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1.
Clin Cardiol ; 46(2): 117-125, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36448417

ABSTRACT

Left atrial appendage occlusion is not inferior to oral anticoagulants in the prevention of stroke in several randomized controlled trials. However, the clinical efficacy and safety comparison of the Watchman and amplatzer cardiac plug (ACP)/Amulet devices for percutaneous left atrial appendage closure (LAAC) in patients with non-valvular atrial fibrillation was controversial. A database search was conducted using PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov for trials that compared Watchman device vs ACP/Amulet device. The effective outcomes were stroke and systemic embolism. Safety outcomes were all-cause death, cardiovascular death, and major bleeding. Device-related complications included device-related thrombus (DRT), peri-device leaks (PDL > 5 mm). A total of 19 articles involving 6224 patients were included in the present study. The Watchman and ACP/Amulet groups comprised 3267 and 2957 patients, respectively. No statistically significant differences were detected in the stroke (odd ratio [OR]:1.24, 95% confidence interval [CI]: 0.92-1.67, p = .17, I2 = 0), systemic embolism (OR:1.10, 95% CI: 0.51-2.35, p = .81, I2 = 0%), all-cause death (OR:0.97, 95% CI: 0.80-1.18, p = .77, I2 = 1%), cardiogenic death (OR:0.99, 95% CI: 0.77-1.29, p = .96, I2 = 0%), major bleeding (OR:1.18, 95% CI: 0.98-1.43, p = .08, I2 = 25%). DRT (OR:1.48, 95% CI: 1.06-2.06, p = .02, I2 = 0%) and PDL > 5 mm (OR:2.57, 95% CI: 1.63-4.04, p < .0001, I2 = 0%) were significantly lower in ACP/Amulet group compared to Watchman group. The effective and safety outcomes were comparable between two groups. ACP/Amulet group had significantly lower rates of DRT and PDL > 5 mm than Watchman group.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Embolism , Stroke , Thrombosis , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Atrial Appendage/diagnostic imaging , Atrial Appendage/surgery , Treatment Outcome , Stroke/etiology , Stroke/prevention & control , Anticoagulants/therapeutic use , Hemorrhage/epidemiology , Hemorrhage/etiology , Embolism/prevention & control , Cardiac Catheterization/adverse effects
2.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-992719

ABSTRACT

Objective:To investigate the therapeutic effects of internal fixation via the posterolateral combined posteromedial approach in the treatment of posterior pilon fracture (Klammer type Ⅲ).Methods:A retrospective study was performed to analyze the 69 posterior pilon fractures (Klammer type Ⅲ) which had been treated by internal fixation with hollow screws or a buttress plate at Department of Orthopaedic Trauma, Yantai Shan Hospital from January 2015 to January 2020. There were 36 males and 33 females with an age of (45.3±10.0) years and duration from injury to surgery of (6.0±1.5) d. They were assigned into 2 groups according to different surgical approaches. The observation group (41 cases) was treated through the posterolateral combined posteromedial approach while the control group (28 cases) through the posterolateral approach alone. The therapeutic effects were evaluated by comparing the 2 groups in terms of incision length, intraoperative bleeding, operation time, fracture union time, fracture reduction (evaluated by the Burrwell-Charnley radiological score), the ankle-hindfoot score of American Orthopaedic Foot and Ankle Society (AOFAS) and complications.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All the 69 cases were followed up for (16.9±4.0) months, revealing primary healing of all the incisions and no vascular injury or wound infection. The incision length [(11.2±1.8) cm] and operation time [(76.0±6.6) min] in the observation group were significantly shorter than those in the control group [(12.4±1.9) cm and (79.7±6.8) min], the excellent and good rate of reduction in the observation group (97.6%, 40/41) was significantly higher than that in the control group (89.3%, 25/28), and the ankle-hindfoot scores of AOFAS at 1, 3 and 12 months after operation in the observation group [(78.4±5.6), (79.5±2.8) and (86.9±2.1)] were significantly higher than those in the control group [(75.2±5.5), (78.0±3.2) and (85.8±2.3)] (all P<0.05). There was no significant difference in the intraoperative bleeding between the 2 groups ( P>0.05). In the control group, 2 patients developed numbness in the dorsum of foot, which gradually disappeared after 3 months of treatment, but no other complications like persistent pain or flexor contracture within 1 year after operation. Conclusion:In the treatment of Klammer type Ⅲ posterior pilon fracture, the posterolateral combined posteromedial approach can result in satisfactory therapeutic effects, because the surgical approach can fully expose the fracture and facilitate better reduction.

3.
Saudi J Biol Sci ; 29(4): 1928-1935, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35531207

ABSTRACT

In recent years, significant progress has been achieved in genome editing applications using new programmable DNA nucleases such as zinc finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs) and the clustered regularly interspaced short palindromic repeats/Cas9 system (CRISPR/Cas9). These genome editing tools are capable of nicking DNA precisely by targeting specific sequences, and enable the addition, removal or substitution of nucleotides via double-stranded breakage at specific genomic loci. CRISPR/Cas system, one of the most recent genome editing tools, affords the ability to efficiently generate multiple genomic nicks in single experiment. Moreover, CRISPR/Cas systems are relatively easy and cost effective when compared to other genome editing technologies. This is in part because CRISPR/Cas systems rely on RNA-DNA binding, unlike other genome editing tools that rely on protein-DNA interactions, which affords CRISPR/Cas systems higher flexibility and more fidelity. Genome editing tools have significantly contributed to different aspects of livestock production such as disease resistance, improved performance, alterations of milk composition, animal welfare and biomedicine. However, despite these contributions and future potential, genome editing technologies also have inherent risks, and therefore, ethics and social acceptance are crucial factors associated with implementation of these technologies. This review emphasizes the impact of genome editing technologies in development of livestock breeding and production in numerous species such as cattle, pigs, sheep and goats. This review also discusses the mechanisms behind genome editing technologies, their potential applications, risks and associated ethics that should be considered in the context of livestock.

4.
Ying Yong Sheng Tai Xue Bao ; 33(4): 915-921, 2022 Apr.
Article in Chinese | MEDLINE | ID: mdl-35543042

ABSTRACT

The coKriging method of selecting effective variables is helpful to improve the spatial prediction accuracy of soil available potassium in county-scale rubber plantation, which is of significance in precision fertilization management of rubber plantation. In this study, we analyzed the spatial variability characteristics of soil available potassium in 0-20 cm layer in the rubber plantation of Baisha County, Hainan Province, by geostatistics. The significant characteristic variables were screened by correlation analysis, and the spatial interpolation precisions of coKriging (COK) of different variables were compared. The results showed that the average soil available potassium content in the study area was 44.65 g·kg-1, generally at a state of shortage. The variable coefficient was 52.6%, which was a moderate intensity of variation. The nugget effect was 12.5%, with a strong spatial autocorrelation. The organic matter and elevation were closely related to soil available potassium content. The COK spatial interpolation prediction precisions of the three covariates of organic matter (COK1), elevation (COK2), and organic matter+elevation (COK3) were all higher than ordinary Kriging (OK), and the fitting precision of the cross-validation model was COK1>COK3>COK2>OK. The fitting precision was not proportional to the number of covariates selected. Selecting more correlated covariates was more conducive to reflecting the spatial heterogeneity of soil properties. The soil available potassium content was higher in the northwest and lower in the central and eastern regions, which provided a theoretical basis for the further development of soil potassium management in rubber plantations.


Subject(s)
Rubber , Soil , China , Potassium , Spatial Analysis
5.
Int J Biol Macromol ; 195: 198-206, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34890637

ABSTRACT

Marbling influences the taste and tenderness of meat and is the main determinant of carcass quality in many countries. This study aims to investigate the influence of KLF6 (Kruppel Like Factor 6) and associated molecular mechanisms on lipid metabolism in bovine adipocytes. In the current study, KLF6 gene expression was down regulated via siRNA (small interfering RNA) in bovine adipocytes in vitro. Subsequently, adipogenic cells were collected from the culture media after 9 days, and subjected to fluorescent imaging and RNA sequencing. After confirming that KLF6 was down regulated in bovine adipocytes by siRNA, differential gene expression analysis was used to characterize the infuence of KLF6 on gene expression profiles in bovine adipocytes. A total of 10,812 genes were characterized as differentially expressed genes (DEGs) of which, 109 were up-regulated and 62 were down-regulated genes. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis identified that the DEGs were associated with lipid metabolism, carbohydrate metabolism, cell growth and death, cancer, and the signaling pathways for calcium, AMPK (Adenosine Monophosphate-Activated Protein Kinase), PI3K-Akt (Phosphatidylinositol 3-kinase), PPAR (Peroxisome proliferator-activated receptors), MAPK (mitogen-activated protein kinase), cAMP (Cyclic adenosine monophosphate), and Wnt (Wingless-related integration site). Similarly, gene ontology analysis indicated that down-regulation of KLF6 gene significantly up regulated the genes that regulate adipogenesis, differentiation and regulation of adipocytes and homeostasis of bovine adipocytes, specifically regulating the cell-type specific apoptotic action, negative regulation of apoptotic pathways, programmed cell death, and growth. Results indicate that KLF6 has a role in regulating lipid metabolism in bovine adipocytes. These findings provide evidence that may inform further investigations into molecular mechanisms that underlie the role of bovine KLF6 gene in regulating adipogenesis.


Subject(s)
Adipocytes/metabolism , Adipogenesis/genetics , Kruppel-Like Factor 6/genetics , Adipocytes/cytology , Adipocytes/physiology , Adipogenesis/physiology , Animals , Cattle , Cell Differentiation/genetics , Gene Expression/genetics , Gene Expression Profiling/methods , Gene Ontology , Kruppel-Like Factor 6/metabolism , Phosphatidylinositol 3-Kinases/metabolism , RNA-Seq/methods , Sequence Analysis, RNA/methods , Signal Transduction/genetics , Transcriptome/genetics
6.
Chinese Critical Care Medicine ; (12): 1305-1310, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991961

ABSTRACT

Objective:To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban.Methods:From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment.Results:In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg·kg -1·min -1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg·kg -1·min -1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg·kg -1·min -1], but without significant difference ( P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg·kg -1·min -1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg·kg -1·min -1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. Conclusion:Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-932980

ABSTRACT

Objectives:To analysis the effect of continuous positive airway pressure (CPAP) on nocturnal blood pressure in patients complicated with obstructive sleep apnea-hypopnea syndrome (OSAHS) and different circadian rhythms of hypertension.Methods:A total of 61 eligible patients were monitored by overnight polysomnography (PSG) at the Sleep Center of the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University between January 2020 and April 2021. During the period of PSG monitoring, continuous non-invasive blood pressure (BP) and heart rate variability (HRV) were monitored simultaneously. Frequency domain analysis was used to measure HRV and low/high frequency was used to indirectly reflect sympathetic activity. According to the nighttime systolic BP decrease rate, patients were divided into three groups: dipper pattern (descent rate ≥10%), non-dipper pattern (descent rate was less than 10% but higher than 0) and reverse dipper pattern (descent rate≤0). The PSG parameters, BP data as well as sympathetic activity etc. were compared within and among groups before and after CPAP treatment. Multiple linear regression analyses were used to explore the influencing factors of antihypertensive effect of CPAP.Results:There were no significant differences in awake systolic BP (SBP) values, the severity of OSAHS, ESS scores, awake sympathetic activity and the other baseline data among the three groups. After CPAP treatment, the mean value of asleep BP in entire group showed a modest decline as compared to the baseline values [SBP decreased 4.6 mmHg (1 mmHg=0.133 kPa); diastolic blood pressure (DBP) decreased 2.4 mmHg, both P<0.001]. Subgroup analysis showed a significant reduction in asleep SBP of 11.1 mmHg and DBP of 4.9 mmHg (both P<0.001) in reverse dipper group, respectively, compared with the baseline values. While in dipper and non-dipper group, there were no significant differences before and after CPAP treatment in terms of BP (both P>0.05). In addition, there was no difference in awake sympathetic activity among three groups, while sleep sympathetic activity showed a gradual increasing trend. Sleep sympathetic activity decreased significantly from baseline after CPAP treatment in reverse dipper group ( P<0.001), while no differences were found in the other two groups before and after treatment. After controlling for baseline data such as age etc., the line regression model showed that the antihypertensive effect of CPAP was correlated with reverse dipper (SBP: β=0.548, P=0.002; DBP: β=0.454, P=0.013) and the improvement of nocturnal MpO 2 (SBP: β=0.410, P=0.046), but not with the severity of OSAHS, daytime sleepiness, or baseline BP values. Conclusion:For patients with moderate to severe OSAHS and hypertension, reverse dipper is an effective indicator to predict the antihypertensive effect of CPAP therapy.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-930148

ABSTRACT

Objective:To explore the curative effect of biofeedback combined with oral Liumo Decoction on functional constipation (FC) and qi constipation syndrome.Methods:According to random number table method, 120 patients with FC of qi constipation meeting inclusion criteria in Beijing Rectum Hospital were divided into two groups between January 2018 and December 2019, 60 in each group. The control group was treated with biofeedback, while the observation group was additionally treated with oral Liumo Decoction. All were treated for 4 weeks. Before and after treatment, TCM syndromes were scored and recorded. The resting anal pressure (RAP) was detected. The anal maximal contraction pressure (AMCP) was detected by forced systolic anus. In relaxation status, gas was injected into rectal balloon to record the rectal sensation threshold (RST) and rectal maximum tolerance (RMT). The levels of serum substance P and NO were detected by double-antibody sandwich ELISA and immunoturbidimetry. The adverse events were recorded, and clinical curative effect was evaluated.Results:The differences in total response rate between the observation group and the control group was statistically significant [89.3% (50/56) vs. 64.4% (38/59)] ( χ 2=9.90, P=0.002). After treatment, scores of TCM syndromes in observation group was significantly lower than that of the control group ( t=-15.36, P<0.01). After treatment, the RAP [(48.31±4.15) mmHg vs. (53.64±5.46) mmHg, t=-5.88], RST [(30.14±3.17) ml vs. (35.42±3.12) ml, t=-9.00] and RMT [(154.21±15.27) ml vs. (160.61±16.38)ml, t=-2.16] in observation group were significantly lower than those in the control group ( P<0.05), while AMCP [(156.67 ± 15.62) mmHg vs. (132.26 ± 13.21) mmHg, t=9.07] was significantly higher than that of the control group ( P<0.01). After treatment, the substance P in observation group was significantly higher than that of the control group ( t=9.08, P<0.01), while NO was significantly lower than that of the control group ( t=-6.58, P<0.01). There were no serious adverse events during treatment in either group. Conclusion:Biofeedback combined with oral Liumo Decoction can alleviate clinical symptoms, improve anorectal dynamics indexes and regulate levels of enteric neurotransmitters in patients with FC of qi constipation with safety.

9.
Article in English | WPRIM (Western Pacific) | ID: wpr-928934

ABSTRACT

OBJECTIVE@#To investigate the molecular mechanism underlying the anti-hepatic fibrosis activity of ethyl acetate fraction Dicliptera chinensis (L.) Juss. (EDC) in human hepatic stellate cells (HSCs) in vitro and in a carbon tetrachloride (CCl4)-induced hepatic fibrosis mouse model in vivo.@*METHODS@#For in vitro study, HSCs were pre-treated with platelet-derived growth factor (10 ng/mL) for 2 h to ensure activation and treated with EDC for 24 h and 48 h, respectively. The effect of EDC on HSCs was assessed using cell counting kit-8 assay, EdU staining, transmission electron microscopy, immunofluorescence staining, and Western blot, respectively. For in vivo experiments, mice were intraperitoneally injected with CCl4 (2 ° L/g, adjusted to a 25% concentration in olive oil), 3 times per week for 6 weeks, to develop a hepatic fibrosis model. Forty 8-week-old male C57BL/6 mice were divided into 4 groups using a random number table (n=10), including control, model, positive control and EDC treatment groups. Mice in the EDC and colchicine groups were intragastrically administered EDC (0.5 g/kg) or colchicine (0.2 mg/kg) once per day for 6 weeks. Mice in the control and model groups received an equal volume of saline. Biochemical assays and histological examinations were used to assess liver damage. Protein expression levels of α -smooth muscle actin (α -SMA) and microtubule-associated protein light chain 3B (LC3B) were measured by Western blot.@*RESULTS@#EDC reduced pathological damage associated with liver fibrosis, downregulated the expression of α -SMA and upregulated the expression of LC3B (P<0.05), both in HSCs and the CCl4-induced liver fibrosis mouse model. The intervention of bafilomycin A1 and rapamycin in HSCs strongly supported the notion that inhibition of autophagy enhanced α -SMA protein expression levels (P<0.01). The results also found that the levels of phosphoinositide (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and p-p70S6K all decreased after EDC treatment (P<0.05).@*CONCLUSIONS@#EDC has anti-hepatic fibrosis activity by inducing autophagy and might be a potential drug to be further developed for human liver fibrosis therapy.


Subject(s)
Animals , Male , Mice , Acetates , Autophagy , Carbon Tetrachloride , Hepatic Stellate Cells , Liver/pathology , Liver Cirrhosis/pathology , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt/metabolism , Ribosomal Protein S6 Kinases, 70-kDa , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
10.
Chinese Journal of Lung Cancer ; (12): 291-294, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-928811

ABSTRACT

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
.


Subject(s)
Humans , Angiogenesis Inhibitors/pharmacology , Bevacizumab/therapeutic use , Brain/metabolism , Consensus , Lung Neoplasms/drug therapy , Necrosis/etiology , Radiation Injuries/etiology , Vascular Endothelial Growth Factor A/metabolism
11.
Article in English | WPRIM (Western Pacific) | ID: wpr-929045

ABSTRACT

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9), the third-generation genome editing tool, has been favored because of its high efficiency and clear system composition. In this technology, the introduced double-strand breaks (DSBs) are mainly repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR) pathways. The high-fidelity HDR pathway is used for genome modification, which can introduce artificially controllable insertions, deletions, or substitutions carried by the donor templates. Although high-level knock-out can be easily achieved by NHEJ, accurate HDR-mediated knock-in remains a technical challenge. In most circumstances, although both alleles are broken by endonucleases, only one can be repaired by HDR, and the other one is usually recombined by NHEJ. For gene function studies or disease model establishment, biallelic editing to generate homozygous cell lines and homozygotes is needed to ensure consistent phenotypes. Thus, there is an urgent need for an efficient biallelic editing system. Here, we developed three pairs of integrated selection systems, where each of the two selection cassettes contained one drug-screening gene and one fluorescent marker. Flanked by homologous arms containing the mutated sequences, the selection cassettes were integrated into the target site, mediated by CRISPR/Cas9-induced HDR. Positively targeted cell clones were massively enriched by fluorescent microscopy after screening for drug resistance. We tested this novel method on the amyloid precursor protein (APP) and presenilin 1 (PSEN1) loci and demonstrated up to 82.0% biallelic editing efficiency after optimization. Our results indicate that this strategy can provide a new efficient approach for biallelic editing and lay a foundation for establishment of an easier and more efficient disease model.


Subject(s)
Alleles , CRISPR-Cas Systems , DNA End-Joining Repair , Gene Editing/methods , Recombinational DNA Repair
12.
Preprint in English | bioRxiv | ID: ppbiorxiv-442029

ABSTRACT

Three prevalent SARS-CoV-2 Variants of Concern (VOCs) were emerged and caused epidemic waves. It is essential to uncover the key genetic changes that cause the high transmissibility of VOCs. However, different viral mutations are generally tightly linked so traditional population genetic methods may not reliably detect beneficial mutation. In this study, we proposed a new pandemic-scale phylogenomic approach to detect mutations crucial to transmissibility. We analyzed 3,646,973 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata. Based on the sequential occurrence order of mutations and the instantaneously accelerated furcation rate, the analysis revealed that two non-coding mutations at the position of 28271 (g.a28271-/t) might be crucial for the high transmissibility of Alpha, Delta and Omicron VOCs. Both two mutations cause an A-to-T change at the core Kozak site of the N gene. The analysis also revealed that the non-coding mutations (g.a28271-/t) alone are unlikely to cause high viral transmissibility, indicating epistasis or multilocus interaction in viral transmissibility. A convergent evolutionary analysis revealed that g.a28271-/t, S:P681H/R and N:R203K/M occur independently in the three-VOC lineages, suggesting a potential interaction among these mutations. Therefore, this study unveils that non-synonymous and non-coding mutations could affect the transmissibility synergistically.

13.
Chinese Journal of Endemiology ; (12): 230-234, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-883699

ABSTRACT

Objective:To study the effect of glucosamine combined with sodium hyaluronate on serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in patients with Kashin-Beck disease (KBD).Methods:In a prospective design, patients with KBD admitted to South Hospital of Yantaishan Hospital from January 2017 to January 2019 were selected and divided into control, observation, and replacement groups. The control group was treated with glucosamine sulfate, the observation group was treated with intra-articular injection of sodium hyaluronate on the basis of the control group, and the replacement group was treated with artificial knee arthroplasty. The clinical efficacy, visual analogue scale (VAS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) of the three groups were compared before treatment, 6 weeks and 6 months after treatment. Blood samples were collected from the patients, and the serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA) to compare the serum levels of IL-1β and TNF-α in the three groups before treatment, 6 weeks and 6 months after treatment.Results:The age of patients in the control group was (53.76 ± 7.33) years old, including 19 males and 23 females. The age of patients in the observation group was (54.18 ± 7.06) years old, including 20 males and 22 females. The age of the replacement group was (55.17 ± 6.43) years old, including 17 males and 13 females. The total effective rate in observation group (92.86%, 39/42) was significantly higher than that of the control group (76.19%, 32/42, χ 2 = 4.459, P < 0.05). At 6 weeks and 6 months after treatment, the VAS scores in the observation group [(4.10 ± 1.21), (3.16 ± 0.95) points] were significantly lower than those in the control group [(5.48 ± 1.17), (4.06 ± 0.74) points, P < 0.05]; at 6 weeks after treatment, the VAS score in the replacement group [(3.28 ± 0.89) points] was significantly lower than that in the observation group ( P < 0.05). At 6 weeks and 6 months after treatment, the WOMAC scores in the observation group [(40.72 ± 4.19, 25.86 ± 3.02) points] were significantly lower than those in the control group [(48.29 ± 2.16), (36.81 ± 3.13) points, P < 0.05]; the WOMAC scores in the replacement group [(29.68 ± 4.22), (23.57 ± 3.86) points] were significantly lower than those of the observation group ( P < 0.05). The serum levels of IL-1β [(9.28 ± 2.74), (6.85 ± 2.27) pg/ml] and TNF-α [(12.66 ± 4.54), (10.34 ± 3.48) pg/ml] in the observation group were significantly lower than those in the control group [(12.78 ± 2.79), (10.36 ± 2.63), (15.51 ± 4.63), (14.64 ± 4.27) pg/ml, P < 0.05], the serum levels of IL-1β [(6.12 ± 3.55), (5.39 ± 2.23) pg/ml], TNF-α [(10.42 ± 3.13) , (8.19 ± 3.15) pg/ml] in the replacement group were significantly lower than those in the observation group at 6 weeks and 6 months after treatment ( P < 0.05). Conclusion:Glucosamine combined with intra-articular injection of sodium hyaluronate can relieve inflammation, improve pain and promote joint function recovery in patients with KBD, but there is still a certain gap compared with knee arthroplasty.

14.
Journal of Forensic Medicine ; (6): 87-90, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-985199

ABSTRACT

With the increasingly obvious role of plant evidence in case detection, forensic botany, which provides clues and evidence in crime scene investigation by using botanical research method has attracted growing attention. The common experimental techniques used in forensic botany are morphological examination, physical and chemical examination, molecular genetic examination, and so on. This paper briefly expounds the advantages and disadvantages of different test methods, summarizes the problems that need to be paid attention to in the application of forensic botany by arranging the related literatures and cases of forensic botanical research, in order to provide reference for scene investigation of cases.


Subject(s)
Botany , Crime , Forensic Medicine , Forensic Sciences , Plants
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-910509

ABSTRACT

Objective:To analyze the prognosis of patients with isolated regional recurrence (RR) after mastectomy, and evaluate the efficacy of radiotherapy and identify the optimal radiation target volumes.Methods:Clinical data of 144 patients with first isolated RR after mastectomy between 2001 and 2018 were retrospectively analyzed. All patients had not received post-mastectomy radiotherapy. The primary endpoints consisted of the subsequent locoregional recurrence (sLRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS).Results:With a median follow-up of 82.5 months after RR, the 5-year sLRR, DM, PFS and OS rates for the entire group were 42.1%, 71.9%, 22.9% and 62.6%, respectively. Local plus systemic therapy was an independent favorable prognostic factor for sLRR ( P<0.001) and PFS ( P=0.013). The sLRR rate in the surgery plus radiotherapy group was the lowest ( P<0.001). Surgery plus radiotherapy significantly reduced the 5-year risk of recurrence within the initially involved nodal regions ( P<0.001). Patients with chest wall irradiation obtained the 5-year subsequent chest wall recurrence rate of 12.1% compared to 14.8%( P=0.873) for those without chest wall irradiation. The subsequent supraclavicular recurrence rate was lower in patients with prophylactic supraclavicular irradiation than that without prophylactic supraclavicular irradiation (9.9% vs. 23.8%, P=0.206). The incidence rates of initially uninvolved axillary and internal mammary nodal recurrence were below 10% regardless of prophylactic irradiation or not. Conclusions:Patients with RR alone have an optimistic 5-year OS in the contemporary era. Comprehensive locoregional treatment including surgery and radiotherapy combined with systemic therapy is recommended. The chest wall, axillary and internal mammary nodal prophylactic irradiation should not be routinely performed for all patients with RR. The value of supraclavicular prophylactic irradiation remains to be evaluated.

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Article in Chinese | WPRIM (Western Pacific) | ID: wpr-910489

ABSTRACT

Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.

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Journal of Chinese Physician ; (12): 146-149, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-884020

ABSTRACT

Gastric cancer is one of the most common malignant tumors in China, and its pathogenesis is complex. At present, there is no good method for the diagnosis and treatment of gastric cancer. However, studies have shown that microRNA (miRNA) has abnormal expression in gastric cancer, which participates in the regulation of gastric cancer related genes, and has an impact on the occurrence, development, diagnosis and treatment of gastric cancer. This paper aims to review the relationship between miRNA and the diagnosis and treatment of gastric cancer, as well as the drug resistance in the treatment, so as to lay the foundation for the follow-up research and clinical diagnosis and treatment.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-870018

ABSTRACT

Objective:To investigate the correlation between serum bilirubin level and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus of different sexes.Methods:A total of 1 304 patients with type 2 diabetes mellitus were included in this study. The clinical data were collected and fundus examination was performed. According to the results of fundus examination, the patients were divided into DR group and Non-DR (NDR) group. The correlation between the levels of serum total bilirubin, direct bilirubin, indirect bilirubin, and the occurrence of DR was analyzed.Results:The levels of total bilirubin, direct bilirubin, and indirect bilirubin in DR group were significantly lower than those in NDR group. Univariate analysis showed that the levels of total bilirubin and indirect bilirubin were negatively correlated with the occurrence of DR ( P<0.01). There was no significant correlation between the level of direct bilirubin and the occurrence of DR. Smooth curve fitting showed that there was a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in women, while a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in men. The results of multiple regression analysis showed that in men total bilirubin increased by 1 μmol/L, the risk of DR decreased by 8% ( OR=0.92, 95% CI 0.88-0.98, P<0.01). Indirect bilirubin increased by 1 μmol/L, and the risk of DR decreased by 9% ( OR=0.91, 95% CI 0.84-0.96, P<0.01). In women, when total bilirubin<12.8 μmol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR decreased by 17%( OR=0.83, 95% CI 0.72-0.95, P<0.01); When total bilirubin≥12.8 umol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR increased by 10%( OR=1.10, 95% CI 1.01-1.20, P<0.05); When indirect bilirubin<9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR decreased by 20%( OR=0.80, 95% CI 0.68-0.94, P<0.01); When indirect bilirubin≥9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR increased by 13%( OR=1.13, 95% CI 1.01-1.25, P<0.05). Conclusion:This study shows that there is a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in female patients with type 2 diabetes mellitus, and there is a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in male patients. However, there was no significant correlation between direct bilirubin and DR risk.

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Article in Chinese | WPRIM (Western Pacific) | ID: wpr-869273

ABSTRACT

Objective:To investigate the association between oxygen desaturation rate and blood pressure (BP) among severe obstructive sleep apnea syndrome (OSAS) and the possible mechanism.Methods:Patients with snoring were enrolled from the Department of Sleep Medicine Center, the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University form March 2018 to January 2019 and underwent polysomnography (PSG). Noninvasive BP and Heart rate variability were full-night monitored continuously and synchronized with PSG. Based on the PSG results and exclusion criteria, a total of 86 severe OSAS patients were enrolled in this study and divided into two groups according to the ambulatory BP measurements: hypertensive group ( n=44) and normotensive group ( n=42). Oxygen desaturation rate was expressed as the change in the percentage of pulse oxyhemoglobin saturation (SpO 2) per second during desaturation events after the obstructive apnea events occurred. The PSG parameters were compared between the two group and the multiple regression analyses were used to explore the association between oxygen desaturation rate and BP and its possible mechanism. Results:The apnea-hyperpnoea index (AHI) and respiratory event-related arousals (RERAs) were significantly higher in hypertensive group than those in normotensive group [(69.8±18.2) vs. (56.5±13.9) event/h; (40.5±17.4) vs. (30.2±14.6) event/h, both P<0.01]. In addition, hypoxia exposure conditions in the hypertensive group were more severe than those in the normotensive group, especially oxygen desaturation rate [(0.45±0.14)%/s vs. (0.33±0.10)%/s, P<0.001]. After adjusting for age, sex, neck circumference, waist circumference, smoking, drinking, the regression analyses showed that only the oxygen desaturation rate was significantly associated with both awake and asleep BP in OSAS patients ( β=0.473, 0.478, both P<0.01) and the correlation analyses suggested that the oxygen desaturation rate was related to the both awake and asleep sympathetic-parasympathetic imbalance ( r=0.367, 0.337, both P<0.01). Conclusion:Oxygen desaturation rate is closely related to BP levels in patients with severe OSAS, and the underlying mechanism is associated with the increased sympathetic activity.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-828382

ABSTRACT

To clarify the difference of soil moisture characteristics between mixed broad leaf-conifer forest soil and artificial cultivation of Notopterygium incisum, the HYPROP system and the dew point potential meter were used to determine soil water retention curves(SWRC) for samples of two horizons(i.e. 2-7 cm, 10-15 cm). The basic physical and chemical properties of soil and its water characteristic parameters were also determined. The result showed as fllows:①The bulk density of mixed coniferous-broad leaf forest soil was between 0.33 and 0.52 g·cm~(-3), significantly lower than the corresponding value of field soil(1.01-1.18 g·cm~(-3))(P<0.05), While the organic matter content was significantly higher than the corresponding value of field soil(P<0.05). ②The saturated water content(θ_s), field water holding capacity(θ_(FC)) and Water that can be effectively utilized by plants(θ_(PAC)) of mixed coniferous-broadleaved forest soil were significantly higher than the corresponding value of field soil(P<0.05), while the retained water content(θ_r) value that cannot be effectively utilized by plants was significantly lower than that of field soil(P<0.05). ③The values of structural porosity(0.13-0.24 cm~3·cm~(-3)) and Matrix porosity(0.34-0.44 cm~3·cm~(-3)) of mixed coniferous-broadleaved forest soil were higher than the corresponding values of field soil. Therefore, with low bulk density and high content of organic matter, mixed coniferous-broadleaved forest soil can store more water in soil in the form of effective water to meet the needs of plants for water, thus possibly forming high quality medicinal materials of Notopterygii Rhizoma et Radix. In conclusion, the results of this study can provide theoretical basis guidance for soil structure improvement and water management to form high quality medicinal materials in the artificial cultivation of N. incisum.


Subject(s)
Apiaceae , China , Forests , Soil , Tracheophyta , Water
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