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 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.

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 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

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 causes and the clinical significance of the female lower urinary tract symptoms (LUTS). Methods Of the 72 female patients (mean age,48 years;range,8 to 86 years) with LUTS,46 had dysuria,14 with incontinence,10 with frequency and urgency of micturition and 2 with nocturnal enuresis.Urodynamic examinations were conducted in these patients. Results Among the 46 cases with difficulty of urination,whose bladder volumes were 60 to 800 ml,20 had the bladder detrusor contractility of 0,and 26,of 9 to 160 cm H 2O.Linearised passive urethral resistance relation (Linp-URR) figure showed at least grade Ⅲ obstruction in 19 cases.The urethral pressure profiles (UPPs) were 25 to 130 cm H 2O.Dyssynergia of detrusor-external sphincter occurred in 33 cases with voiding dysfunction.Ten cases with frequency of micturition had bladder volume of 97 to 450 ml.Two cases had the bladder detrusor contractility of 0,the other 8 cases were of 9 to 160 cm H 2O.Linp-URR figure showed at least grade Ⅲ obstruction in 2 cases.One case with urgent incontinence had hyper-sensitive bladder.The abdominal leak point pressures were 44 to 76 cm H 2O in 6 cases of stress incontinence.3 cases of overflowing urinary incontinence had no contraction of bladder detrusor and the UPPs were 32 to 42 cm H 2O.The UPPs were 0 to 16 cm H 2O in the 4 cases of total urinary incontinence.Two cases of nocturnal enuresis had detrusor instability with impaired contractility. Conclusions Urodynamic examination is necessary to the diagnosis of female LUTS and it also has significant value in predicting the treatment and prognosis of LUTS.

[Objective]To probe the efficacy of total hip arthroplasty(THA)in the treatment of patients with ankylosing spondilitis(AS).[Method]Ninety-eight THA were performed in 56 patients who had AS,and 42 patients(76 hips)were analyzed retrospectively with an average follow-up period of 5.6 years(ranged,2.5 to 5.5 years).The clinical results were evaluated by the Harris hip scoring system and radiographic analysis.[Result]For the latest follow-up,the average Harris hip score improved from 26.8 points(ranged,4 to 51 points)preoperatively to 85.2 points(ranged,55 to 94 points)at the final postoperatively evaluation.89.5% of the patients had an excellent or good results evaluated by Harris hip scoring system postoperatively.One patient was revised for infection,fissured fracture of neck of femur or calcar femorale above the lesser trochanter happended in two patients,one patient had footdrop and recovered 3 months later,1 patient had deep vein thrombosis.There was no sign of loosening,dislocation or fracture of the prosthesis.According to the system of Brooker,the incidence of heterotopic ossification was 9.2 %(7 hips).[Conclusion]THA can greatly relieve the pain of the patients who have AS and reconstruct the function of hip joint.Compared with THA operated for other cause of disease,THA in AS leads to no high risk.

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.

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.