1.Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.
Yongxian LI ; Jinbo YUAN ; Wei DENG ; Haishan LI ; Yuewei LIN ; Jiamin YANG ; Kai CHEN ; Heng QIU ; Ziyi WANG ; Vincent KUEK ; Dongping WANG ; Zhen ZHANG ; Bin MAI ; Yang SHAO ; Pan KANG ; Qiuli QIN ; Jinglan LI ; Huizhi GUO ; Yanhuai MA ; Danqing GUO ; Guoye MO ; Yijing FANG ; Renxiang TAN ; Chenguang ZHAN ; Teng LIU ; Guoning GU ; Kai YUAN ; Yongchao TANG ; De LIANG ; Liangliang XU ; Jiake XU ; Shuncong ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):90-101
Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals
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NFATC Transcription Factors/genetics*
;
Drugs, Chinese Herbal/pharmacology*
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Ovariectomy
;
Osteoclasts/metabolism*
;
Female
;
Osteogenesis/drug effects*
;
Rats, Sprague-Dawley
;
Rats
;
NF-kappa B/genetics*
;
Osteoporosis/genetics*
;
Signal Transduction/drug effects*
;
Bone Resorption/genetics*
;
Cell Differentiation/drug effects*
;
Humans
;
RANK Ligand/metabolism*
;
Mitogen-Activated Protein Kinases/genetics*
;
Transcription Factors
2.Health economic evaluation of minimally invasive surgery in treatment of digestive tract cancers: a Meta-analysis
Xiaoyue YIN ; Ning ZHOU ; Xueli YANG ; Zhuoyu SUN ; Yinghui BAO ; Shengshu WANG ; Ke HAN ; Jing LONG ; Min ZHAO ; Haowei LI ; Rongrong LI ; Shimin CHEN ; Junhan YANG ; Huaihao LI ; Yueting SHI ; Guoning ZHU ; Jianhua WANG ; Shanshan YANG ; Boyan LI ; Wenchang WANG ; Shengyan DU ; Yao HE ; Enqiang LING-HU ; Huikai LI ; Miao LIU ; Juan XIE
Chinese Journal of Epidemiology 2025;46(1):154-165
Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.
3.Feasibility analysis of bilateral uterine artery embolization via distal radial artery access
Faliang DAI ; Chunhai LI ; Jun HOU ; Tianshu LIU ; Yongqi JI ; Fangfang ZHANG ; Yan JIAO ; Guoning TIAN ; Yixing LIU
Journal of Practical Radiology 2025;41(9):1549-1552
Objective To explore the feasibility and safety of bilateral uterine artery embolization(UAE)via distal radial artery access.Methods Thirty patients who underwent bilateral UAE were selected.They were divided into distal radial artery group(14 cases)and femoral artery group(16 cases).The clinical signs,puncture times,operation time,compression hemostasis time,discomfort scores,microcatheter non-use rates,and complication rates of the two groups were analyzed,the feasibility and safety of bilateral UAE via distal radial artery access were evaluated.Results The mean number of puncture times in the distal radial artery group was 1.6 times that of the femoral artery group,and the puncture pain score was 1.5 times that of the femoral artery group(P<0.05).The operation time and puncture point compression hemostasis time in the distal radial artery group were shorter than those in the femoral artery group,and the discomfort score of compression hemostasis in the distal radial artery group was lower than that in the femoral artery group(P<0.01).The proportions who did not use microcatheters in the two groups accounted for 28.6%and 6.3%,respectively,the difference was not statistically significant(P>0.05).Four patients with poor access vessels were found in the distal radial artery group(P<0.05).Conclusion Bilateral UAE via distal radial artery access is safe and feasible.
4.Impact of cryostorage duration on clinical outcomes: a retrospective cohort study of vitrified high-quality embryos
Xiaoni GUO ; Xiaojie LIU ; Xiaodong ZHANG ; Guoning HUANG ; Qi ZHANG
Chinese Journal of Reproduction and Contraception 2025;45(8):802-808
Objective:To evaluate the effect of prolonged cryopreservation duration of high-quality embryos on clinical outcomes.Methods:A retrospective cohort study was conducted, analyzing 8 988 frozen-thawed embryo transfer cycles performed from January 2016 to December 2023 at the Center for Reproductive Medicine, Chongqing Maternal and Child Healthcare Hospital where patients underwent endometrial preparation with artificial cycles and subsequent transfer of high-quality embryos. Embryos were divided into four groups according to the length of time they had been cryopreserved: ≤3-month group ( n=3 030), 4-6-month group ( n=3 193), 7-12-month group ( n=1 465), and >12-month group ( n=1 300). High-quality cleavage-stage embryos and blastocysts were selected according to the Istanbul Consensus and Gardner grading system. High-quality cleavage-stage embryos were defined as those graded ≤2, while high-quality blastocysts were defined as those graded ≥4BB. Generalized estimating equations were employed for multivariate analysis. Primary outcome indicator was clinical pregnancy rate, with secondary outcome indicators comprising live birth rate, miscarriage rate and preterm birth rate. Results:Significant intergroup differences were observed in baseline characteristics, including age, body mass index, anti-Müllerian hormone levels, fertilization method, endometrial thickness on transfer day, infertility etiology, infertility type, number of embryos transferred, embryo culture duration, number of eggs obtained, and preimplantation genetic testing (all P<0.05). Clinical pregnancy rates for the ≤3-month, 4-6-month, 7-12-month, and >12-month groups were 69.04% (2 092/3 030), 70.15% (2 240/3 193), 61.16% (896/1 465), and 57.69% (750/1 300), respectively, and live birth rates were 58.58% (1 775/3 030), 60.04% (1 917/3 193), 51.40% (753/1 465), and 47.00% (611/1 300), with significantly differences (all P<0.001). After adjusting for confounders via multivariate analysis, the 4-6-month group showed no statistically significant difference in clinical pregnancy rate or live birth rate compared with the ≤3-month group (clinical pregnancy: OR=0.982, 95% CI: 0.874-1.103, P=0.754; live birth: OR=0.989, 95% CI: 0.887-1.102, P=0.835). However, both the 7-12-month group (clinical pregnancy: OR=0.772, 95% CI: 0.671-0.888, P<0.001; live birth: OR=0.805, 95% CI: 0.704-0.921, P=0.002) and >12-month group (clinical pregnancy: OR=0.765, 95% CI: 0.662-0.885, P<0.001; live birth: OR=0.772, 95% CI: 0.671-0.888, P<0.001) exhibited significant decreases in clinical pregnancy rate and live birth rate. No significant differences were observed in miscarriage rate and preterm birth rate among the four groups (all P>0.05). Stratified by age, the results were consistent with the total population. Conclusion:The duration of high-quality embryo vitrification freezing exceeding 6 months is negatively correlated with clinical pregnancy rate and live birth rate, and cryostorage time should be considered as a relevant factor in embryo selection.
5.Impact of cryostorage duration on clinical outcomes: a retrospective cohort study of vitrified high-quality embryos
Xiaoni GUO ; Xiaojie LIU ; Xiaodong ZHANG ; Guoning HUANG ; Qi ZHANG
Chinese Journal of Reproduction and Contraception 2025;45(8):802-808
Objective:To evaluate the effect of prolonged cryopreservation duration of high-quality embryos on clinical outcomes.Methods:A retrospective cohort study was conducted, analyzing 8 988 frozen-thawed embryo transfer cycles performed from January 2016 to December 2023 at the Center for Reproductive Medicine, Chongqing Maternal and Child Healthcare Hospital where patients underwent endometrial preparation with artificial cycles and subsequent transfer of high-quality embryos. Embryos were divided into four groups according to the length of time they had been cryopreserved: ≤3-month group ( n=3 030), 4-6-month group ( n=3 193), 7-12-month group ( n=1 465), and >12-month group ( n=1 300). High-quality cleavage-stage embryos and blastocysts were selected according to the Istanbul Consensus and Gardner grading system. High-quality cleavage-stage embryos were defined as those graded ≤2, while high-quality blastocysts were defined as those graded ≥4BB. Generalized estimating equations were employed for multivariate analysis. Primary outcome indicator was clinical pregnancy rate, with secondary outcome indicators comprising live birth rate, miscarriage rate and preterm birth rate. Results:Significant intergroup differences were observed in baseline characteristics, including age, body mass index, anti-Müllerian hormone levels, fertilization method, endometrial thickness on transfer day, infertility etiology, infertility type, number of embryos transferred, embryo culture duration, number of eggs obtained, and preimplantation genetic testing (all P<0.05). Clinical pregnancy rates for the ≤3-month, 4-6-month, 7-12-month, and >12-month groups were 69.04% (2 092/3 030), 70.15% (2 240/3 193), 61.16% (896/1 465), and 57.69% (750/1 300), respectively, and live birth rates were 58.58% (1 775/3 030), 60.04% (1 917/3 193), 51.40% (753/1 465), and 47.00% (611/1 300), with significantly differences (all P<0.001). After adjusting for confounders via multivariate analysis, the 4-6-month group showed no statistically significant difference in clinical pregnancy rate or live birth rate compared with the ≤3-month group (clinical pregnancy: OR=0.982, 95% CI: 0.874-1.103, P=0.754; live birth: OR=0.989, 95% CI: 0.887-1.102, P=0.835). However, both the 7-12-month group (clinical pregnancy: OR=0.772, 95% CI: 0.671-0.888, P<0.001; live birth: OR=0.805, 95% CI: 0.704-0.921, P=0.002) and >12-month group (clinical pregnancy: OR=0.765, 95% CI: 0.662-0.885, P<0.001; live birth: OR=0.772, 95% CI: 0.671-0.888, P<0.001) exhibited significant decreases in clinical pregnancy rate and live birth rate. No significant differences were observed in miscarriage rate and preterm birth rate among the four groups (all P>0.05). Stratified by age, the results were consistent with the total population. Conclusion:The duration of high-quality embryo vitrification freezing exceeding 6 months is negatively correlated with clinical pregnancy rate and live birth rate, and cryostorage time should be considered as a relevant factor in embryo selection.
6.Health economic evaluation of minimally invasive surgery in treatment of digestive tract cancers: a Meta-analysis
Xiaoyue YIN ; Ning ZHOU ; Xueli YANG ; Zhuoyu SUN ; Yinghui BAO ; Shengshu WANG ; Ke HAN ; Jing LONG ; Min ZHAO ; Haowei LI ; Rongrong LI ; Shimin CHEN ; Junhan YANG ; Huaihao LI ; Yueting SHI ; Guoning ZHU ; Jianhua WANG ; Shanshan YANG ; Boyan LI ; Wenchang WANG ; Shengyan DU ; Yao HE ; Enqiang LING-HU ; Huikai LI ; Miao LIU ; Juan XIE
Chinese Journal of Epidemiology 2025;46(1):154-165
Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.
7.Feasibility analysis of bilateral uterine artery embolization via distal radial artery access
Faliang DAI ; Chunhai LI ; Jun HOU ; Tianshu LIU ; Yongqi JI ; Fangfang ZHANG ; Yan JIAO ; Guoning TIAN ; Yixing LIU
Journal of Practical Radiology 2025;41(9):1549-1552
Objective To explore the feasibility and safety of bilateral uterine artery embolization(UAE)via distal radial artery access.Methods Thirty patients who underwent bilateral UAE were selected.They were divided into distal radial artery group(14 cases)and femoral artery group(16 cases).The clinical signs,puncture times,operation time,compression hemostasis time,discomfort scores,microcatheter non-use rates,and complication rates of the two groups were analyzed,the feasibility and safety of bilateral UAE via distal radial artery access were evaluated.Results The mean number of puncture times in the distal radial artery group was 1.6 times that of the femoral artery group,and the puncture pain score was 1.5 times that of the femoral artery group(P<0.05).The operation time and puncture point compression hemostasis time in the distal radial artery group were shorter than those in the femoral artery group,and the discomfort score of compression hemostasis in the distal radial artery group was lower than that in the femoral artery group(P<0.01).The proportions who did not use microcatheters in the two groups accounted for 28.6%and 6.3%,respectively,the difference was not statistically significant(P>0.05).Four patients with poor access vessels were found in the distal radial artery group(P<0.05).Conclusion Bilateral UAE via distal radial artery access is safe and feasible.
8.Application of the blastomere count variations “skip value” in the embryo AI assessment
Jingwei YANG ; Wei HAN ; Weiwei LIU ; Junxia LIU ; Guoning HUANG ; Xiaodong ZHANG
Chinese Journal of Obstetrics and Gynecology 2024;59(7):548-558
Objective:To explore the correlation between blastomere count variations “skip value” which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications.Methods:This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children′s Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis.Results:The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the β values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P<0.001); positively correlated with D3-cell number ( β=0.034; P<0.001); negatively correlated with blastocyst formation rate and implantation rate ( OR=0.97, 95% CI: 0.93-0.99, P=0.034; OR=0.96, 95% CI: 0.93-0.98, P=0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age ( OR=0.91, 95% CI: 0.88-0.93; P<0.001), D3 general score ( OR=0.77, 95% CI: 0.59-0.99; P=0.045) and order selection of skip values ( OR=0.98, 95% CI: 0.96-0.99; P=0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred ( OR=1.08, 95% CI:1.05-1.11, P<0.001; OR=1.09, 95% CI:1.06-0.12, P<0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions:The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.
9.Advances in surgical strategies for ossification of posterior longitudinal ligament involving the C 2 segment.
Teng LIU ; Guoning GU ; Chenguang ZHAN ; Haishan LI ; Huizhi GUO ; Yongxian LI ; Guoye MO ; Kai YUAN ; Shuncong ZHANG ; Zhidong YANG ; Yongchao TANG
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(6):742-747
OBJECTIVE:
To evaluate the application of surgical strategies for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving the C 2 segment.
METHODS:
The literature about the surgery for cervical OPLL involving C 2 segment was reviewed, and the indications, advantages, and disadvantages of surgery were summarized.
RESULTS:
For cervical OPLL involving the C 2 segments, laminectomy is suitable for patients with OPLL involving multiple segments, often combined with screw fixation, and has the advantages of adequate decompression and restoration of cervical curvature, with the disadvantages of loss of cervical fixed segmental mobility. Canal-expansive laminoplasty is suitable for patients with positive K-line and has the advantages of simple operation and preservation of cervical segmental mobility, and the disadvantages include progression of ossification, axial symptoms, and fracture of the portal axis. Dome-like laminoplasty is suitable for patients without kyphosis/cervical instability and with negative R-line, and can reduce the occurrence of axial symptoms, with the disadvantage of limited decompression. The Shelter technique is suitable for patients with single/double segments and canal encroachment >50% and allows for direct decompression, but is technically demanding and involves risk of dural tear and nerve injury. Double-dome laminoplasty is suitable for patients without kyphosis/cervical instability. Its advantages are the reduction of damage to the cervical semispinal muscles and attachment points and maintenance of cervical curvature, but there is progress in postoperative ossification.
CONCLUSION
OPLL involving the C 2 segment is a complex subtype of cervical OPLL, which is mainly treated through posterior surgery. However, the degree of spinal cord floatation is limited, and with the progress of ossification, the long-term effectiveness is poor. More research is needed to address the etiology of OPLL and to establish a systematic treatment strategy for cervical OPLL involving the C 2 segment.
Humans
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Longitudinal Ligaments/surgery*
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Ossification of Posterior Longitudinal Ligament/surgery*
;
Treatment Outcome
;
Osteogenesis
;
Decompression, Surgical/methods*
;
Cervical Vertebrae/surgery*
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Laminoplasty/methods*
;
Kyphosis/surgery*
;
Retrospective Studies
10.MS4A6D promotes carrageenan-induced mouse foot pad swelling by activating NLRP3 inflammasome
Guoning GUO ; Ying HE ; Hongye LIU ; Yongjun SHANG
Immunological Journal 2023;39(10):886-892
We here investigated the effect of MS4A6D(the membrane spanning 4-domain subfamily A(MS4A)superfamily protein 6D),one of the tetraspanins which specifically expresses on the membrane of macrophages,on carrageenan(CGN)-induced mouse foot pad swelling and its possible mechanism.Male C57BL/6 wild-type(WT)and various gene knockout(including Ms4a6d-/-,Nlrp3-/-,Casp-1-/-and IlR1-/-)mice were recruited and injected with 100 μl 1%CGN(w/v)and 20 μl CaCl2(50 mmol/L)to establish the foot pad swelling model,and then the severity of foot pad swelling in WT and gene knockout mice were compared.H&E staining was performed to investigate the pathological changes,and immunofluorescence was used to detect the infiltration of F4/80+ macrophages in the foot pad tissue.Finally,Western blot was used to determine the protein expression of NLRP3,IL-1 β,TNF-α and IL-6.Data showed that the combined injection of 100 μl 1%CGN(w/v)and 20 μl CaCl2(50 mmol/L)significantly promoted the swelling of foot pads,while the degree of foot pad swelling in Ms4a6d-/-mice was significantly lower than that in WT littermates(P<0.05);Significant tissue damage and inflammatory infiltration as well as necrotic lesions were observed in the WT foot pads,whereas,the degrees from Ms4a6d-/-foot pads showed significantly reduced;The protein levels of Caspase-1 and IL-1β in the foot pad tissue of the WT model were significantly higher than those of the Ms4a6d-/-groups;Compared with WT controls,the degree of foot pad swelling in Nlrp3-/-,Casp-1-/-,and IlR1-/-mice induced by 1%CGN(w/v)and CaCl2(50 mmol/L)were also significantly reduced(P<0.05).Taken together,MS4A6D promotes the activation of NLRP3 inflammasome in macrophages and induces IL-1β secretion,by thus deteriorates CGN-mediated swelling of mouse foot pads.

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