In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

OBJECTIVE: To analyze the marginal roughness and marginal fitness of chairside computer-aided design and computer-aided manufacturing (CAD/CAM) laminate veneers with different materials and thicknesses, and to provide a reference for the clinical application of laminate veneers. METHODS: The butt-to-butt type laminate veneers were prepared on resin typodonts, the preparations were scanned, and the laminate veneers were manufactured by chairside CAD/CAM equipment. The laminate veneers were divided into four groups (n=9) according to the materials (glass-matrix ceramics and resin-matrix ceramics) and thickness (0.3 mm and 0.5 mm) of the veneers, with a total of 36. The marginal topo-graphies of each laminate veneer were digitally recorded by stereomicroscope, and the marginal rough-nesses of the laminate veneers were determined by ImageJ software. The marginal fitness of the laminate veneers was measured by a fit checker and digital scanning and measuring method. At the same time, the mechanical properties of glass-matrix ceramic and resin-matrix ceramic bars (n=20) were tested by a universal testing device. RESULTS: The marginal roughness of 0.3 mm and 0.5 mm glass-matrix ceramic laminate veneers was (24.48±5.55) μm and (19.06±5.75) μm, respectively, with a statistically significant difference (P < 0.001). The marginal roughness of 0.3 mm and 0.5 mm resin-matrix ceramic laminate veneers was (6.13±1.27) μm and (6.84±2.19) μm, respectively, without a statistically significant difference (P>0.05). The marginal roughness of the glass-matrix ceramic laminate veneers was higher than that of the resin-matrix ceramic laminate veneers with a statistically significant difference (P < 0.001). The marginal fitness of 0.3 mm and 0.5 mm glass-matrix ceramic laminate veneers were (66.30±26.71) μm and (85.48±30.44) μm, respectively. The marginal fitness of 0.3 mm and 0.5 mm resin-matrix ceramic laminate veneers were (56.42±19.27) μm and (58.36±8.33) μm, respectively. There was no statistically significant difference among the 4 groups (P>0.05). For glass-matrix ceramics, the flexural strength was (327.40±54.25) MPa, the flexural modulus was (44.40±4.39) GPa, and the modulus of resilience was (1.24±0.37) MPa. For resin-matrix ceramics, the flexural strength was (173.71±16.61) MPa, the flexural modulus was (11.88±0.51) GPa, and the modulus of resilience was (1.29±0.27) MPa. The flexural strength and modulus of glass-matrix ceramics were significantly higher than those of resin-matrix ceramics (P < 0.001), but there was no statistically significant difference in the modulus of resilience between the two materials (P>0.05). CONCLUSION The marginal roughness of CAD/CAM glass-matrix ceramic laminate veneers is greater than that of resin-matrix ceramic laminate veneers, but there was no statistically significant difference in marginal fitness among them. Increasing the thickness can reduce the marginal roughness of glass-matrix ceramic laminate veneers, but has no effect on the marginal roughness of resin-matrix ceramic laminate veneers.
Ceramics ; Computer-Aided Design ; Dental Porcelain ; Dental Veneers ; Materials Testing ; Surface Properties

Liver is the most common metastatic organ in patients with advanced colorectal cancer. Once colorectal cancer liver metastasis (CRLM) occurs, the prognosis will be poor. Therefore early detection of CRLM has a great clinical significance for improving the prognosis of CRLM patients. Surgical resection of primary and metastatic lesion is the only possible curable option for CRLM, translational therapy, interventional therapy and multidisciplinary team also provide more treatment ideas. Long non-coding RNA, cancer stem cells and phosphatidylinositide-3-kinases/protein kinase B signaling pathway reveal the main mechanism of CRLM from different aspects. This article reviews the recent advances in the early diagnosis, treatments and main mechanisms of CRLM.

OBJECTIVE: To investigate the distribution of Chinese medicine (CM) syndrome in patients with acute myocardial infarction (AMI) on admission and its impact on prognosis. METHODS: A total of 525 AMI patients were prospectively recruited and classifified into 4 groups based on their clinical characteristics: excess-heat, excess-cold, deficiency-heat and deficiency-cold syndromes. Major adverse cardiovascular events (MACEs) were followed up. RESULTS: The excess syndrome was more common than deficiency syndrome (72.95% vs. 27.05%; P<0.05). Totally 495 (94.29%) of 525 AMI patients were followed up (median 277 days). There were 59 (11.92%) MACEs. After adjusted with confounding factors in Cox regression models, the hazard ratio (95% confifidence interval) of excess-heat, excess-cold, defificiency-heat and defificiency-cold syndrome groups were 1, 1.25 (0.63, 2.49; P<0.05), 2.37 (1.14, 4.94; P<0.05), 3.76 (1.71, 8.28; P<0.05), respectively. CONCLUSIONS Excess syndrome was more common in AMI patients and had better prognosis, while defificiency-cold syndrome had the poorest prognosis. CM syndrome was of value in predicting long-term outcomes in AMI patients.

Objective To observed the clinical efficacy and safety of high pressure-resistant double-lumen peripherally inserted central catheter (Power PICC) and central venous catheter (CVC) in patients with stem cell transplantation.Methods This was a matched cross-sectional study with 60 patients with leukemia who were treated with catheterization of central venous (30 cases receiving Power PICC vs.30 cases receiving CVC) during stem cell transplantation in the First Affiliated Hospital of Chinese PLA General Hospital.Indwelling time,success rate of catheterization,complications,velocity and stem cell engraftment time were recorded and compared between the Power PICC group and CVC group.Results There were significant differences between the two groups on indwelling time [(18.47±4.44) min vs.(14.43± 1.72) min,t =3.719,P＜0.001],complications [6.67％ (2/30) vs.30％ (9/30),x2 =48.445,P=0.002] and velocity.However,no significant difference was found in success rate of catheterization and stem cell engraftment time (P＞0.05).Conclusion Power PICC performed better than CVC with well tolerability and satisfactory efficacy,which is worthy of promotion and application in the future.

Background:For Chinese patients with hepatocellular carcinoma (HCC),surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor,and yet the prognosis after surgery is diverse.We aimed to construct a scoring system (Shanghai Score) for individualized prognosis estimation and adjuvant treatment evaluation.Methods:A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital.Age,hepatitis B surface antigen,hepatitis B e antigen,partial thromboplastin time,total bilirubin,alkaline phosphatase,γ-glutamyltransferase,α-fetoprotein,tumor size,cirrhosis,vascular invasion,differentiation,encapsulation,and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion.The Harrell's concordance index (C-index) was used to measure model performance.Shanghai Score is calculated by summing the products of the 14 variable values times each variable's corresponding regression coefficient.Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012,808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010,and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts.Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.Results:Shanghai Score showed good calibration and discrimination in postsurgical HCC patients.The bootstrap-corrected C-index (confidence interval [CI]) was 0.74 for overall survival (OS) and 0.68 for recurrence-free survival (RFS) in derivation cohort (4166 patients),and in the three independent validation cohorts,the CIs for OS ranged 0.70-0.72 and that for RFS ranged 0.63-0.68.Furthermore,Shanghai Score provided evaluation for adjuvant treatment choices (transcatheter arterial chemoembolization or interferon-α).The identified subset of patients at low risk could be ideal candidates for curative surgery,and subsets of patients at moderate or high risk could be recommended with possible adjuvant therapies after surgery.Finally,a web server with individualized outcome prediction and treatment recommendation was constructed.Conclusions:Based on the largest cohort up to date,we established Shanghai Score-an individualized outcome prediction system specifically designed for Chinese HCC patients after surgery.The Shanghai Score web server provides an easily accessible tool to stratify the prognosis of patients undergoing liver resection for HCC.

Objective:To investigate the effect of pancreaticojejunostomy on the occurrence of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. Methods:Data from 145 patients with periampullary tumor who underwent pancreaticoduode-nectomy in Tianjin Medical University Cancer Institute and Hospital between October 2008 and August 2013 were reviewed. Factors potentially associated with POPF were analyzed by Pearson chi-square test and Logistic regression analysis. Results:Among the 145 patients, 27 were diagnosed with POPF, including 5 grade A, 17 grade B and 5 grade C. Neither duct to mucosa nor Blumgart pancreati-cojejunostomy was correlated with POPF in grade C. The univariate analysis showed that gender, pancreatic cancer, portal vein involve-ment, type of pancreaticojejunostomy, texture of pancreas, and diameter of the main pancreatic duct were closely correlated with POPF. The multivariate analysis using Logistic regression showed that different pancreaticojejunal anastomoses and genders were independent predictors of POPF. Conclusion:Different types of pancreatic anastomoses are a risk factor for POPF after pancreaticoduodenectomy.

Objective:To discusse the clinical features of sarcomatoid hepatocellular carcinoma to improve the understanding of diagnosis and treatment for sarcomatoid hepatocellular carcinoma. Methods:Data including clinical features and follow-up from 8 pa-tients admitted in Tianjin Medical University Cancer Institute and Hospital from January 2009 to April 2014 were retrospectively ana-lyzed. Results: The average age of all patients was 56.6 years old, and the male-to-female ratio was 3:1. Preoperative CT or MRI showed specific characteristics but it was difficult to confirm diagnosis. Pathological and immunohistochemical examination revealed an expressed epithelial-like phenotype. All 8 patients had advanced local tumor invasion and high lymph node metastasis rates. These patients received surgery, and the median survival time was 10.8 months (3 months to 35 months). Conclusion:Diagnosis of sarcoma-toid hepatocellular carcinoma mainly depended on postoperative pathological examination. Immunohistochemistry was beneficial for sarcomatoid hepatocellular carcinoma diagnosis and differential diagnosis. Surgical treatment prolonged survival time, but the overall prognosis remained poor.

This study was aimed to explore the possible mechanisms of hepcidin increase in multiple myeloma patients. The clinical information and peripheral venous blood of eligible patients with previously untreated multiple myeloma were collected. Serum concentration of IL-6 was detected by ELISA. Peripheral blood monocytes were isolated by CD14⁺ magnetic beads. The expression of hepcidin, IL-6 and C/EBPα mRNA of monocytes were detected by real time quantitative PCR. The results indicated that the hemoglobin level was reduced in 17 multiple myeloma patients enrolled in study (97.8 ± 27.5 g/L), showing the characteristics of anemia of chronic disease. The hepcidin and C/EBPα expression of peripheral blood monocytes significantly increased (P < 0.01), serum IL-6 was also higher than that in normal controls (P < 0.01). Serum IL-6 positively correlated with monocyte hepcidin and C/EBPα expression (P < 0.05); monocyte C/EBPα expression positively correlated with monocyte hepcidin expression (P < 0.05). It is concluded that the elevated IL-6 may induce hepcidin expression through up-regulating C/EBPα in untreated myeloma patients.
Anemia ; CCAAT-Enhancer-Binding Protein-alpha ; metabolism ; Chronic Disease ; Hepcidins ; metabolism ; Humans ; Interleukin-6 ; Monocytes ; Multiple Myeloma ; metabolism ; RNA, Messenger ; Up-Regulation

H5 subtype avian influenza (AIV-H5) is a major causative agent of animalloimia a rapid and sensitive molecular biological diagnosis is crucial to the control program of AIV-H5. AIV-H5 real-time fluorescent reverse transcription loop-mediated isothermal amplification (qRT-LAMP) was established by means of heat treatment of the samples. The sensitivity, specificity and repeatability of this method were assessed and the performance of Calcein,SYBR Green I,HNB,SYTO 81 in colorimetric detection was comparatively analyzed to screen the optimum dye. The results showed the sensitivity of this method was 100 times higher than that of standard real-time fluorescent RT-PCR, and the detection limit was one copy of the gene per reaction. This method had no cross-reactivity with other common avian respiratory tract infectious disease-related pathogens such as IBV and NDV. The present study suggested Calcein was the optimum dye. Small-scale tests suggested this method was reliable for survey monitoring of AIV-H5 on the spot, indicating its potential applications in field investigation.
Animals ; Chickens ; Hemagglutinin Glycoproteins, Influenza Virus ; genetics ; Influenza A Virus, H5N1 Subtype ; genetics ; isolation & purification ; Influenza in Birds ; diagnosis ; virology ; Poultry Diseases ; diagnosis ; virology ; Reverse Transcriptase Polymerase Chain Reaction ; instrumentation ; methods ; Sensitivity and Specificity