To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Glioblastoma (GBM), one of the most common malignant tumors in the central nervous system (CNS), is characterized by diffuse and invasive growth as well as resistance to various combination therapies. GBM is the most prevalent type with the highest degree of malignancy and the worst prognosis. While current clinical treatments include surgical resection, radiotherapy, temozolomide chemotherapy, novel molecular targeted therapy, and immunotherapy, the median survival time of GBM patients is only about one year. Radiotherapy is one of the important treatment modalities for GBM, which relies on ionizing radiation to eradicate tumor cells. Approximately 60% to 70% of patients need to receive radiotherapy as postoperative radiotherapy or neoadjuvant radiotherapy during the treatment process. However, during radiotherapy, the radioresistant effect caused by DNA repair activation and cell apoptosis inhibition impedes the therapeutic effect of malignant glioblastoma.Ferroptosis was first proposed by Dr. Brent R. Stockwell in 2012. It is an iron-dependent mode of cell death induced by excessive lipid peroxidation. Although the application of ferroptosis in tumor therapy is still in the exploratory stage, it provides a completely new idea for tumor therapy as a novel form of cell death. Ferroptosis has played a significant role in the treatment of GBM. Specifically, research has revealed the key processes of ferroptosis occurrence, including intracellular iron accumulation, reactive oxygen species (ROS) generation, lipid peroxidation, and a decrease in the activity of the antioxidant system. Among them, glutathione peroxidase 4(GPX4) in the cytoplasm and mitochondria, ferroptosis suppressor protein 1 (FSP1) on the plasma membrane, and dihydroorotate dehydrogenase (DHODH) in the mitochondria constitute an antioxidant protection system against ferroptosis. In iron metabolism, nuclear receptor coactivator 4 (NCOA4) can mediate ferritin autophagy to regulate intracellular iron balance based on intracellular iron content. Heme oxygenase1 (HMOX1) catalyzes heme degradation to release iron and regulate ferroptosis. Radiation can trigger ferroptosis by generating ROS, inhibiting the signaling axis of the antioxidant system, depleting glutathione, upregulating acyl-CoA synthase long chain family member 4 (ACSL4), and inducing autophagy. Interestingly, some articles has documented that exposure to low doses of radiation (6 Gy for 24 h or 8 Gy for 4-12 h) can induce the expression of SLC7A11 and GPX4 in breast cancer and lung cancer cells, leading to radiation resistance, while radiation-induced ferroptosis occurs after 48 h. In contrast, high doses of ionizing radiation (20 Gy and 50 Gy) increase lipid peroxidation after 24 h. This suggests that radiation-induced oxidative stress is a double-edged sword that can regulate ferroptosis in both directions, and the ultimate fate of cells after radiation exposure——developing resistance and achieving homeostasis or undergoing ferroptosis——depends on the degree and duration of membrane lipid damage caused by the radiation dose. In addition, during the process of radiotherapy, methods such as inducing iron overload, damaging the antioxidant system, and disrupting mitochondrial function are used to target ferroptosis, thereby enhancing the radiosensitivity of glioblastoma. By promoting the occurrence of ferroptosis in tumor cells as a strategy to improve radiotherapy sensitivity, we can enhance the killing effect of ionizing radiation on tumor cells, thus providing more treatment options for patients with glioblastoma. In this paper, we reviewed ferroptosis and its mechanism, analyzed the molecular mechanism of radiation-induced ferroptosis, and discussed the effective strategies to regulate ferroptosis in enhancing the sensitivity of radiotherapy, with a view to providing an important reference value for improving the current status of glioblastoma treatment.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Objective:To investigate an accurate and quantitative method to measure the eyeball morphological parameters of guinea pigs through a method that combines programmed digital techniques and mathematical geometric principles.Methods:Twenty-two three-week-old clean-grade male tricolor guinea pigs were selected and sacrificed by anesthesia overdose.Eyeballs were enucleated.The horizontal and sagittal images of the eyeball were taken with the high-speed photographic model of 13 million pixels macro meter, and the pictures were imported into pycharm programming software.Using the pre-written analysis program of Python 3.9, the conversion coefficient between the photo pixel and the actual length was obtained by a scale, and then the corneal surface was fitted by arc fitting and conic curve fitting.The results of arc fitting were converted to calculate the corneal radius of curvature.The corneal eccentricity was calculated according to the general conic equation (Ax 2+ Bxy+ Cy 2+ Dx+ Ey+ F=0). The corneal asphericity was evaluated by curve fitting between the central 3-mm and the whole cornea.The use and care of the animals complied with Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Shanghai Public Health Clinical Center (No.2022-A009-01). Results:The digital method of Python programming can show the corneal contour of guinea pigs completely and clearly.In the transverse plane, there was no significant difference in the corneal curvature measurements among the digital fitting in central 3-mm cornea, digital fitting in whole cornea and curvature meter ( F=1.693, P=0.190). In the sagittal plane, there was a significant difference in the corneal curvature measurements among the three methods ( F=3.500, P=0.030), and the corneal curvature measurements of the whole cornea measured by the curvature meter were significantly greater than those measured by the digital fitting ( P<0.05). There was no statistical significance in the measurements of corneal curvature radius among the three methods in the transverse plane and the sagittal plane ( F=1.817, P=0.170; F=2.050, P=0.133). The horizontal and sagittal corneal eccentricity measured by digital fitting in central 3-mm cornea were 0.55±0.15 and 0.53±0.17, which were lower than 0.66±0.10 and 0.64±0.14 measured by digital fitting in whole cornea, and the differences were statistically significant ( t=-4.860, -5.210; both at P<0.01). Conclusions:It is feasible to use Python programming digital method to measure the corneal curvature and eccentricity of guinea pigs.

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.
Humans ; Pregnancy ; Female ; Hypertension, Pregnancy-Induced/diagnosis* ; Retrospective Studies ; Pre-Eclampsia/epidemiology* ; Risk Factors ; Incidence

ObjectiveTo explore the relapse status based on the positive and negative syndrome scale （PANSS Scale） and related factors of schizophrenics in Shanghai communities， and to analyze the association between socio demographic characteristics， lifestyles， clinical characteristics and relapse. MethodsA dynamic cohort prospective study design was used in this study. From March 2018 to February 2019， a total of 189 schizophrenics in Xuhui， Hongkou， Changning， Jiading， Songjiang and Baoshan districts were enrolled successively. Baseline questionnaires were conducted through face-to-face interviews at baseline， which contained social demographic information， lifestyle information and clinical information. A follow-up was conducted every 2 weeks for a measurement of PANSS Scale for a total of 6 months. Relapse was assessed by a PANSS score increase of ≥25% from baseline （or an increase of 10 points or more if the baseline score was ≤40 points）. Univariate and multivariate Cox regression models were used to analyze the associations between relapse status （assessed by PANSS Scale） and socio demographic characteristics， lifestyles， and clinical characteristics， respectively. ResultsA total of 165 community schizophrenics completed baseline and follow-up surveys， with a loss to follow-up rate of about 12.7%. After exclusion of sociodemographic and clinical information deficits， 132 patients were included in the analysis totally， with an average age of 48.18±12.67 years， among whom 41.67% were male. Totally 33 patients relapsed during the 6-month follow-up period， with a relapse rate of 25.0%. After adjusting for gender， family history， age， employment， education， marital status， smoking， drinking， exercise frequency， medication compliance， insight， social function， violence history， stress recent events， adverse drug reactions and baseline scores of PANSS Scale， risk factors of relapse included the following four factors： age below 40 years （HR=4.47， 95%CI： 1.15-17.40）， primary school or below （HR=7.11， 95%CI： 1.54-32.83）， unemployed （HR=8.34， 95%CI： 1.78-38.98）， and adverse drug reactions （HR=5.02， 95%CI： 1.75-14.37）. ConclusionWe should pay attention to the risk factors such as age， education， employment and adverse drug reactions， in order to identify high-risk patients and to conduct timely interventions during the relapse management of schizophrenics in Shanghai community.

Improving the reproducibility of biomedical research results remains a major challenge. Transparent and accurate reporting of progress can help readers evaluate the reliability of research results and further explore an experiment by repeating or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is the second part of the Chinese translation of the complete interpretation of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (original text can be found at https://arriveguidelines.org) and based on the best practices for following the ARRIVE 2.0 guidelines in international journals. This part includes Items 4-7 of "ARRIVE Essential 10" in the ARRIVE 2.0 guidelines: "Randomization", "Blinding", "Outcome Measurement", and "Statistical Methods". Our Chinese translated version aims to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhancing the standardization of experimental animal research and reporting, and promoting the high-quality development of experimental animal technology and comparative medicine research in China.

Objective To investigate the effects and mechnism of abnormal stress promoting macrophage mobility inhibitory factor(MIF),cyclooxygenase 2(COX2)and prostaglandin E2(PGE2)in the progression of temporomandibular joint osteoarthritis(TMJOA).Methods From January 2020 to December 2021,TMJOA and temporomandibular joint internal derangement(TMJID)patients(30 cases in each group,we divided the TMJOA into group TMJ Ⅰ,Ⅱ,Ⅲ according to the stage)who were admitted to TMJOA special clinic of the First Affiliated Hospital of Xinjiang Medical University and accompanied by abnormal occlusion were collected.The pain score of the occlusal state of the patients was evaluated by visual analogue scale.The expression levels of MIF,COX2 and PGE2 in synovial fluid were detected by ELISA.We used the unilateral anterior crossbite for TMJOA(UAC)rats model(the grouped into:UAC-4 weeks,UAC-8 weeks and UAC-12 weeks group),and control group at the same time(grouped into:Ctrl-4 weeks,Ctrl-8 weeks and Ctrl-12 weeks group),each group had 6 rats.The expression levels of MIF,COX2 and PGE2 in serum and synovial fluid of rats were detected by ELISA.The expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2 in temporomandibular joint of rats were detected by Western blotting.The fluid flow shear stress(FFSS)model of fibroblast-like synovial cells(FLSs)was established,and the mRNA and protein expression levels of above indexes were detected by RT-PCR and Western blotting.Results Visual analogue scale evaluation showed that the pain score of TMJOA Ⅰ and Ⅱ group was significantly higher than that of TMJID(P<0.001).ELISA results showed that the expression levels of MIF,COX2 and PGE2 in synovial fluid in TMJOA group were higher than those in TMJID group(P<0.05),and the expression levels were the highest in TMJOA Ⅱ group.Compared with control group,the expressions of MIF,COX2 and PGE2 in serum and synovial fluid at UAC-4 weeks,8 weeks and 12 weeks were slightly higher,and significantly higher at UAC-8 weeks in rat TMJOA model(P<0.05).In addition,the expression trend of protein levels in temporomandibular joint tissues was similar,which showed higher expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2(P<0.05).In the cell model where FFSS interfered with FLSs,with the increase of FFSS,cell with deformation,incomplete cell membrane and reduced number.Compared with control group,the expression levels of IL-1β,IL-18,MIF,COX2 and PGE2(PTGER2)of FLSs were increased in 1,3,5 and 10 dyn/cm2 intervention groups(P<0.05).Conclusion MIF,COX2 and PGE2 were highly expressed in temporomandibular joint synovial fluid of TMJOA patients with malocclusion.And these three factors were also highly expressed in serum and synovial fluid of UAC rats.The abnormal fluid shear stress promotes the secretion of MIF,COX2 and PGE2 by FLSs to participate in joint microenvironment inflammation and accelerate disease progression.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

ObjectiveTo predict the pharmacodynamic basis and core target of Shengxiantang in the treatment of myasthenia gravis （MG） by network pharmacology and molecular docking and to further verify the molecular mechanism through animal experiment. MethodThe active components and potential targets of Shengxiantang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and the disease-related targets from GeneCards and other databases. Then the common targets of the decoction and the disease were screened out， followed by the construction of protein-protein interaction （PPI） network， and Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the common targets based on STRING database and Cytoscape 3.8.2. Afterward， Cytoscape 3.8.2 was employed to construct the disease-active component-target network. AutoDock and PyMOL were used for molecular docking of key components and hub genes. Finally， we used the Rα97-116 peptide to induce experimental autoimmune myasthenia gravis （EAMG） in rats and then verified the core target yielded in the docking with the model rats. ResultA total of 655 disease-related targets， 118 active components of the decoction， 21 common targets of the disease and the decoction， and 3 hub genes were screened out. The common targets were mainly involved in the GO terms of regulation of active oxygen metabolism， positive regulation of protein transport， and positive regulation of protein localization， and the KEGG pathways of toll-like receptor signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and T cell receptor signaling pathway. The results of molecular docking showed that quercetin and Akt1 had the lowest and stable binding energy and interacted with each other through the amino acid residue LYS-30. Western blot demonstrated that Shengxiantang significantly inhibited the expression of p-Akt protein in the spleen of EAMG rats. ConclusionThe pharmacological mechanism of Shengxiantang in the treatment of MG may be that the main chemical components regulate the expression of the core protein Akt， and then may participate in and affect PI3K/Akt signaling pathways， laying a theoretical and experimental basis for further research.