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Objective To investigate the effect of saikosaponin A regulating myosin light chain kinase(MLCK)/myosin light chain 2(MLC2)signaling pathway on intestinal injury in rats with severe acute pan-creatitis(SAP).Methods A total of 10 rats were randomly selected as sham operation group,and the other rats were injected with sodium taurine cholate solution to construct SAP rat model.SAP rat models were ran-domly divided into SAP group,saikosaponin A group(10.0 mg/kg intraperitoneal injection of saikosaponin A)and iE-DAP group(3.5 mg/kg intraperitoneal injection of MLCK/MLC2 pathway activator iE-DAP),sai-kosaponin A+iE-DAP group(intraperitoneally injected with 10.0 mg/kg saikosaponin A+3.5 mg/kg iE-DAP),10 rats in each group were injected once a day for 1 week,sham operation group and SAP group were injected with the same amount of normal saline.The serum levels of amylase(AMY),lipase(LIP),diamine oxidase(DAO),interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).HE staining was used to detect the pathological morphology of ileum tis-sue in each group.The levels of oxidative stress indexes in ileum tissue were detected by ELISA.Intestinal barrier re-lated proteins and MLCK/MLC2 pathway related proteins were detected by western blot.Results Compared with SAP group,the levels of AMY,LIP,DAO,IL-1β,IL-6 and TNF-α in saikosonin A group were significantly de-creased,while the levels of AMY,LIP,DAO,IL-1β,IL-6 and TNF-α in iE-DAP group were significantly in-creased,with statistical significance(P<0.05).Compared with SAP group,the structure of ileum tissue was improved and the pathological score of ileum tissue was significantly decreased in SA group(P<0.05).Com-pared with SAP group,the levels of glutathione and superoxide dismutase in SA group were significantly in-creased,and the levels of malondialdehyde were significantly decreased in SA group,with statistical signifi-cance(P<0.05).Compared with SAP group,the protein levels of MLCK,p-MLC2/MLC2 in SA group were significantly decreased,and the difference was statistically significant(P<0.05).Conclusion Saikosaponin A may improve intestinal injury in SAP rats by down-regulating the MLCK/MLC2 signaling pathway.
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The type Ⅱ inflammatory response is primarily mediated by type 2 immune cells and cytokines,such as helper 2 cells(Th2)and group 2 innate lymphoid cells(ILC2),along with IL-4,IL-5 and IL-13.This response plays crucial roles in humoral immunity,parasite defense,toxin neutralization,tissue damage repair and regeneration.However,type-Ⅱ immune response can also contribute to the development of diseases.Currently,type Ⅱ inflammation is recognized to have physiological and pathological impli-cations in the skin,respiratory tract,digestive tract and adipose tissues.Moreover,it serves as a major cause of allergic diseases.Due to its unique immune microenvironment,the respiratory tract exhibits a high prevalence of type Ⅱ inflammation encompassing chronic sinusitis,allergic rhinitis,allergic asthma,allergic bronchopulmonary aspergillosis,and chronic obstructive pulmonary disease with eosinophilia among others.This review will focus on the research progress concerning Th2 and ILC2 cells in allergic pulmonary inflam-mation as well as targeted therapy for allergic diseases.
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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.
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Apéndice Atrial , Fibrilación Atrial , Embolia , Accidente Cerebrovascular , Trombosis , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Anticoagulantes/uso terapéutico , Hemorragia/epidemiología , Hemorragia/etiología , Embolia/prevención & control , Cateterismo Cardíaco/efectos adversosRESUMEN
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.
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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.
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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.
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Goma , Suelo , China , Potasio , Análisis EspacialRESUMEN
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.
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Adipocitos/metabolismo , Adipogénesis/genética , Factor 6 Similar a Kruppel/genética , Adipocitos/citología , Adipocitos/fisiología , Adipogénesis/fisiología , Animales , Bovinos , Diferenciación Celular/genética , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Factor 6 Similar a Kruppel/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , RNA-Seq/métodos , Análisis de Secuencia de ARN/métodos , Transducción de Señal/genética , Transcriptoma/genéticaRESUMEN
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.
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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. .
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Humanos , Inhibidores de la Angiogénesis/farmacología , Bevacizumab/uso terapéutico , Encéfalo/metabolismo , Consenso , Neoplasias Pulmonares/tratamiento farmacológico , Necrosis/etiología , Traumatismos por Radiación/etiología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
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.
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Animales , Masculino , Ratones , Acetatos , Autofagia , Tetracloruro de Carbono , Células Estrelladas Hepáticas , Hígado/patología , Cirrosis Hepática/patología , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
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.
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Alelos , Sistemas CRISPR-Cas , Reparación del ADN por Unión de Extremidades , Edición Génica/métodos , Reparación del ADN por RecombinaciónRESUMEN
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.
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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.
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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.
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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.
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Botánica , Crimen , Medicina Legal , Ciencias Forenses , PlantasRESUMEN
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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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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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.
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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.
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"Huajiao" is dried ripe fruit peel of Zanthoxylum bungeanum or Z. schinifolium, is konwn as geoherbs, especially the "Dahongpao" cultivated in Hanyuan, Maoxian and Jiulong of Sichuan province. However, the genetic basis of Dao-di "Huajiao" is virtually unknown. The transcriptome of the fruit and leaf from Sichuan(Hanyuan, Jiulong, Lixian, Maoxian), Gansu(Wudu) province and Shaanxi(Fengxian) province was sequenced. Trinity de novo assembling resulted in a total of 177 616 unigenes. Through the KEGG, NR, SwissProt, Trembl, KOG/COG, GO, Pfam database comparision 106 644 annotated Unigene finally, 4 574 deferentially expressed genes were found in fruit between Sichuan and other provinces, including 3 740 up-regulated genes and 834 down-regulated genes. Among the up-regulated genes, 27 up-regulated genes were raleted to terpenoids, and 8 up-regulated genes were related to isoquinoline alkaloid bio-synthesis. Furthermore, it was also showed remarkable differences in groups which enrichment ratio of the diffe-rent expressed gene compared. The different expressed genes were annotated by the KEGG database into plant-pathogen interaction, plant hormone signal transduction and phenylpropanoid biosynthesis in fruit and leaf, but isoflavonoid bio-synthesis and betaine bio-synthesis were significantly different in fruit and leaf. The study laid a certain reference basis for comparison of quality and different expressed gene of Z. bungeanum from different groups.