ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

AIM: To study the bioequivalence of rosuvastatin calcium tablets produced by two different manufacturers on a fasting and postprandial basis in Chinese healthy subjects. METHODS: A single-center, randomized, balanced, open, two-sequence, two-cycle, double-crossover, and single-dose trial design was used in this study. Each of the fasting group and the postprandial group was enrolled in 52 healthy subjects. Fasting/postprandial oral rosuvastatin calcium tablets 10 mg test preparation or reference preparation, the validated LC-MS/MS method was used to determine the concentration of rosuvastatin calcium tablets in plasma, and the pharmacokinetic parameters were calculated. Human bioequivalence and safety evaluation of two rosuvastatin calcium tablets were evaluated. RESULTS: The t

By using an RAD peptide display system derived from the ATPase domain of recombinase RadA of Pyrococcus furiosus, an anti-hCG antibody-like molecule was prepared by grafting an hCG-binding peptide to the RAD scaffold. After linking to sfGFP gene, a gene of hCG peptide-grafted RAD was synthesized and cloned into a bacterial expression vector (pET30a-RAD/hCGBP-sfGFP). The vector was transformed into Escherichia coli, and expression of the fusion protein was induced. After isolation and purification of the fusion protein, its binding affinity and specificity to hCG were determined by using a process of immunoabsorption followed by GFP fluorescence measurement. A comparison of hCG-binding activity with a similarly grafted single-domain antibody based on a universal scaffold was performed. The measurement of hCG-binding affinity and specificity revealed that the grafted RAD has an optimally high binding affinity and specificity to hCG, which are better than the grafted single-domain antibody. Moreover, the affinity and specificity of grafted RAD molecule are comparable to those of a commercial monoclonal antibody. In addition, the hCG-binding peptide-grafted RAD molecule has a relatively high biochemical stability, making it a good substitute for antibody with potential application.
Antibodies, Monoclonal ; chemistry ; isolation & purification ; metabolism ; Antibody Specificity ; DNA-Binding Proteins ; genetics ; metabolism ; Escherichia coli ; genetics ; Escherichia coli Proteins ; metabolism ; Humans ; Peptides ; Recombinant Fusion Proteins ; genetics ; metabolism

Objective To investigate the clinical effect of S-1 combined with oxaliplatin (SOX regimen) in treatment of the patients with advanced pancreatic cancer. Methods A total of 106 patients with advanced pancreatic cancer in Qingdao Fuwai Hospital from April 2015 to June 2017 were randomly divided into the treatment group (53 cases) and the control group (53 cases) according to the random number table method. Patients in the control group were treated with S-1 combined with cisplatin treatment, and patients in the treatment group were treated with SOX regimen. The cell proportion of CD3+, CD4+, CD8+and CD4+/CD8+before treatment and after 2 cycles of treatment were detected by using flow cytometry of both groups. The clinical curative effects, immunity and adverse reactions of both groups were compared by usingχ2 test and t test. Kaplan-Meier method was used to make the survival analysis. Results After two cycles of treatment, there were 4 cases of complete remission (CR), 23 cases of partial remission (PR), 17 cases of stable disease (SD), 9 cases of progression disease (PD) in the treatment group, and 0 case of CR, 18 cases of PR, 20 cases of SD, 15 cases of PD in the control group. The rate of CR+PR in the treatment group was higher than that in the control group [50.94％(27/53) vs. 33.96％(18/53)], and there was a statistical difference (χ2=5.936, P<0.05). There was a significant difference in the cell proportion of CD4+and ratio of CD4+/CD8+between the two groups before and after treatment [the treatment group: (27.31±2.48)％ vs. (37.05±2.53)％, χ2= 6.491,P< 0.01; 0.91 ±0.23 vs. 1.53 ±0.50, χ2 = 5.913, P< 0.01; the control group: (27.43 ±2.47)％ vs. (30.32 ± 2.41)％,χ2= 11.214, P<0.01; 0.90±0.22 vs. 1.22±0.34,χ2=7.992, P<0.01]. After 2 cycles of treatment, the cell proportion of CD4+and ratio of CD4+/CD8+of the treatment group were higher than those of the control group, and there were statistical differences (χ2=5.309, P<0.01;χ2= 7.112, P< 0.01). The incidence rate of side effects had no significant difference in both groups after two cycles of treatment [22.64％ (12/53) vs. 18.87％ (10/53), χ2= 1.924, P> 0.05]. The progression-free survival time in the treatment group was longer than that in the control group (P<0.05). Conclusions SOX regimen has a favorable effect on the patients with advanced pancreatic cancer. It can help to improve the immunity and prolong the survival time of the patients.

We used the antibody grafting technology to prepare anti-hCG single-domain antibodies on the basis of antigen-binding peptide to simplify the single-domain antibody preparation process and improving the biochemical stability of peptide. By using a universal single-domain antibody backbone (cAbBCII10), CDR1 or CDR3 was replaced by the hCG-binding peptide, and the grafted antibody gene sequences were synthesized and cloned into the prokaryotic expression vector pET30a(+) in fusion with a C-terminal sfGFP gene, i.e. pET30a-(His6)-cAbBCII10-CDR1/hCGBP1-sfGFP and pET30a-(His6)-cAbBCII10-CDR3/hCGBP3-sfGFP. The recombinant plasmids were transformed into E. coli BL21(DE3), and the fusion proteins were induced by IPTG. Highly soluble recombinant fusion proteins were obtained and purified by Ni-NTA affinity column. SDS-PAGE confirmed the purified protein as the target protein. The antigen-antibody binding assay showed that both the CDR1 and CDR3 grafted antibodies have hCG-binding activities. While the titers of the two grafted antibodies were similar, the binding affinity of CDR3 grafted antibody was higher than that of CDR1 grafted protein (about 2-3 times). The grafted antibodies retained the relatively high biochemical stability of the single-domain antibody backbone and were relatively thermostable and alkaline tolerant. The obtained antibodies also had a relatively high antigen-binding specificity to hCG. This study provided a reliable experimental basis for further optimization of anti-hCG single domain antibody by antibody grafting technology using antigen-binding peptide.

In clinical practice, skin defects resulted from various acute and chronic diseases occur frequently. Dermal substitute (DS), known as dermal regenerative template, is used more and more widely, but the slow process of vascularization limits its clinical application. At present, there are many strategies developed to enhance the process of vascularization, such as modifying the structure of dermal scaffolds, prevascularization by seeding stem cells and/or endothelial cells. Recently, negative-pressure wound therapy (NPWT) emerged and rapidly became popular in promoting wound healing due to its intrinsic advantages. Furthermore, some researchers introduced this technique to accelerate the vascularization process of DS. This paper represents a comprehensive overview on the efficiency of NPWT in different combination models, and the related mechanism.

Objective To investigate clinical effect and safety of ostium secundum atrial septal defect(ASD) treatment via one -stop hybrid and classical surgical procedures.Methods 45 patients were diagnosed ostium secun-dum simple ASD by ultrasound cardiogram and clinical manifestation,they were divided into one -stop hybrid proce-dure group (n =20)and classical surgical procedure (n =25).Age,gender,weight,post operation hospital day,on -pump time,blood transfusion amount,drainage flow,incision length and incidence of complication between the two groups were compared.Results Age and weight had no difference between the two groups(t =0.40 and 1.64,P >0.05),but the proportion of female cases in one -stop hybrid procedure group was higher than post operation(χ2 =9.45,P <0.05).Hospital day was shorter(t =11.11,P <0.05),drainage amount was fewer(t =81.68,P <0.05), incision length(t =22.51,P <0.05)was shorter.Incidence of complication had no statistically significant difference between the two groups(χ2 =0.35,P >0.05).And one -stop hybrid procedure group was off -pump without blood transfusion.Conclusion One -stop hybrid procedure was simple,could make a quick recovery post operation and was an ideal method for ostium secundum ASD treatment.

Objective: Based on nationwide cardiovascular surgery registry database, to analyze the current status and future development of minimally invasive cardiovascular surgery (MICS) in China.
Methods: There were 45 institutions from 19 provinces nationwide involved in Chinese cardiovascular surgery technique registry study. A total of 16480 adult patients with cardiovascular surgery from 2010-09 to 2012-03 were divided into 2 groups, Conventional surgery group, n=14503 and MICS group, n=1977. The basic clinical conditions were analyzed and compared between 2 groups in order to explore the current status and future development of MICS in China.
Results: Compared with Conventional surgery group, the patients in MICS group had the younger age, better and stable pre-operative condition. In MICS group, compared with 4 other common procedures, the patients who received hybrid procedure had obviously shorter cardiopulmonary bypass (CPB) time, aortic occlusion time, ventilator using time, ICU and in-hospital stay time, meanwhile decreased post-operative drainage volume;except for Robotic surgery, it required less red blood cells and plasma at during and post-operative time, all P<0.01. There were 12 (0.6%) in-hospital death in MICS group, the total complication rate was at 4%.
Conclusion: MICS are widely used in China, its short-term safety and efifcacy are conifrmed. Upon cardiovascular disease spectrum changing, the MICS procedures will be adjusted accordingly.

Objective To present our initial experience of using transumbilical multi-stab laparoscopic pyeloplasty(TMLP) as a treatment for the infants younger than 3 months with severe hydronephrosis caused by ureteropelvic junction obstruction (UPJO).Methods Seventy-two infants younger than 3 months with severe hydronephrosis caused by UPJO underwent TMLP from June 2010 to March 2013 in our center.The average age received operation was 34 days (7-87 days).The operative indications included:① prenatal diagnosis of Society of Fetal Urology Grade 4 hydronephrosis; ②ipsilateral differential renal function being less than 40％.Patients were followed up with physical examinations,ultrasound and radionuclide scans.Results The operations were successfully performed in all the 72 patients.Neither conversion nor additional trocars placement was required and there was no intraoperative complication.The average operative time was 75 min (range,53-118 min).The patients were followed up for 6-36 months (mean,12 months).The renal pelvic anteroposterior diameters were reduced and the renal functions were improved (P＜ 0.05).The anastomoses were proved to be patent and the renal parenchymal thickeness increased.In addition,the scars were barely noticeable.Conclusions TMLP for the infants younger than 3 months with severe hydronephrosis caused by UPJO is feasible,safe and less invasive.The cosmetic results are excellent.But the surgery must be operated by rich experienced surgeon.

Objective To evaluate maximum intensity projection(MIP) images and apparent diffusion coefficient(ADC) values of MR diffusion weighted imaging with background body signal suppression (DWIBS) on pulmonary diseases.Methods Sixty-one patients with pulmonary diseases underwent DWIBS.The findings in three dimensional(3D) MIP image were observed and the ADC values of diseased region were measured.The diagnostic value of DWIBS on pulmonary diseases was evaluated.Results Lung cancer and inflammatory disease were all demonstrated as dense intensity area on DWIBS.The mean ADC value of central lung cancer was (1.05±0.23)×10-3 mm2/s.The mean ADC value of peripheral lung cancer was(1.10±0.17)×10-3 mm2/s.The mean ADC value of the inflammatory disease was(1.69±0.29)×10-3 mm2/s.The mean ADC value had significant difierence between peripheral lung cancer and the inflammatory disease (P＜0.05). The MR sensitivity,specificity and accuracy in diagnosing the pulmonary diseases with DWIBS(86.84%,82.60%,85.24%,respectively) was higher than conventional MRI(78.94%,78.26%,and 78.68%,respectively).Conclusion DWIBS can demonstrate clearly the lesion's shape with 3D display.The quantitative measurement of ADC values iS feasible.DWIBS may be a potential diagnostic method for differentiation on pulmonary diseases.