Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Objective:To explore the effects of G protein-coupled receptor 55 (GPR55) antagonist CID16020046 on renal fibrosis in mice, and provide a new method and idea for the treatment of renal fibrosis.Methods:(1) GPR55 overexpression and GPR55 antagonist CID16020046 were used in renal fibroblasts (NRK-49F) of rats, respectively. Meanwhile,transforming growth factor-β1 (TGF-β1) was applied in the NRK-49F cells to observe the expression of fibrosis-related factors and inflammatory factors. (2) A mouse model of renal fibrosis with unilateral ureteral obstruction (UUO) was established in vivo. Eight-week-old male C57BL/6J mice (20-25 g) were randomly divided into three groups according to the random number table method: sham group ( n=6), model group (UUO group, n=7), model + CID16020046 drug (UUO+CID group, n=8). The drug CID16020046 (10 mg/kg) was intraperitoneally injected 1 day before modeling, on the day of modeling and every day after surgery in UUO+CID group, and the corresponding dose of 0.9% normal saline was injected intraperitoneally in sham and UUO groups.The mice were sacrificed for sampling 7 days after UUO surgery, and their renal function indicators, liver transaminase, and cardiac markers were examined. Western blotting and quantitative real-time PCR were used to detect the expression of renal fibrosis-related factors and inflammatory factors. Immunohistochemistry staining, Sirius red staining and Masson trichrome staining were used to detect the pathological changes of renal tissues. Results:(1) After NRK-49F cells were stimulated by TGF-β1, the mRNA and protein expression levels of GPR55 were significantly increased (both P<0.05). There was no statistically significant difference in the mRNA expression of fibrosis-related factors fibronectin and collagen Ⅰ, and inflammatory factors interleukin-1β and tumor necrosis factor-α between TGF-β1 group and TGF-β1 + GPR55 overexpression group (all P>0.05). Compared with the TGF-β1 group, the protein expression levels of fibrosis-related factors alpha-smooth muscle actin (α-SMA) and vimentin, and the mRNA expression levels of collagen Ⅰ and α-SMA were lower in the TGF-β1 + CID group (all P<0.05). (2) Compared with sham group, the mRNA and protein expression levels of GPR55 in UUO group were higher (both P<0.05). The serum creatinine in the UUO+CID group was lower compared to the UUO group ( P<0.05). There was no statistically significant difference in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine kinase isoenzyme between UUO group and UUO+CID group (all P>0.05). Compared with the UUO group, the protein expression levels of renal fibrosis-related factors fibronectin, collagen Ⅰ and vimentin, and the mRNA expression levels of fibronectin, collagen Ⅰ, collagen Ⅲ and α-SMA were lower in the UUO+CID group (all P<0.05). The degree of renal tubular dilation and interstitial collagen fiber deposition in the UUO+CID group was significantly reduced compared to the UUO group (all P<0.05). Conclusions:CID16020046 can reduce serum creatinine in UUO mice, protect renal function, and simultaneously decrease the expression of fibrosis-related factors in renal fibroblasts and mouse kidney tissues, thereby alleviating renal fibrosis.

Objective:To investigate the clinical features, risk factors, treatment and prognosis of dermatomyositis (DM) patients with positive anti-melanoma differentiation associated gene 5(MDA5) antibody with rapidly progressive interstitial lung disease (RPILD).Methods:The clinical data of 88 DM patients from June 2019 to June 2020, at the rheumatology department of Guangdong Provincial People's Hospital were collected and retrospectively analyzed. T-test, non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and Logistics regression analysis were used for data analysis. Results:① 37%(36/88) DM patients were positive for anti-MDA5 antibody. The frequency of ulcerative rash, Gottron's sign, arthritis, clinically amyopathic dermatomyositis (CADM), and erythrocyte sedimentation rate (ESR) was significantly higher in patients with anti-MDA5 antibody ( P<0.05). The cell count of white blood cell, neutrophil, lymphocyte, and serum creatine kinase (CK) level were significantly lower in the anti-MDA5 antibody positive group than those in the negative group ( P<0.05). Of anti-MDA5 antibody positive DM patients, 100% developed ILD, 34% (11/32)developed RP-ILD, 16%(5/32) died, which were significantly higher than those of anti-MDA5 antibody negative patients ( P<0.05). ② Of anti-MDA5 antibody positive DM patients, the C reactive protein (CRP) level, positive rate of anti-Ro-52 antibody and mortality rate were significantly higher RPILD group than those in the non-RPILD group [15.70(4.49, 29.00) vs 3.22 (1.66, 7.15), Z=-2.440, P=0.014; 91% vs 43%, P=0.011; 46% vs 0, P=0.002]. Logistics regression analysis indicated that positive anti-Ro-52 antibody [ OR=4.561, 95% CI (1.797, 11.580), P=0.001] might be a risk factor for anti-MDA5 antibody positive DM-RPILD. ③ Among patients with anti-MDA5 antibody with RPILD, serum ferritin and D-dimer level was significantly higher and oxygenation index was significantly lower in the non-survival group than those in the survival group [1 931 (1 377, 7 379) vs 638(196, 876), Z=-2.556, P=0.009; 2 760(1 995, 4 854) vs 985(533, 1 588), Z=-2.379, P=0.017; 230(140, 256) vs 309(262, 382), Z=2.191, P=0.030]. In addition, the delayed intensive treatment time was significantly longer in the non-survival group than those in the survival group [(14.0±2.6) vs (4.5±1.4), t=7.899, P<0.01]. Furthermore, the proportion of combined therapy with two disease modifying antirheumatic drug (DMARDs) was significantly lower in the non-survival group than those in the survival group (0 vs 83%, P=0.015). Conclusion:Anti-MDA5 antibody may be associ-ated with characteristic clinical manifestations of DM, ILD, RPILD and high mortality rate. Positive anti-Ro-52 antibody may be a risk factor for anti-MDA5 antibody positive DM-RPILD. High serum ferritin and D-dimer level and low oxygenation index in RPILD patients may be associated with poor prognosis. Early treatment with two DMARDs may improve the prognosis of RPILD.

Objective:To figure out the association between the expression of m 6A RNA methylation regulators and the prognosis of children AML, and provide genetic markers for monitoring the progression and recurrence of AML. Methods:Twenty two m 6A RNA methylation regulators were firstly analyzed using the data from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) database and The Genotype-Tissue Expression(GTEx) database, Wilcoxon rank test was performed to analyze the differentially expression of m 6A RNA methylation regulators between the AML and normal tissue, 296 AML children were divided into training cohort and validation cohort by simple random sampling method, Lasso regression was used to screen out the risk factors and the multivariate Cox regression was applied for establishing prognosis predicting model in training cohort. Kaplan-Meier survival curve, time-dependent ROC curve and multivariate Cox regression were used to estimate the efficiency of risk score calculated by predictive model in validation cohort. Results:Twenty one m 6A genes were up regulated in AML compared to Normal patients. Five m 6A RNA methylation regulators( ZC3H13, YTHDC2, HNRNPA2B1, METTL3, METTL5) were included in final predicting model. Risk score could independently predict the survival of AML patients in training cohort(HR:2.72, 95% CI: 1.54-4.81, P=0.000 6) and validation cohort(HR:2.01, 95% CI:1.14-3.50, P=0.016). Low-risk patients had better prognoses than high-risk patients both in training cohort( P=0.001 9) and validation cohort( P=0.023). Conclusion:This prognosis predicting model constructed by m 6A RNA methylation regulators could independently predict the survival prognosis in AML children, and should be helpful for clinical therapy.

Objective:To figure out the association between the expression of m 6A RNA methylation regulators and the prognosis of children AML, and provide genetic markers for monitoring the progression and recurrence of AML. Methods:Twenty two m 6A RNA methylation regulators were firstly analyzed using the data from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) database and The Genotype-Tissue Expression(GTEx) database, Wilcoxon rank test was performed to analyze the differentially expression of m 6A RNA methylation regulators between the AML and normal tissue, 296 AML children were divided into training cohort and validation cohort by simple random sampling method, Lasso regression was used to screen out the risk factors and the multivariate Cox regression was applied for establishing prognosis predicting model in training cohort. Kaplan-Meier survival curve, time-dependent ROC curve and multivariate Cox regression were used to estimate the efficiency of risk score calculated by predictive model in validation cohort. Results:Twenty one m 6A genes were up regulated in AML compared to Normal patients. Five m 6A RNA methylation regulators( ZC3H13, YTHDC2, HNRNPA2B1, METTL3, METTL5) were included in final predicting model. Risk score could independently predict the survival of AML patients in training cohort(HR:2.72, 95% CI: 1.54-4.81, P=0.000 6) and validation cohort(HR:2.01, 95% CI:1.14-3.50, P=0.016). Low-risk patients had better prognoses than high-risk patients both in training cohort( P=0.001 9) and validation cohort( P=0.023). Conclusion:This prognosis predicting model constructed by m 6A RNA methylation regulators could independently predict the survival prognosis in AML children, and should be helpful for clinical therapy.

Objective To prospectively summary the piercing-out position,direction,length and piercing-in position of perforator,and investigate the feasibility of preoperative design and optimization of the anterolateral thigh flap and its clinical application.Methods All 58 cases of anterolateral thigh flaps were designed and taken from the lateral thigh area from January,2014 to January,2016.Portable Doppler ultrasound was used before an operation to detect the piercing-out position (point P) of perforators.The direction and length (lower subcutaneous segment of perforators) of perforators after leaving piercing-out position were observed during the operation.And the piercing-in positions (point P') on superficial fascia and the dermis were observed.Based on this,we added line B (anterior superior spine-lateral femoral epicondyle) and line C (anterior superior spine-the middle point of superior border of patella) in the lateral and anterior side of original ilium-patella line in the thigh (line A),respectively.Results All perforators found in 58 cases before and during the operations were located on line A or between line A and line B.No perforators were found between line A and line C.Perforators walked toward the anterior medial side after leaving the muscle membrane.The perforator vascular subcutaneous segment (distance between point P and point P') was (2.02±0.23) cm.There was rectus muscle branch in the descending branch of lateral femoral circumflex artery,while no rectus muscle cutaneous branch was seen.20 cases were designed by one-line method,12 cases were designed by two-line method,while 26 cases were designed by three-line method.Conclusion Advanced three-line method is beneficial to detect of the perforators on the anterior thigh lateral region and to reduce the intraoperative injury perforator vessels at the puncture point.Clinical application of the anterior lateral thigh flap is simple and reliable.

Capillary electrophoresis-based STR genotyping is accepted as the gold standard for human individual identification. Next generation sequencing (NGS) allows for the full resolution of STR base composition, and has the potential to be widely used in the field of forensics. Compared with length polymorphism, STR sequencing could provide more information, and quantitatively calculating the forensic parameters is necessary. In this paper, we established simple models for length-based and sequence-based STRs, and calculated the forensic parameters for both models. The results showed that for a single STR locus, compared with length polymorphism, STR sequence polymorphism could provide higher power of discrimination and power of exclusion, indicating sequence-based STR marker have stronger ability for identifying unrelated individuals and exclude non biological father. By combining 15 non-linkage loci for forensic DNA analysis, the cumulative matching probability values for length-based and sequence-based STR models are at 10-18and 10-26levels, respectively. Only 10 non-linkage sequence-based STR is required to reach a cumulative matching probability of as high as 15 length-based STR loci. It is hoped that these simulated models and calculations can provide a reference for the forensic application of NGS-based STR genotyping.

Objective To explore a novel and highly specific small-molecule TNFβinhibitor by using computer-aid?ed virtual screening and cell-based assays in vitro. Methods Computer-aided drug design and virtual screening were used to design and identify chemical compounds that targeted TNFβbased on the crystal structure of the TNFβ-TNFR1 com?plex. The effect of the small-molecule compound against TNFβ-induced cytotoxicity of L929 cells was detected by MTT as?say, and the efficacy of the compound to inhibit TNFβ-induced apoptosis of L929 cells was determined by flow cytometry as?say. The impact of the compound on L929 cell cycle was examined by Propidium Iodide (PI) staining and flow cytometry, and the influence of the compound on TNFβ-triggered signal pathway was analyzed by Western blot assay and Ultra VIEW VOX 3D Live Cell Imaging System. Results No.35 compound (named as C35 thereafter) could effectively inhibit TNFβ-induced cell death in a dose dependent manner, and the half-maximum inhibition concentration (IC50) was 8.19μmol/L. Furthermore, C35 had lower cytotoxicity and minimal effect on L929 proliferation. Here we further revealed that C35 could affect TNFβ-induced apoptotic pathway by blocking the activation of Caspase 3, and markedly reduce L929 cell apoptosis induced by TNFβ. Conclusion A novel TNFβsmall-molecule inhibitor was identified by combining computer-aided virtual screening with functional assays, and which could block TNFβ-triggered apoptotic pathway and efficiently inhibit the cell death in?duced by TNFβ.

Objective To determine the appropriate size of the tube for the thoracic drainage in good efficiency by the experimental study in the influence of the tube size on the flow rate of the fluid with different properties.Methods Three groups were divided according to the different components in the fluid:group A,whole blood with 30％ hematocrit; group B,2.5％ albumin solution; and group C,0.9％ normal saline.The total volume of the fluid was 1000 mL in each group in the experiment.Different sorts of fluids were drained with the chest tubes with different diameters (6F,8F,10F,12F,14F,16F,18F,20F,22F,24F,26F,28F,30F,32F,34F,36F of French F) separately,and the flow rate was calculated.ANOVA was used for the comparison of the differences in flow rate among the groups with given fluid property.Twofactor analysis of variance was used for the analysis of flow rates of fluid with different fluid properties.Curve fitting was performed according to the Poiseuille formula.Results The flow rate was positively correlated with the size of the chest drainage tube.The difference in flow rate among the tubes with difference in size was statistically significant (P ＜ 0.05) but there was no noticeable difference in flow rate between 6F and 8F (P =0.513).The flow rate of the 6F and 8F tubes was higher than that of the control (3.33 mL/min) but there was no significant difference between them (P ＞ 0.05).The flow rate of the tubes in 10F and above was obviously higher than that of control (P ＜ 0.05).The curve was estimated that group A was Q =0.002 9x4,R2 =0.991; group B Q=0.003 2x4,R2 =0.981; group C Q =0.003 4x4,R2 =0.975.When the flow rate was fixed at 3.33 mL/min,the estimated curve in group A was X ≈ 5.82F.Conclusions Our experiment indicated that the chest tube with small diameters (6F-14F) could meet the demand of high efficient drainage in the patients with hemothorax or pleural effusion.

The development status of acupuncture and moxibustion in Tunisia is introduced in this article. Although acupuncture and moxibustion only has a history of more than 30 years in Tunisia, it is very popular among the local people. Until now, there is one acupuncture and moxibustion center aided and built with the help of the Chinese government. Acupuncture and moxibustion clinical department has been set in some of the hospitals, and acupuncture and moxibustion clinical practice is also carried out in some private clinics. Cost of acupuncture and moxibustion in public hospitals has already been covered by medical insurance. As for education of acupuncture and moxibustion, training courses were set up in medical colleges of Tunisia by Tunisian government which is lectured by Chinese acupuncture experts. Acupuncture and moxibustion has been used to treat many diseases in Tunisia and is warmly welcomed by Tunisian.
Acupuncture ; economics ; education ; history ; Acupuncture Therapy ; economics ; history ; trends ; History, 20th Century ; History, 21st Century ; Humans ; Moxibustion ; economics ; history ; trends ; Tunisia