As a novel branch of combinational chemistry, dynamic combinatorial chemistry (DCC) can be viewed as a technique which combines library synthesis and screening in one pot. By addition of molecular target, ligangds, which show binding affinity or strong interaction with the molecular target, can be amplified an young but rapidly growing branch of combinatorial chemistry, has been widely used in organic chemistry, biochemistry, material fields. Ligands in the library can be amplified, since synthesis of the library is screened by a molecular target. Therefore, these structures could be identified easily. Consequently DCC has been widely used in the lead discovery, material chemistry and other fields. On the basis of the principle and method of DCC, this review emphasizes the three factors of DCC, including molecular targets (bio-enzyme, lectin, nucleic acid, organic molecule, inorganic molecule); reaction (disulphide chemistry, ammoniation reduction reaction, hydrazone chemistry, etc.) and analytical method. Meanwhile, limitation, current situation and future development of DCC were also discussed in this paper.

Objective To assess the predictive value of neutrophil gelatinase associated protein lipocalin (uNGAL) in urine for detection of acute kidney injury(AKI) in patients with severe traumatic brain injury. Methods Patients with severe traumatic brain injury from the ICU were collected from Jan. 2011 to May. 2013 in our hospital. 43 cases that met the RIFLE criteria for diagnosis of AKI in the ICU within 7 days were selected as AKI group. Another 43 cases that were matched for age ,gender ,illness severity , surgery method with AKI cases ,selected as non‐AKI group. The levels of uNGAL and Scr were measured when the patients admit‐ted in the ICU with 15 min ,at 24 h ,48 h ,72 h. the sensitivity and specificity of uNGAL and Scr for diagnosis for AKI were evalua‐ted by ROC curve. Results The incidence of severe traumatic brain injury AKI was 42. 16% (43/102). The uNGAL levels in the AKI group were higher when the patient stayed in the ICU longer and no obvious in the non AKI group. When admitted to the ICU 24 h ,the level of uNGAL(720. 32 ± 684. 25)ng/mL in AKI group was significantly higher than that (421. 92 ± 351. 20)ng/mL in non AKI group. The difference was statistically significant (P< 0. 05). The levels of Scr between two groups were not statistically significant. The area under ROC curve of uNGAL and Scr were 0. 879 (95% CI :0. 807 - 0. 949) and 0. 612 (95% CI :0. 493 -0. 731). When the cutoff value of uNGAL was 180 ng/mL ,the sensitivity and specificity were 0. 890 and 0. 823 respectively. The sensitivity was superior to Scr. Conclusion uNGALis superior to Scr for early diagnosis of AKI in patients with severe traumatic brain injury and it could be used as a biomarker for early diagnosis of AKI.

Objective To investigate the effects of salvianolate lyophilized injection(SLI) on neural functional recovery and the expression of microtubule associated protein-2(MAP2) after focal cerebral ischemia-reperfusion injury in the diabetic rats.Methods Diabetes model was made by intraperitoneal injection of streptozotocin (STZ) and cerebral ischemia-reperfusion model was developed by Longa suture occluded method in the middle cerebral artery of diabetic rats.The rats were randomly divided into five groups: sham operation group, model group, SLI (21.0 mg.kg-1,10.5 mg.kg-1) treatment groups, and edaravone (6 mg.kg-1) treatment group.3 hours after ischemia,rats were respectively given normal saline or drugs followed by the injection once a day for 14 days and the neurological impairment was assessed.2 h after the last injection,the rats were decapitated and the brains were collected.The expression of MAP2 protein and mRNA in the bilateral hippocampal ischemia and infarcted area was detected with immunohistochemistry and RT-PCR.Results Severe neurological dysfunction was found in diabetic rats that had been subjected to cerebral ischemic injury (1.850±0.457).A significant improvement on neurological function was found in the SLI treatment groups (1.581 ± 0.314, 1.345 ± 0.425) compared with model group(P＜0.01, P＜0.05).Moreover,the expression of MAP2 in ischemia bilateral hippocampal CA1 and penumbra was represented by the average optical density value respectively (0.743±0.250,0.561± 0.224).In the hippocampal CA1 region, the number of MAP2-positive cells (0.781 ± 0.420 , 0.851 ± 0.136) in the treatment group showed significant increase than those in model group (P＜0.01, P＜0.05).In the ischemic penumbra region,the number of MAP2-positive cells (0.753±0.235,1.203±0.326) in the treatment group showed significant increase than those in model group (P＜0.01, P＜0.05).Conclusion The SLI can promote the post-injury neurocognitive function in diabetic rats.The increase of MAP2 expression may be involved in the mechanisms.

Objective:To explore the possible mechanism of astragaloside involved in the mouse podocytes injury induced by TGF-β1 in vitro.Methods:Mouse podocytes were cultured in vitro and then all cell were divided into 5 groups:normal control group , TGF-β1 treatment group ,TGF-β1 treatment +astragaloside low dose group ,TGF-β1 treatment +astragaloside middle dose group and TGF-β1 treatment +astragaloside high dose group.The proliferation rate of each group was investigated by MTT assay ,the expression of TRPC6 protein and mRNA were measured by Western blot and RT-PCR respectively after 48 hours.Results:TGF-β1 can significantly inhibit the proliferation of podocytes ( P<0.05) ,fusions of foot processes or even effaced of podocytes were observed .TGF-β1 could also increase the expression of TRPC6.Astragaloside could reduce the inhibition of TGF-β1 to the proliferain of podocytes significantly ,make the cell shape tend to be normal,and reduce the expression of TRPC6 mRNA and protein with dose-effect relation.Conclusion:TRPC6 play an impor-tant role in the TGF-β1 induecd podocytes injury .Astragaloside can alleviate podocytes injury by reduce the expression of TRPC 6.

In order to evaluate the response to vector-expressed M1 and HA genes of influenza virus in mice, we prepared recombinant plasmid pStar-M1/HA and recombinant adenovirus Ad-M1/HA containing both the full-length matrix protein 1(M1) and hemagglutinin (HA) genes of human H5N1 influenza virus strain A/Anhui/1/2005. We then combined the DNA vaccine and adenoviral vaccine in immunization of BALB/c mice with a prime-boost regime. We immunized the mice with DNA vaccine at day 0 and 28 and with recombinant adenoviral vaccines at day 14 and 42. We took blood samples before each injection and 14 days after the final injection for detection of humoral immune responses. At day 56, we sacrificed the mice and collected splenocytes for detection of cellular immune responses. ELISA and hemagglutination inhibition (HI) assay showed that specific IgG Abs against H5N1 influenza virus was induced in serum of the immunized mice. ELISPOT results confirmed that the specific cellular immune responses were successfully induced against the M1 and HA proteins of H5N1 influenza virus. This study provides new strategy for development of novel influenza vaccines.
Adenoviridae ; genetics ; metabolism ; Animals ; Antibodies, Viral ; blood ; Hemagglutinin Glycoproteins, Influenza Virus ; genetics ; immunology ; Immunization ; Influenza A Virus, H5N1 Subtype ; immunology ; Influenza Vaccines ; immunology ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; genetics ; immunology ; Vaccines, DNA ; immunology ; Viral Matrix Proteins ; genetics ; immunology

BACKGROUND:In the initial stage of multiple sclerosis,central immune cells activate and release a large number of inflammatory factors,causing white matter demyelination and even involving gray matter neurons.The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis.The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice,and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE:To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS:Female C57BL/6 mice were divided into the normal control group,experimental autoimmune encephalomyelitis disease model group,and astragaloside IV treatment group(n=8 per group).Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups.On day 10 to 28 after immunization,the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically.Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day.On the 28th day after immunization,the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord.Percentage of splenic T cell subsets was detected using flow cytometry.Western blot assay was used to determine the protein expression of interferon-γ,interleukin-17 and interleukin-6 in the spinal cord.Levels of interferon-γ,interleukin-17,interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION:(1)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice(P<0.05),ameliorate clinical symptoms(P<0.05),inhibit the infiltration of inflammatory cells and alleviate myelin loss(P<0.01,P<0.05).(2)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could inhibit the proportion of CD4+T cell subsets expressing interferon-γ(P<0.001)and interleukin-17(P<0.001),but increase percentages of CD4+ interleukin-10+(P<0.001)and CD4+ transforming growth factor-β+(P<0.01)T cell subsets.(3)Astragaloside IV could inhibit the expression of interferon-γ(P<0.05,P<0.01),interleukin-17(P<0.05,P<0.05),and interleukin-6(P<0.05,P<0.05)in the spinal cord and spleen,and up-regulate the expression of interleukin-4(P<0.01)in spleen.(4)These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice,which may be related to regulating the splenic T cell subsets,therefore,inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination.

AIM:To investigate the influencing factors of abnormal telangiectasia secondary to diabetic retinopathy(DR).METHODS: Prospective studies. A total of 153 cases(240 eyes)with DR treated in our hospital from January 2021 to January 2023 were selected to analyze the risk factors of abnormal telangiectasia secondary to DR and its predictive efficacy.RESULTS: The patients were divided into dilated group(77 eyes of 40 cases)and non-dilated group(163 eyes of 113 cases)according to whether they had secondary abnormal telangiectasia. There were significant differences in diabetic macular edema, hard exudates grade and fasting blood glucose level between the two groups(P<0.05). Logistic regression analysis showed that diabetic macular edema, high hard exudates grade and high blood glucose level were the risk factors for abnormal telangiectasia secondary to DR(P<0.05).CONCLUSION: The occurrence of telangiectasia secondary to DR may be related to diabetic macular edema, grade 3 hard exudates and high blood glucose level.

Objective:To examine the effects of Zishenwan Prescription on bile acid metabolism in mice with diabetic encephalopathy; To explore its mechanism of improvement of diabetic encephalopathy.Methods:Male C57BL/6J mice were used to replicate the mouse model of type 2 diabetes mellitus by using high-fat chow and a single intraperitoneal injection of streptozotocin (120 mg/kg). The mice were screened for diabetic encephalopathy by using the Morris water maze test after 8 weeks of continuous stimulation with hyperglycemia, and were divided into model group and Zishenwan Prescription group according to random number table method, with 12 mice in each group. The mice in the Zishenwan Prescription group were treated with the crude extract of Zishenwan Prescription (9.36 g/kg) by gavage, and the normal group and the model group were treated with the same volume of distilled water once a day for 8 weeks. At the end of the treatment, Morris water maze test was used to investigate the cognitive function of diabetic encephalopathy mice; cresyl violet staining was used to detect the number of granule neurons in the hippocampus; serum and feces were collected to detect the content of bile acids by liquid-liquid coupling; hepatic bile acid synthase CYP7a1 and CYP27a1, farnesol X receptor (FXR), fibroblast growth factor 15 (FGF15), fibroblast growth factor receptor 4 (FGFR4), and ileocecal apical sodium-dependent bile acid transporter protein (ABST) mRNA levels were detected by using fluorescence quantitative PCR assay.Results:Compared with the model group, mice in the Zishenwan Prescription group had shorter evasion latency time ( P<0.05 or P<0.01), decreased time to first reach the platform ( P<0.01), increased number of times to traverse the platform ( P<0.01), and reduced neuronal cell damage in hippocampal area; mice in the Zishenwan Prescription group showed decreased serum and fecal total bile acid content ( P<0.05 or P<0.01); the liver CYP7a1 and CYP27a1 mRNA expressions increased ( P<0.01), and FXR and FGF15 mRNA expressions decreased ( P<0.01); ileal ABST mRNA expression decreased ( P<0.01). Conclusion:Zishenwan Prescription may regulate bile acid metabolism, inhibit FRX-FGF15/FGFR4 signaling and ABST expression to promote new bile acid synthesis and conjugated bile acid reabsorption, and thus improve cognitive function in diabetic encephalopathy mice.

Objective:To observe the imaging features of optical coherence tomography (OCT) in peripheral retinal abnormalities of high myopia (HM).Methods:A retrospective series of case studies were conducted. From March 2019 to March 2021, 38 cases (50 eyes) in high myopia with peripheral retinal abnormalities who were confirmed to Henan Eye Hospital were enrolled in the study. There were 21 eyes in 17 males and 29 eyes in 21 females, age was 39.58±15.29 years, diopter was (-9.10±2.44) D. All patients underwent wide-angle fundus photography and OCT examination. According to wide-angle fundus photography and OCT, HM with peripheral retinal abnormalities were classified into white-without-pressure, black-without-pressure, lattice degeneration, peripheral pigmented degeneration, retinoschisis and retinal holes. OCT imaging features of peripheral abnormalities in high myopia was observed.Results:In 50 eyes, 65 peripheral retinal abnormalities were observed by OCT. In 6 white-without-pressure, intense hyperreflectivity was shown at the level of the ellipsoid zone that abruptly transitions to relative hyporeflectivity at the dark border of the lesion. In 16 black-without-pressure, reflectivity of the ellipsoid zone decreased. In 10 sites of lattice degeneration, cystoid degeneration, local thinning, retinal tear at the posterior edge and boundary of the lesion was shown, whcih may be accompanied by local vitreous condensation and traction. In 4 peripheral pigmented degeneration, retinal interlayer hyperreflectivity was shown. In 12 retinoschisis, neuroepith-elial separation was connected by vertical bridge or columnar light bands, of which 3 were accompanied with localized retinal detachment and 2 with splitting-related retinal vascular abnormalities. In 17 retinal holes, full layer of neuroepithelium lost, that 12 zones were accompanied with retinal detachment with vitreous adhesion or traction.Conclusion:OCT manifestations of peripheral retinal abnormalities in HM varies.

Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.