subtotal temporal bone resection or infratemporal fossa approach, and postoperative adjuvant radiotherapy was applied if necessary. Results:One of the two chondrosarcoma patients was cured by complete resection of the tumor for 75 months, the other one recurred after the first excision of the tumor and underwent infratemporal fossa approach resection of skull base mass again with no recurrence found yet for 112 months. One patient with fibrosarcoma survived for 28 months after surgery with a positive margin and post-operative radiotherapy. One patient with endolymphatic cystic papillary adenocarcinoma recurred 12 months after subtotal lithotomy, and underwent subtotal temporal bone resection again, combined with radiotherapy. No recurrence was found for 63 months. Conclusion:The incidence of rare temporal bone malignant tumors is extremely low, the location is hidden, and the symptoms are atypical. Attention should be paid for early detection and early treatment. Surgical resection is the main treatment, and radiotherapy can be supplemented in the advanced stage or with a positive margin.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condrossarcoma/cirurgia , Fibrossarcoma , Recidiva Local de Neoplasia , Estudos Retrospectivos , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/cirurgia , Osso Temporal/patologia , Resultado do TratamentoRESUMO
@#Adoptive cellular immunotherapy has been widely recognized in recent years due to its remarkable results, especially the success of CD19-specific chimeric antigen receptor (CAR) autologous T cell therapy for malignant hematoma. Previous studies have found the existence of tumor immune microenvironment, heterogeneous targets, and immunosuppressive receptors in solid tumors, which has led to the shortcomings of CAR-T treatment of solid tumors. This article proposes the methods to improve CAR-T cells to increase T cell infiltration, co-expression of cytokines and enzymes and modification of related receptors in order to enhance the anti-solid tumor activity of CAR-T, laying a theoretical foundation for the follow-up CAR-T cell treatment of solid tumors.
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Objective:To investigate the value of D-dimer, carbohydrate antigen 199 (CA199) and insulin-like growth factor binding protein 2 (IGFBP2) for postoperative monitoring and prediction of survival time in patients with resectable pancreatic cancer.Methods:The data of 119 patients with pancreatic cancer who were admitted to the First Hospital of Qinhuangdao from May 2010 to January 2014 were collected. Immunoturbidimetry was used to determine the level of D-dimer before surgery, at postoperative stable disease stage and disease progression stage; electrochemiluminescence was used to determine the level of CA199, and enzyme-linked immunosorbent assay (ELISA) was used to determine the serum IGFBP2 level. A total of 30 healthy people and 40 patients with pancreatic serous cystadenoma were treated as the controls. The correlations of the levels of preoperative D-dimer, CA199 and IGFBP2 with clinicopathological characteristics and survival time of patients with pancreatic cancer were analyzed.Results:The levels of preoperative D-dimer, CA199, IGFBP2 in patients with pancreatic cancer were higher than those in the both control group (all P < 0.01). The levels of serum D-dimer, CA199 and IGFBP2 after the progression of pancreatic cancer were higher than those at postoperative stable disease stage [1 496.0 ng/ml (590.0 ng/ml, 2 280.4 ng/ml) vs. 578.1 ng/ml (381.7 ng/ml, 671.5 ng/ml), 207.0 U/ml (54.5 U/ml, 736.5 U/ml) vs. 31.9 U/ml (14.1 U/ml, 44.0 U/ml), (435±107) ng/ml vs. (249±83) ng/ml, all P < 0.01]. There were no statistical differences in the proportion of pancreatic cancer patients stratified by different clinicopathological factors with the increased levels of D-dimer before operation (all P > 0.05). The proportion of the increased levels of CA199 and IGFBP2 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis (both P < 0.05); there was no association of the increased levels of CA199 and IGFBP2 with other factors (all P > 0.05). The preoperative progression-free survival (PFS) time and overall survival (OS) time of pancreatic cancer patients with elevated D-dimer level was shorter than that for those with normal D-dimer level [(10.6±1.2) months vs. (20.4±2.4) months, (18.9±1.9) months vs. (29.2±2.6) months, both P < 0.01]. When the threshold value of CA199 was 37 U/ml, there was no correlation between CA199 and survival of pancreatic cancer patients (all P > 0.05); when the threshold value was 253.8 U/ml (median CA199 for the enrolled patients) and 1 000 U/ml, patients with elevated CA199 level had shorter OS time and PFS time compared with the patients with normal CA199 level [253.8 U/ml: (11.5±1.5) months vs. (21.0±2.6) months, (19.9±2.1) months vs. (29.0±2.7) months, both P < 0.01; 1 000 U/ml: (8.9±1.9) months vs. (19.1±1.9) months, (15.5±2.3) months vs. (28.0±2.0) months, both P < 0.01]. When the threshold value of IGFBP2 was 339.1 ng/ml, patients with elevated preoperative IGFBP2 level had shorter PFS time and OS time compared with the patients with normal IGFBP2 level [(10.8± 1.1) months vs. (21.1±2.6) months, (18.9±1.8) months vs. (30.3±2.8) months, both P < 0.01]. Cox multivariate analysis showed that preoperative D-dimer and IGFBP2 levels were independent factors affecting PFS and OS in patients with pancreatic cancer (D-dimer: HR = 0.561, 95% CI 0.336-0.936, P = 0.027; HR = 0.515, 95% CI 0.303-0.874, P = 0.014; IGFBP2: HR = 0.430, 95% CI 0.253-0.731, P = 0.002; HR = 0.361, 95% CI 0.202-0.644, P = 0.001). Conclusions:For patients with resectable pancreatic cancer, D-dimer, CA199 and IGFBP2 can be used for postoperative condition monitoring, and preoperative D-dimer and IGFBP2 can be used for survival time prediction.
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Objective To explore the efficacy and safety of apatinib combined with S-1 in patients with advanced NSCLC without sensitive gene mutation or unknown mutation status.Methods One hundred and four patients with advanced NSCLC without sensitive gene mutation or unknown mutation status were selected from the oncology department of the First Hospital of Qinhuangdao City,Hebei Province from April 2015 to April 2017.All patients refused intravenous chemotherapy.One hundred and four patients were randomly divided into treatment group (apatinib combined with S-1 group) and control group (S-1 alone group) by 1:1 digital method.However,two patients in the treatment group transferred to the control group for personal reasons.There is 50 cases in apatinib combined with S-1 group and 54 cases in S-1 group.The efficacy and adverse reactions of the two groups were evaluated.Results The objective remission rate was 48.0% (24/50) and 27.8% (15/54) (x2=4.530,P =0.033),the disease control rate was 82.0% (41/50) and 74.1% (40/54) (x2=0.947,P=0.331),the median PFS was 6.6 months and 3.4 months (t=25.555,P =0.000),the median OS was 16.0 months and 10.5 months (t =59.439,P =0.000),respectively.The overall incidence of adverse reactions was 82.0% (41/50) and 70.4% (38/54) respectively (x2 =1.923,P=0.166),of which 18.0% (9/50) and 13.0% (7/54) were more than grade 3 respectively (x2 =0.506,P =0.477).There was no death caused by treatment-related adverse reactions in both groups.Conclusion Appatinib combined with S-1 capsule has good short-term and long-term efficacy in the treatment of advanced non-small cell lung cancer without gene mutation or unknown mutation.The adverse reactions are tolerable and can be used as first-line treatment for patients unwilling to receive intravenous chemotherapy.
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Objective To prepare quercetin liposome and to explore the antitumor effect of quercetin liposome.Methods The cholesterol and lecithin were used as membrane materials,quercetin nano liposome was prepared by thin film ultrasound method.The zeta potential and particle size distribution of quercetin liposome were tested by Malvern laser particle size analyzer and transmission electron microscope respectively.In order to explore the anti-tumor effect of quercetin nano-liposome,the mouse model of cervical cancer was established.After tail vein injection of quercetin and quercetin nano-liposome for 15 days,the tumor inhibitory rate,the thymus (spleen) index were analyzed,and the pathology of tumor tissues was further observed.Results Under the condition of lecithin∶cholesterol ∶ quercetin =8 ∶ 2 ∶ 1,the hydration time of 15 min and the ultrasonic time of 15 min,the quercetin nano-liposome was prepared,and the particle size distribution was uniform and the potential was-10.8.The tumor inhibitory rate of quercetin nano-liposome treatment group was 54.16%,which was significantly higher than that of the quercetin treatment group (x2 =6.477,P < 0.05).The pathology results of the tumor tissues showed that nanocrystallization of quercetin could increase the anti-cancer effect of quercetin.Conclusion Both quercetin and quercetin nano-liposome exhibit significant effect on the tumor growth,and the inhibitory rate is increased after quercetin was nanocrystallization.Our study will provide theoretical basis for the application of quercetin nano-liposome in the treatment of cervical cancer.
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Objective To evaluate the diagnostic value of the level of plasma D-dimer,high-density lipoprotein (HDL),carcino embryonic antigen (CEA) and carbohydrate antigen 724 (CA724) in gastric cancer.Methods The plasma and clinicopathological data of 103 gastric cancer patients and 111 normal controls were collected.The levels of D-dimer,HDL,CEA and CA724 were detected.SPSS 13.0 statistical software was applied to analysis the sensitivity and specificity of each examination method and to find out the appropriate combination.Results The levels of D-dimer,CEA and CA724 in patients with gastric carcinoma were 0.87 (2.69) μg/ml,2.66 (4.38) ng/ml,5.10 (7.79) U/ml,respectively,they were distinctly higher than those in normal controls [0.22 (0.21) μg/ml,1.28 (1.60) ng/ml,1.81 (1.60) U/ml,all P =0.000].HDL level was significantly lower in patients than that in normal controls [0.86 (0.35) mmol/L vs 1.29 (0.44) mmol/L,P=0.000].The area ofROC curve of D-dimer,HDL,CEA,CA724 were 0.799,0.859,0.739,0.743,respectively.The cut-off of D-dimer was 0.46 μ.g/ml,the sensitivity was 68.0 %,the specificity was 86.5 %.The cut-off of HDL was 0.995 mmol/L,the sensitivity was 73.8 %,the specificity was 84.7 %.The cut-off of CEA was 3.585 ng/ml,the sensitivity was 44.7 %,the specificity was 92.0 %.The cut-off of CA724 was 3.765 U/ml,the sensitivity was 57.3 %,the specificity was 89.2 %.The sensitivity of D-dimer+HDL+CA724 was 83.5 %,the specificity was 89.2 %.The sensitivity and specificity of D-dimer+HDL+CEA+CA724 were 84.5 % and 89.2 %,respectively.Conclusions The D-dimer+HDL+CEA+CA724 may provide the evidence for diagnosis of gastric cancer.Combined detection has higher sensitivity and specificity.
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Objective To evaluate the feasibility, efficacy and safety of new nano material occluder of single rivet type (left-disk with no-hub) in treating ventricular septal defect (VSD) in order to provide experimental basis for clinical application. Methods A total of 26 healthy adult dogs were selected for this study . Under thoracotomy , VSD model was established through fluoroscopically-guided percutaneous puncturing of the right ventricular free wall. The models were randomly and equally divided into the study group(n=13, using nano material VSD occluder) and the control group(n=13, using double-hub nitinol occluder). Every two dogs from each group were sacrificed each time at one, 2, and 3 months after percutaneous closure of VSD with corresponding occluder, the tissue samples were collected and sent for gross examination as well as for the optical and electronic microscopy study;the blood concentration of nickel ion was also determined. The state of endothelialization after implantation of the new type occluder was evaluated, and the complications such as residual shunt and superficial thrombus formation were recorded. The results were analyzed. Results By open chest operation with small incision and percutaneous puncturing of the right ventricular free wall, VSD model was successfully established in all 26 dogs. The success rate of the implantation of the VSD occluder in the study group was 100%, while it was 91.7% in the control group. One, 2, 3 and 6 months after the implantation, the heart specimens of 25 dogs were removed and gross examination showed that neither occluder displacement nor alloy wire fracture occurred in both groups. No thrombus formation or vegetation attached on the disk surface was observed. One month after the procedure , in the study group the bilateral disk surfaces of the occluder were covered with thin layer transparent tissue , which were proved to be composed of the fibrous tissue and endothelial cells through pathologic and electronic microscopy study. Six months after implantation, the superficial tissue of the occluder became further thickened and the occluder edge became fused with the surrounding heart tissue. Conclusion The design of the new VSD nano materials occluder, which has a left-disk with no hub, is very scientific. Compared with double-hub nitinol occluder, the new device can shorten the time of complete endothelialization and effectively occlude the VSD. Therefore, this new nano material occluder has promising prospect in clinical application.
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Objective To discuss the correlation between SIRT3 protein and clinicopathological parameters of gastric carcinoma.Methods Immunohistochemistry and Western blot were used to detect the expression of SIRT3 in the gastric carcinoma and normal gastric tissue.The correlation between the expression of SIRT3 and clinicopathological parameters was analyzed.Results The immunohistochemistry showed that the positive expression rate of SIRT3 protein in gastric carcinoma tissue (53.8 %,43/80) was obviously lower than that in normal gastric tissue (86.0 %,43/50),and the expression of SIRT3 protein showed close relationship with invasion depth,lymph node metastasis and TNM stage (P < 0.05),rather than the age,gender,tumor size,or differentiation status (P > 0.05).The Western blot showed that the expression rate of SIRT3 protein (SIRT3/β-actin) in gastric carcinoma tissue (0.655±0.317) was lower than that in normal gastric tissue (0.803±0.329) (P < 0.05).Conclusion The expression of SIRT3 protein is lower in gastric cancer than that in normal gastric tissue,and relates to invasion depth,lymph node metastasis and TNM stage.SIRT3 may inhibit the occurrence and development of gastric cancer.
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Objective To investigate the significance of plasma D-dimers,high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol (LDL-C) and apolipoprotein a (LP (a)) of patients with gastrointestinal cancer.Methods One hundred and thirty-nine cases with gastrointestinal cancer and 155 healthy persons were selected as subjects.Latex enhanced immunoassays method was used to measure the D dimer concentration.Direct method was applied to detect the levels of serum HDL-C,LDL-C,LP (a)Chemiluminescence method was applied to detect serum carcinoembryonic antigen (CEA)concentration.Determine the sensitivity and specificity of each index in gastrointestinal cancer,and explore the relationship between the concentration and the lymph node metastasis and distant metastasis.Results The levels of D-dimer,LDL-C,LP (a),CEA in patients with gastrointestinal carcinoma were 0.80 (2.37) mg/L,3.46 (1.46) mmol/L,317 (262) mg/L,2.61 (3.62) μ,g/L respectively,significant higher than those of health control(0.21 (0.22) mg/L,2.86 (0.98) mtmol/L,139 (187) g/L,1.29 (1.42) μg/L respectively; Z =-8.388,-6.150,-8.589,-7.142,P <0.001).The level of HDL-C in gastrointestinal cancer patients was 0.86(0.38) mmoL/L,lower than that of health control(1.29(1.42) mmol/L; Z =-10.643,P <0.001)The area of ROC curve of D-dimmer,HDL-C,LDL-C,LP (a),CEA were 0.783,0.859,0.708,0.790,0.741 respectively.Compared with area of ROC curve of CEA,that of D-dimer,LDL-C,LP(a) were significant different (Z =1.110,0.809,1.257 ; P =0.27,0.42,0.21).Compared with CEA AUC,HDL-C AUC was significant different (Z =3.225,P =0.0013).Compared with patients with no lymph node metastasis,the levels of D-dimers,LDL-C,LP (a) in patients with lymph node metastasis were higher (P =0.003,0.002,0.005 respectively).And the concentration of HDL-C decreased significantly (P =0.001).Compared with patients without metastases,serum D-dimer,LDL-CLP (a) concentration in patients with distant metastasis were significant higher(P < 0.001) and the concentration of HDL-C decreased (P < 0.001).Conclusion The levels of D-dimer and lipoprotein might be proved the base for diagnosis or assessment of gastrointestinal malignant tumor.
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Objective To evaluate the diagnostic value of the level of plasma D-dimer, lipoproteins and carcino-embry-onic antigen(CEA) in gastrointestinal cancer.Methods The plasma D-dimer ,lipoproteins,CEA and clinicopathological data of 139 gastrointestinal cancer patients and 155 normal controls were collected and analyzed .Lipoproteins included high-density lipoprotein(HDL),low-density lipoprotein(LDL) and lipoprotein a[LP(a)].SPSS 13.0 statistical software was used to analyze the sensitivity and specificity of each examination method and to find the appropriate combination .Results The plasma D-dimer,LDL,LP( a) and CEA levels were distinctly higher in patients than those in normal controls ( P<0.001).HDL levels were significantly lower in patients than those in normal controls (P<0.001).The cutoff of D-dimer was 0.495 μg/ml , the sensitivity of D-dimer was 62.6%,and the specificity was 86.5%.The cutoff of HDL was 1.025 mmol/L, the sensitivity was 72.7%,and the specificity was 85.2%.The cutoff of LDL was 3.375 mmol/L, the sensitivity was 54%,and the specificity was 82.6%.The cutoff of LP(a) was 27.3 mg/dl, the sensitivity was 58.3%,and the speci-ficity was 87.1%.The cutoff of CEA was 2.14 ng/ml, the sensitivity was 59.7%,and the specificity was 76.8%.The sensitivity and specificity of HDL +CEA were 77.7%and 88.4%, respectively.The sensitivity and specificity of HDL +D-dimer were 70.5% and 96.1%, respectively.The sensitivity of HDL +LP(a) was 76.3%,and the specificity was 93.5%.The sensitivity of D-dimer +HDL+LP(a) was 84.2%,and the specificity was 92.3%.The sensitivity of D-dimer +HDL+CEA was 87.1%, and the specificity was 85.8%.The sensitivity and specificity of HDL +LP(a) +CEA were 85.6%and 92.3%, respectively.The sensitivity of D-dimer +HDL+CEA +LP(a) was 89.9%while the specificity was 92.3%.Conclusions Plasma D-dimer and lipoproteins can serve as tumor markers in gastrointestinal cancer .Combined detection has higher sensitivity and specificity .
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OBJECTIVE@#To investigate the features of nasal septum cellule in computed tomographic (CT) images and its clinical significance.@*METHOD@#CT scans data of nasal septum in 173 patients were randomly obtained from January 2001 to June 2005. Prevalence and clinical features were summarized in the data of 19 patients with nasal septum cellule retrospectively.@*RESULT@#(1) Nineteen cases with nasal septum cellule were found in 173 patients. (2) All nasal septum cellule of 19 cases located in perpendicular plate of the ethmoid bone, in which 8 cases located in upper part of nasal septum and 11 located in middle. (3) There were totally seven patients with nasal diseases related to nasal septum cellule, in which 3 cases with inflammation, 2 cases with bone fracture, 1 case with cholesterol granuloma, 1 case with mucocele.@*CONCLUSION@#Nasal septum cellule is an anatomic variation of nasal septum bone, and its features can provide further understanding of some diseases related to nasal septum cellule.
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Osso Etmoide , Diagnóstico por Imagem , Osso Nasal , Diagnóstico por Imagem , Septo Nasal , Diagnóstico por Imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
To investigate the chemical constituents of the roots of Aconitum taipaicum, silica gel column chromatography was used for the isolation and purification of compounds. A new norditerpenoid alkaloid, isodelelatine (1), along with five known alkaloids, atisine (2), delfissinol (3), liangshanine(4), hypaconitine (5) and delelatine (6) were isolated and identified. The structure of the new compound was elucidated on the basis of spectral data.
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Objective To evaluate the relationship of gastric function of its proximal portion and electrogastrogram in healthy youths with obesity.Methods A total of 35 healthy young volunteers with normal weight participated in the study,including 16 females and 19 males.On the first day,the water load test was performed.On the second day,determination of function of proximal portion of stomach was done using electronic barostat and electrogastrogram.Results Water load test:females were found to consume significantly less water than males(P0.05)between male group and female group in the minimal distention pressure(MDP),initial intragastric pressure(IP)and the maximal tolerance pressure(MP).The initial gastric compliance(IC)in female group was less than that in male group(P0.05).The parameter of EGG:with the intragastric pressure increased,DF in Normal Range(N%)showed decreasing tendency,while bradygastria(B%),tachygastria(T%),instable coefficient of dominant frequency(DFIC)and dominant power(DP)increased.Conclusion The gastric capacity,the parameters of visceral sensitivity and IC are remarkably different between sexes.The gastric electrical activity varies in different states of proximal gastric function.The gastric contraction may be enhanced by an improvement of dominant power(DP).