1.HAPLN1 secreted by synovial fibroblasts in rheumatoid arthritis promotes macrophage polarization towards the M1 phenotype.
Chenggen LUO ; Kun HUANG ; Xiaoli PAN ; Yong CHEN ; Yanjuan CHEN ; Yunting CHEN ; Mang HE ; Mei TIAN
Chinese Journal of Cellular and Molecular Immunology 2025;41(5):413-419
Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans
;
Arthritis, Rheumatoid/genetics*
;
Macrophages/immunology*
;
Fibroblasts/metabolism*
;
Phenotype
;
Extracellular Matrix Proteins/genetics*
;
Proteoglycans/genetics*
;
Synovial Membrane/cytology*
;
Tumor Necrosis Factor-alpha/genetics*
;
Interleukin-1beta/genetics*
;
Nitric Oxide Synthase Type II/genetics*
;
Cell Differentiation
;
Coculture Techniques
;
THP-1 Cells
2.Genetic Differences of Thalassemia Gene Among Ethnic Groups in Hechi, Guangxi.
Man-Ting SONG ; Feng-Yan WANG ; Dan LAN ; Gao CHEN ; Shuai WEI ; Li-Mang GUO
Journal of Experimental Hematology 2025;33(4):1098-1103
OBJECTIVE:
To retrospectively analyze the genetic differences of thalassemia gene mutations among ethnic groups in Hechi, Guangxi.
METHODS:
A total of 15 595 whole blood samples of residents of Hechi from January 1, 2020 to June 30, 2023 were screened for thalassemia, and the Gap-PCR method and RDB-PCR method were used to perform genetic testing on the positive samples. Gene sequencing was performed on the samples with positive screening results but negative genotyping results.
RESULTS:
Among the 15 595 samples, 10 501 cases were screened positively, and 8 506 cases were thalassemia gene carriers among the positive samples, with a positive coincidence rate of 81.00%. Among them, there were 5 374 cases of α-thalassemia, 2 531 cases of β-thalassemia, and 601 cases of α+β compound thalassemia. A total of 13 mutant types were detected in α-thalassemia, including --SEA (48.57%), -α 3.7 (31.31%), α CS (8.57%) and -α 4.2 (8.07%). A total of 17 mutant types were detected in β-thalassemia, mainly CD17 (48.27%) and CD41-42 (41.24%). The thalassemia gene carriers were mainly from the Zhuang (6 106 cases), Han (969 cases), Yao (793 cases), Mulam (275 cases), and Maonan (228 cases) ethnic groups. The comparison of constituent ratios within the above five ethnic groups demonstrated that there were differences in the proportions of -- SEA, -α 3.7, α CS , and -α 4.2 among the Zhuang, Han, and Yao ethnic groups (P < 0.005). The proportion of α CS in the Mulam ethnic group was not significantly different from -α 3.7 and -α 4.2. The proportions of -- SEA, -α3.7, and α CS in the Maonan ethnic group were not significantly different. There were no significant differences in the proportion of CD17 and CD41-42 among the Han, Yao, Mulam and Maonan ethnic groups. The proportion of --SEA was the highest in the Mulam ethnic group (56.68%), which was statistically different from 35.92% in the Maonan ethnic group. The proportion of -α 3.7 was the highest in the Zhuang ethnic group (33.25%), and the difference was statistically significant compared to the Mulam ethnic group which had the lowest proportion (18.72%). The proportion of α CS was the highest in the Maonan ethnic group (27.46%), and the differences were statistically significant compared with other ethnic groups. The proportions of CD17 in the Zhuang and Maonan ethnic groups (50.79%, 55.68%) were higher than those in the Han (39.12%), Yao (39.63%) and Mulam (30.00%), and the differences were statistically significant. There was no significant difference in the proportion of CD41-42 among the above five ethnic groups.
CONCLUSIONS
The mutation type and distribution differences of genes causing thalassemia among main ethnic groups in the minority inhabited areas of Hechi, Guangxi, show the characteristics of ethnic differentiation. The result is helpful to develop a special prevention and control plan for thalassemia in line with the population distribution characteristics, and provide reference for revealing the genetic background and geographical distribution of thalassemia in this area.
Humans
;
China
;
beta-Thalassemia/genetics*
;
Ethnicity/genetics*
;
alpha-Thalassemia/genetics*
;
Mutation
;
Genotype
;
Retrospective Studies
;
Asian People/genetics*
;
Thalassemia/genetics*
;
Male
3.Application effect of different doses of dexmedetomidine in thyroid surgery under recurrent laryngeal nerve monitoring
Wenbo MANG ; Lei LYU ; Longyuan ZHOU ; Yuan YUAN ; Gaoxiang CHEN
Chongqing Medicine 2024;53(13):1947-1951
Objective To observe the application effect of different doses of dexmedetomidine in thyroid surgery under recurrent laryngeal nerve monitoring.Methods A total of 60 patients with thyroid surgery un-der general anesthesia,moreover adopting recurrent laryngeal nerve monitoring during the operation,in this hospital from October 2021 to June 2023 were selected as the study subjects and divided into the control group(group A),low dose group(group B)and high dose group(group C)by the random number table method.The group B and group C respectively used dexmedetomidine 0.3 μg/kg and 0.6 μg/kg as a loading dose be-fore anesthesia induction,0.3 μg·kg-1·h-1 and 0.6 μg·kg-1·h-1 were respectively injected by mi-cropump for anesthesia maintenance,while the group A adopted the same amount of normal saline.The other anesthesia management methods were the same in the three groups.The mean arterial pressure(MAP)and heart rate after entering the room(T0),before anesthesia induction(T1),after anesthesia intubation(T2),at 1 min after anesthesia intubation(T3),immediately after surgical incision(T4),isolation of the thyroid gland(T5)and at 1 min after extubation(T6),incidence rate of adverse reactions,choking reaction score,extubation time after stopping medication and dosage of propofol and remifentanil were recorded.Results The choking reaction score,extubation time after stopping medication and propofol dosage were manifested as the group C<group B<group A(P<0.05).The remifentanil dosage in group C and group B was less than that in group A(P<0.05).MAP at T1 in the group C was lower than that in the group A and group B(P<0.05),but there was no statistical difference between the group A and group B(P>0.05).MAP at T2-T6 in the group B and group C was lower than that in the group A(P<0.05),but the difference between the group B and group C had no statistical significance(P>0.05).The heart rate at T1-T6 in the group B and group C was lower than that in the group A(P<0.05).The heart rate at T1,T2,T4,T5 and T6 in the group C was lower than that in the group B(P<0.05).Bradycardia during operation did not occur in various groups.The intraoperative recurrent laryngeal nerve monitoring process was smooth without appearing interference.The incidence rate of adverse reactions had no statistical difference in various groups(P>0.05).Conclusion He-modynamics by using 0.6 μg/kg dexmedetomidine in the patients with thyroid operation under recurrent la-ryngeal nerve monitoring is more smooth and steady,which could reduce the use amounts of anesthetic drugs,decrease the occurrence of choking reaction,shorten the operation extubation time after operation,moreover does not increase the incidence rate of postoperative adverse reactions.
4.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
5.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
6.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
7.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
8.Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release
Han-Wen CHUANG ; Chih-Chia HUANG ; Kuang-Ti CHEN ; Yen-Yu KUO ; Jou-Hua REN ; Tse-Yen WANG ; Mang-Hung TSAI ; Po-Ting CHEN ; I-Hua WEI
Psychiatry Investigation 2024;21(11):1286-1298
Objective:
Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods:
Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results:
Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion
Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
9.Relationship between cortical fragments and avascular necrosis of femoral head in young adult femoral neck fractures based on CT imaging.
Mang-Mang CHEN ; Xiao-Sheng CAI ; Yang-Xun LYU ; Sheng-Lei LIN ; Li-Peng HUANG ; Zhou LIN
China Journal of Orthopaedics and Traumatology 2024;37(11):1096-1100
OBJECTIVE:
To explore the effect of femoral neck cortical fragments and surfacial area on avascular necrosis(AVN) after internal fixation of femoral neck fractures based on CT imaging in young adult.
METHODS:
From January 2011 to January 2021, 218 young and middle-aged patients with femoral neck fractures were reverse triangle fixed with three cannulated lag screws, including 104 males and 114 females;aged 19 to 60 years old with a mean of (48.22±10.58) years old. The preoperative waiting time≤48 h was 155 cases, and the preoperative waiting time> 48 h was 63 cases; 68 cases were comminuted cortex of the femoral neck, 32 of them with superficial area of the comminuted cortex>25 mm2. All patients were followed up for at least 2 years, the age, gender, injury side, body mass index, injury mechanism, preoperative waiting time, operation time, Garden classification, whether femoral neck cortex fracture and size by CT analysis and complications were analyzed the correlation to the definite occurrence of AVN. The AVN group and the non-AVN group were divided according to the final efficacy results.Univariate analysis yielded significant independent variables, Multiple Logistic regression analysis was further performed to identify the independent risk factors for AVN.
RESULTS:
By univariate analysis, the AVN and non-AVN groups were significant in injury mechanism(χ2=18.552, P=0.000), preoperative waiting time( χ2=2.065, P=0.033), Garden classification (χ2=12.598, P=0.006), comminuted cortex (χ2=16.357, P=0.000), and the superficial area of the comminuted cortex(χ2=23.371, 0.000, P=0.000). Multiple Logistic regression indicated injury mechanism high energy injury[Exp(B)=3.487, 95%CI(1.583, 10.464), P=0.002], comminuted cortex of the femoral neck[Exp(B)=2.494, 95%CI(1.315, 10.861), P=0.002];the superficial area of the comminuted cortex>25 mm2[Exp(B)=22.161, 95%CI(3.922, 1242.828), P=0.001] were independent risk factors for AVN after internal fixation of femoral neck fractures.
CONCLUSION
High energy injury mechanism, with comminuted cortex of the femoral neck and the superficial area of the comminuted cortex> 25 mm2 were independent risk factors for AVN.The larger the superficial area of the cortex fragment may suggest more complicated injury mechanism and worse outcome.
Humans
;
Male
;
Female
;
Adult
;
Femoral Neck Fractures/diagnostic imaging*
;
Tomography, X-Ray Computed
;
Middle Aged
;
Femur Head Necrosis/etiology*
;
Young Adult
;
Fracture Fixation, Internal/methods*
10.Pressure side and tension side comminution of femoral neck cortex are independent risk factors for aseptic necrosis after femoral neck fracture surgery.
Mang-Mang CHEN ; Yang-Xun LYU ; Sheng-Lei LIN ; Li-Peng HUANG ; Qi-Rong DONG
China Journal of Orthopaedics and Traumatology 2021;34(3):203-208
OBJECTIVE:
To investigate the related factors of aseptic necrosis of femoral head after closed reduction and internal fixation of femoral neck fracture.
METHODS:
From January 2009 to January 2016, 236 patients with femoral neck fracture were treated with closed reduction and internal fixation with 3 hollow lag screws, including 111 males and 125 females, aged from 19 to 89 (50.17±12.88) years. According to the follow-up results, the correlation of aseptic necrosis of femoral head was analyzed. Univariate analysis of age, gender, injured side, body weight, injury mechanism, preoperative waiting time, Garden classification and whether there was comminution of femoral neck cortex was conducted to obtain the independent variables with significant difference. Then binary logistic regression analysis was conducted to explore the independent risk factors of avascular necrosis of femoral head.
RESULTS:
The average follow-up period of 236 cases was 4.58 years. There were significant differences in the range of injury (24.69% vs. 5.16%,
CONCLUSION
High energy injury, preoperative waiting time (>48 h) and comminution of femoral neck cortex were independent risk factors for aseptic necrosis of femoral head. In addition, cortical comminution on the pressure side and tension side of the femoral neck is a strong prognostic risk factor for aseptic necrosis of the femoral head, because it indicates a more serious and complex injury mechanism.
Aged
;
Female
;
Femoral Neck Fractures/surgery*
;
Femur Head Necrosis/surgery*
;
Femur Neck
;
Fracture Fixation, Internal/adverse effects*
;
Fractures, Comminuted
;
Humans
;
Male
;
Risk Factors

Result Analysis
Print
Save
E-mail