Objective To explore the effect of salidroside(Sal)on endoplasmic reticulum stress and connexin 43 in rats with myocardial ischemia-reperfusion injury(MIRI).Methods SD rats were randomly divided into Sham group,MIRI group,low-does Sal(Sal-L)group and high-does Sal(Sal-H)group.The Sham group and MIRI group were intraperitoneal injec-ted with 0.9％sodium chloride solution(10 mL·kg-1·d-1),the Sal-L group and Sal-H group were intraperitoneal injected at a volume of 10 mL·kg-1 with Sal(12,36 mg·kg-1·d-1),respectively.Each group was given a corresponding intervention once a day for 3 d.The MIRI model was established 30 min after the last administration in all groups except the Sham group.The patho-logical changes of myocardial tissue were observed by Hematoxylin-eosin(HE)staining.TdT-mediated-dUTP nick end labeling(TUNEL)was used to observe the apoptosis of cardiomyocyte,the genes and proteins expression of Cx43 and endoplasmic reticu-lum stress related factors such as GRP78,Caspasel2,CHOP and so on were detected by quantitative real-time polymerase chain reaction(q-PCR)and western blot analysis.Results Compared with the MIRI group,the degree of tissue and cell injury in each Sal group was alleviated,with a decreased apoptosis rate observed in the Sal-H group(P＜0.05),the gene expression of Cx43 was up-regulated while GRP78,Caspase12,and CHOP gene expressions were down-regulated in both does groups of Sal.The protein expressions of Cx43 and GRP78 were also be up-regulated and down-regulated respectively in both dose groups of Sal,meanwhile the protein expressions of CHOP,Bax,Caspasel2 and cleaved-Caspase3 were down-regulated and the protein expres-sion of Bcl-2 was up-regulated in SAL-H group(P＜0.05).Conclusion The protective effect of salidroside on cardiomyocytes may be related to the inhibition of endoplasmic reticulum stress-induced apoptosis and the imbalance of Cx43 metabolism.

Objective To explore the effect of salidroside(Sal)on endoplasmic reticulum stress and connexin 43 in rats with myocardial ischemia-reperfusion injury(MIRI).Methods SD rats were randomly divided into Sham group,MIRI group,low-does Sal(Sal-L)group and high-does Sal(Sal-H)group.The Sham group and MIRI group were intraperitoneal injec-ted with 0.9％sodium chloride solution(10 mL·kg-1·d-1),the Sal-L group and Sal-H group were intraperitoneal injected at a volume of 10 mL·kg-1 with Sal(12,36 mg·kg-1·d-1),respectively.Each group was given a corresponding intervention once a day for 3 d.The MIRI model was established 30 min after the last administration in all groups except the Sham group.The patho-logical changes of myocardial tissue were observed by Hematoxylin-eosin(HE)staining.TdT-mediated-dUTP nick end labeling(TUNEL)was used to observe the apoptosis of cardiomyocyte,the genes and proteins expression of Cx43 and endoplasmic reticu-lum stress related factors such as GRP78,Caspasel2,CHOP and so on were detected by quantitative real-time polymerase chain reaction(q-PCR)and western blot analysis.Results Compared with the MIRI group,the degree of tissue and cell injury in each Sal group was alleviated,with a decreased apoptosis rate observed in the Sal-H group(P＜0.05),the gene expression of Cx43 was up-regulated while GRP78,Caspase12,and CHOP gene expressions were down-regulated in both does groups of Sal.The protein expressions of Cx43 and GRP78 were also be up-regulated and down-regulated respectively in both dose groups of Sal,meanwhile the protein expressions of CHOP,Bax,Caspasel2 and cleaved-Caspase3 were down-regulated and the protein expres-sion of Bcl-2 was up-regulated in SAL-H group(P＜0.05).Conclusion The protective effect of salidroside on cardiomyocytes may be related to the inhibition of endoplasmic reticulum stress-induced apoptosis and the imbalance of Cx43 metabolism.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC₅₀ values of 34.89 and 19.88 μmol·L^-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC₅₀ values of 32.67, 79.38, and 16.74 μmol·L^-1, respectively.
Flavonoids/chemistry* ; SARS-CoV-2 ; Rhizome ; COVID-19 ; Peptide Hydrolases ; Antiviral Agents/chemistry*

Aim To study the potential molecular anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology methods,molecular docking technology and cell experiment. Methods The active ingredients targets and disease targets of Aconitum tanguticum were collected through literature and database. The common targets were utilized by mixture of them and the core targets were obtained by constructing the protein protein interaction(PPI)network. Then the component-target-disease network diagram was constructed. The gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed for common targets. AutoDock Vina(1.1.2)software was utilized for combining some of the core targets and the diterpenoid alkaloids in the chemical components of Aconitum tanguticum. Finally,the influence of alcoholic extract of Aconitum tanguticum(ATS)on RAW264.7 cell inflammation model was preliminarily verified by MTT assay,Griess reagent and realtime RT-PCR. Results A total 17 main active ingredients were obtained from literature and 284 common targets were obtained via intersecting with disease targets. Altogether 108 pathways were screened by KEGG enrichment,mainly including PI3K-Akt,Ras,MAPK and HIF-1. Molecular docking results indicated that the active ingredients of Aconitum tanguticum had a high affinity with the core target to be docked. In vitro experiment suggested that ATS treatment inhibited LPS-induced NO production and iNOS mRNA in RAW264.7 cells. Realtime RT-PCR detection suggested that ATS played an anti-inflammatory effect by regulating the PI3K-Akt signaling pathway. Conclusions Aconitum tanguticum exerts anti-inflammatory effects through PI3K-Akt pathways,which provides the scientific basis for better promoting the development of Aconitum tanguticum.

In December 2022, the European Thyroid Association(ETA) and American Thyroid Association(ATA) jointly released a consensus statement on the diagnosis and management of thyroid eye disease(TED). Taking into account the benefits and risks, the consensus provides specific recommendations for essential therapeutic agents. It also covers 34 key recommendations on the diagnosis and treatment decision-making, basic therapy and care, and risk factor control for TED.

The 2021 European Group on Graves′ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy was released in July, 2021. Based on the 2016 version, the new guidelines updated the first-line management algorithm for patients with Graves′ orbitopathy in moderate-to-severe and active period, provided multiple second-line treatment pathways and made detailed recommendations from aspects of clinical assessment, general measures, and management of specific conditions, etc. At the same time, efficacy evaluation and management during COVID-19 period were explained in detail. The new guidelines also mentioned some novel treatment strategies of GO which still need further efficacy and safety verification.

The clinical translation of stem cells and their extracellular vesicles (EVs)-based therapy for central nervous system (CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal (IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain‒blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.

Objective:To quantify the fat of extraocular muscle in TAO patients with MRI fat-water separation technique.Methods:66 patients (129 eyes) with TAO were included in this study from November 2017 to July 2019. The age, gender, course of disease, disease activity and severity were collected. Fat fraction(FF) of the heaviest inflamed extraocular muscle was used as FFmax, the average FF of each orbital was recorded as FFmean. FF differences between groups of severity and activity were compared, the correlation between FF and clinical characteristics was also analyzed. Meanwhile, the changes of FF in follow-up patients before and after treatment were compared.Results:FFmean and FFmax of mild group were higher than moderate-to-severe as well as sight-threatening group. In male patients, active group′s FFmean and FFmax were lower. FF was different in groups which based on disease course ( P<0.05). Spearman correlation analysis showed a positive correlation between FF and disease course. Besides, there was a negative correlation between FF, disease activity, and disease severity ( P < 0.05). FF increased after treatment(FFmean: 34.03%±6.75% vs 32.26%±6.06%, P=0.040; FFmax: 33.43%±9.44% vs 29.04%±8.45%, P=0.006). Conclusion:MRI fat fraction can quickly and objectively quantify the fat of extraocular muscle, providing a new reference index for TAO′s disease evaluation.

Objective To explore and understand limitations and needs of support for conducting clinical research among clinicians in China.Methods The in-service clinician in our hospital were enrolled in as survey participants,survey questionnaires were designed and filled up by target audience in the questionnaire star platform.Results Main problems identified as restrictions for conducting clinical studies including lack of data platform,have ideas but not protocols,lack of research funding and project management.On the other hand,identified needs for support including research-related technical support,project management facilitation,training,external communication and exchange,as well as quality risk management.Conclusions Hospital should establish Clinical Research Unit to help clinicians to improve research quality by training,providing technical support and administrative service of clinical research.

Objective To summarize the practical experiences of Clinical Research Unit (CRU) platform established by Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine,provide reference for domestic institutions that have prepared or to prepare to establish CRU platform.Methods Oriented by demand,this platform has set up six modules including project management module,methodology support module,data management module,quality risk management module,project transformation module and training and international exchange module.Besides,it also establishes and improves the corresponding module system,quality assurance,technical support and information data platform system.Results With this platform,the enthusiasm of departments to carry out clinical research has been continuously enhanced,the talent pool of clinical research has been expanded;the awareness of clinical research cooperation has been improved and the international cooperation fields have been further extended;the number of clinical research projects and funding have increased rapidly.Conclusions CRU Platform in Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine provides all-dimensional technical support and whole-process informatization management to improve clinical research quality and efficiency.While learning from the advanced international concepts,we still need to explore and improve the platform construction and management mode in line with general research-oriented hospitals in China,further to enhance the academic research internationally.