RESUMO
[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].
RESUMO
Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.
RESUMO
CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.
RESUMO
The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.
RESUMO
Objective To compare ultrasound-and endoscopy-guided methods in nasogastrojejunal tube placement in critical ill patients at bedside.Methods A tot al of 95 critical ill patients planed to perform enteral nutrition (EN) were enrolled.They were divided randomly into ultrasound-guided group (48 patients)and endoscopy-guided group (47 patients).The success rate,the incidence of complications and the time they took were compared between two groups.Results Ultrasound guided group was compared to endoscopy guided group with a lower success rate (81.3％ vs 100％,P =0.003),mainly because of the initial 24-stage having a very low success rate (66.7％ vs 100％,P =0.000),but the success rate of the following 24 cases was significantly improved (95.8％ vs 100％,P =0.338).Ultrasound guided group didn 't cause more complications (2.1％ vs 0,P =1.000),and consumed less time [(13.3 ± 2.8)min vs (15.0 ± 1.4) min,P =0.000].Compared to the following 24 cases,the initial 24 cases of ultrasound guided group in nasogastrojejunal tube placement had the lower success rate (66.7％ vs 95.8％,P =0.023),the longer time-consuming [(15.4 ±2.1)rin vs (11.2 ± 1.4) min,P =0.000],and but didnt cause more complications (4.2％ vs 0,P =1.000).The success rate of different diseases [severe acute pancreatitis(SAP) vs cerebrovascular disease] hadn't statistically significant difference (94.9％ vs 87.5 ％,P =0.300),but the SAP group consumed less time [(12.6 ± 1.9)min vs (15.5 ± 2.0)min,P =0.000].Conclusions The placement of nasogastrojejunal tube under ultrasound guidance represented a safe,quick and effective method to provide enteral nutrition.
RESUMO
Objective To investigate the correlation between dynamic changes in esophageal impedance and dilated intercellular space (DIS) of patients with acid-induced non erosive reflux disease (NERD).Methods From September 2013 to July 2014,a total of 35 patients with NERD and 20 healthy controls were selected and underwent 24 h multichannel intraluminal impedance and pH monitoring (MII-pH monitoring),acid perfusion test and gastroendoscopy examination.One piece of mucosa tissue was taken under gastroendoscope from the anterior and posterior walls at 2 cm above the dentate line of the esophagus.Intercellular space (ICS) of the esophageal epithelia cells was measured by software after hematoxylin and eosin staining.t test and variance analysis were performed for statistical analysis.Pearson correlation analysis was used for correlation analysis.Results Impedance baseline of distal esophagus and impedance recovery rate of patients with NERD were lower than those of healthy control group,which were (2 998±701) Ω vs (3 880±1 054) Ω and (30.1±14.0) Ω/min vs (53.0±14.5) Ω/min,and the differences were statistically significant (t=3.65,5.41;both P＜0.01).Compared with healthy control group,ICS of the esophageal epithelial cells was obviously wider (1.03 ± 0.20) μm vs (0.66±0.14) μm,and the difference was statistically significant (t=-6.57,P＜0.01).Impedance baseline of esophagus and impedance recovery rate of patients with positive acid perfusion test were lower than those of patients with negative acid perfusion test,which were (2 755±680) Ωvs (3 411±536) Ω and (25.4±13.0) Ω minvs (33.4±9.8) Ω /min,and the differences were statistically significant (t =2.99,2.03;both P＜0.05).The correlation between impedance recovery rate and ICS was negative (r=-0.70,P＜0.01).Conclusions Recurrent reflux induced injury and delayed mucosal headline may be the factors of impaired mucosal integrity in patients with NERD.The changes esophageal of impedance baseline to a certain extent reflected the degree of esophageal mucosal integrity impairment.
RESUMO
Objective To investigate changes and the significance of Th17/Treg immune imbalance in secondary systemic infection in patients with severeacute pancreatitis.Methods We selected 21 patients with severe acute pancreatitis and secondary systemic infection (infection group),25 patients with severe alone (non-infection group),20 healthy cases undergoing annual health checkup (control group) in this study.The expression levels of Th17/Treg cells and related cytokines were compared between groups.Results There were significant differences in mortality rate and duration of ICU stay between infection group and non-infection group [23.8％ vs.4.0％,(11.3±3.4) d vs.(7.5±2.8) d,x2=3.949,t=2.890,P=0.047 and0.045].The percentages of Th17 cell andTreg cell,Th17/Treg ratio,mRNA expressions of IL-6,IL-17,IL-23,TGF-β and orphan receptor γt were higher in infection and non infection groups than in control group [(26.4 ± 1.2) ％,(12.8 ± 0.9)％ vs.(3.1±0.8) ％;(6.7±1.6)％,(4.2±1.3)％ vs.(1.3±0.4)％;(4.3±1.0)％,(3.2±1.1)％ vs.(2.4±0.9)％;(7.1±0.8)ng/L,(5.3±0.7)ng/L vs.(0.2±0.1)ng/L;(22.9±2.4)ng/L,(15.6±2.8)ng/L vs.(10.3± 1.5)ng/L;(15.7±2.1)ng/L,(10.2± 1.5)ng/L vs.(8.3± 1.4)ng/L;(23.6±2.2)ng/L,(16.3±1.7)ng/L vs.(11.6±1.1)ng/L;(0.052±0.014),(0.035± 0.010) vs.(0.004±0.001);F=15.761,55.745,9.437,102.788,21.038,16.239,36.957,23.924,respectively,P=0.555,0.000,0.014,0.000,0.002,0.004,0.000,0.000].The mRNA expressions of IL-10 and Foxp3-T were lower in infection and non-infection groups than in control group [(6.4±1.1)ng/L,(10.5 ± 2.1) ng/L vs.(15.4±2.0)ng/L;(0.005±0.001),(0.020±0.007) vs.(0.032±0.009),F=18.995 and 20.608,P=0.003 and 0.002].Conclusions The secondary infection can aggravate the Th17 / Treg immune imbalance in patients with severe acute pancreatitis,and extend the ICU hospitalization days.
RESUMO
Objective To Analyze the immunity to secondary infection in the elderly with severe acute pancreatitis.Methods Totally 105 old patients were included in the present study.The ratio of CD4+ to CD8+,and serum levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),interleukin-10 (IL-10),and interleukin-4 (IL-4) were determined by flow cytometer analysis or ELISA within 3 days after diagnosis of secondary infection.Results Among 105 old patients,58 cases experienced secondary infection.At 3th day after severe acute pancreatitis,the levels of TNF-α,IL-6,IL-4,IL-10,CD4+,CD8+ and CD4+/ CD8+ were (81.3±5.5)ng/L,(141.2±13.7)ng/L,(61.1±7.4) ng/L,(153.8 ±15.2) ng/L,(43.5±5.5)％,(20.7±2.9)％ and (2.4±0.3) in infection group,as compared with those of (50.8±4.7)ng/1,(81.4±11.7)ng/L,(30.8±7.8)ng/L,(100.3± 13.8)ng/L,(31.6±4.6)ng/L,(29.7±3.5)and (1.1±0.4)in control group,respectively,with statistically significant differences betwveen the two groups (t=7.30,6.51,4.87,4.52,2.88,3.41,4.26,all P＜0.05).At 28th day after SAP,the levels of TNF-α,IL-6,IL-4,IL-10,CD4+,CD8 ± and CD4+ /CD8+ were (29.3±5.8)ng/L,(51.7±7.9)ng/L,(33.8±5.1)ng/L,(82.6±9.5)ng/L,(22.1±3.3)％,(47.1±4.3)％ and (0.6±0.3) in infection group,as compared with those of (44.4±5.5)ng/L,(82.2±7.1)ng/L,(65.3±5.5)ng/L,(109.1±9.5)ng/L,(40.5±2.7)ng/L,(33.4±4.5)ng/L and (1.8±0.4) in control group,respectively,showing statistically significant differences between the two groups(t=3.26,4.93,7.32,3.43,7.41,3.81,4.33,all P＜0.05).Conclusions An early excessive immune response and subsequent immune injury is closely related to secondary severe acute pancreatitis.
RESUMO
Objective To observe the effect of acute retrograde gastric electrical stimulation (RGES) on gastric accommodation,emptying and gastrointestinal hormones releasing in obese patients. Methods Sixteen obese patients were examined. On the first day,a pair of mucosal gastric electrodes was placed under endoscope. The liquid meal load test and the standard solid meal gastric emptying test were carried out on the second day. RGES was performed starting at 30 minutes before each test and through the whole testing process. The serum leptin,ghrelin,resistin and peptide YY were examined before and after the standard solid meal gastric emptying test. On the third day,sham stimulation was given. The effect of acute RGES on related index was compared by self-control.Results BMI of the 16 patients was (32. 90±2. 99) kg/m2. Acute RGES significantly reduced the liquid meal volume of fullness [(460±148) ml and (630±219) ml,t=-7. 200,P＜0. 01] and the maximal tolerable meal volume [(699±215) ml and (926±295) ml,t=- 5. 390,P＜0. 01]. The effects of RGES and sham RGES on half-emptying time of standard solid meal was (109±26) min and (103±31) min (t=1. 009,P= 0. 329);on the retention rate of standard solid meal at one hour and two hour was (63. 37±9. 75)% and (59. 73±12.87)% (t=1. 834,P= 0. 087),(42.22±13.97)%and (38. 33±16. 87)% (t= 1.780,P= 0. 095),respectively. The ratio of gastrointestinal hormones after and before the stimulation also of the sham stimulation,leptin was 1. 03±0. 34 and 1. 08±0. 38(t=-0.386,P=0. 705),ghrelin was 0. 99±0. 11 and 0. 98±0. 12 (t= 0. 413,P=0.685),resistin was 1. 11±0. 25 and 0. 99±0. 24 (t= 1. 753,P= 0. 100),and peptide YY was 1. 56±0. 71 and 1. 33±0. 61 (t=1. 402,P= 0. 181). Conclusions In obese patients,acute RGES significantly reduce the liquid meal volume by lower gastric accommodation,to certain extent which will delay gastric emptying. There is no significant influence on gastrointestinal hormones releasing.
RESUMO
Nine sorts of the preparations containing P.aeruginosa LPS were,With hot phenol- water method of Westphal,extracted from the cells or the cultures of P.aeruginosa (strain 017 of serotype 2 and its dissociative strains of both La.form and Sm.form), of which some cells or cultures had been pretreated respectively through homogenating, ultrasonic wave,autoclaving at 120c,and autolysis. The LPS preparations from Sm.from strain have higher contents of both KDO (2-Keto-3-Deoxyoctonic acid)and hexose than the rest do.Each of nine vaccines proved to be protecting mice against the challenge of strain 017 of over 10 LD_(?). The preparation extracted from the cultures having been pretreated through auto- claving at 12oC for 90 rain and ultrasonic wave shows the infrared absorption spectrum with decreased characteristic absorption peaks of lipopolysaccharide,but possesses the similar protective effect like the rest and otherwise lower toxicity.It indic-ates that the immuno comp etent substance is quite a heat-stable.