In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Metal-organic frameworks (MOFs) are crystalline materials with a multidimensional porous network structure, formed through coordination bonds with metal ions as nodes and organic ligands as connecting bridges. Due to their excellent physicochemical properties, MOFs have extensive applications in the field of biomedicine, ranging from antibacterials, drug carriers, imaging to sensors. Nanoscale metal-organic frameworks (nMOFs), commonly utilized drug carriers, can gain enhanced safety, targeted delivery, and superior therapeutic effect through endocytosis. In this review, we comprehensively summarize the factors influencing the endocytosis of nMOFs, focusing on three key physicochemical properties, particle size, morphology and surface modification. Based on different illness models, the review succinctly summarizes the latest advancements in understanding the endocytosis pathways of nMOFs while critically reflecting on the inherent limitations of current research methods. Lastly, the review offers valuable insights into future research methodologies and objectives, aiming to lay the groundwork and provide meaningful guidance for the synthesis and development of nMOFs as promising versatile drug carriers.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo understand the experience， knowledge and attitudes of e-cigarette users in Shanghai， and to provide evidence for the development of intervention programs for e-cigarette use. MethodsThe Respondent-Driven Sampling （RDS） method was used to recruit 40 e-cigarette users for qualitative interviews from November 2020 to February 2021. NVivo （11.0） software was used to code interview records， and the thematic pattern and relationship analysis were conducted. ResultsIn terms of the reasons and user experience of e-cigarette use， most respondents used e-cigarettes for the first time after recommendation of friends； The reasons for the current use of e-cigarettes focus on the subjective feelings generated by the use of e-cigarettes （easy to use， replacing traditional tobacco， and having many flavors）. Compared with traditional tobacco use， respondents said e-cigarettes tasted good and had no physical impact （they could be used all the time without making them uncomfortable）. In terms of the awareness of e-cigarette use related knowledge， the respondents' opinions on whether e-cigarettes caused health risks were mostly based on their own experience of using them， and they said it was difficult to identify real information online. As for whether they were interested in relevant knowledge， most respondents said they wanted to learn about the professional knowledge related to e-cigarettes. Regarding the attitude related to the use of e-cigarettes， most respondents believed that e-cigarettes are addictive， e-cigarettes are not a safe alternative to traditional tobacco， ande-cigarettes couldn't help them quit smoking. Three out of ten respondents said they supported including e-cigarettes in the Regulation on Smoking Control in Public. ConclusionThere are certain characteristics of e-cigarette users' feelings， related knowledge and attitude towards e-cigarette use that should be targeted to carry out publicity， education and intervention.

This paper reports the clinical data of a patient with recurrent metastatic parathyroid carcinoma. The causes, clinical manifestation, diagnose, treatment and prognosis of parathyroid carcinoma were discussed in order to perfect the experience of diagnosis and treatment and improve the survival rate of such patients.

OBJECTIVE: To explore the transcriptional gene expression profile up-regulated in human macrophages stimulated by interferon-γ (IFN-γ) and the underlying intracellular signaling mechanisms. METHODS: RNA-seq was used to sequence and compare the differential gene expression profiles of human macrophage cell line U937 before and after IFN-γ stimulation, and the significantly up-regulated genes were screened out, which were verified by fluorescence-based real-time quantitative polymerase chain reaction (qPCR) in U937 and THP1 cell lines, respectively. JAK/STAT, MAPK/ERK and PI3K/AKT pathway inhibitors were added to simultaneously to the cultured U937 cells upon IFN-γ priming to detect their effects on the expressions of the up-regulated genes to explore the key regulatory mechanisms. RESULTS: RNA-seq and qPCR results showed that, the well-recognized chemokines CXCL9, CXCL10 and CXCL11, the APOL family including APOL1, APOL2, APOL3, APOL4, APOL6 and GBP family GBP1, GBP2, GBP3, GBP4 and GBP5 as well were significantly up-regulated in IFN-γ-stimulated U937 cells. JAK/STAT3 pathway inhibitor inhibited the upregulation of APOL1, APOL4, GBP1, GBP4 and GBP5 genes induced by IFN-γ, while MAPK/ERK pathway inhibitor inhibited the upregulation of CXCL10 gene. PI3K/AKT pathway inhibitor inhibited the upregulation of APOL1,APOL4, APOL6, GBP1 and GBP5 genes induced by IFN-γ, all three signal pathway inhibitors could inhibit the upregulation of CXCL9 gene, and none of them could inhibit the upregulation of APOL3 gene. CONCLUSION Upon IFN-γ stimulation, some family molecules of APOL and GBP in macrophages are significantly up-regulated, and PI3K/AKT, JAK/STAT3 and MAPK/ERK pathways have positive regulation on their expressions, respectively.
Apolipoprotein L1/pharmacology* ; Humans ; Interferon-gamma/pharmacology* ; Macrophages/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ² test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant (P<0.05). In 2019, the students seeing close friend smoking (OR=27.381, 95%CI: 12.037-62.287), seeing someone smoking in school (OR=2.477, 95%CI: 1.155-5.312), believing that SHS may not be harmful (OR=8.471, 95%CI: 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR=8.688, 95%CI: 1.922-39.266), exposure to SHS in outdoor public place (OR=8.608, 95%CI: 1.048-70.692), close friend smoking (OR=8.115, 95%CI: 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact (OR=0.105,95%CI: 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant (P<0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.
Adolescent ; China/epidemiology* ; Electronic Nicotine Delivery Systems ; Humans ; Prevalence ; Students ; Tobacco ; Tobacco Smoke Pollution

Objective: To explore the mechanism of reactive oxygen species/thioredoxin-interacting protein/nucleotide-binding oligomerization domain-like receptor 3 (ROS/TXNIP/NLRP3) pathway in the skin injury of trichloroethylene (TCE) sensitized mice. Methods: In August 2020, 40 female BALB/c mice were randomly divided into control group (n=5) , solvent control group (n=5) , TCE treatment group (n=15) and TCE+(2-(2, 2, 6, 6-Tetrameyhylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito TEMPO) treatment group (n=15) . The TCE sensitization model was established. Mice in the TCE treatment group and TCE+Mito TEMPO treatment group were divided into the sensitized positive group and the sensitized negative group according to the skin erythema and edema reactions on the back of the mice 24 h after the last stimulation. The mice were sacrificed 72 h after the last stimulation, the back skin of the mice was taken, and the skin lesions were observed. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3, and the Western Blot was performed to detect the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) , cysteinyl aspartate specific proteinase 1 (Caspase 1) , Interleukin-1β (IL-1β) and TXNIP proteins in the skin of the mice, the reactive oxygen species (ROS) kit was used to detect the level of intracellular ROS in the back skin tissue. Results: The sensitization rates of TCE treatment group and TCE+Mito TEMPO treatment group were 40.0% (6/15) and 33.3% (5/15) , respectively, and there was no significant difference between the two groups (P>0.05) . The back skin of the mice in the TCE sensitized positive group was thickened and infiltrated by a large number of inflammatory cells. The number of mitochondria in the epidermis cells was significantly reduced, the mitochondrial crest disappeared and vacuolar degeneration occurred. TCE+Mito TEMPO sensitized positive group had less damage, more mitochondria and relatively normal cell structure. Compared with the solvent control group and corresponding sensitized negative groups, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE sensitized positive group and TCE+Mito TEMPO sensitized positive group were significantly increased (P<0.05) . Compared with TCE sensitized positive group, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE+Mito TEMPO sensitized positive group were significantly decreased (P<0.05) . Conclusion: ROS/TXNIP/NLRP3 pathway was activated and then encouraged the release of IL-1β, finally aggravated the TCE-induced skin injury.
Animals ; Carrier Proteins ; Caspase 1/metabolism* ; Female ; Inflammasomes/metabolism* ; Mice ; Mice, Inbred BALB C ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Solvents ; Thioredoxins/metabolism* ; Trichloroethylene/toxicity*

Objective:To construct a simple, precise and personalized comprehensive nomogram for prediction the risk of multidrug-resistant tuberculosis (MDR-TB) and to evaluate its prediction value among individuals with previous tuberculosis history (PTBH).Methods:A matched case-control study (1∶2 ratios) was performed in 1 881 patients with PTBH treated in 12 designated tuberculosis hospitals in Hangzhou City between January 1, 2005 and December 31, 2019, and there were 1 719 patients in training set, and 162 in validation set. A multivariable Cox regression analysis was used to evaluate independent predictors for the incident of MDR-TB in individuals with PTBH. A comprehensive nomogram was developed based on the multivariable Cox model. The accuracy of the prediction was assessed using concordance index (C-index), calibration curve and area under the receiver operator characteristic (ROC) curve.Results:The nomogram constructed based on the multivariable Cox regression model incorporated 10 independent predictors of the risk of MDR-TB. A history of direct contact (grade 1, 0-100.0 points) ranked on the top of all risk factors, followed by duration of positive sputum culture (grade 2, 0-84.5 points), unfavorable treatment outcome (grade 3, 0-52.0 points), human immunodeficiency virus infection (grade 4, 0-48.5 points), retreated tuberculosis history (grade 5, 0-40.0 points), non-standardized treatment regimens of retreated tuberculosis (grade 6, 0-32.5 points), duration of pulmonary cavities (grade 7, 0-31.0 points), passive mode of tuberculosis case finding (grade 8, 0-25.0 points), age<60 years (grade 9, 0-17.5 points), and standard frequencies of chest X-ray examination (grade 10, 0-14.0 points). The C-indexes of this nomogram for the training and validation sets were 0.833 (95% confidence interval ( CI) 0.807-0.859) and 0.871 (95% CI 0.773-0.969), respectively, indicating that the nomogram had good fitting effect. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively.The areas under ROC curve of the 1-year, 5-year, and 10-year MDR-TB risk probability of the training set were 0.904, 0.921, and 0.908, respectively, and those of the validation set were 0.954, 0.970, and 0.919, respectively. Conclusion:Through this nomogram model, clinicians could precisely predict the risk of incident MDR-TB among individuals with PTBH in the clinical practice.

Objective To investigate the effect of voluntary wheel running on negative affective of mice induced by formaldehyde. Methods Thirty male Kunming mice were randomly divided into three groups, including normal saline control group (NS), formaldehyde model group (F), and voluntary wheel running with formaldehyde injection group ( R+ F). The pain model was established by right hindpaw intraplantar formalin injection, the mice of R+F group experienced voluntary wheel running for three weeks before intraplantar formaldehyde injection. The spontaneous pain behavior was determined by the cumulative time of licking paw. The anxiety-like behavior of each group was determined by open field test (OFT) and elevated plus-maze test (EPM) while the depression-like behavior of each group was determined by forced swimming test (FST). The expression of doublecortin ( DCX ) in the hippocampus was determined by immunohistochemistry. Results Compared with the NS group, the typical two-phase pain response was observed in the F group, and compared with the F group, the second phase pain duration was significantly reduced in the R+F group (P<0. 01). In the open field test, the F group showed remarkably reduced time in the inner area(P<0. 001) compared with the NS group, while the R+F group increased time in the inner area (P<0. 05) compared with the F group. In the elevated plus-maze test, the F group showed remarkably reduced time (P< 0. 001) spent in the open arm compared with the NS group, however, compared with the F group, R+F group increased time spent in the open arm (P<0. 05). In the forced swimming test, the immobility time of the F group significant increased (P<0. 01) compared with the NS group, which was decreased in the R+F group (P<0. 05). The Immunohistochemistry showed that the area of DCX positive cells in the hippocampus of the F group was downregulated compared with the NS group, which was upregulated in the R+F group. Conclusion Our findings indicate that voluntary wheel running can improve anxiety and depression-like in mice induced by formaldehyde injection, which may be related to enhanced neurogenesis in the hippocampus.