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Oligonucleotide drugs have experienced accelerated development in the past 10 years, and some of them have been used in clinical treatment. Because of its convenient design, flexible sequence, and high specificity, it is expected to solve the “undruggable” challenge of many targets which are difficult in drug development. Moreover, its clinical transformation period and cost are relatively low, which makes oligonucleotide drug become the frontier of emerging biotechnology drug discovery. Brain diseases include a series of incurable diseases, such as neurodegenerative diseases, glioma, and motor neuron diseases. Many of them are age-related and regarded as aging-associated brain diseases. Due to the complex etiology, many targets are difficult to be drugged. At the same time, the existence of the barrier system “blood-brain barrier” in the brain makes most drugs unable to achieve effective accumulation at brain lesions, and many small molecule drugs have failed in clinical transformation. The specificity and sequence flexibility of oligonucleotide acid drugs provide new possibilities for drug development, but they also face the challenge of brain delivery. Although a variety of oligonucleotide drugs have been used in the medical market, brain-targeted oligonucleotide drugs are still extremely rare. This article reviewed recent advances and discussed key topics and clinical transformation challenges in this field, such as clinical approval cases, bottlenecks of brain-targeted delivery and current strategies, as well as potential targets for aging-related brain diseases.
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Objective:To study the effect of lifestyle intervention and Irbesartan intervention on vascular endothelial function in elderly people with prehypertension.Methods:Seventy elderly people with prehypertension were randomly divided into the lifestyle intervention group and the Irbesartan intervention group.After one year of intervention, the level of cyclic endothelial microparticles(EMPs)and brachial-ankle pulse wave conduction velocity(baPWV)before and after the intervention were compared between the two groups.Results:There were significant differences in levels of circulating EMPs[(1 946±234)/μl vs.(1 745±416)/μl, t=2.530, P=0.011]and baPWV[(1 653±172)cm/s vs.(1 511±230)cm/s, t=2.448, P=0.017]before and after one year of lifestyle intervention.There were also significant differences in levels of circulating EMPs[(19 507±146)/μl vs.(1 446±286)/μl, t=3.340, P=0.002]and baPWV[(1 639±165)cm/s vs.(1 361±211)cm/s, t=3.156, P=0.005]before and after one year of Irbesartan intervention and between the lifestyle intervention group and the Irbesartan intervention group after one year( t=2.238 and 2.475, P<0.05). Conclusions:Lifestyle intervention and Irbesartan intervention have protective effects on vascular endothelial function and delay the initiation and progression of atherosclerosis in elderly people with prehypertension, and irbesartan intervention is more effective than lifestyle intervention.
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Background: The intake of red meat and processed meat will increase the risk of colorectal cancer. Heterocyclic amines (HCAs), the intermediate mutagen in the processing of meat food, may be a potential risk factor for meat food to cause cancer. Aims: To investigate the association between HCAs intake and colorectal cancer, thereby providing a basis for prevention of colorectal cancer. Methods: Case-control and cohort studies concerning the association between HCAs intake and colorectal cancer were retrieved from PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang and CQVIP databases. The literature was screened according to the inclusion and exclusion criteria. Meta-analysis was conducted by Stata 12.1 software. Results: A total of 17 studies involving 18 295 colorectal cancer patients were included, of which 14 were case-control studies and 3 were cohort studies. MeIQx intake could increase the risk of colorectal cancer (OR=1.16, 95% CI: 1.01-1.32, P=0.032), DiMeIQx intake (OR=1.20, 95% CI: 1.01-1.43, P=0.045), MeIQx intake (OR=1.24, 95% CI: 1.03-1.50, P=0.023) could increase the risk of colon cancer. No association between PhIP, HCAs and colorectal cancer, colon cancer, or rectal cancer was found. No dose-response relationship between DiMeIQx, MeIQx, PhIP, HCAs and colorectal cancer was found. Conclusions: MeIQx intake may increase the risk of colorectal cancer, DiMeIQx, MeIQx intake may increase the risk of colon cancer, and no dose-response relationship between HCAs intake and colorectal cancer was found.
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OBJECTIVE@#To investigate the value of preoperative three-dimensional image reconstruction in the treatment of ureteropelvic junction obstruction (UPJO).@*METHODS@#We reviewed data on 40 patients (22 male cases, and 18 female cases) diagnosed with UPJO in Peking University First Hospital from May 2017 to April 2019. The median age was 26.5 years (IQR 23.25-38.75) years. There were 11 patients complicated with ectopic vessels, 14 patients with kidney stones, 3 patients with horseshoe kidney, and 6 patients with obstruction after pyeloplasty. All the patients underwent preoperative enhanced CT scan, and the CT data were reconstructed into three-dimensional image models. The obstruction position of ureteropelvic junction and the relationship between ureteropelvic junction and blood vessels and organs were observed by three-dimensional models to assist planning surgery. Thirty-seven patients underwent laparoscopic pyeloplasty (including 3 cases combined with pyelolithotomy with flexible cystoscope, 1 case combined with pyelolithotomy by sun-style cystoscope, 1 case with laparoscopic ureter resection and anastomosis, 3 cases of laparoscopic pyeloplasty of horseshoe kidney), 2 patients underwent laparoscopic ventral onlay lingual mucosal graft ureteroplasty, and 1 patient underwent robot-assisted laparoscopic pyeloplasty.@*RESULTS@#Three-dimensional CT image clearly showed the relationship between the obstruction of ureteropelvic junction and blood vessels and organs after three-dimensional reconstruction. The type, diameter, position and direction of the ectopic vessels could be observed clearly before operation according to the three-dimensional reconstruction model, and the number, size, location and shape of renal calculi or other masses, the number of involved renal calyces and the anatomical distribution in the renal pelvis and calyces could be also evaluated preoperatively. After comprehensive analysis of the above information, individualized operation plans were performed on the patients, all the 40 cases were successfully completed with the surgery without any transfer to open surgery. The average operative time was (129.91±37.90) min (range: 75 to 273), the average blood loss was (48.1±78.0) mL (range: 10 to 400), the average hospitality was (5.04±1.99) d (range: 2 to 10), and the average postoperative drainage time was (3.8±1.4) d (range: 2 to 8).@*CONCLUSION@#The preoperative three-dimensional image reconstruction has a high clinical value in the treatment of ureteropelvic junction obstruction, and it is of great help to assist surgery planning and is worthy of further clinical promotion and application.
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Adult , Female , Humans , Male , Young Adult , Imaging, Three-Dimensional , Kidney Pelvis , Laparoscopy , Retrospective Studies , Treatment Outcome , Ureteral Obstruction/diagnostic imaging , Urologic Surgical ProceduresABSTRACT
@#Age-related macular degeneration(ARMD)is a multifactorial disease, genetic factors play important roles in the pathogenesis of the disease. To date, intraocular injection of anti-vascular endothelial growth factor drugs is the first choice for the treatment of wet ARMD, but the response is variable. This review summarizes vascular endothelial growth factor(<i>VEGF</i>)gene, complement factor H(<i>CFH</i>)gene, age-related maculopathy susceptibility 2(ARMS2)gene and high-temperature requirement A-1(<i>HTRA1</i>)gene single-nucleotide polymorphisms(SNP)in the study of pharmacological genetics of wet ARMD. It is still worthy of further investigations that the genetic mechanism of the disease, so that we can provide individualized treatment sequences and predict the response to anti-VEGF therapy.
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@#Proper assessment of the establishment of stereopsis after strabismus surgery continues to be challenging for the strabismus surgeon. In view of the stereopsis, the timing of surgery for strabismus has been controversial because of concerns that it may result in an overcorrection or lateness. Recent literature on the strabismus surgeon has shown that the establishment of postoperative stereoscopic vision is closely related to the age of onset, types of strabismus, course of disease and ocular deviation. This review will summarize the recent points as below.
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To investigate the value of diffusion-weighted imaging(DWI)and apparent diffusion coefficient(ADC)in the diagnosis and differential diagnosis of posterior fossa solid hemangioblastoma(PFSH). We retrospectively analyzed the clinical data of 15 PFSH patients and 58 patients with other hypervascular tumors in the posterior fossa(the latter included 23 cases of meningioma,5 cases of medulloblastoma,8 cases of acoustic neuroma,4 cases of hemangiopericytoma,5 cases of lymphoma,9 cases of metastatic tumor,3 cases of astrocytoma,and 1 case of choroid plexus papilloma)confirmed by operation and pathology.All patients underwent axial DWI scans,and the mean ADC value of solid part of the tumors and the adjacent normal cerebellar white matter were measured,and then the normalized ADC was calculated.In addition, test was used to compare the differences in mean ADC and normalized ADC between these two groups,and receiver operating characteristic(ROC)curve was applied to analyze the diagnostic performance of normalized ADC. Of all the 15 PFSH patients,DWI appeared hypointense in 12 patients and isointense in 3 patients;the signals on ADC maps were isointense or hyperintense;the mean ADC value of PFSHs was(1.881±0.445)×10 mm /s and the normalized ADC was 2.70±0.62.In contrast,in 58 patients with other tumors in the posterior fossa,DWI appeared hyperintense in 51 cases,isointense in 3 cases,and hypointense in 4 cases;the mean ADC value was(0.771±0.202)×10 mm /s,and the normalized ADC was 1.17±0.33.Thus,the ADC value and normalized ADC value were significantly higher in PFSH than in other tumors in the posterior fossa(=9.419,<0.001;=9.184,<0.001).The cut-off value of the normalized ADC for the diagnosis of solid hemangioblastoma was 1.89,with the sensitivity and specificity being 100%and 96.6%respectively,and the area under the ROC curve was 0.989. ADC and normalized ADC are valuable in the differential diagnosis of PFSH from other tumors with abundant blood supply.
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Humans , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging , Hemangioblastoma , Diagnosis , ROC Curve , Retrospective StudiesABSTRACT
Objective To investigate whether the conjoint combined with fascial sheath( CFS) suspension can be used as an effective method for correction of moderate and severe ptosis. Methods Thirty-five patients (39 eyes) with moderate or severe ptosis were treated in our hospital from January 2014 to March 2017 by means of CFS suspension,frontalis suspension and shortening of levator palpebrae superior-is,and all the patients were followed up for 3~12 months. Results The CFS suspension and the other two operations appeared effective;and compared with the other two methods,the difference was statistically significant(P<0. 05). The CFS suspension for the treatment of moderate and severe ptosis with a higher positive rate(95%) and the positive rate of the other two methods was 67%. In terms of complications,the CFS suspension showed eyelid dysraphism incidence rate was exposure keratitis occurred in 85. 7% and entropion occurrence rate of 4. 7%;with the other two methods,the surgical eyelid dysraphism occurred in 100% and the conjunctival prolapse occurred in 5. 6%. Conclusion The CFS suspension in correction of moderate and severe ptosis has the advantages of less trauma,less complications and good correction effect.
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Objective To study and analyze the effect of clozapine treatment and rehabilitation nursing on social dysfunction of schizophrenia. Methods 88 patients with schizophrenia in Tongde Hospital were selected as the subjects. The control group was treated with clozapine, with an initial dose of 50 mg, once a day. On the basis of the experimental group received rehabilitation nursing measures, health education, establishing harmonious doctor-patient relationship, according to the actual situation of patients received psychological counseling measures, pay attention to patients with mood changes, the patients were encouraged to manual labor and rehabilitation activities. Results Before treatment, the scores of social function disability screening scale of the experimental group and the control group were (6.89±1.65) points and (6.57±1.63) points, and the difference between the two groups was not statistically significant. After treatment, the defect score of the experimental group was (4.32 ±1.10), significantly lower than the control group, the scale score was (5.67 ± 1.37), and the difference between the two groups was statistically significant (P<0.05). Conclusion Clozapine combined with rehabilitation nursing in the treatment of schizophrenia social function defects, the clinical efficacy is ideal, can significantly improve the social function defects of patients, and has clinical significance.
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Objective To study and analyze the effect of clozapine treatment and rehabilitation nursing on social dysfunction of schizophrenia. Methods 88 patients with schizophrenia in Tongde Hospital were selected as the subjects. The control group was treated with clozapine, with an initial dose of 50 mg, once a day. On the basis of the experimental group received rehabilitation nursing measures, health education, establishing harmonious doctor-patient relationship, according to the actual situation of patients received psychological counseling measures, pay attention to patients with mood changes, the patients were encouraged to manual labor and rehabilitation activities. Results Before treatment, the scores of social function disability screening scale of the experimental group and the control group were (6.89±1.65) points and (6.57±1.63) points, and the difference between the two groups was not statistically significant. After treatment, the defect score of the experimental group was (4.32 ±1.10), significantly lower than the control group, the scale score was (5.67 ± 1.37), and the difference between the two groups was statistically significant (P<0.05). Conclusion Clozapine combined with rehabilitation nursing in the treatment of schizophrenia social function defects, the clinical efficacy is ideal, can significantly improve the social function defects of patients, and has clinical significance.
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By detecting SRY gene of cell-free fetal DNA ( cffDNA) in maternal peripheral blood, the sex of fetuses was determined, the risks of sex-linked genetic disorders were assessed and the birth rate of sick fetuses was decreased. A method of real-time polymerase chain reaction ( PCR) coupled with invader assay was established to detect SRY gene. This method possessed the advantages such as high sensitivity, high specificity and non-contaminated with closed tube detection. Under the optimized reaction conditions such as 250 nmol/L detection probes, 7. 5 U FEN1 enzyme, 0. 5 U Taq polymerase and 67℃ of annealing temperature in pre-amplification, the simulated samples as low as 4% ( 4 copies/μL ) were detected and two clinical samples with the gestation age of 9 weeks and 10 weeks were successfully detected. The detection results showed that this method could be used to detect SRY gene of cffDNA in maternal peripheral blood, providing an effective technique for clinical non-invasive prenatal diagnosis based on SRY gene.
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By detecting SRY gene of cell-free fetal DNA ( cffDNA) in maternal peripheral blood, the sex of fetuses was determined, the risks of sex-linked genetic disorders were assessed and the birth rate of sick fetuses was decreased. A method of real-time polymerase chain reaction ( PCR) coupled with invader assay was established to detect SRY gene. This method possessed the advantages such as high sensitivity, high specificity and non-contaminated with closed tube detection. Under the optimized reaction conditions such as 250 nmol/L detection probes, 7. 5 U FEN1 enzyme, 0. 5 U Taq polymerase and 67℃ of annealing temperature in pre-amplification, the simulated samples as low as 4% ( 4 copies/μL ) were detected and two clinical samples with the gestation age of 9 weeks and 10 weeks were successfully detected. The detection results showed that this method could be used to detect SRY gene of cffDNA in maternal peripheral blood, providing an effective technique for clinical non-invasive prenatal diagnosis based on SRY gene.
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BACKGROUND:Hot-melt adhesive is safe and environmental friendly adhesive due to free of solvent, which is particularly suitable for medical applications. OBJECTIVE:To describe the types and characteristics of currently used hot-melt adhesives and to prospect the technical research and development of hot-melt adhesive for polyolefin tubes or catheters as wel as to point out the corresponding key points to the hot-melt adhesion. METHODS:Literature search was carried out in SCI, Elsevier, and CNKI with the key words of“hot melt adhesive, medical application”in English and Chinese, respectively, for the initial retrieval of relevant articles or patents published January 1995 to December 2015. RESULTS AND CONCLUSION:To date, the medical hot-melt adhesives reported in the literature could be grouped as amorphous polyolefin, thermoplastic elastomer, acrylic and polyurethane types. The heat resistance of the most of the hot-melt adhesives does not meet the requirement for steam sterilizing process. In the present review, a strategy is proposed to develop a novel hot-melt adhesive which is good for binding polyolefin parts and can undergo the sterilization process. Given this, it is essential to choose a kind of polypropylene random copolymer with a suitable melting point as a substrate. With the aid of an adjuvant agent, therefore, we can develop a novel hot-melt adhesive that exhibits a lower melting point than the polyolefin tube, withstands steam sterilization temperature to ensure that the tube is not deformed during melt adhesion and is not become invalid during sterilization.
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<p><b>OBJECTIVE</b>To summarize the management of anastomotic leak following surgery for esophageal carcinoma.</p><p><b>METHODS</b>The medical records of the patients developing digestive tract leak after surgery for esophageal carcinoma in our hospital from January 2003 to March 2011 were retrospectively analyzed.</p><p><b>RESULTS</b>A total of 36 patients were included, in whom 13 developed cervical anastomotic leak, 18 had intra-thoracic anastomotic leak, and 5 had intra-thoracic gastric necrosis. Of these patients, 7 were treated with resurgery, 6 with esophageal stent implantation, and 23 with conservative treatment. Treatment lasted for 5 to 181 days, averagely 47.0 +/- 31.9 days. After management, 9 patients died (25.0%). Among seven patients with resurgery, four had deceased, two were cured, and one developed leak again and was switched to conservative treatment until discharged. All the 6 patients treated with stent implantation were cured. Of the 24 patients receiving conservative treatment (including one switched from resurgery), 18 (75.0%) were cured and 1 was not cured but survived.</p><p><b>CONCLUSIONS</b>Anastomotic leak following surgery for esophageal carcinoma should be treated individually based on the onset time, location, size, and extent of the leakage. Conservative treatment is still a safe and effective method. The efficacy of stent implantation needs further investigation to confirm.</p>
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Adult , Aged , Humans , Male , Middle Aged , Anastomotic Leak , Therapeutics , Esophageal Neoplasms , General Surgery , Precision Medicine , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To study the alveolar bone surrounding situation and the length of the root of the maxillary labial inverted impacted incisor in mixed dentition after orthodontic treatment.</p><p><b>METHODS</b>Fourteen cases with maxillary labial inverted impacted incisor in mixed dentition were collected. Modified Nance arch and conventional appliance were used. Cone-bean CT (CBCT) was taken after the treatment. Simplant13.0 three-dimensional reconstruction and multi-planer reconstruction (MPR) method were used to observe the labial and lingual alveolar bone crest morphology, besides, the labial and lingual length from the alveolar bone crest to cemento-enamel junction (CEJ) of the impacted incisor and the homonym tooth after treatment, along with their root length and their labial and lingual length ratio of the root surrounded by the alveolar bone to the total root length were measured. The idependent samples t-test were used to analyze the variable differences.</p><p><b>RESULTS</b>The labial and lingual alveolar bone of fourteen cases crest of the diseased tooth after treatment presented general symmetry U shape from qualitative observation through the three-dimensional reconstruction. The labial and the lingual length of the diseased incisor from alveolar bone crest to CEJ [(2.47 ± 1.35) and (1.47 ± 0.84) mm] was significant increased than those of the homonym incisor [(1.03 ± 0.35) and (0.90 ± 0.37) mm] (P < 0.05); the length of the diseased incisor's post-treatment root [(9.82 ± 2.82) mm] was no statistically significant decreased than that of the homonym incisor root [(10.28 ± 1.38) mm, P = 0.59]; the labial and the lingual length ratio of the impacted tooth's root surrounded by the alveolar bone to the total root length [(72.83 ± 17.16)% and (85.32 ± 5.98)%] was statistically significant decrease than those of homonym teeth[(89.66 ± 3.98)% and (90.84 ± 4.61)%] (P < 0.05).</p><p><b>CONCLUSIONS</b>The diseased tooth's root had gotten enough length after the treatment. The labial and lingual alveolar bone of the maxillary labial inverted impacted incisor in mixed dentition can't offer sufficient adaptive hyperplasia after treatment, of which labial alveolar bone is more apparent, prompting careful protection when they were used.</p>
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Child , Female , Humans , Male , Alveolar Process , Diagnostic Imaging , Pathology , Cone-Beam Computed Tomography , Dentition, Mixed , Follow-Up Studies , Incisor , Diagnostic Imaging , Pathology , General Surgery , Maxilla , Diagnostic Imaging , Pathology , General Surgery , Orthodontic Extrusion , Tooth Root , Diagnostic Imaging , Pathology , Tooth, Impacted , Diagnostic Imaging , General SurgeryABSTRACT
AIM: To establish human umbilical vein endothelial cells (HUVECs) to express green fluorescent protein (GFP), and to study the suppression of GFP by siRNA in HUVECs. METHODS: Using lipofectamine 2000 to transform plasmid pN_3-EGFP encoding GFP into HUVECs. The HUVEC containing pN_3-EGFP, named HUVEC-GFP, was screened and selected by antibiotic G418. Using in vitro transcription T7 kit, GFPsiRNA targeting GFP mRNA and control-siRNA used as control were synthesized. The siRNAs were transfected into HUVEC-GFP with oligofectamine. 48 h later, the expression levels of GFP protein and mRNA in HUVEC-GFP were determined. RESULTS: The HUVEC-GFP was screened to express GFP in the presence of G418. The agarose gel electrophoresis analysis showed that the siRNAs prepared were integrated. 48 h after transfection with siRNAs, compared to control group, the level of GFP fluorescence was obviously decreased in the HUVEC-GFP transfected with GFPsiRNA. The results of RT-PCR detection showed that GFP mRNA expression was obviously suppressed by GFPsiRNA at the rate of 40%, and no obvious suppression of GFP mRNA expression was found in the HUVEC-GFP transfected with control siRNA. CONCLUSION: The siRNA targeting GFP mRNA, synthesized in vitro, efficiently suppresses the GFP expression in HUVECs.