1.Research progress of exercise delaying the development of osteoarthritis by regulating pyroptosis
Dongfeng WAN ; Manling LI ; Xi CHEN
Chinese Journal of Orthopaedics 2025;45(14):960-966
Osteoarthritis is a chronic degenerative disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling. Its pathogenesis involves multiple links such as joint mechanical stress imbalance, extracellular matrix degradation, and inflammatory responses. Physical exercise has been widely recognized in the treatment of osteoarthritis. Although mechanism of action remains incompletely understood, appropriate exercise can effectively relieve pain caused by osteoarthritis, improve joint dysfunction, and reduce inflammation. In recent years, pyroptosis has been proven to exacerbate the pathological process of osteoarthritis by promoting the release of pro-inflammatory factors such as IL-1β and HMGB1 from synovial fibroblasts (FLSs) and chondrocytes. The pyroptosis of FLSs is regulated by the NLRP1/3 inflammasome, HIF-1α, and the SDF-1/AMPK pathway. In contrast, chondrocyte pyroptosis is closely related to the activation of the P2X7 receptor, the NF-κB/NLRP3 signaling axis, microRNAs (for example, miR-140-5p inhibits CTSB/NLRP3, while miR-155 promotes pyroptosis), and certain traditional Chinese medicine extracts (such as morroniside and loganin). Both exercise and pyroptosis are closely associated with the inflammatory response in osteoarthritis. Recent studies have found that exercise/mechanical stress stimulation can directly or indirectly regulate chondrocyte pyroptosis and delay the progression of osteoarthritis. In terms of direct regulation, moderate-intensity exercise can downregulate the expression of the P2X7 receptor, activate the AMPK/mTOR pathway to promote autophagy, and thereby inhibit chondrocyte pyroptosis. Mechanical stretch stimulation can upregulate TGF-β1 to activate the Smad2/3 pathway and inhibit the NF-κB/NLRP3 signaling axis. In terms of indirect regulation, exercise can inhibit the PI3K/Akt/NF-κB pathway by increasing the secretion of irisin, and simultaneously promote the production of lipoxin A4 (LXA4) to induce the polarization of synovial macrophages into the anti-inflammatory M2 type. In addition, exercise can also upregulate the expression of Metrnl protein and block the NLRP3/caspase-1/GSDMD pyroptosis signaling cascade.
2.Cohort study on cumulative atherosclerosis-related index in evaluating new-onset non-alcoholic fatty liver disease
Jiayi DENG ; Xinlei MIAO ; Manling HU ; Meng LI ; Yangxuan HE ; Fei XU ; Song LENG
Chinese Journal of Digestion 2025;45(8):526-533
Objective:To explore the correlation of cumulative atherogenic index of plasma (cumAIP) and cumulative atherosclerosis index (cumAI) with new-onset non-alcoholic fatty liver disease (NAFLD).Methods:From January 2017 to December 2023, 2 472 subjects who underwent health checkups at the Second Affiliated Hospital of Dalian Medical University for 3 consecutive years were enrolled. Triglyceride, total cholesterol, high density lipoprotein cholesterol and their measurement time intervals were used to calculate cumAIP and cumAI. The subjects were divided into Q1, Q2, Q3 and Q4 groups with the threshold values of 25th percentile, median and 75th percentile of the baseline atherogenic index of plasma (AIP) and atherosclerotic index (AI) subjects. Cox regression model was used to analyze the effects of cumAIP and cumAI on the new-onset NAFLD, restricted cubic spline was performed to analyze the nonlinear association between cumAIP and cumAI and new-onset NAFLD, and the clinical decision curve was used to compare the decision value of different indicators for NAFLD. Results:The risk of NAFLD gradually increased along with the increasing of cumAIP and cumAI. In the quartile groups of cumAIP, the incidence of Q1 to Q4 groups was 6.15%, 8.74%, 15.05%, and 25.08%, respectively. In the quartile groups of cumAI, the incidence of Q1 to Q4 groups was 5.99%, 11.17%, 15.21%, and 22.65%, respectively. After adjusting the confounding factors, the risk of new-onset NAFLD in the high-level group ( Q4) was higher than that in the low-level cumAIP group ( Q1) ( HR=3.15, 95% confidence interval (95% CI): 2.15 to 4.63, P<0.001) and the high-level cumAI group ( Q4) ( HR=2.74, 95% CI: 1.82 to 4.10, P<0.001). cumAIP and cumAI showed a significant nonlinear association with new-onset NAFLD ( χ2=119.15, 94.53; both P<0.001). The cumAIP had higher predictive value for NAFLD than the other cumulative lipid metrics and baseline AIP or AI. Conclusion:CumAIP and cumAI can be served as new predictive indicators of NAFLD, with a particular focus on the dynamic cumulative changes of AIP, which can achieve effective early screening for NAFLD.
3.Association of systemic immune-inflammation index and pan-immune-inflammation value with incident non-alcoholic fatty liver disease
Yangxuan HE ; Xinlei MIAO ; Manling HU ; Fei XU ; Jiayi DENG ; Meng LI ; Song LENG
Chinese Journal of Health Management 2025;19(9):707-713
Objective:Investigating the association of the systemic immune-inflammation index and the pan-inflammation index with incident non-alcoholic fatty liver disease (NAFLD).Methods:This retrospective cohort study included 42 891 participants who underwent at least two health examinations at the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Based on their levels of the systemic immune inflammation index (SII) and the pan immune inflammation value (PIV), participants were respectively divided into four quartile groups (Q1 to Q4). Cox proportional hazards models were employed to analyze the association of different SII and PIV levels, as well as their quartile groups, with new onset NAFLD in the total population and across various subgroups. Restricted cubic splines were used to examine the dose response relationship between these inflammatory indices and incident NAFLD. Additionally, sensitivity analyses were conducted to confirm the robustness of the findings.Results:After adjusting for confounding factors, the natural logarithm-transformed lnSII ( HR=1.247, 95% CI: 1.184-1.314, P<0.001) and lnPIV ( HR=1.192, 95% CI: 1.148-1.238, P<0.001) were significantly positively associated with the risk of NAFLD. When the subjects were grouped by SII quartiles (Q1-Q4), compared with those in Q1, participants in Q2, Q3, and Q4 exhibited progressively higher risks of incident NAFLD:11.9% ( HR=1.119, 95% CI: 1.051-1.192, P<0.001), 17.1% ( HR=1.171, 95% CI: 1.100-1.248, P<0.001), and 29.1% ( HR=1.291, 95% CI: 1.211-1.377, P<0.001), respectively. Quartile analysis of PIV yielded similar trends: the risk of incident NAFLD increased for 10.4% ( HR=1.104, 95% CI: 1.034-1.179, P=0.003), 18.7% ( HR=1.187, 95% CI: 1.112-1.266, P<0.001), and 30.5% ( HR=1.305, 95% CI: 1.223-1.393, P<0.001) in Q2, Q3, and Q4 group respectively when compared to that in Q1 group. Subgroup analysis confirmed consistent associations of SII and PIV with elevated NAFLD risk across all subgroups. Conclusion:Elevated levels of SII and PIV are significantly associated with increased risk of NAFLD.
4.Research progress of exercise delaying the development of osteoarthritis by regulating pyroptosis
Dongfeng WAN ; Manling LI ; Xi CHEN
Chinese Journal of Orthopaedics 2025;45(14):960-966
Osteoarthritis is a chronic degenerative disease characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling. Its pathogenesis involves multiple links such as joint mechanical stress imbalance, extracellular matrix degradation, and inflammatory responses. Physical exercise has been widely recognized in the treatment of osteoarthritis. Although mechanism of action remains incompletely understood, appropriate exercise can effectively relieve pain caused by osteoarthritis, improve joint dysfunction, and reduce inflammation. In recent years, pyroptosis has been proven to exacerbate the pathological process of osteoarthritis by promoting the release of pro-inflammatory factors such as IL-1β and HMGB1 from synovial fibroblasts (FLSs) and chondrocytes. The pyroptosis of FLSs is regulated by the NLRP1/3 inflammasome, HIF-1α, and the SDF-1/AMPK pathway. In contrast, chondrocyte pyroptosis is closely related to the activation of the P2X7 receptor, the NF-κB/NLRP3 signaling axis, microRNAs (for example, miR-140-5p inhibits CTSB/NLRP3, while miR-155 promotes pyroptosis), and certain traditional Chinese medicine extracts (such as morroniside and loganin). Both exercise and pyroptosis are closely associated with the inflammatory response in osteoarthritis. Recent studies have found that exercise/mechanical stress stimulation can directly or indirectly regulate chondrocyte pyroptosis and delay the progression of osteoarthritis. In terms of direct regulation, moderate-intensity exercise can downregulate the expression of the P2X7 receptor, activate the AMPK/mTOR pathway to promote autophagy, and thereby inhibit chondrocyte pyroptosis. Mechanical stretch stimulation can upregulate TGF-β1 to activate the Smad2/3 pathway and inhibit the NF-κB/NLRP3 signaling axis. In terms of indirect regulation, exercise can inhibit the PI3K/Akt/NF-κB pathway by increasing the secretion of irisin, and simultaneously promote the production of lipoxin A4 (LXA4) to induce the polarization of synovial macrophages into the anti-inflammatory M2 type. In addition, exercise can also upregulate the expression of Metrnl protein and block the NLRP3/caspase-1/GSDMD pyroptosis signaling cascade.
5.The effects of IgD on the proliferation and apoptosis of acute myeloid leukemia cells Molm-13
Danyan Liu ; Xin Zhang ; Mengqin Chen ; Xi Ling ; Manling Dong ; Tiantian Wu ; Yueye Wang ; Tao Li ; Wei Wei ; Yujing Wu
Acta Universitatis Medicinalis Anhui 2025;60(8):1513-1519,1534
Objective :
To investigate the role and related mechanisms of IgD on the viability , proliferation , apoptosis , and other functions of Molm_13 cells.
Methods:
Peripheral blood serum was collected from AML patients and healthy controls. The sIgD levels were quantified by ELISA. For in vitro studies , Molm_13 cells were treated with varying concentrations of IgD. Cell viability and proliferation were assessed via CCK_8 assays , CFSE staining , and colony formation assays. Apoptosis rates were determined using an Annexin V/PI apoptosis detection kit. Preliminary exploration of the mechanisms related to IgD_induced proliferation of Molm_13 were analyzed through differential gene analysis.
Results:
Compared with healthy controls , the levels of sIgD in AML patients were significantly el_ evated (P < 0. 001 ) . IgD treatment dose_dependently increased Molm_13 cell viability and proliferation ( P < 0. 05) , inhibited apoptosis rates (P < 0. 001) .
Conclusion
IgD promotes the viability and proliferation of Molm_ 13 cells , and reduces apoptosis.
6.Epidemiological characteristics and relationship analysis of food intolerance in children in Zhuzhou area
Xiang CHEN ; Sheng LI ; Hui LIN ; Xiuying YI ; Juan LI ; Manling TANG
International Journal of Laboratory Medicine 2025;46(18):2226-2230,2236
Objective To investigate the prevalence of food intolerance among children in Zhuzhou area and its relationship with age,gender,systemic diseases,and food allergies,so as to provide a basis for the scientific adjustment of children's dietary structure.Methods A retrospective analysis was conducted on totally 1 592 children who underwent food intolerance and food allergen testing in the hospital,the positive rate and distri-bution of 14 kinds of food intolerance were assessed,and their correlation with various factors was analyzed.Results Among 14 kinds of food tested,milk and eggs had the highest positive rates of intolerance,at 82.22%and 55.78%,respectively.The majority of children were intolerant to 1 to 2 kinds of food,with a de-creasing trend in the number of children intolerant to multiple kinds of food.Among the 14 types of food,ex-cept for mushrooms and pork,there were statistically significant differences in the distribution of negative,mild,moderate,and severe intolerance in other foods(P<0.05).Children tended to have moderate or even se-vere intolerance to milk and eggs,while they tended to have mild intolerance to other foods.There was no sta-tistically significant difference in the overall food intolerance rate between boys and girls(P=0.654),but the positive rate of tomato intolerance in girls was slightly higher than that in boys(P=0.043).Except for pork,there were statistically significant differences in the positive rates of intolerance to 14 different foods among different age groups(P<0.05).The positive rates of intolerance to cod,mushrooms,and crabs increased with age,while the positive rates of intolerance to beef decreased with age.There was a statistically significant difference in the positive rate of milk intolerance between healthy children and children with skin allergies(P<0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to milk compared to hose who were intolerant and allergic to milk(P<0.05).There was a statistically significant difference in the proportion of individuals who were tolerant and not allergic to eggs compared to those who were intolerant and allergic to eggs(P<0.05).Conclusion The positive rate of food intolerance among children in Zhuzhou area is relatively high,with milk and eggs being the main intolerant foods.There are differences in the positive rate of intolerance among different gender and age groups,and in-tolerance to milk and eggs is associated with food allergies to some extent.
7.Cohort study on cumulative atherosclerosis-related index in evaluating new-onset non-alcoholic fatty liver disease
Jiayi DENG ; Xinlei MIAO ; Manling HU ; Meng LI ; Yangxuan HE ; Fei XU ; Song LENG
Chinese Journal of Digestion 2025;45(8):526-533
Objective:To explore the correlation of cumulative atherogenic index of plasma (cumAIP) and cumulative atherosclerosis index (cumAI) with new-onset non-alcoholic fatty liver disease (NAFLD).Methods:From January 2017 to December 2023, 2 472 subjects who underwent health checkups at the Second Affiliated Hospital of Dalian Medical University for 3 consecutive years were enrolled. Triglyceride, total cholesterol, high density lipoprotein cholesterol and their measurement time intervals were used to calculate cumAIP and cumAI. The subjects were divided into Q1, Q2, Q3 and Q4 groups with the threshold values of 25th percentile, median and 75th percentile of the baseline atherogenic index of plasma (AIP) and atherosclerotic index (AI) subjects. Cox regression model was used to analyze the effects of cumAIP and cumAI on the new-onset NAFLD, restricted cubic spline was performed to analyze the nonlinear association between cumAIP and cumAI and new-onset NAFLD, and the clinical decision curve was used to compare the decision value of different indicators for NAFLD. Results:The risk of NAFLD gradually increased along with the increasing of cumAIP and cumAI. In the quartile groups of cumAIP, the incidence of Q1 to Q4 groups was 6.15%, 8.74%, 15.05%, and 25.08%, respectively. In the quartile groups of cumAI, the incidence of Q1 to Q4 groups was 5.99%, 11.17%, 15.21%, and 22.65%, respectively. After adjusting the confounding factors, the risk of new-onset NAFLD in the high-level group ( Q4) was higher than that in the low-level cumAIP group ( Q1) ( HR=3.15, 95% confidence interval (95% CI): 2.15 to 4.63, P<0.001) and the high-level cumAI group ( Q4) ( HR=2.74, 95% CI: 1.82 to 4.10, P<0.001). cumAIP and cumAI showed a significant nonlinear association with new-onset NAFLD ( χ2=119.15, 94.53; both P<0.001). The cumAIP had higher predictive value for NAFLD than the other cumulative lipid metrics and baseline AIP or AI. Conclusion:CumAIP and cumAI can be served as new predictive indicators of NAFLD, with a particular focus on the dynamic cumulative changes of AIP, which can achieve effective early screening for NAFLD.
8.Association of systemic immune-inflammation index and pan-immune-inflammation value with incident non-alcoholic fatty liver disease
Yangxuan HE ; Xinlei MIAO ; Manling HU ; Fei XU ; Jiayi DENG ; Meng LI ; Song LENG
Chinese Journal of Health Management 2025;19(9):707-713
Objective:Investigating the association of the systemic immune-inflammation index and the pan-inflammation index with incident non-alcoholic fatty liver disease (NAFLD).Methods:This retrospective cohort study included 42 891 participants who underwent at least two health examinations at the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Based on their levels of the systemic immune inflammation index (SII) and the pan immune inflammation value (PIV), participants were respectively divided into four quartile groups (Q1 to Q4). Cox proportional hazards models were employed to analyze the association of different SII and PIV levels, as well as their quartile groups, with new onset NAFLD in the total population and across various subgroups. Restricted cubic splines were used to examine the dose response relationship between these inflammatory indices and incident NAFLD. Additionally, sensitivity analyses were conducted to confirm the robustness of the findings.Results:After adjusting for confounding factors, the natural logarithm-transformed lnSII ( HR=1.247, 95% CI: 1.184-1.314, P<0.001) and lnPIV ( HR=1.192, 95% CI: 1.148-1.238, P<0.001) were significantly positively associated with the risk of NAFLD. When the subjects were grouped by SII quartiles (Q1-Q4), compared with those in Q1, participants in Q2, Q3, and Q4 exhibited progressively higher risks of incident NAFLD:11.9% ( HR=1.119, 95% CI: 1.051-1.192, P<0.001), 17.1% ( HR=1.171, 95% CI: 1.100-1.248, P<0.001), and 29.1% ( HR=1.291, 95% CI: 1.211-1.377, P<0.001), respectively. Quartile analysis of PIV yielded similar trends: the risk of incident NAFLD increased for 10.4% ( HR=1.104, 95% CI: 1.034-1.179, P=0.003), 18.7% ( HR=1.187, 95% CI: 1.112-1.266, P<0.001), and 30.5% ( HR=1.305, 95% CI: 1.223-1.393, P<0.001) in Q2, Q3, and Q4 group respectively when compared to that in Q1 group. Subgroup analysis confirmed consistent associations of SII and PIV with elevated NAFLD risk across all subgroups. Conclusion:Elevated levels of SII and PIV are significantly associated with increased risk of NAFLD.
9.Latent tuberculosis infection and preventive treatment among in-school students: a review
QIU Manling ; JIANG Yi ; LI Mengying ; PAN Xiaoyan
Journal of Preventive Medicine 2024;36(1):30-33
School is a densely populated place, which can easily lead to tuberculosis clusters, then affect the physical and mental health of students and the normal teaching order of school. Tuberculosis latent infection (LTBI) screening for new students and close contacts of tuberculosis patients has become important parts of school tuberculosis prevention and control strategies. Previous studies have shown that the LTBI rate of Chinese in-school students is about 5.74% to 11.67%, and there are differences in gender, studying phase and urban-rural distributions. Preventive treatment is an effective measure to prevent LTBI from developing into active tuberculosis, but the proportion of LTBI preventive treatment for students in most areas is low. The difficulties in implementing preventive treatment may be attributed to concerns about adverse reactions to medication and sense of shame towards illness among students, and lack of awareness about preventive treatment among medical staff. This review searches the research literature published from 2016 to 2023, and summarizes the prevalence of LTBI in Chinese students and progress on preventive treatment, so as to provide insights into prevention and control of tuberculosis among students.
10.Long-term hypomethylating agents in patients with myelodysplastic syndromes: a multi-center retrospective study
Xiaozhen LIU ; Shujuan ZHOU ; Jian HUANG ; Caifang ZHAO ; Lingxu JIANG ; Yudi ZHANG ; Chen MEI ; Liya MA ; Xinping ZHOU ; Yanping SHAO ; Gongqiang WU ; Xibin XIAO ; Rongxin YAO ; Xiaohong DU ; Tonglin HU ; Shenxian QIAN ; Yuan LI ; Xuefen YAN ; Li HUANG ; Manling WANG ; Jiaping FU ; Lihong SHOU ; Wenhua JIANG ; Weimei JIN ; Linjie LI ; Jing LE ; Wenji LUO ; Yun ZHANG ; Xiujie ZHOU ; Hao ZHANG ; Xianghua LANG ; Mei ZHOU ; Jie JIN ; Huifang JIANG ; Jin ZHANG ; Guifang OUYANG ; Hongyan TONG
Chinese Journal of Hematology 2024;45(8):738-747
Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.


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