At the end of 2020, the FDA issued emergency use authorization for two mRNA vaccines（BNT162b2 and mRNA-1273）, which had provided important support in the response to the COVID-19 pandemic. The great success of these COVID-19 vaccines based on non-viral vectors has promoted the research and application of mRNA vaccines in the treatment of diseases such as tumors. Compared with virus-based delivery systems, non-viral carriers have significant advantages in biological safety and versatility. Therefore, non-viral vectors have become a research hotshot for mRNA tumor vaccines. In this paper, the latest research progress on lipid nanoparticles, polymers, peptides and inorganic materials were introduced. In addition, recent clinical trials of mRNA tumor vaccines were reviewed and the challenges and prospects of non-viral vectors in clinical transformation of mRNA tumor vaccines were discussed.

Objective To improve the cellular uptake efficiency and the therapeutic effect through the structural modification of paclitaxel(PTX)and the preparation of corresponding liposomes.Methods The prodrug of paclitaxel,PTX-PA,was prepared by esterification reaction,and the quantitative detection method of PTX-PA was established.Next,the optimal formulation and preparation of PTX-PA/Lip was obtained through single factor screening based on their appearance,particle size,and encapsulation efficiency.Results The PTX-PA was successfully synthesized,and the established HPLC quantitative analysis method for PTX-PA met the methodological requirements.After the optimal preparation and formulation research through single factor screening,the particle size of optimized PTX-PA/Lip was(62.75±1.81)nm with a PDI of(0.076±0.02),while the drug encapsulation rate reached more than 90%.Conclusion This research successfully prepared palmitic acid modified paclitaxel liposomes based on nanotechnology,enhancing the drug delivery efficiency of paclitaxel and laying the foundation for the pharmacodynamics research of PTX-PA.

Objective To explore the diagnostic value of magnetic resonance imaging(MRI)and high-frequency ultrasound for synovitis of the hip in children(SHC).Methods A total of 107 children suffering from hip pain were enrolled and underwent MRI and ultrasound examinations.The value of MRI and ultrasound for diagnosing SHC and identifying different types of SHC was analyzed.Results The result consistency between high-frequency ultrasound and clinical diagnosis was higher than that between MRI and clinical diagnosis(Kappa:0.717 vs 0.586).The AUC of the combined detection for diagnosing SHC was greater than that of MRI(0.844 vs 0.812,P<0.05).For the differential diagnosis of different types of SHC,the result consistency between high-frequency ultrasound and clinical diagnosis was higher than that between MRI and clinical diagnosis(Kappa:0.813 vs 0.630).The AUC of high-frequency ultrasound and the combined detection for differentiation between joint swelling type and joint effusion type of SHC was 0.903 and 0.912,higher than 0.815 of MRI(P<0.05).The detection rates of joint space abnormality,joint effusion,joint swelling and joint cartilage changes were 92.45%(49/53),73.91%(17/23),90.70%(39/43),and 77.78%(14/18)when using MRI,and those were 96.23%(51/53),91.30%(21/23),95.35%(41/43),and 88.89%(16/18)when using high-frequency ultrasound.There was no significant difference in the detection rates of pathological changes such as joint space abnormality between the two methods(P>0.05).Conclusion The combined detection of MRI and high-frequency ultrasound has high diagnostic value for SHC.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

AIM: To guide the multiple imputation of missing data in clinical longitudinal studies and its sensitivity analyses, and highlight the importance of sensitivity analyses by taking the clinical trial of Qizhitongluo Capsule in treating ischemic stroke as an example. METHODS: To implement PROC MI process in SAS to perform multiple imputation and its sensitivity analysis. RESULTS: In the example, after multiple imputation, improvements in lower limb motor scores of the Qizhitongluo group were greater than those of the placebo group (all P<0.01), and the results of two sensitivity analyses under "missing not at random" were consistent with those under "missing at random". CONCLUSION: Multiple imputations combined with sensitivity analyses can ensure a robust result. It is recommended that clinical researchers perform sensitivity analyses after filling missing data.

Functional diarrhea is a common disease of the digestive tract system. Traditional Chinese medicine (TCM) mainly included herbal formulea, acupuncture and moxibustion to treat the functional diarrhea, according to the principles of strengthening spleen and moistening, nourishing spleen and kidney, and soothing liver. In recent years, many studies have been conducted on the effective mechanism of TCM treatment of functional diarrhea. However, further researches needed to be done on the micro-mechanism of TCM syndrome differentiation for functional diarrhea.

Objective To explore the mechanism of Dahuanglinxian Capsule for intervening gallstone formation by regulating the expression levels of ABCB11 and ABCC2 mRNA and protein.Methods Forty male C57BL/6 mice were divided into the normal group(group N),model group (group M),ursodeoxycholic acid group (group U) and Dahuanglinxian Capsule treatment group (group D),10 cases in each group.The group N was fed with normal diet,while the group M,U and D were fed with lithogenic fodder for 8 weeks.Meanwhile the group U and D were given the medication intervention,once daily,for continuous 8 weeks of gavage.After successful modeling,mRNA and protein expression levels of ABCB11 and ABCC2 were detected by RT-PCR and immunohistochemistry.Results Compared with the other three groups,the expressions of ABCB11 and ABCC2 mRNA gene and protein in M group were significantly reduced(P＜0.01);while,there was no statistical difference in the expressions of ABCB11 and ABCC2 mRNA and protein between the group D and N(P＞0.05).Conclusion Dahuanglinxian Capsule can prevent the gallstone formation by regulating the expression of ABCB11 and ABCC2 mRNA and protein.

Objective: To study the value of three-dimensional(3D) visualization in the diagnosis and surgical treatment for pancreatic tumor. Methods: From June to September 2016, 26 patients with pancreatic tumors in Jinling Hospital, Medical School of Nanjing University were involved. The study included 26 patients(8 females and 18 males) with mean age of (57±12)years (ranging from 23 to 77 years). And there were 20 malignant tumors and 6 benign tumors. All of them were examined with abdominal thin slice CT scanning and the CT images were imported into 3D visualization system for 3D visualization. The main elements examined by 3D visualization included tumor shape, size, and location; distribution and morphology of the peripancreatic lymph node; the relationships among neoplasms, organs and blood vessels. Results: Among the 26 patients, there were 21 cases with pancreatic cancer, of which 15 cases successfully underwent standard pancreatectomy. All patients were operated underwent accurate assessment. The 3D model demonstrated the origination and bifurcations of blood vessels, and the relationships among neoplasms, organs and blood vessels efficiently. The 3D technique could facilitate to evaluate response of neiadjuvant chemotherapy in the pancreatic cancer patients (n=5).3D reconstruction could detect the lymph-node metastases accurately (n=12) in patients with pancreatic cancer. 3D reconstruction were applied to evaluate the the size and range of tumor on 5 cases. Conclusions 3D reconstruction allows stereoscopic identification of the spatial relationships between physiologic and pathologic structures.The 3D technique could facilitate to evaluate distribution and morphology of the peripancreatic lymph node, and to evaluate the relationships among neoplasms, organs and blood vessels.

Background Primary angle-closure glaucoma (PACG) is the most common type of glaucoma in China.A screening to identify the possible angle closure is important in the prevention and treatment of PACG.Objective This study was to determine the characteristics and the optimal parameters measured by the scanning peripheral anterior chamber depth analyzer (SPAC) in the screening of occludable angle of a sample of adult Chinese population.Methods A cross-sectional study was performed in Handan from February to April in 2013.One hundred and eighty Chinese adults were enrolled with the age of 40 years and older and acceptable criteria during 5-year following-up duration of the Handan Eye Study.Routine eye examinations were carried out in all subjects under the informed consent,including visual acuity,optometry,anterior ocular segment examination under the slit lamp microscope,and then SPAC measurement and gonioscopy were performed in a dark room.Occludable angle was defined as posterior trabecular meshwork being invisible in ≥ 180° range under the static gonioscope.Occludable angle by SPAC was estimated using available central chamber depth (ACD) and a combined indicator,numerical grade was 5 or fewer and/or the categorical grade was S or P,separately.Receiver operating characteristic (ROC) curve was calculated to assess the performance of these parameters in detecting eyes with occludable angle for the population-based sample,and area under curve (AUC) was drown to compare the screening efficiencies between available ACD and combined indicator.Results In 180 subjects,occludable angles were found in 62 and open angles were in 118.Compared to the subjects with open angle,the subjects with occludable angle showed the older age (P＜0.001),more females (P＜0.05),lower visual acuity (P＜0.001),greater hyperopic diopter (P＜0.05),smaller ACD value (P＜0.001) and shorter axial length(P＜0.001).In eyes with occludable angle by using SPAC,the ACD showed an AUC of 0.832.Using a cutoff of 2.7 mm for ACD,the sensitivity and specificity were 85.48％ and 68.64％,and under the cutoff of 2.8 mm,the sensitivity and specificity was 90.32％ and 61.02％,respectively.For the combined parameters,the sensitivity and specificity was 62.90％ and 90.68％,respectively and the AUC was 0.768.Conclusions When gonioscopy is used as a reference,a cutoff of 2.8 mm ACD by SPAC shows the highest sensitivity for the screening of occludable angle in Chinese population.

Background Myopia is one of the main blinding diseases worldwide.At present,a lot of studies on ocular structure focus on the changes of corneal curvature(CC),central corneal thickness (CCT),anterior chamber depth (ACD),ocular axial length (AL) and choroid and retina,but the research of anterior chamber angle section structure form and ciliary body shape is lack.Objective This study was to measure and analyze the changes of the anterior chamber angle and related tissue structure in myopic eyes.Methods One hundred and forty-nine eyes of 149 subjects were included from May 2008 to May 2010 in Eighth Hospital of Qingdao City with the ages of 18-40years old under the informed consent.The subjects were assigned to the emmetropia group (30 eyes) ([0.02±0.18] D),low myopia group(46 eyes) ([-1.64±0.69] D),moderate myopia group (35 eyes) ([-4.56±0.66] D) and high myopia group (38 eyes) ([-7.04 ± 1.02] D).Conventional indexes including intraocular pressure (IOP),CCT,CC,AL and ACD were measured,and the indexes including chamber angel open distance (AOD),iris thickness (IT1,IT2,IT3),the position of ciliary body such as A-angel,B-angel,trabecular ciliary process distance (TCPD),irisciliary process distance (ICPD) and ciliary body thickness (CBT1,CBT2,CBT3) were measured by ultrasound biomicroscope(UBM).Results The IOP,CC and CCT values showed slight change in different groups without remarkable difference among them (all at P＞0.05).As the increase of myopic degree,AL was extended and ACD was deepened,showing significant differences among the groups (both at P＜0.05).There were no significant differences in IT1,IT2 and IT3 among the four groups (all at P＞0.05).However,the measuring values of angle opening degree (TIA and AOD500),ciliary position (A-angle,B-angle,TCPD,ICPD) and CBT (CBT1,CBT2,CBT3) elevated with the increase of myopic degree (all at P＜0.05).Positive correlations were found between AOD500 and ACD,A-angle,CBT1,CBT2,AL,negative correlations was found between AOD500 and myopic degree (r =0.573,0.513,0.325,0.398,0.542,-0.435,all at P＜0.01);Positive correlations were found between TIA and ACD,A-angle,CBT1,CBT2,AL,negative correlations was found between AOD500 and myopic degree (r =0.573,0.464,0.276,0.410,0.539,-0.435,all at P ＜ 0.01).Conclusions Within certain limits,as the increase of myopic degree,ACD deepens,the anterior chamber angle widens,ciliary process thickens and ciliary body backward shifts.