Real-World Use of Oral and Subcutaneous Semaglutide in Routine Clinical Practice in the UK: A Single-Centre, Retrospective Observational Study.

INTRODUCTION: Semaglutide, the only glucagon-like peptide-1 receptor agonist (GLP-1 RA) available in subcutaneous and oral formulation for treatment of type 2 diabetes (T2D), has demonstrated clinically significant improvements in glycaemic control and weight in clinical trials. This study aimed to gain insights into the use of both formulations and evaluate their clinical effectiveness in a secondary care clinic in Wales. METHODS: This was a retrospective observational analysis of adults with T2D initiated on oral or subcutaneous semaglutide. Changes from baseline in glycated haemoglobin (HbA1c), weight and other metabolic parameters were evaluated. RESULTS: At baseline, participants (n = 103) had a mean age of 57.3 years, mean HbA1c of 79.1 mmol/mol (9.38%), mean weight of 111.8 kg and body mass index (BMI) of 39.6 kg/m2 (no statistically significant differences between oral and subcutaneous groups). At 6-month follow-up, statistically significant improvements in HbA1c (- 19.3 mmol/mol [- 1.77%] and - 20.8 mmol/mol [- 1.90%]), body weight (- 9.0 kg and - 7.2 kg), and BMI (- 3.3 kg/m2 and - 2.5 kg/m2) were observed for oral and subcutaneous semaglutide, respectively. No statistically significant differences between the formulations were observed, and safety profiles were comparable. CONCLUSIONS: Both formulations of semaglutide provided clinically and statistically significant reductions in HbA1c and weight in real-world practice. Oral GLP-1 RA may offer a practical and effective option for the management of T2D.

Proton and molecular permeation through the basal plane of monolayer graphene oxide.

Two-dimensional (2D) materials offer a prospect of membranes that combine negligible gas permeability with high proton conductivity and could outperform the existing proton exchange membranes used in various applications including fuel cells. Graphene oxide (GO), a well-known 2D material, facilitates rapid proton transport along its basal plane but proton conductivity across it remains unknown. It is also often presumed that individual GO monolayers contain a large density of nanoscale pinholes that lead to considerable gas leakage across the GO basal plane. Here we show that relatively large, micrometer-scale areas of monolayer GO are impermeable to gases, including helium, while exhibiting proton conductivity through the basal plane which is nearly two orders of magnitude higher than that of graphene. These findings provide insights into the key properties of GO and demonstrate that chemical functionalization of 2D crystals can be utilized to enhance their proton transparency without compromising gas impermeability.

Unexpected catalytic activity of nanorippled graphene.

Graphite is one of the most chemically inert materials. Its elementary constituent, monolayer graphene, is generally expected to inherit most of the parent material's properties including chemical inertness. Here, we show that, unlike graphite, defect-free monolayer graphene exhibits a strong activity with respect to splitting molecular hydrogen, which is comparable to that of metallic and other known catalysts for this reaction. We attribute the unexpected catalytic activity to surface corrugations (nanoscale ripples), a conclusion supported by theory. Nanoripples are likely to play a role in other chemical reactions involving graphene and, because nanorippling is inherent to atomically thin crystals, can be important for two-dimensional (2D) materials in general.

[Association of vitamin D deficiency with severity of symptoms in children with vasovagal syncope].

Objective: To investigate the correlation between vitamin D deficiency and the severity of symptoms in children with vasovagal syncope (VVS). Methods: A prospective study was conducted. One hundred and twenty-two children diagnosed with VVS by head up tilt test in Department of Pediatric Cardiology and 130 healthy children without symptoms who underwent physical examination in the outpatient department of Child Healthcare Department of Second Hospital of Lanzhou University from December 2019 to May 2021 were selected and assigned to VVS group and control group, respectively. According to the diagnostic criteria of vitamin D deficiency, children in the VVS group were assigned to three subgroups: non-vitamin D deficiency, vitamin D deficiency, and severe vitamin D deficiency. All children underwent detailed history taking, physical examination, and level determination of serum 25 (OH) D. Children in the VVS group were scored for orthostatic intolerance (OI) symptoms including 10 symptoms: syncope, dizziness, nausea, palpitation, headache, tremor, chest tightness, blurred vision, profuse perspiration, and attention deficit. The differences in the age, gender, body mass index, blood pressure, and serum 25 (OH) D levels between VVS group and control group, and the differences regarding the age, gender, body mass index, blood pressure, serum 25 (OH) D levels and symptom scores among the three VVS subgroups were compared. Comparisons were performed using independent sample t test, ANOVA analysis, Chi square test and rank sum test. Pearson correlation analysis was used to analyze the correlation between serum 25 (OH) D levels and OI symptom scores in children with VVS. Results: The serum 25 (OH) D levels were significantly lower in the VVS group than those in the control group ((31±11) vs. (46±10) nmol/L, t=10.89, P<0.001). Vitamin D deficiency was more frequent in the VVS group (73.0% (89/122) vs. 24.6% (32/130), χ²=58.91, P<0.001). There were significant differences among the severe vitamin D deficiency subgroup, vitamin D deficiency subgroup, and non-vitamin D deficiency subgroup regarding the serum 25 (OH) D levels ((9.8±0.4) vs. (26.6±6.5) vs. (45.8±5.9) nmol/L, F=142.77, P<0.001) and the OI symptom scores ((14±1) vs. (10±2) vs. (7±2) scores, F=44.97, P<0.001). The scores of syncope, nausea, profuse perspiration, blurred vision and dizziness among the severe vitamin D deficiency subgroup, vitamin D deficiency subgroup, and non-vitamin D deficiency subgroup were statistically significant (H=9.01, 7.52, 12.11, 7.07 and 9.54, respectively, all P<0.05). Pearson correlation analysis showed that the serum 25 (OH) D levels were negatively correlated with OI symptom scores in children with VVS (r=-0.769, P<0.001). Conclusions: VVS children have significant vitamin D deficiency. The severity of symptoms increases with decreasing of vitamin D level. Syncope, nausea, and profuse perspiration are more likely to occur in children with severe vitamin D deficiency, and dizziness and blurred vision are more likely to occur in children with vitamin D deficiency.

APLNR stimulates the development of glioma via the NFAT5/AKT feedback loop.

OBJECTIVE: To detect the role of APLNR in influencing the proliferative ability and development of glioma. PATIENTS AND METHODS: APLNR levels in 42 matched glioma tissues and adjacent normal brain tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between APLNR level and clinical features of glioma patients was assessed. Regulatory effects of APLNR on glioma cell functions were evaluated by cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assay, respectively. At last, the involvement of NFAT5 in APLNR-regulated glioma cell phenotypes was examined. RESULTS: APLNR was upregulated in glioma tissues than the adjacent ones. Glioma patients expressing higher level of APLNR had more advanced stage and worse prognosis. Knockdown of APLNR inhibited proliferative ability of glioma. NFAT5 level was negatively regulated by APLNR. Notably, NFAT5 could partially abolish the regulatory effect of APLNR on glioma cell phenotypes. CONCLUSIONS: APLNR level is closely linked to tumor grading and prognosis of glioma patients. It stimulates proliferative ability in glioma cells by targeting NFAT5.

Limits on gas impermeability of graphene.

Despite being only one-atom thick, defect-free graphene is considered to be completely impermeable to all gases and liquids1-10. This conclusion is based on theory3-8 and supported by experiments1,9,10 that could not detect gas permeation through micrometre-size membranes within a detection limit of 105 to 106 atoms per second. Here, using small monocrystalline containers tightly sealed with graphene, we show that defect-free graphene is impermeable with an accuracy of eight to nine orders of magnitude higher than in the previous experiments. We are capable of discerning (but did not observe) permeation of just a few helium atoms per hour, and this detection limit is also valid for all other gases tested (neon, nitrogen, oxygen, argon, krypton and xenon), except for hydrogen. Hydrogen shows noticeable permeation, even though its molecule is larger than helium and should experience a higher energy barrier. This puzzling observation is attributed to a two-stage process that involves dissociation of molecular hydrogen at catalytically active graphene ripples, followed by adsorbed atoms flipping to the other side of the graphene sheet with a relatively low activation energy of about 1.0 electronvolt, a value close to that previously reported for proton transport11,12. Our work provides a key reference for the impermeability of two-dimensional materials and is important from a fundamental perspective and for their potential applications.

CpG Oligodeoxynucleotide1826 combined with radioresistant cancer cell vaccine confers significant antitumor effects.

Immunotherapy is a hot issue in cancer research over the years and tumor cell vaccine is one of the increasing number of studies. Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. CpG Oligodeoxynucleotides (CpG ODNs), synthetic oligonucleotides containing a cytosine-phosphate-guanine(CpG) motif, was shown to enhance immune responses to a wide variety of antigens. In this study, we generated the radioresistant Lewis lung cancer cell by repeated X-ray radiation and inactivated it as a whole tumor cell vaccine to enhance the immunogenicity of tumor cell vaccine. Mice were subcutaneously immunized with this inactivated vaccine combined with CpG ODN1826 and then inoculated with autologous Lewis lung cancer (LLC) to estimate the antitumor efficacy. The results showed that the radioresistant tumor cell vaccine combined with CpG ODN1826 could significantly inhibit tumor growth, increased survival of the mice and with 20% of the mice surviving tumor free in vivo compared with the unimmunized mice bearing LLC tumor. A significant increase of apoptosis was also observed in the tumor prophylactically immunized with vaccine of inactivated radioresistant tumor cell plus CpG ODN1826. The potent antitumor effect correlated with higher secretion levels of tumor necrosis factor-alpha(TNF-α) and lower levels of interleukin-10(IL-10) concentration in serum. Furthermore, the results suggested that the antitumor mechanism was probably depended on the decreased level of programmed death ligand-1(PD-L1) which plays an important role in the negative regulation of immune response by the inhibition of tumor antigen-specific T cell activation. These findings clearly demonstrated that the radioresistant tumor cell vaccine combined with CpG ODN1826 as an appropriate adjuvant could induce effective antitumor immunity in vivo.

Pressure induced second-order structural transition in Sr3Ir2O7.

We conducted in situ angle dispersive high pressure x-ray diffraction experiments on Sr3Ir2O7 up to 23.1 GPa at 25 K with neon as the pressure transmitting medium. Pressure induces a highly anisotropic compressional behavior seen where the tetragonal plane is compressed much faster than the perpendicular direction. By analyzing different aspects of the diffraction data, a second-order structural transition is observed at approximately 14 GPa, which is accompanied by the insulating state to nearly metallic state at 13.2 GPa observed previously (Li et al 2013 Phys. Rev. B 87 235127). Our results highlight the coupling between electronic state and lattice structure in Sr3Ir2O7 under pressure.

Novel magnetism of Ir5+(5d4) Ions in the double perovskite Sr2YIrO6.

We synthesize and study single crystals of a new double-perovskite Sr2YIrO6. Despite two strongly unfavorable conditions for magnetic order, namely, pentavalent Ir5+(5d4) ions which are anticipated to have Jeff=0 singlet ground states in the strong spin-orbit coupling (SOC) limit and geometric frustration in a face-centered cubic structure formed by the Ir5+ ions, we observe this iridate to undergo a novel magnetic transition at temperatures below 1.3 K. We provide compelling experimental and theoretical evidence that the origin of magnetism is in an unusual interplay between strong noncubic crystal fields, local exchange interactions, and "intermediate-strength" SOC. Sr2YIrO6 provides a rare example of the failed dominance of SOC in the iridates.

Effect of preconditioning with hyperbaric oxygen on neural cell apoptosis after spinal cord injury in rats.

AIM: The aim of this study was to study the effect of preconditioning with hyperbaric oxygen on neural cell apoptosis after spinal cord injury in rats at different times, and to study the mechanism of neuroprotection with hyperbaric oxygen preconditioning after spinal cord injury. METHODS: Fifty-five adult Sprague-Dawley rats were randomly divided into 3 groups, a hyperbaric oxygen preconditioning group (Hoping, N.=25), a normal injury group (NI, N.=25) and a control group (CON, N.=5). The acute spinal cord injury rat models were established using Allen's method, the spinal cord injury selections were obtained separately after injury day 1, 5, 7, 10 and 14, the neural cell apoptosis after the spinal cord injury in the rat was detected by the HE staining and TUNEL method. RESULTS: The TUNEL-positive apoptotic cells were found in both the hyperbaric oxygen preconditional group and in the normal injury group. However, There was a statistically significant difference between each group (P<0.05). In the hyperbaric oxygen preconditioning group, the number of apoptotic cells decreased, while the neurofunction of the spinal cord was improved compared with the other two groups. CONCLUSION: HBO preconditioning can reduce the number of apoptotic cells and promote the nerve functional recovery in rats after spinal cord injury, which provide some experimental basis for currently clinical hyperbaric oxygen therapy.

Enzyme-mediated amperometric biosensors prepared via successive surface-initiated atom-transfer radical polymerization.

The development of enzyme-mediated amperometric biosensors on the indium-tin oxide (ITO) glass electrode via surface-initiated atom-transfer radical polymerization (ATRP) was investigated. A trichlorosilane coupling agent, containing the sulfonyl halide ATRP initiator, was immobilized initially on the ITO electrode surface for consecutive surface-initiated ATRP of ferrocenylmethyl methacrylate (FMMA) and glycidyl methacrylate (GMA). Glucose oxidase (GOD) was subsequently immobilized on the modified ITO electrode surface via coupling reactions between the epoxide groups of GMA and the amine groups of GOD. The surface composition after each functionalization step was ascertained by X-ray photoelectron spectroscopy (XPS). With the introduction of redox-P(FMMA) block as the electron-transfer mediator, the enzyme-mediated ITO electrode exhibits high sensitivity, as revealed by cyclic voltammetry measurement. The sensitivities of the ITO-g-P(GMA-GOD)-b-P(FMMA) and ITO-g-P(FMMA)-b-P(GMA-GOD) electrodes are about 3.6 microA/(mM cm(2)) (in the linear concentration range 0-5 mM of glucose) and 10.9 microA/(mM cm(2)) (in the linear concentration range of 0-17 mM of glucose), respectively. For both biosensors, the steady-state response time and the detection limits are estimated to be less than 20 s and 0.4+/-0.1 mM of glucose concentration, respectively. Furthermore, the spatial effect of the redox mediator on the electrode surface is revealed by the fact that the block copolymer brush-functionalized ITO electrode with P(FMMA) as the inner (first) block is more sensitive to glucose than that with P(GMA) as the inner block.

Antibacterial inorganic-organic hybrid coatings on stainless steel via consecutive surface-initiated atom transfer radical polymerization for biocorrosion prevention.

To enhance the corrosion resistance of stainless steel (SS) and to impart its surface with antibacterial functionality for inhibiting biofilm formation and biocorrosion, well-defined inorganic-organic hybrid coatings, consisting of a polysilsesquioxane inner layer and quaternized poly(2-(dimethyamino)ethyl methacrylate) (P(DMAEMA)) outer blocks, were prepared via successive surface-initiated atom transfer radical polymerization (ATRP) of 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The cross-linked P(TMASPMA), or polysilsesquioxane, inner layer provided a durable and resistant coating to electrolytes. The pendant tertiary amino groups of the P(DMAEMA) outer block were quaternized with alkyl halide to produce a high concentration of quaternary ammonium groups with biocidal functionality. The so-synthesized inorganic-organic hybrid coatings on the SS substrates exhibited good anticorrosion and antibacterial effects and inhibited biocorrosion induced by sulfate-reducing bacteria (SRB) in seawater media, as revealed by antibacterial assay and electrochemical analyses, and they are potentially useful to steel-based equipment under harsh industrial and marine environments.

Grafting of antibacterial polymers on stainless steel via surface-initiated atom transfer radical polymerization for inhibiting biocorrosion by Desulfovibrio desulfuricans.

To enhance the biocorrosion resistance of stainless steel (SS) and to impart its surface with bactericidal function for inhibiting bacterial adhesion and biofilm formation, well-defined functional polymer brushes were grafted via surface-initiated atom transfer radical polymerization (ATRP) from SS substrates. The trichlorosilane coupling agent, containing the alkyl halide ATRP initiator, was first immobilized on the hydroxylated SS (SS-OH) substrates for surface-initiated ATRP of (2-dimethylamino)ethyl methacrylate (DMAEMA). The tertiary amino groups of covalently immobilized DMAEMA polymer or P(DMAEMA), brushes on the SS substrates were quaternized with benzyl halide to produce the biocidal functionality. Alternatively, covalent coupling of viologen moieties to the tertiary amino groups of P(DMAEMA) brushes on the SS surface resulted in an increase in surface concentration of quaternary ammonium groups, accompanied by substantially enhanced antibacterial and anticorrosion capabilities against Desulfovibrio desulfuricans in anaerobic seawater, as revealed by antibacterial assay and electrochemical studies. With the inherent advantages of high corrosion resistance of SS, and the good antibacterial and anticorrosion capabilities of the viologen-quaternized P(DMAEMA) brushes, the functionalized SS is potentially useful in harsh seawater environments and for desalination plants.

Surface functionalization of Cu-Ni alloys via grafting of a bactericidal polymer for inhibiting biocorrosion by Desulfovibrio desulfuricans in anaerobic seawater.

A novel surface modification technique was developed to provide a copper nickel alloy (M) surface with bactericidal and anticorrosion properties for inhibiting biocorrosion. 4-(chloromethyl)-phenyl tricholorosilane (CTS) was first coupled to the hydroxylated alloy surface to form a compact silane layer, as well as to confer the surface with chloromethyl functional groups. The latter allowed the coupling of 4-vinylpyridine (4VP) to generate the M-CTS-4VP surface with biocidal functionality. Subsequent surface graft polymerization of 4VP, in the presence of benzoyl peroxide (BPO) initiator, from the M-CTS-4VP surface produced the poly(4-vinylpyridine) (P(4VP)) grafted surface, or the M-CTS-P(4VP) surface. The pyridine nitrogen moieties on the M-CTS-P(4VP) surface were quaternized with hexylbromide to produce a high concentration of quaternary ammonium groups. Each surface functionalization step was ascertained by X-ray photoelectron spectroscopy (XPS) and static water contact angle measurements. The alloy with surface-quaternized pyridinium cation groups (N+) exhibited good bactericidal efficiency in a Desulfovibrio desulfuricans-inoculated seawater-based modified Barr's medium, as indicated by viable cell counts and fluorescence microscopy (FM) images of the surface. The anticorrosion capability of the organic layers was verified by the polarization curve and electrochemical impedance spectroscopy (EIS) measurements. In comparison, the pristine (surface hydroxylated) Cu-Ni alloy was found to be readily susceptible to biocorrosion under the same environment.

Inorganic-organic hybrid coatings on stainless steel by layer-by-layer deposition and surface-initiated atom-transfer-radical polymerization for combating biocorrosion.

To improve the biocorrosion resistance of stainless steel (SS) and to confer the bactericidal function on its surface for inhibiting bacterial adhesion and biofilm formation, well-defined inorganic-organic hybrid coatings, consisting of the inner compact titanium oxide multilayers and outer dense poly(vinyl-N-hexylpyridinium) brushes, were successfully developed. Nanostructured titanium oxide multilayer coatings were first built up on the SS substrates via the layer-by-layer sol-gel deposition process. The trichlorosilane coupling agent, containing the alkyl halide atom-transfer-radical polymerization (ATRP) initiator, was subsequently immobilized on the titanium oxide coatings for surface-initiated ATRP of 4-vinylpyridine (4VP). The pyridium nitrogen moieties of the covalently immobilized 4VP polymer, or P(4VP), brushes were quaternized with hexyl bromide to produce a high concentration of quaternary ammonium salt on the SS surfaces. The excellent antibacterial efficiency of the grafted polycations, poly(vinyl-N-pyridinium bromide), was revealed by viable cell counts and atomic force microscopy images of the surface. The effectiveness of the hybrid coatings in corrosion protection was verified by the Tafel plot and electrochemical impedance spectroscopy measurements.

Thermo-responsive porous membranes of controllable porous morphology from triblock copolymers of polycaprolactone and poly(N-isopropylacrylamide) prepared by atom transfer radical polymerization.

Stimuli-responsive polymers are of crucial importance in the design of smart biomaterials. The thermo-responsive triblock copolymers of polycaprolactone (PCL) and poly( N-isopropylacrylamide) (P(NIPAAm)), or P(NIPAAm)- b-PCL- b- P(NIPAAm) copolymers, were synthesized in this work via atom transfer radical polymerization (ATRP). The P(NIPAAm)- b-PCL- b-P(NIPAAm) copolymers were cast by phase inversion in water into porous membranes with well-defined and uniformly distributed pores. The P(NIPAAm) content in the P(NIPAAm)- b-PCL- b- P(NIPAAm) copolymers and the temperature of the aqueous medium for phase inversion could be used to control the pore size and porosity of the membranes. The thermo-responsive characteristics of the membranes were illustrated in the controlled water uptake and temperature-dependent glucose transport through the membranes. These temperature-sensitive membranes with controllable morphology have potential applications in biomedical engineering, drug delivery, and tissue engineering.

Microbiologically influenced corrosion of 304 stainless steel by aerobic Pseudomonas NCIMB 2021 bacteria: AFM and XPS study.

Microbiologically influenced corrosion (MIC) of stainless steel 304 by a marine aerobic Pseudomonas bacterium in a seawater-based medium was investigated by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). AFM was used to observe in situ the proliferation of a sessile Pseudomonas cell by binary fission. The development of a biofilm on the coupon surface and the extent of corrosion damage beneath the biofilm after various exposure times were also characterized by AFM. Results showed that the biofilm formed on the coupon surface increased in thickness and heterogeneity with time, and thus resulting in the occurrence of extensive micro-pitting corrosion; whilst the depth of pits increased linearly with time. The XPS results confirmed that the colonization of Pseudomonas bacteria on the coupon surface induced subtle changes in the alloy elemental composition in the outermost layer of surface films. The most significant feature resulting from microbial colonization on the coupon surface was the depletion of iron (Fe) and the enrichment of chromium (Cr) content as compared to a control coupon exposed to the sterile medium, and the enrichment of Cr increased with time. These compositional changes in the main alloying elements may be correlated with the occurrence of extensive micropitting corrosion on the surface.

[Study of apoptosis and expression of apoptotic related genes P53 bcl-2 C-myc in oral lichen planus].

OBJECTIVE: To investigate the difference of apoptosis and expression of apoptotic related genes p53 bcl-2 C-myc in the development of oral lichen planus(OLP). METHODS: Apoptotic cells were detected by TUNEL and immunohistochemical method was used to study P53 bcl-2 C-myc expression in 45 samples with OLP(23 cases of erosive OLP group and 22 cases of non erosive OLP group). RESULTS: Apoptosis occurred in 100% of the cases and apoptotic index(AI) was 24.3%+/-12.0% (1.9%-50.5%). AI of erosive OLP group was 19.0%+/-10.4% (1.9%-50.5%), and AI of non erosive OLP was 29.4%+/-11.2% (10.4%-49.3%). The obvious differences existed between erosive group and non erosive group (P<0.05). The expression of p53 bcl-2 C-myc positive rates were 31.1% 35.5% 33.3% respectively. The p53 bcl-2 C-myc positive rates in erosive OLP group were 39.1% 52.2% 43.2%and that with non-erosive OLP group were 22.7% 18.2% 22.7% respectively. There was only statistically significance between erosive group and non-erosive group (P<0.05) in expression of bcl-2. CONCLUSION: Apoptosis and apoptotic related genes p53 bcl-2 C-myc participate in clinical development of OLP. The changes of AI are related to the chronic inflammation of lesion with OLP. We should attach importance to over expression of bcl-2 in erosive OLP.

Application of secondary structure prediction in antisense drug design targeting protein kinase C-alpha mRNA and QSAR analysis.

AIM: To optimize the design of antisense drug targeting protein kinase C-alpha (PKC-alpha) mRNA and obtain better antisense drugs than ISIS3521 that is undergoing clinical trials. METHODS: RNAstructure (version 3.21, 1999) was utilized to predict the optimal and suboptimal secondary structures of human PKC alpha mRNA (GenBank, X52479), and 29 antisense phosphorothioate oligodeoxynucleotides (S-ODN) targeting the secondary structural elements, 3 partly matched S-ODN and 1 scrambled 3521 were designed. ISIS3521 was set as positive control. Mean (n = 3-5) 50% inhibitory effects on proliferation of A549 cells (IC50) of S-ODN were evaluated. Free energies (delta G degree 37) relating to the target secondary structural elements were calculated according to the nearest neighbor model. The quantitative structure-activity relationship (QSAR) analysis through multiple regression was obtained by SPSS. RESULTS: Three S-ODN; (5'-AGCCCA-GCCGCTTGGCTGGG-3', 5'-AGGAGTGCAGCTGC-GTCAAG-3', 5'-TCAGAGGG-ACTGATGACTTT-3') had lower IC50[(48 +/- 7), (50 +/- 4), (64 +/- 2.7) nmol.L-1, respectively] than that of ISIS3521 [(81 +/- 25) nmol.L-1]. The number of bases comprising the target secondary structural element bulge loop, internal loop, and knot, the free energy of S-ODN (delta G degree 37S), and reaction (delta G degree 37R) were important parameters in QSAR equation. In the multiple regression, R was 0.68, P = 0.0193. Not tally with the equation, two S-ODN (5'-TCAAATGGAGG-CTGCCCGGC-3', 5'-AAAACGTCAGCCATGGTCCC-3') with favorable target structures and delta G degree 37 did not behave good activities. CONCLUSION: Computer aided design was helpful to obtain S-ODN with better in vitro effect than current positive drug. The degree of instability of secondary structural elements and delta G degree 37 were important factors for drug activity. Other important factors needed for further investigation.

Extended parietal cell vagotomy in the treatment of perforation, hemorrhage and stenosis due to duodenal ulcer.

Ninety-five patients with perforation, hemorrhage or stenosis due to duodenal ulcer were treated by extended parietal cell vagotomy. Postoperative follow-up ranged from 3.5 to 10 years (mean 6 years) in 88 patients (92%) with acute perforation (60), hemorrhage (8) and stenosis (20). There was no operative mortality. Ulcer recurrence was 2.3%. Only one patient (5%) had restenosis and required reoperation. There was no recurrent hemorrhage and there were few long-term complications. According to the Visick classification, 67 patients (76%) belonged to grade I, 13 (14.7%) grade II, 4 (4.5%) grade III, and 4 (4.5%) grade IV. Extended parietal cell vagotomy proved to be safe with excellent results, low ulcer recurrence and few complications. Moreover, recurrent ulcers healed rapidly following medical therapy. The authors believe that extended parietal cell vagotomy should be the treatment of choice for acute perforation, hemorrhage or stenosis due to duodenal ulcer.