DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

Objective:To explore the effects of acupuncture combined with Buyang Huanwu Decoction on intestinal flora in cerebral blood flow hypo perfusion model rats with carotid artery stenosis.Methods:Totally 40 rats were randomly divided into sham-operation group, model group, TCM treatment group and acupuncture and drug combination treatment group, with 10 rats in each group. Except the sham-operation group, the other groups were prepared cerebral ischemia model by needle control and thread embolism method. TCM treatment group received Buyang Huanwu Decoction 100 mg/kg for gavage, once a day, and the intervention lasted for 2 weeks. In the acupuncture and drug combination group, based on the TCM treatment group, Baihui and its left and right sides of 2 mm were selected for acupuncture, once a day, and continuous intervention was performed for 2 weeks. Neurological function evaluation and behavioral function score were performed 7 and 14 days after administration, respectively. 16S rRNA sequencing was used to comprehensively characterize the structure and composition of fecal microflora of rats in each group. Linear discriminant analysis Effect Size (LEfSe) was used to analyze the difference of intestinal bacteria among groups.Result:On the 7th and 14th day after administration, compared with the model group, the neurological function score in the TCM treatment group and the acupuncture and drug combination group decreased ( P<0.05), and the behavioral function score increased ( P<0.05). Compared with model group, the Shannon index of TCM treatment group and acupuncture and drug combination group increased ( P<0.05). The abundance of Firmicutes increased ( P<0.05), and the abundance of Bacteroidetes and Proteobacteria decreased ( P<0.05); the abundance of Clostridia increased ( P<0.05), and the abundance of Gammaproteobacteria decreased ( P<0.05). The abundance of Escherichia-Shigella and Bacteroides decreased ( P<0.05); the abundance of lactobacillus significantly increased ( P<0.05). Conclusion:Acupuncture combined with Buyang Huanwu Decoction can improve the symptoms of cerebral hypoperfusion model rats with carotid artery stenosis, and the mechanism may be to increase the abundance of probiotics.

Objective To establish an evaluation index system that can be used for medical quality assessment in clini-cal departments.Methods Based on literature analysis and key informant interview,the Delphi method was used to analyze the-importance and operability of the evaluation index system of medical quality in clinical departments.Results A clinical depart-ment medical quality assessment and evaluation system was established,consisting of 3 primary indicators,14 secondary indica-tors,and 24 tertiary indicators.Conclusion By building a medical quality assessment and evaluation index system in clinical departments,a simple,standardized,and highly operational management model is established for medical institutions to carry out medical quality management.It is conducive to directing clinical departments to focus on medical quality management,improving their medical quality awareness and management level,and promoting the high-quality development of public hospitals.

OBJECTIVE To provide reference for strengthening the standardized management of off-label drug use in cancer hospitals. METHODS The evaluation system for off-label drug use was established to standardize the application， approval， and filing process for off-label drug use in our hospital. The changes in off-label drug application quantity， proportion， disease category and drug category in our hospital were compared before （October 1st， 2021-September 30th， 2022） and after （October 1st， 2022- September 30th， 2023） the establishment of the evaluation system； drug items supported by high-level evidence screened by pharmacy department were analyzed statistically. RESULTS The number of off-label drug use applications in our hospital had gradually increased， from 306 pieces in the fourth quarter of 2021 to 3 828 pieces in the third quarter of 2023. In the year before the construction of the evaluation system， there were a total of 4 482 applications for off-label drug use， and in the year after the construction of the evaluation system， there were 11 840 applications for off-label drug use. After the construction of the evaluation system， the proportion of unregistered off-label drug use significantly decreased， compared to the same period last year （P＜0.05）. Among them， there were no unregistered applications for off-label drug use for digestive system tumors， head and neck tumors， and radioactive drugs； lymphoma， breast tumors，urogenital system tumors， cytotoxic drugs and new anti-tumor drugs all had a decrease of over 70% in unregistered off-label drug applications. Twenty-seven off-label drug use items related to 19 drugs supported by high-level evidence were screened by the pharmacy department of our hospital， among which 25 items were drug use beyond indication. CONCLUSIONS The establishment of off-label drug use evaluation system in cancer hospital is helpful to the rational use and refined management of clinical anti-tumor drugs.

Three novel,highly oxygenated polyketides,multioketides A-C(1-3),and three previously described multioxidized aromatic polyketides(4-6),were isolated from an endophytic Penicillium sp.YUD17006 associated with Gastrodia elata.Their chem-ical structures were elucidated using extensive spectroscopic data,electronic circular dichroism calculations,and single X-ray diffrac-tion analysis.All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation.Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core.Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities.Plausible biosynthetic pathways for 1-6 were proposed.Additionally,compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyr-osine phosphatase 1B.

Objective To explore the expression of serine proteinase inhibitor family E member 1(SERPINE1)in colon cancer and its effect on the malignant biological behaviors of colon cancer cells.Methods starBase and TISIDB databases were used to analyze the expression of SERPINE1 in 471 patients with colon cancer and 41 paracancerous tissues,and the relationships of its differential expression with clinical stage and prognostic survival were analyzed.The cancer specimens and paracancerous tissues from 5 patients with colon cancer were collected in No.940 Hospital of Joint Logistic Support Force,and RT-qPCR and Western blotting were employed to detect the expression of SERPINE1 at mRNA and protein levels.After lentiviral vectors of SERPINE1 overexpression and interference were constructed and transfected into colon cancer RKO and LoVo cells.The experimental cells were assessed by RT-qPCR and Western blotting to verify the efficiency of overexpression and interference.Then cell proliferation,migration,invasion and apoptosis were evaluated by CCK-8 assay,clone formation test,Transwell test and Hoechst apoptotic nuclear staining,respectviely.Finally,Western blotting was applied to determine the effect of SERPINE1 on phosphatidyl-inositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.Results Database analysis showed that SERPINE1 was highly expressed,positively correlated with the clinical stage and negatively correlated with the overall survival in colon cancer patients(P＜0.05).Transfection of overexpression lentiviral vector resulted in enhanced cell proliferation,invasion and migration abilities while weakened apoptosis in RKO and LoVo cells.On the contrary,SERPINE1 interference reduced the abilities of cell proliferation,invasion and migration but improved cell apoptosis(P＜0.05).Western blotting showed that overexpression of SERPINE1 had no effect on the expression of PI3K and AKT,but increased the expression of p-PI3K and p-AKT,and SERPINE1 interference also had no change in PI3K and AKT expression and reduced the levels of their phosphorylation levels.Statistical differences were observed in relative quantitative analysis on the ratios of p-PI3K/PI3K and p-AKT/AKT(P＜0.05).Conclusion SERPINE1 is highly expressed,and correlated with clinical stage and prognosis of patients with colon cancer.Its overexpression promotes the proliferation,migration,invasion and inhibits apoptosis of colon cancer RKO and LoVo cells through PI3K/AKT signaling pathway.

Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.

Objective To explore the diagnostic value of Young's modulus obtained by real-time shear wave elastography (SWE) for liver fibrosis in autoimmune hepatitis (AIH) patients. Methods A total of 75 AIH patients in the First Affiliated Hospital of Zhengzhou University from January 2013 to April 2022 were retrospectively enrolled. Scheuer scoring system was used to evaluate degrees of liver fibrosis (S0-S4). By using pathological examination of liver tissues as the golden standard, the receiver operating characteristic curve (ROC) was plotted and the area under the curve (AUC) was used to evaluate the diagnostic value of SWE for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3), and liver cirrhosis (S4), respectively. Independent sample t test was used for comparison of continuous data with normal distribution between the two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and Bonferroni method was used for further comparison between two groups. The Spearman correlation coefficient was used for correlation analysis. The logistic regression analysis was used to predict the impact factors in diagnosis accuracy. Results The Young's modulus measured by SWE was statistically significant different among various fibrosis groups ( H =35.186, P < 0.001) although there was no statistical significance in patients' age and platelet, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, and glutamyl transpeptidase levels (all P > 0.05). The Young's modulus measurement was positively correlated with liver fibrosis ( r =0.675, P < 0.05). The AUCs of SWE in the diagnosis of≥S2, ≥S3, and S4 were 0.839, 0.820 and 0.898, respectively and the corresponding optimum cut-off values were 9.2, 10.9, and 14.4 kPa, respectively. The overall concordance rate of the liver Young' s modulus measurements vs . fibrosis stages was 57.33%. Moreover, the alkaline phosphatase level was an independent predictor for diagnostic accuracy of SWE for stage 0-1 fibrosis ( OR =1.009, 95% CI : 1.001-1.018, P =0.029). Conclusion The SWE possessed a diagnosis value for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3) and liver cirrhosis (S4), although there was a low overall concordance rate in the liver Young's modulus measurements obtained using SWE vs. fibrosis stages.

Objective To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits. Methods The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study. Results Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.