Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design ; Drug Discovery ; Small Molecule Libraries

This paper presented the effects of experimental hyperinsulinemia on the main apolipoproteins (At, B) and on tbe process of reverse cholesterol transport in rabbit, which consisted of 1) uptake of cholesterol from peripheral tissue by HDL; 2) cholesterol esterification and 3) cholesterol ester transfer. The results showed that insulin could significantly decrease both serum and lymph Apo A1 levels and inhibit all the three steps of reverse cholesterol transport. The larger the dose of insulin, the greater the effects. Apo B did not seem to be influenced by insulin. It was further demonstrated by a series of statistical analyses that insulin had both direct and indirect inhibitory actions, to different extent, on each of the three main steps of reverse cholesterol transport.

The release kinetics research of sustained-release formulations of traditional Chinese medicines (TCM) is an inalienable part of the chain of TCM modernization, which plays an important role in the development of modern compound TCM preparation. However, the research method or pattern in line with the specific characteristics of TCM, i.e., multi-component and multi-target, is still lacking. On the basis of material rough set theory, this paper reviewed the advantages and disadvantages of the existing evaluation patterns and methods, a tentative idea about the "total amount" release characteristics evaluation on TCM compound sustained-release preparation has suggested so as to evaluate the release kinetics and to promote the development of evaluation methodology on TCM sustained-release preparations.

Objective To compare the efficacy and complications of percutaneous nephroscope decortication of cystic renal disease with transureteroscopic decompression of cystic renal disease.Methods Retrospectively analyze the clinical data of 42 simple renal cyst cases,who under treatment of surgical in Zhongnan Hospital of Wuhan University from Sep.2010 to Sep.2014 via percutaneous nephrolithotomy as well as ureteroscope.There were 21 patients in each group.Comparisons were made between the two groups on operation time,peripheral tissue injury,blood loss,postoperative infection,hospitalzation time.Postoperative recurrence were followed up.Results For the percutaneous nephroscope decortication of cystic renal disease group and transureteroscopic decompression of cystic renal disease group,the operation time were (38.43 ± 9.76) minutes,(28.95 ± 8.67) minutes,the number of tissue injury were 8,6;the blood loss were (28.62 ± 9.82) mL,(23.48 ± 7.65) mL;the number of postoperative infection was 4,10;the postoperative recurrence were 2,5;the hospitalzation time were 2 days and 8 days.Compared with the transureteroscopic decompression group,the percutaneous nephroscope decortication group had a less postoperative infection and fewer postoperative recurrence (P ＜ 0.05).But the operation time was longer in the percutaneous nephroscope decortication group (P ＜ 0.05).Conclusions The therapeutic effect of percutaneous nephroscope decortication is much better than that of transureteroscopic decompression,but also has a little disadvantage.

AIM: To observe effect of the iris location to femtosecond - combined wavefront guided LASIK for myopia and astigmatism.?METHODS:The patients with astigmatism >1. 0D during the same time and followed up for 1a were selected. A total of 129 eyes in 67 patients were treated under iris location with femtosecond-combined wavefront guided LASIK ( experimental group) and 161 eyes in 82 cases with femtosecond-combined wavefront guided LASIK ( control group) . Laser cutting went with the same laser machine. The uncorrected visual acuity ( UCVA ) , best corrected visual acuity ( BCVA) , and wavefront aberration between the two groups were compared at 1, 3, 6mo and 1a after surgery.?RESULTS:At 1 and 3mo after surgery, the number of patients with better postoperative UCVA than preoperative BCVA between the two group showed a statistically significant difference (χ2=6. 423, P=0. 011,χ2=14. 431, P=0. 01 ); at 1d and 1mo after surgery, the residual astigmatism showed a statistically significant difference between two groups (t=1. 98, P<0. 05; t=2. 23, P<0. 05). At 3, 6mo and 1a after surgery, the differences on the change of residual astigmatism between the two groups weren’t significant ( P > 0. 05 ). At 6mo and 1a after surgery, the differences on UCVA between the two groups weren’t significant ( P > 0. 05 ). Until 1a after surgery, the root mean square ( RMS ) of high order wavefront aberration of the two groups, spherical aberration and coma aberration ( COMA ) were all enhanced compared to before surgery(P<0. 05). At 1, 3mo after surgery, the RMS showed a statistically significant difference between two groups (P<0. 05). At 1, 3, 6mo, 1a after surgery, the increase of COMA in experimental group was significantly lower than that in control group (P<0. 05).? CONCLUSION: Iris location technology applied in femtosecond - combined wavefront guided LASIK for myopia and astigmatism, can make the vision recovery faster, the RMS of high order and COMA increase less, the residual astigmatism less, show better and more stable treatment effect.

AIM:To contrast analysis of postoperative variation of corneal posterior surface heights after Femtosecond LASlK ( FS - LASlK ) and small incision lenticule extraction ( SMlLE) for high myopia.
●METHODS: Sixty-seven cases of high myopic patients (132 eyes) operated with laser corneal refractive in our hospital from May to Dec. in 2015 (-6. 00D≤spherical equivalent degree≤-10. 00D) were selected and divided into FS-LASlK group and SMlLE group. The thickness of corneal flaps at FS-LASlK and the thickness of map at SMlLE were designed to be 110μm. Corneal posterior surface heights were examined by Pentacam at preoperation, postoperative 3 and 6mo after FS-LASlK and SMlLE operation. Surface height changes after preoperative, postoperative 3 and 6mo were compared by measuring Pentacam corneal analysis system.
●RESULTS: Six months after operation, the FS-LASlK posterior corneal surface height was 6. 47 ± 1. 65mm, significantly higher than 5. 20 ± 1. 32mm before operation. SMlLE posterior corneal surface height was 6. 40 ± 1. 33mm, significantly higher than 5. 18 ± 1. 25mm before operation, the differences were statistically significant( P<0. 05). Six month after surgery, two methods of corneal surface height variation obtained was 1. 29 ± 1. 28mm and 1. 22 ± 0. 89mm, there was no significant difference ( P>0. 05).
●CONCLUSION:After FS-LASlK and SMlLE, the corneal posterior surface is protrusive. FS - LASlK is slightly obvious than SMlLE in early period. The stability of the posterior surface is better after SMlLE.

Objective To understand the evaluation on graduates' professional quality from the employment institutions,and to provide the references for the higher vocational schools in improving students' training model and strengthening students' professional quality. Methods The questionnaires designed independently were answered by the employment institutions hiring 2003-2005 four majors(namely nursing,laboratory science,dental technology,optometry) graduates from Shanghai Institute of Health Sciences. Results The overall evaluation of employment institutions on the graduates was quite good,but the evaluation on graduates' professional ability was low. Conclusion With strengthening the student' specialized knowledge and skill training,higher vocational schools must pay more attention to the students' professional ability education.

ObjectiveTo observe the effect and safety of continuous epidural analgesia with sufentanil in different concentrations combined with 0.125% bupivacaine on pain after thoracotomy.Methods30 patients with ASA grade Ⅱ～Ⅲ and underwent thoracotomy were randomly divided into 3 groups treated with 0.125% bupivacaine combined with sufentanil 0.25 μg/ml (group A), 0.50 μg/ml (group B) and 0.75 μg/ml (group C) respectively. Before operation starting, epidural puncture was performed at T7～T8 and a catheter was put in. After operation, continuous epidural analgesia was performed by connecting the catheter and a analgesic pump. Analgesia effect was evaluated by visual analogous score (VAS) at sixth, twelfth, twenty-fourth and forty-eighth hours after operation. Dosage of assistant drug and side effects such as calmness, nausea, vomiting, skin pruritus and respiratory inhibition were also recorded.ResultsVAS scores and dosage of assistant drug of group B and group C were not different, but they were all lower than that of group A (P<0.05). Scores of skin pruritus of group A and group B were lower than that of group C (P<0.05), but there was no significant difference between group A and group B. No respiratory inhibition occurred in patients of all three groups.ConclusionContinuous epidural analgesia of 0.50 μg/ml sufentanil combined with 0.125% bupivacaine is safe and effective for patients after thoracotomy.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Abdominal Pain ; etiology ; Child ; Child, Preschool ; Endoscopy, Gastrointestinal ; Female ; Humans ; Male ; Purpura, Schoenlein-Henoch ; complications ; pathology