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OBJECTIVES: To observe the clinical outcomes of visual rehabilitation using rigid gas-permeable contact lenses (RGPCLs) after penetrative ocular trauma in children younger than 12 years in China. METHODS: Patients younger than 12 years with penetrative ocular trauma fitted with an RGPCL for visual rehabilitation from 2017 to 2021 were included. In the case cohort, the best-corrected visual acuity (BCVA) with spectacles was measured when the RGPCL was fitted, and the initial BCVA with RGPCL, and the BCVA at the last visit were compared. RESULTS: Fifteen patients, aged 4 to 12 (mean 8.0±2.7) years, who wore an RGPCL for 7 to 53 (mean 20.3±15.7) months, were included. The BCVA was log of minimal angle of resolution 0.4 (0.2-0.7) with spectacles and 0.1 (0.1-0.2) for RGPCL at the initial visit, and 0.0 (0.0-0.1) for BCVA at the last visit, with a statistically significant difference between the three comparisons ( P <0.001). Six of the 15 (40%) children abandoned wearing RGPCL because of discomfort and lens rejection (n=3, 50%), lens loss and inability to replace broken lens because of travel distances and epidemics (n=2, 33%), and cost (n=1, 17%). CONCLUSIONS: Although application is complicated and initial wearing comfort is poor, an RGPCL is still a beneficial, safe tool for postoperative visual rehabilitation in children with open ocular trauma.
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Lentes de Contacto , Lesiones Oculares , Humanos , Niño , Agudeza Visual , Ojo , AnteojosRESUMEN
PURPOSE: This study aimed to evaluate the pharmaceutical and pharmacokinetic effects of the natural nanoparticles (Nnps) isolated from Coptidis Rhizoma extract on berberine hydrochloride (BBR) and systematically explore the related mechanisms. METHODS: Firstly, Nnps were isolated from Coptidis Rhizoma extract and then an Nnps-BBR complex was prepared. After qualitative and quantitative analysis in terms of size, Zeta potential, morphology, and composition of the Nnps and the Nnps-BBR complex, the effects of the Nnps on the crystallization of BBR were characterized. The effects of the Nnps on the solubility and dissolution of BBR were then evaluated. In addition, the effects of the Nnps on BBR in terms of cellular uptake, transmembrane transport, metabolic stability, and pharmacokinetics in mice were studied. RESULTS: The Nnps had an average size of 166.6 ± 1.3 nm and Zeta potential of -12.5 ± 0.2 mV. The Nnps were formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The Nnps adsorbed or dispersed BBR, thereby promoting BBR transformation from crystal to amorphous form and improving its solubility and dissolution. The Nnps carried and promoted BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp (MDCK-MDR1) cells. Moreover, the Nnps improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption in mice, as shown by increased peak BBR concentration (Cmax, 1182.3 vs 310.2 ng/mL) and exposure level (AUC0-12 h, 2842.8 vs 1447.0 ng·h/mL) in mouse portal vein. In addition, the Nnps increased BBR exposure level in mouse livers (95,443.2 vs 43,586.2 ng·h/g liver). CONCLUSION: The proteinaceous nanoparticles isolated from Coptidis Rhizoma extract can form a natural nano-drug delivery system with BBR, thereby significantly improving the pharmacokinetics of oral BBR.
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Berberina , Medicamentos Herbarios Chinos , Animales , Células CACO-2 , Coptis chinensis , Perros , Humanos , Absorción Intestinal , RatonesRESUMEN
The development of chiral ligands with privileged scaffolds plays an important role in transition-metal-catalyzed asymmetric reactions. Herein we present anthracene-photodimer-derived chiral monophosphine ligand 1, which features dual chirality and a rigid scaffold. This ligand exhibits remarkable efficiency in Pd-catalyzed desymmetric intermolecular C-N coupling under mild conditions with excellent chemo- and enantioselectivity.
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A sequential cross-coupling/annulation of ortho-vinyl bromobenzenes with aromatic bromides was realized, providing a direct and modular approach to access polycyclic aromatic compounds. A vinyl-coordinated palladacycle was proposed as the key intermediate for this sequential process. Excellent chemoselectivity and regioselectivity were observed in this transformation. The practicability of this method is highlighted by its broad substrate scope, excellent functional group tolerance, and rich transformations associated with the obtained products.
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The asymmetric rhodium-catalyzed alkenylation of enones and imines with arylboronic acids has been developed. A highly controllable aryl to vinyl 1,4-rhodium migration is the key step. Stereodefined vinyl moieties were installed in excellent enantioselectivies for most examined examples. DFT calculations reveal that the driving force of this rhodium migration is a kinetically favored process.
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Structural designs combining oligoparaphenylene-derived nanohoops with other functional organic building blocks should lead to novel molecular architectures with intriguing properties. Herein, we describe the synthesis of a pentiptycene-derived chiral dual nanohoop molecule with key steps including ring expansion through dianthracene cycloreversion and transannular [4+2] cycloaddition across a 64-membered macrocycle. The crystal structure of the nanohoop molecule displays an ordered packing pattern with long-range channels in the solid state. Furthermore, nonracemizable enantiomers of the nanohoop were obtained through resolution and exhibited promising chiroptical properties.
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OBJECTIVE: To observe the effect of Schistosoma japonicum cysteine protease inhibitor (rSjCystatin) for treatment of lipopolysaccharide (LPS)-induced sepsis in mice. METHODS: After a week of adaptive feeding, 54 BALB/c mice were randomly divided into normal control group (group A), sepsis group (group B), and rSjCystatin intervention group (group C). The mice in group A received an intraperitoneal injection of PBS (100 µL), and those in groups B and C were injected with PBS (100 µL) containing LPS (10 mg/kg); the mice in group C were also intraperitoneally injected with 25 µg sjCystatin in 100 µL PBS 30 min after LPS injection. From each group, 10 mice were randomly selected 24 h after PBS or LPS injection for detecting serum levels of TNF-α, IL-6, and IL-10 using ELISA and the levels of ALT, AST, BUN, and Cr using automatic biochemical analyzer; the pathological changes in the liver, lung and kidney were observed with HE staining. The remaining 8 mice in each group were used for observing the changes in the general condition and the 72-h survival. RESULTS: The 72-h survival rates of the mice was 100% in group A, 0 in group B, and 36% in group C, showing a significant difference among the 3 groups (P<0.05). Compared with those in group A, the mice in group B exhibited obvious liver, lung, and renal pathologies with increased levels of ALT, AST, BUN, Cr, IL-6, and TNF-α (P<0.05). Treatment with sjCystatin significantly lessened LPS-induced organ pathologies, lowered the levels of liver and renal functional indexes and the pro-inflammatory cytokines, and increased the serum level of IL-10 in the mice (P<0.05). CONCLUSION: SjCystatin can produce a significant therapeutic effect on sepsis induced by LPS in mice.
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Inhibidores de Cisteína Proteinasa/uso terapéutico , Schistosoma japonicum/enzimología , Sepsis/tratamiento farmacológico , Animales , Cisteína , Lipopolisacáridos , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Sepsis/sangre , Sepsis/etiología , Sepsis/mortalidad , Tasa de Supervivencia , Factor de Necrosis Tumoral alfaRESUMEN
Objective: To analyze the component of adult worm excretory/secretory protein(AWESP) from Trichinella spiralis using the shotgun method, and find out the active component underlying its regulatory effect on colitis in humans. Methods: The T. spiralis AWESP was prepared, separated by SDS-PAGE, lysed with trypsin, and analyzed by shotgun LC-MS/MS. The protein components were determined with the Masco software and classified using the Gene Ontology(GO) method in cellular components, molecular functions, and biological processes. Results: The AWESPs isolated by SDS-PAGE had a Mr of 15 000-116 000. A total of 280 proteins were revealed by LC-MS/MS, of which 96 were identified by Masco software, 98 were putative, and the remaining 86 were unclear. Preliminary results showed that 4 proteins had regulatory potential for colitis, including cysteine protease inhibitor, serine protease, 53 000 excretory/secretory antigen, and glutathione-S-transferase. GO enrichment analysis showed that the identified proteins had 104 different molecular functions, involved in 363 biological processes. Conclusion: As revealed by the Masco software, T. spiralis AWESP has complex components and 96 have been identified in this study. Four of them are preliminarily shown to be associated with the anti-colitis effect of T. spiralis.
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Trichinella spiralis , Animales , Antígenos Helmínticos , Electroforesis en Gel de Poliacrilamida , Proteínas del Helminto , Larva , Ratones , Espectrometría de Masas en Tándem , TriquinelosisRESUMEN
OBJECTIVE: To observe the effect of Trichinella spiralis and its worm-derived proteins on cecal ligation and puncture (CLP)-induced sepsis in mice. METHODS: Eighty male BALB/c mice were randomly divided into sham-operated group, CLP group, Trichinella spiralis muscle larvae (ML) pre-infection group (ML+CLP group), soluble muscle larvae proteins (SMP) treatment group (SMP+CLP group) and excretory-secretory proteins (MES) treatment group (MES+CLP group). In ML+CLP group, the mice were orally infected with 300 Trichinella spiralis muscle larvae at 28 days before CLP and those in the other groups were intraperitioneally injected with PBS or SMP (25 µg/mice) or MES (25µg/mice) 30 min after CLP. The general condition and 72-h survival after CLP of the mice were observed. The levels of alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), creatinine (Cr), TNF-α, IL-6, IL-1ß, IL-10 and TGF-ß were measured at 12 h after the operation, and the pathological changes of the liver and kidney were observed. RESULTS: s Compared with the sham-operated mice, the mice in CLP group showed decreased 72-h survival, obviously increased ALT, AST, BUN, Cr, TNF-α, IL-6, IL-1ß, IL-10, and TGF-ß with hepatic cords disorder, hepatocytes swelling, glomerulus shrinkage, and renal tubular cell edema. Compared with CLP group, the mice in ML+CLP group showed lowered levels of ALT, AST, Cr, TNF-α and IL-1ß and increased levels of IL-10 and TGF-ß; in SMP+CLP group, the levels of ALT, AST, Cr, TNF-α and IL-1ß were decreased and TGF-ß increased. In MES+CLP group, the mice showed obviously increased 72-h survival with lowered levels of ALT, AST, BUN, Cr, TNF-α, IL-6 and IL-1ß, increased levels of IL-10 and TGF-ß, and alleviated liver and kidney damages. CONCLUSION: Trichinella spiralis and its worm-derived proteins can decrease the levels of pro-inflammatory cytokines and increase immunomodulatory cytokines, and MES has more potent effect to reduce structural and functional damages of the liver and kidney.
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Antígenos Helmínticos/farmacología , Proteínas del Helminto/farmacología , Enfermedades Renales/terapia , Hepatopatías/terapia , Sepsis/terapia , Trichinella spiralis , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Nitrógeno de la Urea Sanguínea , Ciego , Creatinina/sangre , Citocinas/sangre , Riñón/fisiopatología , Ligadura , Hígado/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
OBJECTIVE: To investigate the protective effects of parecoxib from oxidative stress induced by hydrogen peroxide (H2O2) in rat astrocytes in vitro. METHODS: All experiments included 4 groups: (1) negative control (NC) group, without any treatment; (2) H2O2 treatment group, 100 µmol/L H2O2 treatment for 24 h; (3) and (4) parecoxib pretreatment groups, 80 and 160 µmol/L parecoxib treatment for 24 h, respectively, and then treated with 100 µmol/L H2O2. Several indices were investigated, and the expressions of Bax, Bcl-2, and brain-derived neurotrophic factor (BDNF) were quantified. RESULTS: Compared to the NC group, exposure to H2O2 resulted in significant morphological changes, which could be reversed by pretreatment of parecoxib. In addition, H2O2 treatment led to loss of viability (P=0.026) and increased intracellular reactive oxygen species (ROS) levels (P<0.001), and induced apoptosis (P<0.01) in the primary astrocytes relative to the NC group. However, in the parecoxib pretreatment groups, all the above changes reversed significantly (P<0.05) as compared to the H2O2 treatment group, and were nearly unchanged when compared to the NC group. Mechanical investigation showed that dysregulated Bax, Bcl-2, and BDNF could be implicated in these changes. CONCLUSIONS: Our results indicated that parecoxib provided a protective effect from oxidative stress induced by exposure to H2O2.
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Astrocitos/efectos de los fármacos , Peróxido de Hidrógeno/química , Isoxazoles/farmacología , Estrés Oxidativo , Animales , Apoptosis , Astrocitos/citología , Astrocitos/metabolismo , Factor Neurotrófico Derivado del Encéfalo/química , Supervivencia Celular , Células Cultivadas , Inhibidores de la Ciclooxigenasa 2/química , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The century-old yet synthetically underexplored anthracene photodimerization-cycloreversion reactions have been employed as the key steps to access highly strained aromatic hydrocarbons. Herein we report the chemical syntheses of oligoparaphenylene-derived nanohoops in five steps or less featuring a rigid dianthracene synthon. The newly synthesized nanohoops display intriguing experimental and computational properties.
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Trichinella spiralis and its derivative antigens stimulate T cell activation by inducing dendritic cell semimaturation, thereby regulating the Th1/Th2 type immune response and alleviating or inhibiting allergy and autoimmune diseases. The regulatory T cell and anti-inflammatory factors play important roles in this immunomodulatory process. This article reviews the modulatory effects and their mechanisms of Trichinella spiralis and its derivatives in autoimmune disorders.
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Trichinella spiralis , Animales , Antígenos Helmínticos , Enfermedades Autoinmunes , Citocinas , Células Dendríticas , Hipersensibilidad , Activación de Linfocitos , Ratones , Linfocitos T Reguladores , TriquinelosisRESUMEN
Objective: To investigate the killing effect of hypericin on tachyzoites of Toxoplasma gondii RH strain in vitro. Methods: Normal saline ï¼group Aï¼ and different concentrations of hypericin (5 µg/ml, group B; 50 µg/ml, group C; 500 µg/ml, group Dï¼ were added to T. gondii tachyzoites in 24-well plateï¼1×10(6)/wellï¼. The tachyzoites were harvested after 2, 4 and 6 h, and underwent the following treatment: trypan blue staining to calculate the dyeing rate, Giemsa staining to observe the morphological and structural alterations of tachyzoites, and transmission electron microscopy to observe the ultrastructure of tachyzoites. In addition, flow cytometry was performed to calculate the survival rate of YFP-carrying Toxoplasma with the same treatment. Results: The trypan blue dyeing rate at 2 h after treatment in groups B, C and D wasï¼11.0±3.6ï¼%, ï¼25.0±6.3ï¼% andï¼40.0±2.7ï¼% respectively, with a significant difference of group D versus B and C ï¼P<0.01ï¼, and groups C and D versus group A ï¼»ï¼6.0±3.0ï¼%ï¼ï¼½. The dyeing rate at 4 h and 6 h in group D wasï¼97.0±2.0ï¼% and ï¼98.0±1.7ï¼%, respectively, both significantly higher than that of groups C ï¼»ï¼30.0±7.2ï¼%, ï¼42.7±5.5ï¼%ï¼½, B ï¼»ï¼20.0±3.0ï¼%, ï¼34.0±6.6ï¼%ï¼½ and A ï¼»ï¼10.0±1.0ï¼%, ï¼19.3±4.9ï¼%ï¼½ï¼P<0.01ï¼. Giemsa staining showed gradual end swelling and necrosis of tachyzoites with increased treatment duration and dosage. Transmission electron microscopy showed swelling of worm body, gap between cell membrane and matrix, increase and enlargement of vacuoles inside worm body, disruption of cell membrane, and dissolving of inner structures, with increased treatment duration. Flow cytometry showed significant difference of tachyzoite survival rate at 2, 4 and 6 h after hypericin treatment with that of the control groupï¼P<0.01ï¼. The survival rate of group C at 2 h after hypericin treatment wasï¼7.9±1.9ï¼%, significantly lower than that of groups B ï¼»ï¼38.1±5.5ï¼%ï¼½ and A ï¼»ï¼81.8±6.0ï¼%ï¼½ ï¼P<0.01ï¼. No tachyzoite was found to survive in group D at 2 h and in group C at 4 h. The survival rate of group B at 4 and 6 h after hypericin treatment wasï¼14.3±7.9ï¼% and ï¼1.4±1.8ï¼%, respectively, both significantly lower than that of group Aï¼»ï¼73.8±11.3ï¼% andï¼64.1±14.4ï¼%, respectivelyï¼½ ï¼P<0.01ï¼. Conclusion: Hypericin has a remarkable killing effect on T. gondii tachyzoites, and the efficacy positively correlates with the dose and treatment duration.
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Toxoplasma , Antracenos , Microscopía Electrónica de Transmisión , Perileno/análogos & derivadosRESUMEN
Parasitic worms (helminth) or their derivates can inhibit allergy and autoimmune diseases by inducing the activation of immune cells and thus the release of regulatory factors. A large number of animal experiments have shown that adoptive transfer of lymphocytes can protect against immune deregulation and have potential clinical applications. In this review, we discuss the research progress on the role of adoptive transfer of immune cells in worm-induced regulation of allergy and autoimmune diseases.
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Traslado Adoptivo , Enfermedades Autoinmunes , Hipersensibilidad , Animales , HumanosRESUMEN
Total knee arthroplasty has become one of the effective operation methods on end-stage knee osteoarthritis. However,the postoperative pain has been plaguing the clinicians. The cause of postoperative pain can be divided into iatrogenic, prosthesis and patient. Pain treatment in perioperative period includes preoperative education, analgesia in advance, and the selection and design of reinforcement; during operation mainly includes the appropriate surgical approach, keep the balance of soft tissue around the knee joint, cocktail analgesia pain around the knee joint; after operation mainly includes oral analgesic drugs, femoral nerve tissue and patient controlled analgesia. And the multimodal analgesi.a which is the analgesic methods combined application in perioperative period raised in resent years fully intervene the pain in perioperative period,so that it can effectively reduce the pain of patients after knee replacement, promote the patients do functional exercise more better and get better operation result.
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Artroplastia de Reemplazo de Rodilla , Manejo del Dolor , Dolor Postoperatorio/etiología , Analgesia Controlada por el Paciente , Humanos , Bloqueo Nervioso , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
A new method for the construction of five-membered spirocyclic oxindoles is based on a Michael-Mannich cascade reaction of a ketimine intermediated catalyzed by a bifunctional quinine-derived squaramide. The desired products were obtained in excellent yields (up to 94%) and stereoselectivities (up to >20:1 d.r., >99% ee). A scaled-up variant also proceeded smoothly showing that the one-pot reaction might find application in the synthesis of bioactive-compound libraries.
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Iminas/química , Indoles/síntesis química , Nitrilos/química , Quinina/análogos & derivados , Compuestos de Espiro/síntesis química , Catálisis , Dominio Catalítico , Indoles/química , Estructura Molecular , Quinina/química , Compuestos de Espiro/química , EstereoisomerismoRESUMEN
OBJECTIVE: To study the lethal effect of exogenous nitric oxide donor sodium nitroprusside (SNP) on the muscle larvae of Trichinella spiralis in vitro cultivation. METHODS: T. spiralis muscle larvae isolated from the infected BALB/c mice were formulated into a 1,000 larva/ml suspension with RPMI 1640 medium, and 0.1 ml suspension per orifice was cultured with SNP at 37°C in a humidified 5% CO2 atmosphere. The final concentrations of SNP were 0.02, 0.05, 0.10, 0.20, 0.50 and 1.00 mmol/L, respectively, and then the experiments were divided into 5 groups:1.00 mmol/L SNP (control group, Group A), 0.15 mmol/L FeSO4+ 1.00 mmol/L SNP (Group B), 1.00 mmol/L L-cysteine + 1.00 mmol/L SNP (Group C), 0.15 mmol/L FeSO4+ 1.00 mmol/L L-cysteine + 1.00 mmol/L SNP (Group D) and 0.15 mmol/L Hemoglobin + 1.00 mmol/L SNP (Group E). All the groups were incubated with T. spiralis muscle larvae in RPMI 1640 medium. The survivability of the muscle larvae was observed by steromicroscope and the differences of inhibition ratio among these groups were analyzed 4 d after the incubation. Results SNP 0.02 mmol/L was not cytotoxic to the muscle larvae with an inhibition of (5.50 ± 1.80) %. The mortality rates of SNP 0.05, 0.10, 0.20, 0.50, 1.00 mmol/L groups were (20.19±2.71)%, (29.21±2.12)%, (41.81±2.03)%, (47.85±3.79)%, (60.98±5.19)%, respectively, significantly higher than that of the control group[(4.93±0.25) %, all P < 0.051]. There was a positive liner correlation between the mortality of muscle larvae and SNP concentrations in the range of 0.02-1.00 mmol/L. Next, Group A, B, C, D and E led to the mortalities from (60.98±5.19)% to (49.48±1.34)%, (47.29±2.79)%, (26.28±1.37)%, (17.93±3.49)%, respectively, and all the differences between Group A and the other four groups were statistically significant (all P < 0.05). CONCLUSIONS: Exogenous nitric oxide released from SNP can kill the muscle larvae of T. spiralis. However, hemoglobin, L-cysteine, and FeSO4 can reverse the lethal effect on the parasites. The best inhibitor was hemoglobin.
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Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Trichinella spiralis/efectos de los fármacos , Animales , Femenino , Larva/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad ParasitariaRESUMEN
Cysticercosis due to larval cysts of Taenia solium, is a serious public health problem affecting humans in numerous regions worldwide. The oncospheral stage-specific TSOL18 antigen is a promising candidate for an anti-cysticercosis vaccine. It has been reported that the immunogenicity of the DNA vaccine may be enhanced through codon optimization of candidate genes. The aim of the present study was to further increase the efficacy of the cysticercosis DNA vaccine; therefore, a codon optimized recombinant expression plasmid pVAX1/TSOL18 was developed in order to enhance expression and immunogenicity of TSOL18. The gene encoding TSOL18 of Taenia solium was optimized, and the resulting opt-TSOL18 gene was amplified and expressed. The results of the present study showed that the codon-optimized TSOL18 gene was successfully expressed in CHO-K1 cells, and immunized mice vaccinated with opt-TSOL18 recombinant expression plasmids demonstrated optTSOL18 expression in muscle fibers, as determined by immunohistochemistry. In addition, the codon-optimized TSOL18 gene produced a significantly greater effect compared with that of TSOL18 and active spleen cells were markedly stimulated in vaccinated mice. 3H-thymidine incorporation was significantly greater in the opt-TSOL18 group compared with that of the TSOL18, pVAX and blank control groups (P<0.01). In conclusion, the eukaryotic expression vector containing the codon-optimized TSOL18 gene was successfully constructed and was confirmed to be expressed in vivo and in vitro. The expression and immunogenicity of the codon-optimized TSOL18 gene were markedly greater compared with that of the un-optimized gene. Therefore, these results may provide the basis for an optimized TSOL18 gene vaccine against cysticercosis.