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*

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

【Objective】 To investigate the correlation between heart rate variability (HRV) and the degree of nervousness before blood donation. 【Methods】 The psychological state of 253 blood donors before blood donation was assessed by the self-rating anxiety scale (SAS) and the degree of nervousness and their HRV were measured. The correlation between the SAS score, the degree of nervousness and the HRV parameters was analyzed, and the differences were compared among different types of donors by multivariate linear regression. 【Results】 A total of 247 blood donors were included in the study. Five HRV parameters in blood donors aged 18-24 were higher than in those aged 25 years and above(all P<0.05), and the anxiety level was higher in female donors(SAS score 41-46) than in males(SAS score 35-43)(P<0.001); the pre-donation SAS score was consistent with the assessment of the tension level (r=0.970, P<0.001); the pre-donation tension level and the SAS score were all significantly negatively correlated with VLF in HRV parameters(r=0.179, P=0.005), and the associations were independent of confounders such as age, body mass index and gender (P<0.05). 【Conclusion】 Compared with SAS and tension assessment, HRV is more objective, and can be used as one of the tests for assessing the tension level of blood donors. The inclusion of HRV in the routine screening of blood donors deserves further study for its application in assessing the anxiety level of blood donors before blood donation, identifying people prone to blood donation-related vasovagal reaction (DRVR), preventing and reducing the risk of DRVR, and improving the safety of blood donation.

Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.

OBJECTIVE: To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial. METHODS: This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments. RESULTS: During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group. CONCLUSIONS CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626).
Pregnancy ; Female ; Humans ; Surgical Wound Infection/etiology* ; Medicine, Chinese Traditional ; Anti-Bacterial Agents/therapeutic use* ; Cesarean Section/adverse effects* ; Double-Blind Method ; Treatment Outcome

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China