BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q

Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn³⁺SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn²⁺SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn²⁺SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn²⁺SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn²⁺ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O₂^• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O₂^• into the inner sphere, and avoid O₂^•/Mn²⁺ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH^-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Objective To explore the value of tuberculosis infected T cells spot test(T-SPOT.TB),heated mycobacterium tuberculosis nucleic acid amplification testing(TB-SAT),and adenosine deaminase(ADA)in diagnosing tuberculous pleural effusion.Methods A total of 135 patients with pleural effusion treated at the First Affiliated Hospital of Xinxiang Medical University from January 2021 to December 2021 were selected as the research subjects,including 83 patients with tuberculous pleural effusion and 52 patients with non-tuberculous pleural effusion.All these patients received peripheral blood T-SPOT.TB,chest water TB-SAT and chest water ADA tests,and the sensitivity and specificity of the above three methods in detecting tuberculous pleural effusion alone and in combination were compared.Results In terms of sensitivity and specificity,there was no statistically significant difference among the T-SPOT.TB,TB-SAT and ADA tests in detecting tuberculous pleural effusion alone(P＞0.05).The sensitivity of the T-SPOT.TB+TB-SAT combined test in detecting tuberculous pleural effusion was significantly higher than that of the T-SPOT.TB,TB-SAT and ADA tests alone(x2=4.990,13.410,14.590;P＜0.05),while the specificity of the T-SPOT.TB+TB-SAT combined test in detecting tuberculous pleural effusion showed no significant difference with that of the T-SPOT.TB,TB-SAT and ADA tests alone(x2=0.000,2.420,0.060;P＞0.05).The sensitivity of the T-SPOT.TB+ADA combined test in detecting tuberculous pleural effusion was significantly higher than that of the ADA test alone(x2=4.069,P＜0.05),but showed no significant difference with that of the T-SPOT.TB and TB-SAT tests alone(x2=0.055,3.384;P＞0.05).The specificity of the T-SPOT.TB+ADA combined test in detecting tuberculous pleural effusion was significantly lower than that of the T-SPOT.TB,TB-SAT and ADA tests alone(x2=4.370,12.511,5.371;P＜0.05).The sensitivity of the TB-SAT+ADA combined test in detecting tuberculous pleural effusion showed no significant difference with that of the T-SPOT.TB,TB-SAT and ADA tests alone(x2=0.000,2.604,3.213;P＞0.05).The specificity of the TB-SAT+ADA combined test in detecting tuberculous pleural effusion was significantly lower than that of the TB-SAT test alone(x2=5.765,P＜0.05),but showed no significant difference with that of the T-SPOT.TB and ADA tests alone(x2=0.782,1.251;P＞0.05).The sensitivity of the T-SPOT.TB+TB-SAT+ADA combined test in detecting tuberculous pleural effusion was significantly higher than that of the T-SPOT.TB,TB-SAT and ADA tests alone(x2=6.760,15.755,16.966;P＜0.05),while the specificity of the T-SPOT.TB+TB-SAT+ADA combined test in detecting tuberculous pleural effusion was significantly lower than that of the T-SPOT.TB,TB-SAT and ADA tests alone(x2=4.370,12.511,5.371;P＜0.05).The sensitivity of the T-SPOT.TB+TB-SAT combined test in detecting tuberculous pleural effusion was significantly higher than that of the T-SPOT.TB+ADA and TB-SAT+ADA combined tests(x2=4.090,4.990;P＜0.05);there was no statistically significant difference in the sensitivity in detecting tuberculous pleural effusion between the T-SPOT.TB+ADA combined test and the TB-SAT+ADA combined test(x2=0.060,P＞0.05).The specificity of the T-SPOT.TB+TB-SAT combined test in detecting tuberculous pleural effusion was significantly higher than that of the T-SPOT.TB+ADA combined test(x2=4.371,P＜0.05);the specificity of the TB-SAT+ADA combined test showed no significant difference with that of the T-SPOT.TB+TB-SAT and T-SPOT.TB+ADA combined tests(x2=0.780,1.490;P＞0.05).There was no statistically significant difference in the sensitivity in detecting tuberculous pleural effusion between the T-SPOT.TB+TB-SAT+ADA combined test and the T-SPOT.TB+TB-SAT combined test(x2=0.210,P＞0.05);the sensitivity of the T-SPOT.TB+TB-SAT+ADA combined test in detecting tuberculous pleural effusion was significantly higher than that of the T-SPOT.TB+ADA and TB-SAT+ADA combined tests(x2=5.750,6.760;P＜0.05).The specificity of the T-SPOT.TB+TB-SAT+ADA combined test in detecting tuberculous pleural effusion was significantly lower than that of the T-SPOT.TB+TB-SAT combined test(x2=4.370,P＜0.05);the specificity of the T-SPOT.TB+TB-SAT+ADA combined test in detecting tuberculous pleural effusion showed no significant difference with that of the T-SPOT.TB+ADA and TB-SAT+ADA combined tests(x2=0.000,1.490;P＞0.05).Conclusion The combined detection performs better than the single detection in diagnosing tuberculous pleural effusion,and the peripheral blood T-SPOT.TB combined with chest water TB-SAT performs the best in detecting tuberculous pleural effusion.The combined detection can effectively reduce the missed diagnosis rate and the misdiagnosis rate,and has high clinical application value for diagnosing tuberculous pleural effusion.

OBJECTIVE: To investigate the effects of LASS2/TMSG1 gene overexpression on proliferation and apoptosis of human lung cancer A549 cells and explore the possible mechanism. METHODS: We examined LASS2/TMSG1 expression level in a previously constructed A549 cell line overexpressing LASS2/TMSG1 using Western blotting. The proliferation and apoptosis of the cells were detected using colony-forming assay, CCK-8 assay, Hoechst/PI double staining and flow cytometry. Fourteen nude mice were randomized into 2 groups (n=7) to receive subcutaneous injection of A549 cells with or without LASS2/TMSG1 overexpression on the back of the neck, and the cell proliferation in vivo was observed. The expression levels of p38 MAPK protein and p-p38 MAPK protein in the xenografts were detected with Western blotting. ELISA was used to detect the levels of ceramide and p38 MAPK protein in cultured A549 cell supernatants and the xenografts in nude mice. RESULTS: Compared with the negative control cells, A549 cells with LASS2/TMSG1 overexpression had significantly lowered proliferation ability in vitro with increased early apoptosis rate (P < 0.05), and showed obvious growth inhibition after inoculation in nude mice(P < 0.05). Western blotting showed that in both cultured A549 cells and the xenografts in nude mice, LASS2/TMSG1 gene overexpression significantly increased the expression levels of p38 MAPK protein and p-p38 MAPK protein (P < 0.05); the results of ELISA also revealed significantly increased levels of ceramide and p38 MAPK protein in the cell supernatant andxenografts as well (P < 0.05). CONCLUSION Overexpression of LASS2/TMSG1 gene can significantly inhibit the proliferation and promote early apoptosis of human lung cancer A549 cells both in vitro and in vivo possibly by upregulating the expressions of ceramide and p38 MAPK protein to activate a signal transduction cascade.
Animals ; Humans ; Mice ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Lung Neoplasms ; Membrane Proteins/metabolism* ; Mice, Nude ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Signal Transduction ; Tumor Suppressor Proteins/metabolism*

With the increasing aging population, the incidence of wet age-related macular degeneration(wARMD)is gradually rising. The formation of neovascularization leads to recurrent hemorrhage in the macular region, which is one of the main causes of blindness in the elderly. Currently, the primary clinical treatment for wARMD is intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs. However, there are still some patients who have poor or no response to anti-VEGF drugs, resulting in suboptimal or ineffective clinical outcomes. Analyzing the specific influencing factors will be beneficial in guiding clinical decision-making. This article reviews the impact of factors such as advanced age, treatment duration, number of injections, characteristics of neovascular lesions, macular structure, intraocular cytokine levels, and genetics on the response to anti-VEGF therapy. In addition, recent studies have found that pericytes, as cellular components of microvascular walls, can influence the sensitivity to anti-VEGF therapy. This review summarizes the current research on the mechanisms of pericytes in poor or non-response to anti-VEGF therapy and discusses targeted strategies focusing on pericytes.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

Chronic obstructive pulmonary disease （COPD） is a common and frequently-occurring disease of the respiratory system， characterized by persistent respiratory symptoms and airflow restriction， which is prone to attack repeatedly and affect patients' quality of life seriously. At present， the combination of bronchodilators and inhaled corticosteroids is commonly used in clinic. Although these drugs can alleviate the symptoms of COPD patients， there are certain limitations of the difficulty in controlling the course of the disease effectively and reversing the decline of patients' lung function. Therefore， searching for safer and more effective therapeutic drugs has become a hot research topic nowadays. Traditional Chinese medicine （TCM） has remarkable curative effects and advantages in the prevention and therapy of COPD recently. Based on the increasing research and application of the active components of TCM in the therapy of COPD， studies on their pharmacodynamic mechanism are also more in depth. More and more studies have found that the active components of TCM can treat COPD patients effectively， and the mechanism involved mainly includes the anti-inflammatory， the antioxidant， and the inhibition of apoptosis. By searching and screening the domestic and foreign literatures on the treatment of COPD with the active components of TCM in recent years， the active components of TCM including flavonoids， terpenoids， phenols and saponins have been studied as the research objects， and their effects in improving the pulmonary function and oxidative stress， relieving inflammation and inhibiting apoptosis are expounded. Besides， the mechanism of action， signaling pathways and index molecules have been emphatically summarized， in order to provide the ideas for the clinical therapy and the basic research of COPD.

Berberine(BBR)is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes,hyperlipidemia and inflammation.Due to the low oral bioavailability of BBR,its mechanism of action is closely related to the gut microbiota.This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques.First,the docking of BBR and CYP51 was performed;then,the pharma-cokinetics of BBR was determined in ICR mice in vivo,and the metabolism of BBR in the liver,kidney,gut microbiota and single bacterial strains was examined in vitro.Moreover,16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota.Finally,recombinant E.coli con-taining cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express.The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system.The results showed that CYP51 in the gut microbiota could bind stably with BBR,and the addition of voriconazole(a specific inhibitor of CYP51)slowed down the metabolism of BBR,which prevented the production of the demethylated metabolites thalifendine and berberrubine.This study demonstrated that CYP51 promoted the deme-thylation of BBR and enhanced its intestinal absorption,providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo.