PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To investigate the effects of sarcopenia on therapeutic response and prognosis of newly diagnosed acute myeloid leukemia (AML) patients, and reveal its predictive value for the clinical outcomes of AML patients. METHODS: A total of 122 AML patients who were initially diagnosed and treated with induction chemotherapy at the Department of Hematology in the Affiliated Hospital of Nantong University from January 2017 to December 2020 were included in this study. The sarcopenia was diagnosed by measuring body composition parameters with multifrequency bioelectrical impedance analyzer, and all AML patients were divided into sarcopenia and non-sarcopenia groups. Kaplan-Meier curves and log-rank test were used to compare the survival difference between the two groups. The relationship between sarcopenia and overall survival (OS) of AML patients was further determined by the univariate and multivariate Cox regression analysis. RESULTS: Among 122 AML patients, 46 (37.7%) were diagnosed with sarcopenia before induction chemotherapy. The body mass index (BMI) of patients with sarcopenia was significantly lower than that of non-sarcopenia patients ( t =4.258, P <0.001), and the complete response (CR) and partial response (PR) rates of sarcopenia patients after induction chemotherapy were significantly lower than those of nonsarcopenia patients (χ²=6.348, P =0.042). Kaplan-Meier curves showed that sarcopenic patients had a shorter OS than non-sarcopenic patients, and the median OS of the two groups were 20.7 (95%CI : 12.6-27.8) months and 27.8 (95%CI : 22.3-31.9) months, respectively (χ²= 5.659, P =0.017). Subgroup analysis indicated that the median OS of sarcopenic and non-sarcopenic AML patients who received standard induction chemotherapy were 12.2 (95%CI : 5.4-24.7) months and 26.1 (95%CI : 16.7-35.4) months, respectively (χ²=3.949, P =0.047). The multivariate Cox regression analysis revealed that sarcopenia (HR=1.671, 95%CI : 1.034-2.701, P =0.036) was an independent predictor for poor prognosis in AML patients. CONCLUSION Sarcopenia is significantly associated with low response rate of induction chemotherapy and poor prognosis in AML patients, and it might be an useful tool for predicting the clinical outcome of AML patients.
Humans ; Sarcopenia/complications* ; Leukemia, Myeloid, Acute/diagnosis* ; Prognosis ; Male ; Female ; Induction Chemotherapy ; Middle Aged ; Body Mass Index ; Kaplan-Meier Estimate

ObjectiveTo understand the measles, rubella, and mumps antibody seroprevalence among the children aged 18 years and younger in Karamay City, and to evaluate the effectiveness of vaccination. MethodsA stratified whole cluster random sampling method was used to investigate the antibody seroprevalence of measles, rubella, and mumps among the healthy children aged 18 years and younger in Karamay City, and to further analyze the positive antibody rates and the geometric mean concentration (GMC) of antibodies. ResultsA total of 620 people were investigated, and the positive rates of IgG to measles, rubella, and mumps were 72.74%,62.26%, and 86.45%, respectively, with a GMC of308.94 mIU·mL^-1, 21.81 mIU·mL^-1, and 249.10 U·mL^-1. There were statistically significant differences in the positive rates of antibodies to measles, rubella, and mumps among different age groups (χ²_measles=76.707, P<0.001; χ²_rubella=60.804, P<0.001; χ²_mumps=35.407, P<0.001). The differences in positive rates were statistically significant among individuals with different intervals from the time of their last dose vaccination (χ²_measles=60.533, P<0.001; χ²_rubella=46.331, P<0.001; χ²_mumps=22.825, P<0.001). ConclusionThe antibody levels of measles, rubella and mumps among the people aged 18 years and younger in Karamay City are found to be low. Two doses of measles-mumps-rubella (MMR) vaccine should be given to children born before 2020, and if necessary, supplementary immunization with MMR vaccine should be carried out before they are enrolled in nursery and kindergarten. Additionally, regular population-based antibody surveillance should be conducted to promptly identify the people with weak immunity, which is conducive to effectively reducing and controlling the epidemic situation of measles, rubella and mumps in schools.

OBJECTIVE To establish a management index system for off-label drug use in medical institutions， offering a reference for the improvement of the management of off-label drug use in medical institutions from Xizang region. METHODS The framework of the management index of off-label drug use was initially developed based on regulations， literature retrieval and group discussion. Then，two rounds of Delphi consultation were conducted via the “Wenjuanxing” mobile mini-program involving 10 in-hospital experts from the fields of medicine， pharmacy， and hospital management. The consultation results were then sorted， revised and statistically analyzed， the final index system was established. RESULTS The questionnaire recovery rates of the two rounds of expert consultation were both 100%. The judgment coefficients were both 0.93， the familiarity degrees were both 0.74， and the authority coefficients were 0.84 in both rounds. Kendall’s coordination coefficients were 0.278 and 0.308， respectively （P＜ 0.001）， and the full score rates in both rounds were no less than 20%. The final management index system for off-label drug use in the hospital was established， including 3 first-level indicators（off-label drug use graded management regulations， off-label drug use supervision model， off-label drug use management level quantitative assessment system）， 14 second-level indicators （such as management level classification and key points of informed consent， etc.）， and 52 third-level indicators（such as general use level， restricted-use level， and special-use level， etc.）. CONCLUSIONS The management indicators for off-label drug use developed in this study， which are established based on Delphi method， are aligned with practical needs of hospital operations and meet the standards of expert enthusiasm， authority， and consistency.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Glioma, the most prevalent primary tumor of the central nervous system (CNS), is also the most lethal primary malignant tumor. Currently, there are limited chemotherapeutics available for glioma treatment, necessitating further research to identify and develop new chemotherapeutic agents. A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products (NPs) and optimizing their structures. Additionally, targeted drug delivery systems (TDDSs) are employed to enhance drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can penetrate deep into the brain, increase drug concentration and retention time in the CNS, and improve the targeting efficiency of NPs, thereby reducing adverse effects and enhancing anti-glioma efficacy. This paper reviews the research progress of anti-glioma activities of NPs, including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones, and their synthetic derivatives over the past decade. The review also summarizes anti-glioma mechanisms, such as suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversal of immunosuppression. Furthermore, the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined. The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.
Humans ; Glioma/metabolism* ; Biological Products/therapeutic use* ; Animals ; Brain Neoplasms/genetics* ; Drug Delivery Systems ; Antineoplastic Agents/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Apoptosis/drug effects*

Objective: To investigate the impact of temperature changes between neighboring days (TCN) on the mortality risk of respiratory diseases, so as to provide the evidence for the study of deaths from respiratory diseases caused by climate change. Methods: The monitoring data of deaths from respiratory diseases in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance. The meteorological and air pollutant data of the same period were collected from China Meteorological Data Website and ChinaHighAirPollutants dataset. The effect of TCN on the risk of deaths from respiratory diseases was examined using a generalized additive model combined with a distributed lag non-linear model, and subgroup analyses for gender and age were conducted. The disease burden attributed to TCN at different intervals was assessed by calculating attributable fraction. Results: Totally 11 767 deaths from respiratory diseases were reported in Zibo City from 2015 to 2019, including 6 648 males (56.50%) and 5 119 females (43.50%). There were 1 307 deaths aged <65 years (11.11%), and 10 460 deaths aged 65 years and older (88.89%). A monotonically increasing exposure-response relationship was observed between TCN and deaths from respiratory diseases in the general population, females, and the population aged 65 years and older. The 95th percentile of TCN (P95, 3.84 ℃) reached the peak at a cumulative lagged of day 11 (RR=2.063, 95%CI: 1.261-3.376). The results of subgroup analyses showed greater impacts on females and the population aged 65 years and older, with cumulative lagged effects peaking at day 12 (RR=3.119, 95%CI: 1.476-6.589) and day 11 (RR=2.107, 95%CI: 1.260-3.523). The results of attributional risk analysis showed that next-day warming might increase the attributable risk of deaths from respiratory diseases, and next-day cooling might decrease the attributable risk. Conclusion Next-day warming may increase the mortality risk of respiratory diseases, and has greater impacts on females and the population aged 65 years and older.

Objective To analyze the characteristics of adult anomalous aortic origin of coronary artery(AAOCA)and the causes of missed diagnosis by transthoracic echocardiography(TTE)so as to facilitate TTE in diagnosing adult AAOCA.Methods A total of 37 adult patients with AAOCA diagnosed by non-invasive coronary CT angiography(CCTA)and/or invasive coronary angiography(ICA)were selected as research samples at some hospital from January 2019 to December 2022,and their clinical symptoms and the findings of 12-lead electrocardiogram,cardiac enzymes and TTE were summarized;the patients were typed according to the site of origin of coronary artery anomalies,and the causes for the missed diagnosis of TTE were eplored.Chi-square test was used to compare the differences in TTE missed diagnoses.Results Of the 37 patients,31 ones had no or only mild symptoms;most ones had negative results in terms of 12-lead electrocardiography,cardiac enzymes,changes in the size of the cardiac chambers,segmental ventricular wall motion abnormalities and left ventricular systolic function.The patients with anomalous origin of the right coronary artery from left sinus(ARCA-L)gained the largest proportion of 59.45％(22/37);21 patients were diagnosed with anomalous origin of coronary artery arising from the opposite sinus(ACAOS)in the two examinations of TTE,of whom there were 19 cases of ARCA-L,and the detection rate of ACAOS by TTE was 87.5％;all the 13 patients origins in branches and high-grade openings were missed by TTE.The detection rate of ACAOS by TTE was significantly higher than that of coronary artery anomalies originating in branches and in high openings,and the difference was statistically significant(21/24 vs 0/13,P＜0.001).Conclusion Most adult AAOCA patients lack specificity in symptoms and related examination results.TTE has a high detection rate of ACAOS,while it is easy to miss the diagnosis of coronary artery anomalies originating from branches and high openings.Ultrasonographers have to identify false negative AAOCA by multi-section and multi-angle scanning and color Doppler flow imaging in order to reduce the rate of missed diagnosis.[Chinese Medical Equipment Journal,2024,45(1):71-75]