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 realize the present resistance characteristics of enterococci to common antimicrobial agents,and to provide reference for clinical therapy. METHODS A total of 79 isolates of enterococci were collected from samples during the period of 2000-2003.The broth microdilution test and ?-lactamase determination were performed for each of the strains.The laboratory data were analyzed. RESULTS The rates of Enterococcus faecalis and E.faecium were 73.4%,and 26.6% of all enterococci isolates.The most common sites of infection were urinary tract(35.4%),surgical secretion(24.1%),and sputum(15.2%).The rate of E.faecium approached 50% of enterococci in urinary tract.The antibiotic resistance of E.faecium was more than E.faecalis to ampicillin,penicillin,and rifampin.The ratio of HLAR enterococci and VRE to total enterococci isolates were 61.9% and 0;?-lactamase producing rate was 6.3%. CONCLUSIONS Urinary infection caused by enterococci is most frequent.E.faecium is found more easily in urinary tract than in the others and very resistant to antibiotics.Vancomycin shows fairly high activity against enterococci.The different regimens should be adopted for different enterococci.

Objective To reproduce an animal model of psychological simulation training,and to investigate the influence of psychological training on the ability of counter physical stress.Methods Thirty-two Wister rats were assigned to four groups,8 for each,namely control group(group A),psychological training group(group B),stress group(group C)and psychological training prior to stress(group D).Rats in group A received neither psychological training nor stress,group B received psychological training without stress,group C received stimulation including stress of strong noise and strong light,but without psychological training,and group D,after psychologically training for 4 weeks,received the same stress stimulation as group C.Twenty-four hours after stress,open-field experiment was done on group C and D.At last,rats in all the 4 groups were anesthetized by ether and 5ml of blood was drawn from each rat in order to detect the content of beta-endorphin(?-EP),corticosterone and IL-1?.Results In the open-field experiments,the psychologically trained groups(B and D)showed remarkably lower scores than the un-trained groups(A and C).The levels of ?-EP and corticosterone were significantly elevated in rats after receiving stress stimulation,while that of IL-1? lowered dramatically.The level of ?-EP and corticosterone in psychological training group(group D)was remarkably lower,while that of IL-1? was higher,than the stress group(group C)during the stress.Conclusion Psychological training can lessen the inhibitory effects of harmful stress on endocrine and immunologic functions,and enhance the physical ability to confront stress.

Ojective To study the application and the effect of extrathoracic minimally invasive surgery on the patients with mediastinal mass. Methods The therapeutic result of 6 cases of mediastinal mass resected through minimal extrathoracic approach were retrospectively reviewed. Results 6 patients underwent successfully operation and recovered smoothly without any complication or operation death. A following up period lasting two years showed that no recurrence or metastasis occurred. Conclusions Extrathoracic minimally invasive surgery has the advantages of minimal invasion, quicker recovery and complete resected tumor. It may substitute the classical thoracotomy and could obtain the same therapeutic in the selective cases.

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 Observed the mobilization effects、 the safety and feasibility of autologous circulating blood stem cell by G-CSF in acute myocardial infarction (AMI). Methods 45 patients with AMI were randomly allocated to receive either inclusive type Granulocyte Colony-Stimulating Factor (G-CSF), to mobilize the stem cell. The patients received the dose of G-CSF 300?g-600?g/day, by hypodermic injection, and the duration of applying G-CSF was 5 days. In the process of the mobilization of the circulating blood stem cell, prior to applying G-CSF and on the 3rd、4th、5th、6th、7th after applying G-CSF, the white blood cell (WBC) and CD34+ cell count in the circulating blood should be observed; and the following side effects also should be paid attention to, such as: bone pain, tetter, fever, gastrointestinal effects( nausea 、vomit、 coprostatis ),deteriorated of angina or heart failure and some rare effects(spontaneous spleen rupture, severe purulent infection, hypercoagulable state, autologous immune diseases). Results Prior to applying G-CSF and the 3rd、4th、5th、6th、7th after applying G-CSF, the counts of WBC were (8.42?2.59)?10 9/L、(31.28?8.34)?10 9/L、(35.24?9.38)?10 9/L、(37.03?13.07)?10 9/L、(35.34?14.68)?10 9/L、(20.35?9.22)?10 9/L;the counts of CD34+ cell were (14.89?11.46)?10 6、(67.78?50.88)?10 6、(124.79?136.13)?10 6、(208.92?206.97)?10 6、(206.10?184.57)?10 6、(66.63?56.56)?10 6;The peak of curve that WBC and CD34 + cell count changed with applying days was on the 5th .The count of CD34 + cell in the circulating blood was positive referent with the count of WBC in the circulating blood(r=0.835);was not reference with age、 sex、body weight、and the onset time of AMI. There were total 17 complications during the mobilization of circulating blood stem cell. The incidence of complications during mobilization is 37.8%(17/45), including bong pain being 15.6%(7/45)、fever being 6.7 %(3/45)、pale being 4.4 %(2/45)、tetter being 4.4 %(2/45)、deterioration of heart failure being 4.4 %(2/45),spleen thrombosis being 2.2 %(1/45).No death happened. Conclusion : In patients with AMI, the mobilized peak of WBC and CD34 + cell counts changed with applying days was at the 5th, and the count of CD34 + cell in the circulating blood was positive referent with the count of WBC in the circulating blood(r=0.940),was negative referent with body weight of patients(r=-0.398). And mobilization of autologous circulating blood stem cell was feasible and safe.

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 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 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