Objective Endothelial injury plays a crucial role in forming deep vein thrombosis.This study aims to compare the effectiveness of various methods for creating rabbit femoral vein thrombotic models after the endothelial injuryso as to provide a solid experimental foundation for further research on the endothelial injury and deep vein thrombosis.Methods Forty-five rabbits were randomly divided into three groups(A,B,C),with 15 cases in each group and subjected to the endothelial injury using the methods of simple clamping,combined complete ligation,and combined incomplete ligation,respectively.The intravascular ultrasonic manifestations and local endothelial pathological changes were compared at 1,3,and 7 days after modeling.Results Significant differences in vascular diameter and Young's modulus values were observed after 7 days of modeling(P<0.05).In pairwise comparisons between the groups,the Young's modulus values in group C were significantly higher than those in groups A and B after 7 days of modeling(P<0.05).Pathological examination confirmed the presence of fibr-inoid thrombus in the blood vessels of group C on the seventh day of modeling.Conclusion Combining simple clam-ping and incomplete ligation can produce a relatively stable endothelial injury and thrombus formation.This method provides a robust experimental model for further investigation into deep vein thrombosis after the endothelial injury.

OBJECTIVE To establish comprehensive quality evaluation method based on multi-index components combined with multivariate statistical analysis， and to comprehensively evaluate the quality of Periploca forrestii. METHODS Taking 11 batches of P. forrestii medicinal materials from different areas in Guizhou as samples， the contents of neochlorogenic acid， cryptochlorogenic acid， chlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C were determined by HPLC. Clustering heat map analysis， grey correlation analysis（GRA） and technique for order preference by similarity to ideal solution（TOPSIS） were used to evaluate the quality of P. forrestii. RESULTS The results of methodological investigation of content determination were in accordance with the relevant regulations， and the linear relationship and accuracy of each component were good in their respective sampling range. The contents of chlorogenic acid， cryptochlorogenic acid， neochlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C in 11 batches of samples were 3.650-7.302， 0.888-2.575， 1.371- 2.386， 0.947-1.469， 0.084-0.169 and 0.725-1.067 mg/g， respectively. The content of each component was significantly different， with the highest content of chlorogenic acid and the lowest content of isochlorogenic acid A. The comprehensive results of cluster heat map， GRA and TOPSIS analysis showed that the comprehensive quality of S5 and S10 was relatively good. CONCLUSIONS The established method is accurate， stable and simple. Combined with multivariate statistical analysis method， it can be used for quality evaluation of P. forrestii. The quality of samples from Jiuzhou Town and Caiguan Town of Xixiu District in Anshun City of Guizhou Province are relatively good among 11 different origin samples.

OBJECTIVE To provide reference for quality control of Gentiana rhodantha. METHODS Taking 52 batches of G. rhodantha as subject， ultra-high performance liquid chromatography （UPLC） fingerprint was adopted. The similarity of 52 batches of medicinal materials samples was evaluated by the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2004A edition）； the content of mangiferin was determined； chemometric analyses [cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）] were performed. RESULTS UPLC fingerprints of 52 batches of G. rhodantha were established， 17 common peaks were identified， and 6 of them were identified， which were loganic acid （peak 1）， neomangiferin （peak 3）， swertiamarin （peak 5）， dangyin （peak 6）， mangiferin （peak 7） and isoorientin （peak 9）. The similarities of 52 batches of medicinal materials samples were all greater than 0.9； cluster analysis showed that S1-S46， S48-S52 clustered into one class， and S47 alone； PCA results showed that the cumulative variance contribution rate of the first six principal components was 82.928%； OPLS-DA results showed that the corresponding components of swertiamarin， mangiferin and chemical composition represented by peak 4， 14， 15， 16 were the main iconic components affecting the quality differences of G. rhodantha medicinal materials. The contents of mangiferin in 52 batches of medicinal material samples ranged from 18.2 to 101.0 mg/g， mostly in accordance with 2020 edition of Chinese Pharmacopoeia. CONCLUSIONS The established UPLC fingerprint and chemometric analysis methods combined with content determination method of mangiferin can comprehensively evaluate the quality of G. rhodantha.

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; beta Catenin/metabolism* ; Biomarkers, Tumor/metabolism* ; Cell Line, Tumor ; Coenzyme A Ligases/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Lipoylation ; Prognosis ; Wnt Signaling Pathway

Objective:To investigate the clinical effect of homemade adjustable mirabilite vest in patients with severe acute pancreatitis and supply reference for clinical nursing.Methods:This was a randomized controlled study. One hundred patients with acute severe pancreatitis admitted to Putuo Hospital, Shanghai University of Traditional Chinese Medicine from January 2021 to June 2022 were selected, and were divided into the pocket group and the vest group according to the order of admission with 50 cases in each group. The pocket group used traditional mirabilite bag for external application, the vest group used adjustable mirabilite vest for external application. The other treatment measures were the same for both two group. The comfort degree, itching severity and average length of hospital stay of these two groups were compared.Results:The basic data of the two groups were homogeneous. The difference were not statistically significant( P>0.05). After intervention, the comfort degree of the pocket group was (65.90 ± 7.95) points while the comfort degree of the vest group was (77.04 ± 5.96) points. The difference was statistically significant ( t = 7.93, P<0.01). The degree of pruritus was (12.72 ± 3.95) points in the pocket group and (8.00 ± 1.20) points in the vest group.The difference was statistically significant ( t = 8.08, P<0.05). The mean length of hospital stay in the pocket group was (15.86 ± 5.83) days and (11.02 ± 3.38) days in the vest group. The difference was statistically significant ( t = 5.08, P<0.01). Conclusions:When using topical mirabilite for patients with acute severe pancreatitis, the use of adjustable mirabilite vest can significantly improve patients′ comfort, reduce itching, and reduce the number of hospital days, which has the value of promotion and use.

Objective:To observe the influence of NOD-like receptor thermal protein domain associated protein 6 (NLRP6) on hepatic ischemia-reperfusion injury (IRI), and elucidate the related mechanism.Methods:Thirty C57BL/6 mice with body weight of (18.80±1.99) g, were divided randomly into 5 groups, with 6 mice in each group: the mice that experienced only exploratory laparotomy were Sham group; that only underwent an operation to establish a hepatic IRI model were IRI group; that were treated with tail intravenous injection of clodronate (Clo) liposomes before the establishment of hepatic IRI model were Clo group; that received tail intravenous injection of clodronate liposomes and transfusion of bone marrow derived macrophages (BMDM) before the operation were Clo+ BMDM group; that received preoperative tail intravenous injection of clodronate liposomes and transfusion of BMDM with NLRP6 knockdown were Clo+ NLRP6-knockdown group. Real time quantitative polymerase chain reaction analysis (RT-PCR) and Western blot were performed to analyze the expressions of pyroptosis related proteins and factors. Simulate a hypoxia/reoxygenation (H/R) model in vitro, and set up experimental groups: lipopolysaccharide (LPS) + adenosine triphosphate (ATP), LPS+ ATP+ NLRP6-knockdown, H/R, and H/R+ NLRP6-knockdown. The changes of expressions of pyroptosis related proteins and factors were detected by RT-PCR and Western blot. Expression of NF-κB in vivo and in vitro was measured.Results:Compared with those in Sham group, protein expressions of NLRP6, NLRP3, Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 were remarkably increased in IRI group, but the levels of these proteins were dramatically decreased in Clo group with the exhaustion of macrophages in comparison with in IRI group, which were significantly different statistically (all P<0.05). The levels of these proteins were enhanced again in Clo+ BMDM group with the reconstruction of macrophages in contrast to those in Clo group, while the enhancements were more obvious in Clo+ NLRP6-knockdown group comparing to those in Clo+ BMDM group, with significant differences (all P<0.05). In vitro, pyroptosis rate for LPS+ ATP group was (16.39±1.06)%, which was lower than (27.34±2.79)% for LPS+ ATP+ NLRP6-knockdown group, with a statistical significance ( P<0.05). Meanwhile, pyroptosis rate for H/R group was (20.59±5.66)%, also much more reduced than (37.76±2.00)% for H/R+ NLRP6-knockdown group ( P<0.05). Expressions of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 and NF-κB p65 in LPS+ ATP+ NLRP6-knockdown group were more elevated than in LPS+ ATP group, and these indices were also more enhanced in H/R+ NLRP6-knockdown group than which in H/R group. Compared to the Sham group, expression of NF-κB p65 significantly increased in IRI group, which was reversed in Clo group, but enhanced again in Clo+ BMDM group and reached a peak in Clo+ NLRP6-knockdown group. Conclusions:Macrophage plays a critical role in immune response to hepatic IRI, wherein NLRP6 functions specifically. NLRP6 acts to suppress inflammation during hepatic IRI through regulating macrophage pyroptosis via inhibiting NF-κB.

Objective:To explore the risk factors for shunt dependent hydrocephalus (SDHC) in patients with traumatic subarachnoid hemorrhage (tSAH) and establish their risk nomogram model.Methods:Two hundred and sixty-nine patients with tSAH, admitted to our hospital from February 2018 to February 2022, were chosen in our study. All patients were followed up for 3 months after discharge; 51 patients were complicated with SDHC and 218 patients were not complicated with SDHC. The clinical data of patients with and without SDHC were compared. Multivariate Logistic regression analysis was used to determine the independent influencing factors for SDHC in tSAH patients; according to the results of multivariate Logistic regression analysis, a nomogram model was constructed to predict SDHC in tSAH patients; and the consistency index (C-index) and calibration curve were used to evaluate the predictive performance and compliance of the nomogram model.Results:As compared with patients without SDHC group, patients with SDHC had significantly lower Glasgow Coma Scale (GCS) scores on admission, and significantly higher proportions of patients with cerebral hernia, diffuse tSAH, tSAH thickness ≥5 mm, intraventricular hemorrhage, midline shift>12 mm, and epidural effusion at discharge, and patients accepted decompressive craniectomy ( P<0.05). Multivariate Logistic regression analysis showed that GCS scores of 13-15 ( OR=0.134, 95%CI: 0.024-0.740, P=0.021), diffuse tSAH ( OR=4.391, 95%CI: 1.680-11.475, P=0.003), tSAH thickness≥5 mm ( OR=4.114, 95%CI: 1.689-10.018, P=0.002), decompressive craniectomy ( OR=3.283, 95%CI: 1.278-8.433, P=0.014) and epidural hydrops ( OR=3.302, 95%CI: 1.137-9.593, P=0.028) were independent influencing factors for SDHC in tSAH patients. A nomogram model established based on the above 5 influencing factors showed high predictive accuracy with C-index of 0.877. Conclusion:The tSAH patients with low GCS scores at admission, diffuse tSAH, tSAH thickness≥5 mm, and epidural effusion, and patients accepted decompressive craniectomy are prone to have SDHC; the nomogram model based on the above variables has a high efficiency in predicting the risk of tSAH complicated with SDHC.

Objective:To study the effect of medical social workers combined with ICU diary on the prevention and treatment of post-traumatic stress disorder in ICU traffic accident patients, and to explore the application of continuing nursing services and ICU diary to ICU traffic accident patients.Methods:A total of 47 patients who were admitted to the ICU of Suzhou Science and Technology City Hospital from January to December 2019 due to traffic accidents were selected by convenient sampling method. Twenty-three patients admitted to the hospital in the first 6 months were selected as the control group (before the introduction of medical social workers and ICU diaries) for routine ICU treatment and nursing mode. Twenty-four patients admitted to the hospital in the last 6 months were selected as the experimental group (after the introduction of medical social workers and ICU diaries), and the medical social workers combined with the ICU diary were intervened. The scores of the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were compared between the two groups of patients when they were admitted to the ICU, stayed in the ICU for a week, and transferred out of the ICU. The incidence of post-traumatic stress disorder was evaluated and compared by the scores of the Impact of Event Scale-Revised of the two groups of patients one month after leaving the ICU, three months after leaving the ICU, and six months after leaving the ICU.Results:The scores of SAS in the experimental group were 58.67 ± 7.45, 44.13 ± 5.47 and 39.08 ± 5.52 when they were admitted to the ICU, stayed in the ICU for a week, and transferred out of the ICU, and were 58.17 ± 6.75, 50.87 ± 6.35 and 42.74 ± 4.85, respectively in the control group. There was no statistical difference in the scores of the SAS between the two groups of patients when they were admitted to the ICU ( P>0.05), but there was a time difference between the two groups with time changes and different interventions ( Ftime = 110.98, P<0.01), there were also differences between groups ( Fbetween groups = 5.91, P<0.05). Compared with the control group, the SAS score of the experimental group decreased more significantly( Finteraction = 0.28, P<0.05). The scores of SDS in the experimental group were 57.75 ± 4.06, 45.29 ± 3.39 and 36.63 ± 3.49 when they were admitted to the ICU, stayed in the ICU for a week, and transferred out of the ICU, and were 57.48 ± 2.29, 49.04 ± 5.65 and 43.57 ± 4.07 respectively in the control group. There was no statistical difference in the scores of the SDS between the two groups of patients when they were admitted to the ICU ( P>0.05), but there was a time difference between the two groups of patients with time changes and different interventions ( Ftime = 248.24, P<0.01), there are also differences between groups ( Fbetween groups = 24.39, P<0.05). Compared with the control group, the SDS score of the experimental group decreased more significantly ( Finteraction=10.44, P<0.05). The incidences of post-traumatic stress disorder in the experimental group were 9, 8, 6 cases at one month, three months and six months after leaving the ICU, which were lower than 12, 11, 8 cases in the control group. The generalized estimation equation showed that the difference was statistically significant ( χ2=4.21, P<0.05). Conclusions:The intervention model of medical social workers combined with ICU diary is conducive to the use of ICU diary and the development of continuous nursing, which improves patients′negative emotions and reduces the incidence of post-traumatic stress disorder.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*