Nucleic acids, as a next generation of biotechnology drugs, not only can fundamentally treat diseases, but also own significant platform characteristics in view of technology and production. Therefore, nucleic acid-based drugs have broad clinical applications in biomedical fields. However, nucleic acids are degradable and unstable, and have very low intracellular delivery efficiency in vitro and in vivo, which greatly limits their applications. In recent years, ionizable lipid-based lipid nanoparticles have shown promising application potentials and have been successfully applied to COVID-19 (Coronavirus Disease 2019) vaccines in clinic. Lipid nanoparticles demonstrate high in vivo delivery efficiency and good safety profile due to their unique structural and physicochemical properties, which provides many possibilities for their clinical applications for nucleic acid delivery in the future. This review focused on the characteristics of nucleic acid drugs and their delivery barriers, and discussed the approved nucleic acid drugs to illustrate the key aspects of the success of their delivery carrier system. In addition, problems to be solved in the field were highlighted.

Objective To analyze the etiology,diagnosis and therapy of benign biliary strictures and im-prove curative and preventive effects. Methods 212 patients suffering from benign biliary strictures in Nankai Hos-pital from January 2004 to December 2006 were retrospectively analyzed. Results Inflammatory strictures (65.12%,140/215) and strictures caused by operations (20.46%,44/215) were the most two causes. Strictures parts were mainly located in the latter segment of common bile duct 52.09% (112/215). In our group,the stent of strictures parts took 31.37% (64/204), bilioendodraignage 18.13% (37/204), and the modification of strictures parts 43.63% (89/204) as well as resection of stricture parts 1.96% (4/204). Conclusions Inflammatory stricture is the main cause in benign biliary strictures and the main locus is the hinder segment of common bile duct. The di-agnesis of benign biliary strictures before operation is important because it can help to decide the approach way and prognosis. The strategies of curing benign biliary strictures could include operations and endoscopy. The stent of stric-tures parts, bilioendodraignage and the modification of strictures parts are the main treaments for benign biliary stric-tures.

objective To construct the recombinant adenovirus containing p53 up-regulated modulator of apoptosis(Ad-PUMA)and investigate its growth inhibition effect on pancreatic callCer cells in vitro and in vivo.Methodls Ad-Easy system was used to construct Ad-PUMA by recombination in E.coli.The virus was Dackaged in 293 cells and subsequently identified valid.The AsPC-1 cells were infected with AdPUMA.Before and after Ad-PUMA infection,the expression of PUMA protein wag investigated by western blot,the inhibition rate of AsPC-1 cells was examined by MTY assay.The in vivo tumor suppressive effect was detected in nude mice with human AsPC-1 xenograft.PUMA protein and the apoptosis of AsPC-1 xenograft were detected by western blot and TUNEL(terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling)method.Results In vitro,the expression of PUMA protein was increased with titer of Ad-PUMA,the proliferation of AsPC.1 cells were suppressed,significantly,and the effect was in a viral dose-dependent nlanner.In vivo,the growth in nude mice of AsPC-1 infected with Ad-PUMA was significantly inhibited with an inhibition rate of 44.2%.The expression of PUMA was significantly up-regulated,and the apoptosis index wa8 significantiv increased in tumor after Ad-PUMA infection as determined by western blot and TUNEL.Conclusion The expression of PUMA call inhibit the proliferation of pancreatic cancer in vitro and in vivo,and may be used 88 a potential tool for cancer therapy

Secondary lymphoid tissue chemokine (CCL21) is a double-edged sword, which exerts antitumor, anti-infection immune response by binding to the receptor CCR7 on the surface of the multiple immune cells. However, a variety of tumor cells also express the receptor CCR7, the combination of CCL21 with CCR7promotes the invasion and metastasis of tumor cells, leading to the facilitation of tumor development. Therefore,exploring the mechanism(s) of tumor invasion and metastasis might be helpful for use of CCL21 as tumor gene therapy through blocking of CCL21's promotion of tumor invasion and metastasis.

Objective To clarify the involvement of the free fatty acids(FFA)and lipid peroxida-tion in rat pancreatic tissue during the development of pancreatic injuries inducecd by long-term high-fat diet.Mehtods The male Sprague-Dawley rats (n=72) were randomized into 6 groups (n=12).One group (group control) received standard chow for 18 weeks, the other five groups (group HFD) were fed with a high-fat diet respectively for 2, 4, 6, 10 and 18 weeks.Serum TG and TCH, the his-topathological changes, pancreatic malondialdehyde (MDA) content, superoxide dismutase (SOD) ac-tivity and the concentration of free fatty acids in pancreatic tissues were examined.Pancreatic fibrosis was assessed using Sirius Red staining.The expression of desmin, a smooth muscle actin (α-SMA), platelet-derived growth factor receptor type β (PDGFRβ) and transforming growth factor131 (TGFβ1) was determined with immunohistochemistry.Results Pancreatic MDA content, the number of desmin and α-SMA positive cells were significantly increased in all the HFD groups.The FFA content, PDGFRβ, and TGFβ1 in pancreatic tissues increased in rats of 2, 4 and 6 week HFD groups accompa-nied with typical histological alternations including edema, capillary vessels hyperplasia, and focal aci-nar degeneration, vaculation of acinar and islet cells.In 6, 10 and 18 weeks HFD groups, the lesions had progressed and acinar cell atrophy, fatty replacement, deposition of hemosiderin, and interstitial collagen deposition were observed.Conclusions The increased amounts of FFA and lipid peroxidant in pancreatic tissues are associated with pancreatic cell injuryies and synthesis of collagen by activated PSCs during the chronic high-fat diet intake.

Objective To investigate the main predisposing factors of hematoma enlargement in spontaneous intracerebral hemorrhage,reduce the early mortality,and improve clinical outcomes.Methods By a retrospective study of 268 patients,all patients underwent their first computed tomography (CT)scan within 24 hours of arrival and a second CT scan within 72 hours of admission.These predisposing factors were analyzed by means of univariate and multivariate logistic regression analyses.Results The patients occurred early hematoma enlargement were accounted for 27.99％ (75/268).Univariate analyses indicated that hematoma shape,midline shift,breaking into the ventricle,thrombin clotting time (TT),white blood cells,neutrophil percentage,serum creatinine,fasting plasma glucose (FPG),and Glasgow coma scale (GCS) were significantly different between the patients with or without hematoma enlargement (P ＜0.05).Furthermore,multivariate logistic regression analyses revealed that the following four factors were independently associated with hematoma enlargement:the midline shift [OR (95％ CI) =3.356 (1.251-8.999),P =0.000],the GCS score [OR (95 ％ CI) =0.745 (0.671-0.827),P =0.023],the FPG [OR (95％ CI) =3.022 (1.232-7.408),P =0.016],and the breaking into the ventricles [OR (95％ CI) =2.851(1.158-7.019),P =0.005].Conclusions The midline shift of brain CT scan,the GCS score,the FPG,and the breaking into the ventricles maybe the independent predisposing factors of hematoma enlargement.Therefore,timely review of CT scan and dynamic monitoring of peripheral blood biochemical indicators should be very important for further therapy.

Objective To investigate the prevalence,radiological features and the association between HRCT changes and different diseases or clinical features in interstitial lung disease(ILD)caused by diffuse connective tissue diseases(CTD).Methods Retrospective analysis was performed based on the medical records of 412 in-patients with the diagnosis of diffuse connective tissue diseases from June 2003 to June 2005 in our hospital.268 cases were SLE,83 cases were SS,40 cases were DM/PM,21 cases were SSe.All patients had chest X-ray and the suspected cases had HRCT exam.The distribution of ILD among different diffuse CTD.the appearance between X-ray and HRCT appearances were compared.The correlation among HRCT appearance,different diseases and clinical features was studied.Results①In the 412 cases of CTD,ILD de- tected by HRCT was 9.7%(40 case in total),3,9% by X-ray.Among the 40 cases,DM/PM had the highest rate of ILD(25%),23.8% in SS,9.6% in SS and 6.3% in SLE.②The consensus rate between HRCT and X-ray was 40%.The rate of mis-diagnosis of ILD was 60% by X-ray.③The changes of interstitial involvement de- tected by HRCT were:ground glass change(41.0%),consolidation(32.8%),reticular change(16.4%)and hon- eycomb change(9.8%).The concomitant presence of two of the above changes were very common.④More level respiratory symptoms such as cough,panting,chest distress and chest pain and high level of complement were observed in patients with ground glass and consolidation changes,while high CRP level was seen in patients with consolidation and honeycomb changes(P

Acupuncture Therapy ; Adult ; Aged ; Bloodletting ; Combined Modality Therapy ; Female ; Humans ; Hypesthesia ; therapy ; Male ; Middle Aged ; Moxibustion

The microvasculature of the rabbit right ventricle was studied by the method of vascular corrosion cast and scanning electron microscopy. In the endocardium could be seen thin and sparse capillary network i. e. subendothelial capillary network formed by the branches of the arterioles passing through myocardium. In the myocardium, arteriole and its branches distributed in certain area. Sphincters could be seen in the beginning of the arterioles. Capillaries of the papillary muscle in right ventricle were parallel to muscle bundle and were thinner and sparser than those of the papillary muscle in left ventricle. Venous system in right ventricle wall was similar in architecture to that in left ventricle, postcapillary venule joined its corresponding venule in a "turnip root" like pattern. No A-V anastomosis could be seen, yet thebesian vessels and myocardial sinusoids directly opened into ventrical chamber could be found.

Objective To explore whether augmentation index is an independent risk factor for coronary heart disease or not,and the relationship between augmentation index and coronary artery disease severity.Methods In the study,245 subjects who were hospitalized between Dec.2003 and Dec.2004,were classified into 4 groups and their clinical and biological characteristics and the summary of the scores in each of the eight segment and aortic pressure waveform in ascending aorta were recorded respectively.Results The larger the augmentation index was,the more the number of coronary stenosis vessels was.Linear regression analysis indicated that augmentation index was significantly correlated with grade of coronary stenosis.When augmentation index was more than 45%,the sensibility and specificity was 91.5%and 92.6%respectively.In the logistic regression model,augmentation index was the independent risk factor for coronary heart disease,and the odds ratio of coronary heart disease was 1.893.The 95%CI was 1.421~2.521.Conclusion Augmentation index is an independent risk factor for coronary heart disease and a predictor of angiographic coronary artery disease severity.