ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

OBJECTIVE: To identify the protective effect of empagliflozin on ischemic brain injury and neurological dysfunction in mice, and further explore its potential mechanism. METHODS: Acute cerebral ischemia model was induced by the permanent middle cerebral artery occlusion surgery in C57BL/6J mice. Empagliflozin(10 and 30 mg·kg−1) was administered to mice one hour after the onset of occlusion. Brain infarct volume and neurological defect score were assayed 24 h after surgery. Mice were subjected to photo-thrombosis and further administered with empagliflozin 3, 10, 30 mg·kg−1 intragastricly for either 7 or 14 consecutive days. The grid-walking task and the cylinder task were performed daily to determine the sensory-motor function of the mice. Alternatively, the mice were treated with 10 mg·kg−1 empagliflozin simultaneously with 10% glucose(i.p.) for 7 consecutive days after the photo-thrombosis model to evaluate their motor sensory function. Immunofluorescence staining was used to detect the activation of microglia within the infarct area 7 d after the photo-thrombosis. RESULTS: One hour after permanent middle cerebral artery occlusion surgery, gavage of empagliflozin significantly increased the brain infarct volume and neurological dysfunction. While in photo-thrombosis surgery, treatment of empagliflozin(10 mg·kg−1) for consecutive 7 or 14 days significantly decreased the rate of false foot in grid-walking task and the assymetric index in cylinder task. At the dose of 30 mg·kg−1, however, empagliflozin even aggravated photo-thrombosis-induced neurological dysfunction, while the dose of 3 mg·kg−1 showed no effect. Unexpectedly, the protective effect of empagliflozin(10 mg·kg−1) could not be reversed by glucose treatment. The results of immunofluorescence showed that empagliflozin(10 mg·kg−1) significantly alleviated the microglia activation in the ischemic area after the photo-thrombosis operation. CONCLUSION Empagliflozin cannot protect against acute ischemia-induced brain injury in mice. Empagliflozin alleviated ischemia-induced neurological dysfunction with consecutive administration in a dose-related manner. Empagliflozin-conferred neuroprotection may not be attributable to its effects on lowing blood glucose. Alternatively, empagliflozin may play a neuroprotective effect by inhibiting the excessive activation of microglia in ischemic brains.

OBJECTIVE In the context of the era of innovation and entrepreneurship, the training model of pharmaceutical talents is facing challenges. In order to cultivate overall development of pharmaceutical innovative talents, an in-depth research is carried out from multiple perspectives such as education orientation, education mode and education team. METHODS The research systematically analyzed the concept, system, orientation, channels, plan and cooperation of pharmaceutical talent training to build a new cultivation mechanism which adapts to the national strategic adjustments and social situation changes. RESULTS The research summarized the ideas and formulated a model for cultivating innovative application-oriented pharmaceutical talents which was guided by ideological and political education, oriented towards real issues in the industrial, scientific, and clinical sectors. It emphasized multi-chain collaboration, integrating high-quality resources to promote the enhancement of original innovation capabilities. CONCLUSION The research not only provides experience for the training of pharmaceutical innovative talents in the College of Pharmaceutical Sciences of Zhejiang University, but also provides references for the training of pharmaceutical talents in other universities in China.

OBJECTIVE Nowadays, the development of pharmacy discipline has a new trend, which is reflected in the close connection with the national strategy, the integration of basic and applied research, the high degree of discipline intersection, the long achievement cycle, and the high career access, etc. The traditional model of pharmacy talent cultivation can no longer meet the needs of the development of pharmacy discipline and the creation of new drugs in the new era, therefore, it puts forward new paths of the cultivation of innovative talents in pharmacy. METHODS On the basis of analyzing the main problems existing in the process of cultivation of existing pharmacy talents, to describe the new trends and new paths of cultivation of top-notch innovative pharmacy talents in the new era. RESULTS Propose to start from the four aspects of the trinity of the guidance mechanism, the mechanism of the science education and human resources mechanism, the regularization of the joint mechanism, and the mechanism of the cultivation of talents. CONCLUSION It is proposed to build a talent cultivation model with a "Student-Scholar" orientation, to provide new ideas for the cultivation of future pharmacy talents in the new era.

Objective To observe the value of diffusion weighted imaging intravoxel incoherent motion(IVIM)for quantitative evaluating chronic allograft dysfunction(CAD).Methods Totally 104 CAD patients were prospectively enrolled and were assigned into CAD 1,2 and 3 groups(n=11,61,32)based on impairment severity of estimated renal function,and 36 healthy volunteers were enrolled as control group.The true diffusion coefficient(D value),microcirculation perfusion diffusion coefficient(D*value)and perfusion score(f value)of renal cortex and medulla IVIM parameters were compared among groups and within groups to assess the value of IVIM parameters for diagnosing CAD.Results The D value of transplanted renal cortex in all CAD groups were lower than that in control group(all P＜0.05),which decreased among CAD 1,2 and 3 groups(all P＜0.05).The D value of transplanted kidney medulla in CAD 2 and 3 groups were lower than that in control group(both P＜0.05).The D*values of transplanted renal cortex in all CAD groups were lower than that in control group,while of renal medulla in CAD 2 and 3 groups were lower than that in control group(both P＜0.05).The f values of cortex and medulla in CAD 2 and 3 groups were lower than those in control group(all P＜0.05),while of cortex in CAD 3 group was lower than that in CAD 1 and 2 groups(both P＜0.05).The area under the curve(AUC)of cortical IVIM combined model for diagnosing CAD was 0.96,better than the D*value and f value(AUC=0.74,0.83,P＜0.05)but not significantly different with that of the D value(AUC=0.94,P=0.32).AUC of medullary IVIM combined model for diagnosing CAD was 0.91,better than that of D,D*and f value(AUC=0.80,0.67 and 0.80,all P＜0.05).Conclusion IVIM parameters could be used to quantitatively evaluate CAD.

Aim To investigate the effect and mechanism of hydrogen molecule on myocardial injury in severe traumatic brain injury(TBI)rats.Methods Using the fluid percussion injury(FPI)-induced TBI model.72 SD rats were randomly divided into sham group,TBI group and hydrogen molecule-treated group,with 24 rats in each group,and the rats were executed at 48 h after the operation.HE staining was used to observe the myocardial injury and the in-filtration of granulocytes,ELISA was used to detect the level of superoxide dismutase(SOD),Western blot was used to de-tect the expression of inflammation-related factors myeloperoxidase(MPO)and heme oxygenase-1(HO-1)protein,RT-qPCR was used to detect the levels of cardiac troponin T(cTnT),inhibitory factor-1(IF-1),NADH/ubiquinone oxi-doreductase core subunit S7(NDUFS7),nicotinamide adenine dinucleotide phosphate(NADP)and reduced nicotinamide adenine dinucleotide phosphate(NADPH).The changes of post-traumatic echocardiography and the 7-day survival rate and body weight in the rats were observed and recorded.Results Compared with the sham group,rats in the TBI group had significantly higher troponin levels,and the echocardiographic results showed higher left ventricular end-diastolic diameter(LVEDD)and significantly lower left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),and the above pathologic changes were significantly improved after treatment with the hydrogen molecule.Myo-cardial tissue was disorganized with erythrocyte infiltration,and myocardial fibers were infiltrated with granulocytes in the section,which were improved in the hydrogen molecule-treated group.The body weight of the rats decreased dramatically after the operation,and about 5 days later dropped to the lowest level,and then showed a trend of slow recovery.mNSS scores showed that the neurological function of the rats was severely impaired after TBI,and the postoperative myocardial tissues showed an increase in the expression levels of MPO and HO-1 proteins and a decrease in the expression levels of SOD,and the above pathological changes were significantly improved by hydrogen molecule treatment.In the TBI group,the expression levels of NADPH,IF-1 and NDUFS7 were reduced,and the expression levels of the above indicators were significantly increased after hydrogen molecule treatment.Conclusion Hydrogen molecule may be able to increase mitochondrial energy metabolism in cardiomyocytes and reduce myocardial oxidative stress by synergistically enhancing the protein expression of IF-1 and NDUFS7 on the mitochondrial oxidative respiratory chain to increase cardiac function and survival rate in the acute phase of TBI.

The integrated management of multi-campus public hospitals is a mandate for national assessment and compul-sory requirement for high-quality advancement of public hospitals.A challenge in multi-campus hospital management is to accel-erate the standardization of various hospital campuses and facilitate the information sharing among them.Based on the manage-ment practices of multi-campus hospitals in Ningxia,this paper discussed the challenges encountered in the integrated manage-ment of multi-campus hospitals.It proposed strategies to enhance homogeneous management and inter-hospital coordination in multi-hospital and multi-campus hospital to provide valuable references.