OBJECTIVE To explore the effects of prescription pre-review system on rational drug use and off-label drug use management in outpatient and emergency department. METHODS A retrospective analysis was conducted on outpatient and emergency department prescription data from three phases in our hospital： January to May 2023 （silent review phase， control group）， June to October 2023 （systematic automatic review phase， intervention group 1）， and November 2023 to March 2024 （phase combining systematic automatic review with centralized feedback from pharmacists to physicians regarding irrational prescriptions， intervention group 2）. These phases followed the implementation of our hospital’s pre-prescription review software. Statistical analysis of the prompt rate of alert， rate of irrational prescriptions， registered the off-label drug use rate and false positive irrationality prescription rate were conducted. Meanwhile， the composition of irrational prescriptions was analyzed， and evidence- based evaluation of the off-label drug use proposed by clinicians was also conducted. RESULTS Compared with control group， the prompt rate of alert and the rate of irrational prescriptions in intervention group 1 were all decreased significantly after receiving pop-up notification， with statistically significant differences （P＜0.05）. With the help of system warning and the pharmacists feedback， the prompt rate of alert and the rate of irrational prescriptions declined further in the intervention group 2， but there was no statistically significant difference when compared with intervention group 1 （P＞0.05）. The main type of irrational drug use was improper administration routes. When comparing intervention group 1 with the control group， as well as intervention group 2 with intervention group 1， a significant decrease in the rate of improper administration routes was observed， with statistically significant differences （P＜0.05）. Compared with control group， there was no significant difference in the registered off-label drug use rate of intervention group 1 and intervention group 2 （P＞0.05）. The doctor’s awareness of off-label drug use registration increased due to the real-time alerts from the pre-prescription review software， along with the pharmacists’ regular summarization and feedback. Total 13 items registrations of off-label drug use were proposed by clinicians from June 2023 to March 2024， all of which were supported by evidence of varying levels； among them， 3 items received FDA approval， 4 items were included in the Micromedex database， and the remaining 6 items were supported by evidence from system reviews or randomized controlled trials. CONCLUSIONS Prescription pre-review system can improve the level of rational drug use and assist in the standardized management of off-label drug use.

OBJECTIVE To investigate the effects of echinacoside （ECH） on renal injury in uremia （URE） rats and its mechanism. METHODS URE model of the rat was established by 5/6 nephrectomy. Successfully modeled rats were grouped into uremia group （URE group）， ECH low-dose [10 mg/（kg·d）] group， ECH medium-dose [20 mg/（kg·d）] group， ECH high-dose [40 mg/（kg·d）] group， ECH high-dose+anisomycin [p38 mitogen-activated protein kinase （p38 MAPK） pathway activator] group [ECH-H+Ani group， 40 mg/（kg·d） ECH +2 mg/（kg·d） anisomycin]， with a sham operation group， 12 mice in each group. Each drug group was given corresponding ECH intragastrically， while ECH-H+Ani group was further injected with anisomycin via the tail vein， once a day， for 8 consecutive weeks. The serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， blood urea nitrogen （BUN）， β2-microglobulin （β2-MG）， serum creatinine （Scr）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， cystatin C （Cys-C） and 24 h urine protein （24 h UP） as well as the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） activity in renal tissue were all detected； pathological changes of renal tissue were observed； the rate of positive expression of α-smooth muscle protein （α-SMA） and E-cadherin， and the phosphorylation of p38 MAPK and nuclear factor-κB （NF-κB） p65 were determined in renal tissue of rats. RESULTS Compared with URE group， glomerular swelling， damage and necrosis of renal tubular epithelial cells and inflammatory cell infiltration were relieved significantly in ECH groups. The renal injury score， levels of TNF-α， IL-1β， IL-6， BUN， Scr， β2-MG， 24 h UP， NGAL， KIM- 1， Cys-C and MDA， the positive expression rate of α-SMA in renal tissue， the phosphorylation of p38 MAPK and NF-κB p65 were decreased in dose-dependent manner， while SOD activity and the positive expression rate of E-cadherin were obviously increased in dose-dependent manner （P＜0.05）. Anisomycin significantly attenuated the improvement effect of high-dose ECH on renal injury in URE rats （P＜0.05）. CONCLUSIONS ECH may inhibit inflammation and oxidative stress， enhance renal function， and improve renal injury in uremic rats by inhibiting the activation of p38 MAPK/NF-κB signaling pathway.

mRNA vaccines and drugs enter host cells through delivery vectors and produce target proteins using the protein synthesis mechanism of cells. mRNA and target proteins can induce the body to produce innate immunity and adaptive immunity, and the target protein itself can also play a corresponding role. Tumor cells are inhibited and cleared under the above immune effects and target proteins. This article reviews the immunogenicity of mRNA, that is, the specific mechanism of stimulating the body to produce an immune response.At the same time, the main types of cells transfected by mRNA vaccine were briefly introduced. (1) Muscle cells, epidermal cells, dendritic cells and macrophages at the injection site; (2) immune cells in peripheral lymphoid organs;(3) liver cells and spleen cells, etc. Although transfected with a variety of cells, it is mainly enriched in immune cells and liver cells because immune cells express toll-like receptors and liver cells express low-density lipoprotein receptors. mRNA vaccines and drugs are mainly divided into non-replicating mRNA (nrmRNA),self-amplifying RNA (saRNA), trans-amplifying RNA (taRNA) and circular RNA (circRNA).This article reviews how these 4 types of vaccines and drugs work, and compares their advantages and disadvantages. Due to its inherent immunogenicity, instability, and low delivery efficiency in vivo, mRNA vaccines and drugs have been unable to enter the clinic. This article describes in detail how to reformation and modify the 5'cap, 5'UTR, 3'UTR, ORF, 3'Poly(A) and some nucleotides of mRNA to eliminate its immunogenicity and instability. Due to the low efficiency of the delivery carrier, the researchers optimized it. This article briefly introduces the application of non-viral vectors and their targeting, specifically involving the mechanism of action of various types of delivery vectors and their advantages and disadvantages, and summarizes some of the current targeting vectors. Targeted carriers can improve the delivery efficiency of mRNA to specific tissues and prevent side effects of systemic exposure, such as liver injury. The specific methods of using mRNA vaccines and drugs to treat cancer are as follows: mRNA can be used to encode and transcribe tumor-associated antigens, tumor-specific antigens (TSAs), therapeutic antibodies, cytokines, tumor suppressors, oncolytic viruses, CRISPR-Cas9, CARs and TCRs, so as to play an anti-tumor role. In this paper, the specific mechanism of the above methods and the current research and development of corresponding mRNA vaccines and drugs are briefly reviewed. The successful development of the COVID-19 mRNA vaccine has brought mRNA technology to the attention of the world and brought new and effective means for the prevention and treatment of cancer. mRNA vaccines and drugs have the advantages of short development cycle, dual immune mechanism, safety, high efficiency and large-scale production. At the same time, there are also many areas that need further improvement, such as the development of ideal target TSAs, the in-depth development of saRNA, taRNA and circRNA, the development of targeted nano-delivery for different tissues and organs, the expansion of mRNA administration routes, and the development of mRNA that can be stably stored at room temperature or even high temperature. These problems need to be further studied and solved. In addition to cancer therapy, mRNA vaccines and drugs can also be used in the treatment of infectious diseases, genetic diseases, regenerative medicine and anti-aging. mRNA vaccines and drugs are a very promising platform, and we believe that they will benefit cancer patients in the near future.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial A. senticosus samples based on atpI and atpB_rbcL according to the previous chloroplast genome sequencing results, and determinated the content of syringin by HPLC to evaluated the quality of commercial samples. A total of 80 A. senticosus samples were collected from 47 cities in 24 provinces. DNA was extracted to amplify the products of atpI and atpB_rbcL by PCR. The results showed that 7 haplotypes (H2, H5, H8, H10, H12, H14, H23) were formed by the combined analysis of the two gene fragments. H2 from Yichun in Heilongjiang, Shangzhi in Harbin, Suihua in Heilongjiang, Fushun in Liaoning, Benxi in Liaoning, Changbai in Jilin and Jingyu in Jilin were the dominant genotype, representing 58.75% of the total samples. H14 and H23 were the unique haplotypes of the producing area. It is speculated that the commercial A. senticosus samples with haplotypes of H14 and H23 are from Raohe, Shuangyashan, Heilongjiang and Mingshui, Suihua, Heilongjiang, respectively. HPLC analysis indicated that the content of syringin in 73.96% of the samples met the Pharmacopoeia standards. There was a significant difference in the content of syringin among the samples, ranging from 0.003 7% to 0.524 5%, with a difference of 0.520 8%, indicating that the quality of the samples in the market of A. senticosus was uneven. However, there were no significant differences in the contents of syringin in the commercial A. senticosus among different haplotypes. The content of syringin in the haplotype H23 in the market sample is relatively high, so it may be a germplasm with better quality. This study researched the germplasm resources and medicinal materials quality of commercial A. senticosus samples and will help guide the commercial circulation, reasonable medication of A. senticosus, and the screening of excellent germplasm.

OBJECTIVE To investigate the effect of pachymic acid （PA） on renal function and fibrosis in chronic renal failure （CRF） rats and its potential mechanism based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. METHODS Using male SD rats as subjects， the CRF model was established by 5/6 nephrectomy； the successfully modeled rats were divided into model group， PA low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg PA）， high-dose PA+ROCK pathway activator lysophosphatidic acid （LPA） group （20 mg/kg PA+1 mg/kg LPA）， with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein， once a day， for 12 consecutive weeks. During the experiment， the general condition of rats was observed in each group. After the last administration， the serum renal function indexes （blood urea nitrogen， serum creatinine， uric acid） of rats in each group were detected， the renal histopathological changes were observed； the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] and inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6）， the positive expression rates of connective tissue growth factor （CTGF） and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins （RhoA， ROCK1） and fibrosis- related proteins （transforming growth factor-β1， bare corneum homologs 2， α-smooth muscle actin） were determined. RESULTS Compared with the sham operation group， the rats in model group had reduced diet， smaller body size， listless spirit and sluggish response， reduced and atrophied glomeruli， dilated renal tubules with chaotic structure， and a large number of inflammatory cells infiltrated interstitium； the serum levels of renal function indexes， renal tubule injury score， renal fibrosis area proportion， the levels of MDA and inflammatory factors， the positive expression rates of CTGF and collagen Ⅰ， and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased， while SOD level was significantly decreased （P＜0.05）. Compared with the model group， the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees，and the above quantitative indexes were significantly improved in a dose-dependent manner （P＜0.05）. LPA could significantly reverse the improvement effect of PA on the above indicators （P＜0.05）. CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats， which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.

OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide （APS） on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis （PD）. METHODS Rats were randomly divided into normal control group （Control group）， model group （PD group）， 70 mg/kg APS group （APS-L group）， 140 mg/kg APS group （APS-H group）， and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α （HIF-1α） agonist DMOG group （APS-H+DMOG group）， with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， the peritoneal ultrafiltration （UF）， mass transfer of glucose （MTG）， the levels of serum creatinine （Scr） and blood urea nitrogen （BUN） were detected in rats； peritoneal histomorphology and peritoneal fibrosis （peritoneal thickness and proportion of collagen fiber deposition） were observed； the microvascular density and the expression levels of α-smooth muscle actin （α-SMA）， laminin （LN）， HIF-1α and vascular endothelial growth factor （VEGF） proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group， the mesothelium of rats in the PD group was loosely arranged and shed， inflammatory cells infiltrated， the peritoneal thickness and proportion of collagen fiber deposition were increased significantly （P＜0.05）. The levels of MTG， Scr and BUN in serum， microvascular density and the expressions of α-SMA， LN， HIF-1α and VEGF proteins were significantly increased， while the level of UF was significantly decreased （P＜ 0.05）； compared with PD group， the levels of above indexes were significantly reversed in APS-L and APS-H groups （P＜0.05）， and the improvement of APS-H group was better than APS-L group （P＜0.05）. Compared with APS-H group， the levels of above indexes in APS-H+DMOG group were all reversed （P＜0.05）. CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective lo investigate the protective effect of dihydromyricetin(DHM)against exercise-induced muscle damage(EIMD)in mice and its potential mechanism. Methods Adult male C57BL/6J mice were randomly divided into control group(CG),exercise group(EG),and exercise+100 mg/kg weightd DHM(DHM)group.The intervention lasted for four weeks,during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day.The day after the training,a 90-min treadmill exercise(slope:0 and speed:18 m/min)was conducted in both EG and DHM groups.Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise,followed by the measurement of serum creatine kinase(CK)and lactate dehydrogenase(LDH)activities,total superoxide dismutase(T-SOD)activity,malondialdehyde(MDA),and skeletal muscle mitochondrial enzyme complex Ⅰ and Ⅱ activities.Histological changes in the skeletal muscle were observed by transmission electron microscopy,and the protein expressions of mitochondrial function-related pathways were detected by Western blotting. Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG.The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention.Western blotting demonstrated that the expressions of sirtuin type 3(SIRT3),estrogen-related receptor alpha,and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention. Conclusion DHM can relieve EIMD in mice,possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

Objective To investigate the effect of vascular endothelial growth factor(VEGF)on the expression of genes related to ovarian steroid synthesis in mice and its underlying mechanism.Methods A transgenic mouse model with tetracycline-reversible regulation of VEGF expression was used,and the genotype of mice was identified by polymerase chain reaction(PCR).Twenty mice were divided into normal VEGF expression group(Dox+,n=10)and VEGF expression inhibition group(Dox-,n=10)by feeding them doxycycline.Western blotting was used to detect the expression of VEGF protein in ovarian tissues.Fluorescence quantitative PCR was used to detect the mRNA expression of VEGF,KDR and genes known to play roles in follicle development,such as follicle-stimulating hormone(FSH)and inhibin B(INHBB).HE staining was used to observe changes in ovarian tissue.Total RNA was extracted from mouse ovarian tissues for transcriptome sequencing,and the relevant differential genes were analyzed by FPKM and log2FC values.Results Compared with the Dox+group,the mRNA and protein levels of VEGF in the Dox-group significantly reduced,and the mRNA levels of KDR also significantly decreased(P<0.05).HE staining results showed that compared with the Dox+group,follicular development was impaired and atresia follicles appeared in the Dox-group.Sequencing analysis identified that significant differences in follicular development-related genes and steroid synthesis-related genes between the two groups(P<0.05).Enrichment analysis showed that VEGF in mouse ovaries mainly regulates ovarian steroidogenesis and other pathways.Fluorescence quantitative PCR results demonstrated that compared with the Dox+group,the follicular development-related genes(INHBB and FSHR)in the ovarian tissues of the Dox-group were significantly up-regulated(P<0.05),whereas the key genes of steroid synthesis(StAR,CYP11A1,3β-HSD)were significantly down-regulated(P<0.05).The quantitative results were basically consistent with the sequencing results.Conclusion Mice with inhibited VEGF exhibited ovarian follicular dysplasia,potentially due to the mechanism whereby VEGF inhibition downregulated the expression of genes associated with steroid synthesis,such as FSH and INHBB,thereby obstructing cholesterol metabolism.