Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 573
Filter
1.
China Journal of Orthopaedics and Traumatology ; (12): 21-26, 2024.
Article in Chinese | WPRIM | ID: wpr-1009218

ABSTRACT

OBJECTIVE@#To investigate the clinical effect of modified suspension reduction method combined with percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures.@*METHODS@#From February 2020 to October 2021, 92 patients with thoracolumbar osteoporotic compression fracture were treated by percutaneous vertebroplasty. According to different treatment methods, they were divided into the observation group and the control group. The observation group was treated with modified suspension reduction and then percutaneous vertebroplasty, while the control group was treated with percutaneous vertebroplasty alone. The observation group (47 cases), including 20 males and 27 females, the age ranged from 59 to 76 years old with an average of (69.74±4.50) years old, fractured vertebral bodies:T10(2 cases), T11(7 cases), T12(19 cases), L1(14 cases), L2(5 cases);the control group(45 cases), including 21 males and 24 females, the age ranged from 61 to 78 years old with an average of (71.02±3.58) years old, fractured vertebral bodies:T10(3 cases), T11(8 cases), T12(17 cases), L1(12 cases), L2(5 cases);The leakage of bone cement were observed, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI), anterior vertebrae height (AVH), Cobb angle of kyphosis and the amount of bone cement injected before and after operation were recorded and compared between the two groups.@*RESULTS@#All patients were followed up, ranged from 6 to10 with an average of (8.45±1.73) months. Two patients ocurred bone cement leakage in observation group and 3 patients in control group. AVH of observation group increased (P<0.05) and Cobb angle of injured vertebrae decreased (P<0.05). Cobb angle of injured vertebrae and AVH of the control group were not significantly changed (P>0.05). Cobb angle of injured vertebrae of the observation group was lower than that of control group (P<0.05) and AVH was higher than that of the control group (P<0.05). In the observation group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.32±1.05) scores, (3.56±1.18) scores, (1.83±0.67) scores, (1.27±0.34) scores, and ODI were(40.12±14.69) scores, (23.76±10.19) scores, (20.15±6.39) scores, (13.45±3.46) scores. In the control group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.11±5.26) scores, (3.82±0.68) scores, (1.94±0.88) scores, (1.36±0.52) scores, and ODI were(41.38±10.23) scores, (25.13±14.22) scores , (20.61±5.82) scores, (14.55±5.27) scores . The scores of VAS and ODI after operation were lower than those before operation (P<0.05), but there was no significant difference between the two groups (P<0.05).@*CONCLUSION@#Modified suspension reduction method combined with PVP surgery for osteoporotic thoracolumbar compression fractures has achieved good clinical results, which can effectively relieve lumbar back pain, restore vertebral height, correct kyphosis, improve lumbar function and patients' quality of life.


Subject(s)
Male , Female , Humans , Middle Aged , Aged , Bone Cements/therapeutic use , Vertebroplasty/methods , Fractures, Compression/surgery , Quality of Life , Treatment Outcome , Spinal Fractures/surgery , Lumbar Vertebrae/injuries , Osteoporotic Fractures/surgery , Kyphosis/surgery , Retrospective Studies
2.
Acta Pharmaceutica Sinica ; (12): 735-742, 2024.
Article in Chinese | WPRIM | ID: wpr-1016617

ABSTRACT

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

3.
Chinese Journal of Stomatology ; (12): 491-497, 2023.
Article in Chinese | WPRIM | ID: wpr-986101

ABSTRACT

Oral mucositis (OM) is a common complication during hematopoietic stem cell transplantation. When OM occurs, with the destruction of oral mucosal barrier function, the formation of oral bacterial environment is accelerated, which has a negative impact on the life quality and clinical outcomes of patients. OM can be prevented by keeping the oral cavity clean, using the mouthwash properly, and limiting the delivery of cytotoxic drugs to oral tissues. This review describes the research progress on the prevention and local intervention of OM in patients with hematopoietic stem cell transplantation, in order to provide ideas for the selection of clinical intervention and management strategies on OM, and to provide references for exploring effective management methods for OM.

4.
Journal of Experimental Hematology ; (6): 1138-1142, 2023.
Article in Chinese | WPRIM | ID: wpr-1009971

ABSTRACT

OBJECTIVE@#To evaluate the efficacy, safety and relapse of cyclosporine A (CsA) and CsA combined with corticosteroid (CS) as the frontline therapy for patients with newly diagnosed acquired pure red cell aplasia (aPRCA).@*METHODS@#The clinical features, treatment responses, relapses and clinical outcomes of patients with newly diagnosed aPRCA in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2020 were analyzed retrospectively. All the enrolled patients had been treated with either CsA or CsA+CS for at least 6 months and had been followed up for at least 12 months, with complete clinical data and consent forms.@*RESULTS@#96 patients including 72 treated with CsA and 24 treated with CsA+CS were enrolled. With comparable baseline characteristics and follow-up periods, patients treated with CsA or with CsA+CS had similar overall response rates (ORRs) and complete response rates (CRRs) at the 3rd, 6th and 12th month and at the end of follow-up (P>0.05). Meanwhile, no significant difference was found between the two groups in the optimal ORR, optimal CRR, time to response or time to complete response. CsA+CS and CsA groups had similar adverse event (AE) rates, but CsA+CS group had higher CS-related infection rate (P <0.05). One patient in CsA+CS group died of multiple infections. As for the relapse, the two groups had compatible relapse rates at different time points, time to relapse, overall relapse rate and relapse-free survival (P>0.05). CsA exposure time, rather than different therapy regimens, was the only influence factor for either ORR or relapse rate (P <0.05).@*CONCLUSION@#CsA monotherapy has similar efficacy, AE rate and relapse rate as compared with CsA+CS for patients with newly diagnosed aPRCA, and shows less CS-related AEs such as infection.


Subject(s)
Humans , Cyclosporine/therapeutic use , Retrospective Studies , Red-Cell Aplasia, Pure/drug therapy , Adrenal Cortex Hormones/therapeutic use , Remission Induction , Treatment Outcome , Immunosuppressive Agents/therapeutic use
5.
China Journal of Orthopaedics and Traumatology ; (12): 1142-1146, 2023.
Article in Chinese | WPRIM | ID: wpr-1009201

ABSTRACT

OBJECTIVE@#To investigate CT values of cancellous bone in femoral neck in adults over 60 years with proximal femoral fractures.@*METHODS@#From January 2020 to December 2020, a retrospective analysis was performed on 280 subjects aged 60 years or older who underwent bilateral hip CT examination, including 85 males and 195 females, 120 on the left side and 160 on the right side, aged 75 (66, 82) years old. One hundred thirty-six patients with proximal femoral fractures were included in study group and 144 patients without fractures were included in control group. GEOptima CT was used to scan and reconstruct horizontal, coronal and sagittal layers of proximal femur. CT values of cancellous bone in femoral neck were measured and compared between two groups. The relationship between CT values of cancellous bone of femoral neck and proximal femoral fracture was analyzed statistically.@*RESULTS@#In terms of age, fracture group aged 79(73.3, 85.0) years old, non-fracture group aged 69.5 (64.0, 78.8) years old, and had significant difference in age between two groups (P<0.05). In terms of CT value, regional CT value in fracture group was 8.62(-3.62, 27.15) HU, which was lower than that in non-fracture group 34.31(-5.93, 71.74) HU(P<0.05). CT value on coronal view in fracture group was -8.48(-30.96, 17.46) HU, which was lower than that in non-fracture group 40.49(5.55, 80.71) HU (P<0.05). CT value on sagittal view in fracture group was -31.28(-54.91, -5.11) HU, which was lower than that in non-fracture group 7.74(-20.12, 44.54) HU (P<0.05). CT values on horizontal view in fracture group was 0.17(-23.13, 24.60) HU, which was lower than that in non-fracture group 46.40(10.42, 85.18) HU(P<0.05). The mean regional CT values among three planes in the fracture group were lower than those in the non-fracture group. Logistic regression analysis showed coronal CT value was influencing factors of proximal femoral fracture, and it could be written into regression equations that predict probability of fracture.@*CONCLUSION@#In adults aged over 60 years old, CT values of cancellous bone of femoral neck decreased with increasing age. The smaller CT value of cancellous bone of femoral neck, the greater risk of proximal femoral fracture.


Subject(s)
Male , Adult , Female , Humans , Middle Aged , Aged , Aged, 80 and over , Proximal Femoral Fractures , Retrospective Studies , Femur Neck , Hip Fractures/surgery , Tomography, X-Ray Computed , Bone Density
6.
Chinese Medical Sciences Journal ; (4): 265-272, 2023.
Article in English | WPRIM | ID: wpr-1008995

ABSTRACT

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.


Subject(s)
Adult , Humans , Amyotrophic Lateral Sclerosis/diagnostic imaging , Fasciculation/diagnostic imaging , Radiculopathy , Muscle, Skeletal/diagnostic imaging , Ultrasonography/methods
7.
Chinese Journal of Microbiology and Immunology ; (12): 642-646, 2023.
Article in Chinese | WPRIM | ID: wpr-995336

ABSTRACT

The genus Alistipes is mailnly isolated from the human gut microbiome and belongs to the phylum Bacteroidetes. Various species of the genus Alistipes have been isolated from samples of human feces, patients with appendicitis, abdominal cavity and rectal abscesses. Currently, this genus includes species such as Alistipes finegoldii, Alistipes putredinis, Alistipes onderdonkii, Alistipes shahii and Alistipes timonensis. Some studies have shown that Alistipes has a protective effect against certain diseases, including pancreatic cancer, Alzheimer′s disease, liver fibrosis and cardiovascular disease. Conversely, other studies have shown that Alistipes is pathogenic in some diseases such as Parkinson′s disease, colorectal cancer and depression. In addition, Alistipes has also been proved to play a paradoxical role in colitis as it can promote the development of colitis and suppress inflammation. This article was to increase the understanding about the genus Alistipes and to further summarize the relationship between Alistipes and diseases.

8.
Chinese Journal of Pharmacology and Toxicology ; (6): 512-513, 2023.
Article in Chinese | WPRIM | ID: wpr-992193

ABSTRACT

OBJECTIVE To identify the role of mixed lineage kinase domain like protein(MLKL)in cerebral small vessel disease(CSVD)and explore the underlying mechanism.METHODS Transient bilateral common carotid artery occlusion(tBCCAO)was used to establish a mouse model of CSVD.Immunofluorescence staining and Western blotting were used to observe the expres-sions of RIPK3/MLKL signaling molecules in brain tissues at 7,14 and 28 d after tBCCAO.Open field test,rotarod test,Y-maze and novel object recognition test were used to observe the effect of MLKL knockout on cognitive func-tion after tBCCAO.Blood-brain barrier(BBB)disruption was observed by sodium fluorescein permeability test and the expressions of tight junction proteins.Immunoflu-orescence staining and Western blotting were used to detect the expression of microglia marker Iba-1,astro-cyte marker GFAP,and NLRP3/Caspase-1 signaling mol-ecules in the hippocampus of CSVD mice.ELISA was used to detect the level of inflammatory factors(TNF-α,IL-1β,IL-18)in hippocampus.RESULTS The expres-sions of RIPK3/MLKL signaling molecules increased in cortex and hippocampus after tBCCAO,especially on day 14.The expression of pMLKL mainly increased in neurons,glia cells and endothelial cells in CSVD mice.MLKL knockout improved the cognitive functions such as motor learning,spatial learning and working memory,and object recognition ability in CSVD mice.MLKL knock-out alleviated the leakage of sodium fluorescein and attenuated the down-regulation of tight junction proteins at 1 d and 14 d after tBCCAO.At 14 d after tBCCAO,MLKL knock out inhibited the activations of microglia and astrocytes,attenuated the expressions of NLRP3/cas-pase-1 molecules,and decreased the levels of inflamma-tory factors in the hippocampus of mice.CONCLUSION Genetic inhibition of MLKL exerts protective effects against cognitive impairment by ameliorating BBB dam-age and neuroinflammation in a mouse cerebral small vessel disease model.

9.
Journal of Pharmaceutical Analysis ; (6): 442-462, 2023.
Article in Chinese | WPRIM | ID: wpr-991157

ABSTRACT

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

10.
Acta Pharmaceutica Sinica B ; (6): 2778-2794, 2023.
Article in English | WPRIM | ID: wpr-982872

ABSTRACT

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

11.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery ; (12): 562-569, 2023.
Article in Chinese | WPRIM | ID: wpr-982786

ABSTRACT

Objective:To investigate the distribution of allergens in patients with allergic rhinitis (AR) in Ningxia, and provide theoretical data for the prevention and treatment of AR in this region. Methods:A total of 1664 patients diagnosed with AR in the Otorhinolaryngology Head and Neck Surgery Department of Yinchuan First People's Hospital Outpatient Clinic from January 2018 to December 2021 were retrospectively collected. Use the allergen sIgE antibody detection kit (immunoblotting method) to detect inhalation and ingestion allergens in patients.Results: ①Among all AR patients, 1 158 cases were detected positive, resulting in the detection rate was 69.59%; ②The detection rate of inhalation allergen was 65.87%, and the detection rate of ingestion allergen was 19.83%; ③Mugwort was the most sensitive allergen, and 76.32% of the patients having a positive grade ≥3; ④Out of the patients, 294 cases (25.39%) were allergic to only one allergen, 244 cases (21.07%) were allergic to two allergens, and 620 cases (53.54%) were allergic to three or more allergens; ⑤During different seasons, the highest number of positive allergens detected was in the summer, with 968 cases (83.59%). Mugwort was the main allergen during this season (69.01%). After the COVID-19 epidemic, the total positive rate of sIgE tests in AR patients decreased compared to before, and the difference was statistically significant (P<0.001); ⑥Mugwort, dog epithelium, mold combination, egg, peanut, soybean, Marine fish combination and fruit combination all showed statistically significant differences between different gender groups (P<0.05); ⑦Common ragweed, mugwort, dust mite combination, cockroach, egg, milk, Marine fish combination, shrimp, fruit combination and nut combination all showed statistically significant differences among different age groups (P<0.05); ⑧There were statistically significant differences in hay dust among different ethnic groups (P<0.05). Conclusion:Artemisia argyi is the main allergen in Ningxia, and the distribution characteristics of different allergens are influenced by treatment season, the COVID-19 epidemic, gender, age, ethnicity, and other factors, showing certain distribution patterns and rules.


Subject(s)
Humans , Male , Female , Allergens , Artemisia , COVID-19 , Retrospective Studies , Rhinitis, Allergic , Skin Tests
12.
Acta Pharmaceutica Sinica ; (12): 2961-2969, 2023.
Article in Chinese | WPRIM | ID: wpr-999038

ABSTRACT

Pulmonary fibrosis is an interstitial lung disease characterized by inflammatory injury and tissue structure destruction. Currently, there is a lack of effective therapeutic drugs for pulmonary fibrosis, and the mechanism is still unknown. Therefore, it is urgent to seek new targets for effective drugs. In pulmonary fibrosis, the level of autotaxin (ATX) in bronchoalveolar lavage fluid increases and stimulates the production of lysophosphatidic acid (LPA). The involvement of LPA receptors in activating a variety of G-protein-mediated signal transduction pathways leads to a range of related physiological effects, including pro-inflammatory signaling in epithelial cells, activation of transforming growth factor signaling, and stimulation of fibroblast accumulation. LPA receptor antagonists and ATX inhibitors have been concerned as new targets for pulmonary fiber therapy, and currently related drugs have entered clinical trials. In this paper, the pathophysiological effects of LPA and ATX in pulmonary fibrosis disease and related drug development progress were reviewed to provide reference information of new drug development for pulmonary fibrosis based on the ATX-LPA axis.

13.
Chinese Pharmacological Bulletin ; (12): 774-781, 2023.
Article in Chinese | WPRIM | ID: wpr-1013819

ABSTRACT

Aim To express and purify rhα-Gal A with a 6 X His tag via using a serum-free expression system in high-density suspension culture of Chinese hamster ovary cells ( CHO-S) , and to verify the scavenging effect of rhα-Gal A on globular trisaccharide ceramide (Gb3 or GL3) . Methods The construction of recombinant protein expression vector, pcDNA4-GLA, was achieved by fusing the human α-galactosidase cDNA, gla, with 6 X His tag and artificial DNA synthesis. The expression plasmid was transfected into the suspended CHO-S to express rhα-Gal A and then purified. Following this procedure, we determined rhα-Gal A's expression, the enzymatic activity, and the glycosylation of the recombinant enzyme. Co-incubation with cultured cells was performed to examine whether rhα-Gal A could be taken up into the cells and effectively remove Gb3 substrates. Results rhα-Gal A was successfully expressed and purified after transiently transfecting pcDNA4-GLA into the suspended CHO-S, and the yield was up to (100 ±20. 6) mg • L

14.
Chinese Journal of Pediatrics ; (12): 1098-1102, 2023.
Article in Chinese | WPRIM | ID: wpr-1013231

ABSTRACT

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.


Subject(s)
Male , Child , Female , Humans , Child, Preschool , Receptors, Tumor Necrosis Factor, Type I/genetics , Retrospective Studies , Hereditary Autoinflammatory Diseases/drug therapy , Glucocorticoids/therapeutic use , Biological Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Autoantibodies , Familial Mediterranean Fever/diagnosis , Mutation
15.
Acta Pharmaceutica Sinica B ; (6): 4918-4933, 2023.
Article in English | WPRIM | ID: wpr-1011221

ABSTRACT

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

16.
Acta Pharmaceutica Sinica B ; (6): 4185-4201, 2023.
Article in English | WPRIM | ID: wpr-1011167

ABSTRACT

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6Chi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF+CD4+ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

17.
International Eye Science ; (12): 1099-1103, 2023.
Article in Chinese | WPRIM | ID: wpr-976477

ABSTRACT

AIM: To explore the correlation between the expression levels of microRNA-377-3p(miR-377-3p)and microRNA-365-3p(miR-365-3p)in serum and aqueous humor and the degree of diabetes macular edema(DME).METHODS: A total of 60 DME patients(60 eyes)admitted to 363 Hospital from February 2021 to February 2022 were selected in this prospective study(the severe eye was selected if both eyes had DME, while the right eye was selected if the same degree of DME), including 24 mild eyes, 21 moderate eyes and 15 severe eyes. In addition, another 60 patients(60 eyes)with type 2 diabetes(without fundus disease)admitted to our hospital during the same period were selected as the control group. The basic clinical data of all subjects were collected, including body mass index(BMI), smoking history, drinking history, hypertension, hyperlipidemia, the course of diabetes, glycated hemoglobin levels, fasting blood glucose and homocysteine(Hcy); the expression levels of miR-377-3p and miR-365-3p were detected by real-time fluorescent quantitative PCR(qRT-PCR).RESULTS: The course of diabetes, glycosylated hemoglobin, fasting blood glucose and Hcy in DME group were obviously higher than those in control group(all P&#x003C;0.05); the expression levels of miR-377-3p and miR-365-3p in serum of patients in DME group were lower than those in control group(all P&#x003C;0.05); the expression levels of miR-377-3p and miR-365-3p in serum and aqueous humor in severe group were obviously lower than those in moderate group and mild group, and those in moderate group were obviously lower than those in mild group(all P&#x003C;0.05); the expression levels of miR-377-3p and miR-365-3p in serum were negatively correlated with central macular thickness(CMT; r=-0.342, -0.374, all P&#x003C;0.05), the expression levels of miR-377-3p and miR-365-3p in aqueous humor were negatively correlated with CMT(r=-0.425, -0.503, all P&#x003C;0.05); the multivariate Logistic regression analysis showed that the course of diabetes, increased fasting blood glucose and Hcy were risk factors for DME in type 2 diabetes patients, and serum miR-377-3p and miR-365-3p were protective factors for DME in type 2 diabetes patients(P&#x003C;0.05).CONCLUSION: The expression of miR-377-3p and miR-365-3p in serum and aqueous humor of patients with DME is low, which is negatively related to the severity of DME patients.

18.
International Eye Science ; (12): 1007-1011, 2023.
Article in Chinese | WPRIM | ID: wpr-973795

ABSTRACT

In recent years, ophthalmology, as one of the medical fields highly dependent on auxiliary imaging, has been at the forefront of the application of deep learning algorithm. The morphological changes of the choroid are closely related to the occurrence, development, treatment and prognosis of fundus diseases. The rapid development of optical coherence tomography has greatly promoted the accurate analysis of choroidal morphology and structure. Choroidal segmentation and related analysis are crucial for determining the pathogenesis and treatment strategies of eye diseases. However, currently, choroidal mainly relies on tedious, time-consuming, and low-reproducibility manual segmentation. To overcome these difficulties, deep learning methods for choroidal segmentation have been developed in recent years, greatly improving the accuracy and efficiency of choroidal segmentation. The purpose of this paper is to review the features of choroidal thickness in different eye diseases, explore the latest applications and advantages of deep learning models in measuring choroidal thickness, and focus on the challenges faced by deep learning models.

19.
Chinese Journal of Biotechnology ; (12): 3125-3142, 2023.
Article in Chinese | WPRIM | ID: wpr-1007949

ABSTRACT

C1 gases including CO, CO2 and CH4, are mainly derived from terrestrial biological activities, industrial waste gas and gasification syngas. Particularly, CO2 and CH4 are two of the most important greenhouse gases contributing to climate change. Bioconversion of C1 gases is not only a promising solution to addressing the problem of waste gases emission, but also a novel route to produce fuels or chemicals. In the past few years, C1-gas-utilizing microorganisms have drawn much attention and a variety of gene-editing technologies have been applied to improve their product yields or to expand product portfolios. This article reviewed the biological characteristics, aerobic or anaerobic metabolic pathways as well as the metabolic products of methanotrophs, autotrophic acetogens, and carboxydotrophic bacteria. In addition, gene-editing technologies (e.g. gene interruption technology using homologous recombination, group Ⅱ intron ClosTron technology, CRISPR/Cas gene editing and phage recombinase-mediated efficient integration of large DNA fragments) and their application in these C1-gas-utilizing microorganisms were also summarized.


Subject(s)
Gene Editing , Gases , Carbon Dioxide , Genetic Engineering , Cloning, Molecular
20.
Chinese Acupuncture & Moxibustion ; (12): 970-976, 2023.
Article in Chinese | WPRIM | ID: wpr-1007428

ABSTRACT

Evidence shows that acupuncture-moxibustion could promote the healing of pressure injuries (PI), but its action mechanism is not fully understood. This review summarizes the basic research literature of acupuncture-moxibustion for PI and identifies that the mechanism of acupuncture-moxibustion for PI is related with regulation of related signaling pathway target proteins, improvement of inflammatory response, modulation of vascular microenvironment, attenuation of oxidative stress damage, and inhibition of cell apoptosis. The review also points out the current limitations and future research directions. It emphasizes the need for further exploration of the upstream regulatory mechanism, specific cellular molecules, and the interactions among these molecules. A multi-level, multi-target, and multi-dimensional approach is required to fully understand the mechanism underlying the promotion of PI healing by acupuncture-moxibustion.


Subject(s)
Humans , Moxibustion , Pressure Ulcer , Acupuncture Therapy , Acupuncture , Apoptosis
SELECTION OF CITATIONS
SEARCH DETAIL