Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway / 中国药理学通报

Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.

Diallyl disulfide augments sensitivity of DJ-1 overexpressed human gastric cells to 5-FU / 中国药理学通报

Aim To investigate whether diallyl disul-fide (DADS) augments the sensitivity of DJ-1 (protein/ nucleic acid deglycase) overexpressed human gastric SGC7901 cells to 5-FU (5-fluorouracil). Methods The experimental groups include control group, DADS group, VCR (vincristine) group, VCR + DADS group, DJ-1 group, DJ-1 + DADS group. MTT was used to analyze the effect of DADS on 5 -FU (5 -fluorou- racil) induced proliferation inhibition. Flow cytometry was performed to examine the effect of DADS on cell apoptosis. RT-PCR, Western blot, and immunofluo-rescence were used for determine the effect of DADS on the drug resistance associated gene expression. Results DADS enhanced the proliferation inhibitory effect of 5-FU on DJ-1 overexpressed cells and VCR resistant cells. DADS could induce apoptosis in VCR-resistant cells. DADS downregulated the expression of DJ-1 while inducing apoptosis in DJ-1 overexpressed cells. DJ-1 overexpression upregulated the expression of P-gp (P-glycoprotein), Bcl-2, and XIAP (X-linked inhibitor of apoptosis protein), downregulated the expression of caspase-3. DADS decreased the expression of P-gp, Bcl-2, and XIAP, while increased the expression of caspase-3 in DJ-1 overexpressed cells and VCR-resistant cells. Conclusions DADS can augment the sensitivity of DJ-1 overexpressed cells to 5-FU, which is related to its antagonism against DJ-1 mediated upregula- tion of P-gp, Bcl-2, XIAP, and downregulation of caspase-3.

The Ubiquitin Ligase SMURF1 Catalyzes the Polyubiquitination of ADAR1 / 中国生物化学与分子生物学报

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

Evolution and Functional Diversity of Microbial Cold Shock Proteins / 中国生物化学与分子生物学报

Cold shock proteins (CSPs) are highly conserved in structure and diversified in function. Due to the high homology of proteins, the CSP family mostly has a fixed spherical structure. CSPs are mostly the molecular chaperons of nucleic acid, so as to regulate the transcription and translation of genes, so that the cells can recover normal growth and reproduction under adverse environmental conditions. At present, many studies have shown that although CSPs share a high degree of homology, CSPs develop functional diversity to fight against a variety of stress after natural selection under different environmental conditions. For example, CSPC protein can inhibit the expression of related proteins in the type III secretory system, and CSPD protein is mainly suitable for regulating the growth and development of nutrient-deficient cells, while the functions of CSPH and CSPF proteins remain unclear. At first, this paper summarized the details of the high homology and the diversity between CSPs family members. Secondly, the phylogenetic tree for the genetic distance between different CSPs was analyzed. The functional diversity of the family and their mechanisms in transcription and translation levels were also summarized. Finally, the existing problems of the CSP family research and their application in agriculture, food and medical fields are reviewed.

RORα antagonist T0901317 promotes EMT in human gastric cancer MGC803 cells by RORα/β-catenin signal / 中国药理学通报

Aim To investigate the effect of RORα antagonist T0901317 promoting EMT (epithelial-mesenchymal transition) of human gastric cancer MGC803 cells by RORα/β-catenin signal. Methods Cell proliferation was detected by MTT. Cell migration and invasion were detected by cell scratch and Transwell assay respectively. RORα/β-catenin signaling molecules were detected by Western blot and immunofluorescence. RORα binding to β-catenin protein was detected by immunoprecipitation. Results MTT assay showed that the proliferation ability of T0901317 cells increased in a time-dependent manner compared with MGC803 cells (P < 0. 05). Cell scratches and Transwell experiments showed that the migration and invasion ability of T0901317 cells were significantly enhanced compared with MGC803 cells (P < 0. 05). Western blot analysis showed that RORα protein was significantly down-regulated after T0901317 compared with untreated group (P < 0. 05), and total β-catenin protein and nuclear β-catenin in MGC803 cells were up-regulated after T0901317 (P < 0. 05). Compared with the control group, RORα protein binding to β-catenin protein significantly decreased after T0901317 treatment (P < 0. 05). Compared with MGC803 cells treated with T0901317, the long spindle cells increased and the heteromorphism was more obvious. T0901317 significantly up-regulated the expression of Rac1, TGFβ1 and Vimentin in MGC803 cells (P < 0. 05), and inhibited the expression of E-cadherin (P < 0. 05). Conclusion T0901317 can promote the proliferation, migration, invasion and EMT in human gastric cancer MGC803 cells by RORα/β-catenin signal.

Potential targets and mechanism of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease based on network pharmacology / 中国药理学通报

Aim To explore the potential targets and mechanisms of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease. Methods Firstly, TCMSP database, disease database and compound target prediction platform were used to collect active components, disease targets and predict potential targets. Secondly, Cytoscape 3.7.2 and String platform were used to screen key chemical components and core targets, and PPI network diagram was constructed. Finally, The active components with degree greater than 30 were used for molecular docking with key targets, and some docking results were selected for cell experiment. Results The key active components of Houpuwenzhongtang in the treatment of spleen and stomach deficiency cold stomach disease were hesperidin, magnolol, 6-gingerol, and so on. The key targets were JUN, AKT1, IL-8, etc.. The related pathways mainly involved immune response, signaling transduction, cell proliferation and apoptosis. Molecular docking results showed that the key active components had good binding activity with disease targets. The results of cell experiments showed that magnolol, hesperidin and 6-gingerol had different degrees of anti-inflammatory activity against IL-8 in a dose-dependent manner. Conclusions It is speculated that Houpuwenzhongtang may act on IL-8, JUN, AKT1 and other targets through magnolol, hesperidin,6-gingerol and other active ingredients, and participate in the regulation of PI3K-AKT signaling pathway, N F-K B signaling pathway for the treatment of spleen and stomach deficiency cold stomach disease. And it is found for the first time that 6-gingerol could stably bind to multiple disease targets related spleen and stomach deficiency cold stomach disease,such as AKT1,IL-8 and so on. The result suggests that 6-gingerol is worth further research. Through the results of IL-8 cell experiment, it is speculated that the components such as magnolol and hesperidin may play a role in gastric diseases caused by Helicobacter pylori infection by reducing the content of IL-8 in gastric mucosa.

The Value of VR-PVEP in Objective Evaluation of Monocular Refractive Visual Impairment / 法医学杂志

OBJECTIVES@#To study the virtual reality-pattern visual evoked potential (VR-PVEP) P100 waveform characteristics of monocular visual impairment with different impaired degrees under simultaneous binocular perception and monocular stimulations.@*METHODS@#A total of 55 young volunteers with normal vision (using decimal recording method, far vision ≥0.8 and near vision ≥0.5) were selected to simulate three groups of monocular refractive visual impairment by interpolation method. The sum of near and far vision ≤0.2 was Group A, the severe visual impairment group; the sum of near and far vision <0.8 was Group B, the moderate visual impairment group; and the sum of near and far vision ≥0.8 was Group C, the mild visual impairment group. The volunteers' binocular normal visions were set as the control group. The VR-PVEP P100 peak times measured by simultaneous binocular perception and monocular stimulation were compared at four spatial frequencies 16×16, 24×24, 32×32 and 64×64.@*RESULTS@#In Group A, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 24×24, 32×32 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group B, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 16×16, 24×24 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group C, there was no significant difference between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at all spatial frequencies (P>0.05). There was no significant difference in the P100 peak times measured at all spatial frequencies between simulant visual impairment eyes and simultaneous binocular perception in the control group (P>0.05).@*CONCLUSIONS@#VR-PVEP can be used for visual acuity evaluation of patients with severe and moderate monocular visual impairment, which can reflect the visual impairment degree caused by ametropia. VR-PVEP has application value in the objective evaluation of visual function and forensic clinical identification.

Subclassification and clinical treatment options of refractory atlantoaxial dislocation / 中华骨科杂志

Objective:To subdivide clinical classification of refractory atlantoaxial dislocation, and evaluate the reliability of new subdivide clinical classification of refractory atlantoaxial dislocation.Methods:From January 2010 to December 2018, 48 patients with refractory atlantoaxial dislocation were treated, including 19 males and 29 females, aged 16 to 65 years, with an average of 39.2±13.3 years. According to the changes of relative anatomical position of C 1 and C 2 under general anesthesia with heavy traction of 1/6 body weight, subdivide clinical classification of refractory atlantoaxial dislocation were proposed, and refractory atlantoaxial dislocation was divided into traction loosening type (atlantoaxial angle≥5°) and traction stabilization type (atlantoaxial angle<5°). The traction loosening type was directly reduced by posterior atlantoaxial screw-rod fixation and fusion without anterior or posterior soft tissue release. For traction stabilization type, transoral soft tissue release was performed first, and then transoral anterior reduction plate fixation and fusion or posterior atlantoaxial screw-rod fixation and fusion were performed. Atlantodental interval (ADI) and atlantoaxial angle (AAA) were measured and collected before and after surgery to evaluate atlantoaxial reduction. The space available for the spinal cord (SAC) were measured to evaluate spinal cord compression. Visual analogue score (VAS) was used to evaluate the neck pain levels, and Japanese Orthopaedic Association (JOA) scores was used to evaluate the neurological function. American Spinal Cord Injury Association impairment scale (AIS) was used to evaluate the degree of spinal cord injury. One week, 3, 6, 12 months postoperatively and the annual review of the X-ray and CT scan were checked, in order to evaluate the reduction, internal fixation and bone graft fusion. Results:Among all 48 cases, 22 cases were traction loosening type, of which posterior atlantoaxial screw-rod fixation and fusion were performed in 16 cases and occipitocervical fixation and fusion in 6 cases. 26 cases were traction stabilization type, and they all underwent anterior transoral release, and then, anterior TARP fixation and fusion were performed in 24 cases and posterior screw-rod fixation and fusion in the other 2 cases. X-ray, CT and MRI images and of all patients 1 week after surgery showed good atlantoaxial reduction and decompression of spinal cord. In each of the two types, there was one case lost to follow-up. For 46 cases in follow-up, the follow-up time ranged from 6 to 72 months, with an average of 38.0±17.2 months. Among 46 cases, 21 cases of traction loosening type showed that, ADI reduced from preoperative 9.9±2.2 mm to 2.3±0.9 mm at 3 months after surgery and 2.3±1.0 mm at the last follow-up, AAA increased from preoperative 57.9°±12.3° to 91.0°±2.2° at 3 months after surgery and 90.9°±2.2° at the last follow-up, SAC increased from preoperative 9.8±1.3 mm to 15.1±0.7 mm at 3 months after surgery and 14.9±0.7 mm at the last follow-up, VAS score reduced from preoperative 1.5±2.1 to 0.7±1.0 at 3 months after surgery and 0.3±0.6 at the last follow-up, and JOA score increased from preoperative 10.2±1.7 to 13.3±1.3 at 3 months after surgery and 14.9±1.5 at the last follow-up. Twenty-five cases of traction stabilization type presented that, ADI reduced from preoperative 9.7±2.0 mm to 2.1±1.4 mm at 3 months after surgery and 2.1±1.3 mm at the last follow-up, AAA increased from preoperative 55.8°±9.2° to 90.9°±1.4° at 3 months after surgery and 90.9°±1.3° at the last follow-up, SAC increased from preoperative 10.5±1.0 mm to 15.4±0.5 mm at 3 months after surgery and 14.8±2.8 mm at the last follow-up, VAS score reduced from preoperative 1.7±2.1 to 0.7±0.9 at 3 months after surgery and 0.3±0.5 at the last follow-up, and JOA score increased from preoperative 10.1±1.3 to 12.9±1.5 at 3 months after surgery and 14.4±1.3 at the last follow-up. In the traction loosening type, all the 10 grade D patients were improved to grade E at the last follow-up. In the 2 grade C patients of traction stabilization type before surgery, 1 patient was improved to grade E, 1 patient was improved to grade D, and all 11 patients with grade D were improved to grade E at the last follow-up. Bony fusion was obtained in all patients from 3 to 6 months, with an average of 4.4±1.5 months. During follow-up period, no looseness of internal fixation or redislocation happened.Conclusion:Refractory atlantoaxial dislocation can be divided into traction loosening type and traction stabilization type. For traction loosening type, satisfactory reduction can be achieved by using posterior atlantoaxial screw-rod system without soft tissue release. For traction stabilization type, anterior release is preferable, and then anterior TARP or posterior screw-rod can be used to achieve satisfactory reduction.

Antibacterial copper sulfide/graphene oxide nanosheets composite film promotes angiogenic and osteogenic differentiation in vitro / 中华创伤骨科杂志

Objective:To investigate whether the antibacterial copper sulfide (CuS)/graphene oxide (GO) nanosheets composite film can promote angiogenesis and osteogenesis in vitro. Methods:GO and CuS/GO nanosheets were synthesized and mixed into polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC) hydrogel films. The study was conducted in 4 groups: PVA/CMC/GO, PVA/CMC/CuS/GO, PVA/CMC (only PVA/CMC-based film) and blank control (no material). The PVA/CMC, PVA/CMC/GO and PVA/CMC/CuS/GO films were characterized by electron scanning microscopy and energy dispersive spectrometer. The biocompatibility of different films (PVA/CMC/CuS/GO films with concentrations of CuS/GO nanotablets of 0, 50, 100, 200, 400, and 800 μ g/mL) was evaluated by CCK-8, live/dead cell staining, and hemolysis test. The angiogenesis was evaluated by cell migration and tube forming test in vitro. Alkaline phosphatase and alizarin red staining were used to evaluate osteogenesis in vitro, and the expression of osteogenic genes was measured by immunofluorescence staining and RT-qPCR. In addition, the bacterial plate counting method and bacteriostatic circle method were used to evaluate the antibacterial activity of films. Results:In the PVA/CMC/GO and PVA/CMC/CuS/GO groups, the surface of the PVA/CMC-based film was smooth and flat whereas the nanosheets composite films were irregularly flaky and convex. The biosafety experiments showed that the PVA/CMC-based film composited with GO or CuS/GO nanosheets at the concentration of 100 μg/mL had good biocompatibility. The results of angiogenesis in vitro showed that the migration ratio of HUVEC cells in the PVA/CMC/CuS/GO group was significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In the experiment of tube forming area and length, the PVA/CMC/CuS/GO group was significantly better than the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The osteogenic differentiation in vitro displayed that the alkaline phosphatase and alizarin red staining of MC3T3-E1 cells in the PVA/CMC/CuS/GO group were significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In addition, the fluorescence intensity of immunofluorescence staining in alkaline phosphatase and type Ⅰcollagen on MC3T3-E1 cells, and the mRNA expression levels of osteogenic related genes including alkaline phosphatase, bone morphogenetic protein 2, osteocalcin and osteopontin in the PVA/CMC/CuS/GO group were significantly higher than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The antibacterial assay showed that the PVA/CMC/CuS/GO group had a significantly greater antibacterial activity and a significantly larger inhibition zone against Gram-positive bacteria and Gram-negative bacteria than the PVA/CMC/GO, PVA/CMC and control groups ( P< 0.001). Conclusions:PVA/CMC films composited with GO or CuS/GO nanosheets demonstrate ideal biocompatibility and antibacterial properties which promote angiogenesis and osteogenic differentiation in vitro. In particular, antibacterial PVA/CMC/CuS/GO composite films with the coupling function of angiogenesis and osteogenesis are expected to provide a new strategy for infectious bone defects.

Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults (version 2023) / 中华创伤杂志

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Clinical guideline for diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture (version 2023) / 中华创伤杂志

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).@*METHODS@#From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve.@*RESULTS@#Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001).@*CONCLUSION@#Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

The Mechanism of miR-1294 Targeting SOX15 to Regulate Wnt/β-catenin Signaling Pathway and Promote the Proliferation of Acute Lymphoblastic Leukemia Cells in Children / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of abnormal miRNA expression on the proliferation of pediatric acute lymphoblastic leukemia (ALL) cells and its related mechanism.@*METHODS@#15 children with ALL and 15 healthy subjects were collected from the Second Affiliated Hospital of Hainan Medical University from July 2018 to March 2021. MiRNA sequencing was performed on their bone marrow cells, and validated using qRT-PCR. MiR-1294 and miR-1294-inhibitory molecule (miR-1294-inhibitor) were transfected into Nalm-6 cells, and the proliferation of Nalm-6 cells was detected by CCK-8 and colony formation assays. Western blot and ELISA were used to detect apoptosis of Nalm-6 cells. Biological prediction of miR-1294 was performed to find the target gene, which was verified by luciferase reporter assay. Si-SOX15 was transfected into Nalm-6 cells, Western blot was used to detect the expression of Wnt signaling pathway-related proteins and to verify the effect of si-SOX15 on the proliferation and apoptosis of Nalm-6 cells.@*RESULTS@#Compared with healthy subjects, 22 miRNAs were significantly upregulated in bone marrow cells of ALL patients, of which miR-1294 was the most significantly upregulated. In addition, the expression level of SOX15 gene was significantly reduced in bone marrow cells of ALL patients. Compared with the NC group, the miR-1294 group showed increased protein expression levels of Wnt3a and β-catenin, faster cell proliferation, and more colony-forming units, while caspase-3 protein expression level and cell apoptosis were reduced. Compared with the NC group, the miR-1294-inhibitor group showed reduced protein expression levels of Wnt3a and β-catenin, slower cell proliferation, and fewer colony-forming units, while caspase-3 protein expression level was increased and apoptosis rate was elevated. miR-1294 had a complementary base-pair with the 3'UTR region of SOX15 , and miR-1294 directly targeted SOX15 . The expression of miR-1294 was negatively correlated with SOX15 in ALL cells. Compared with the si-NC group, the si-SOX15 group showed increased protein expression levels of Wnt3a and β-catenin, accelerated cell proliferation, and decreased caspase-3 protein expression level and cell apoptosis rate.@*CONCLUSION@#MiR-1294 can target and inhibit SOX15 expression, thus activating the Wnt/β-Catenin signaling pathway to promote the proliferation of ALL cells, inhibit cell apoptosis, and ultimately affect the disease progression.

Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.@*METHODS@#A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.@*RESULTS@#Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.@*CONCLUSIONS@#The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells / 中华肝脏病杂志

Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

Relationship between cadmium exposure and pulmonary function level and chronic obstructive pulmonary disease / 中华劳动卫生职业病杂志

Objective: To analyze the levels and distribution characteristics of blood cadmium and urinary cadmium in American adults, to analyze the relationship between blood cadmium and urinary cadmium and pulmonary function dose response, and to explore the effect of this index on the risk of chronic obstructive pulmonary disease. Methods: In March 2022, 3785 patients from 2007 to 2012 in NHANES database were selected as the subjects. Collect demography data such as gender and age, and test data such as lung function, blood cadmium concentration and Urine cadimium concentration. The relationship between blood and urine cadmium levels and lung function and pulmonary function and chronic obstructive pulmonary diease (COPD) was analyzed by Mann-Whitney U test or Kruskal-Wallis H test, multivariate linear regression and restricted cubic spline method. Results: The geometric mean of blood cadmium and urine cadmium in American adults was 0.37 g/L and 0.28 g/L, FEV(1) and FEV(1)/FVC among different cadmium exposure groups was statistically significant, and there was a negative linear dose-response relationship between serum Cd and urine Cd concentrations and FEV(1)/FVC levels (P(overall)<0.001, P(non-linear)=0.152; P(overall)<0.001, P(non-linear)=0.926). Compared with the lowest quartile concentration (Q1), the highest quartile blood cadmium concentration (Q4) (OR=1.934, P(trend)=0.000) and urinary cadmium concentration (OR=1.683, P(trend)=0.000) may increased the risk of chronic obstructive pulmonary disease. Conclusion: There is a negative correlation between blood cadmium, urinary cadmium levels and lung function in American adults, and cadmium may increase the risk of chronic obstructive pulmonary disease.

Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial / 中华内科杂志

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Research Progress of Age Estimation in the Living by Knee Joint MRI / 法医学杂志

Bone development shows certain regularity with age. The regularity can be used to infer age and serve many fields such as justice, medicine, archaeology, etc. As a non-invasive evaluation method of the epiphyseal development stage, MRI is widely used in living age estimation. In recent years, the rapid development of machine learning has significantly improved the effectiveness and reliability of living age estimation, which is one of the main development directions of current research. This paper summarizes the analysis methods of age estimation by knee joint MRI, introduces the current research trends, and future application trend.