1.Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation.
Peitao XU ; Guiwen YE ; Xiaojun XU ; Zhidong LIU ; Wenhui YU ; Guan ZHENG ; Zepeng SU ; Jiajie LIN ; Yunshu CHE ; Yipeng ZENG ; Zhikun LI ; Pei FENG ; Qian CAO ; Zhongyu XIE ; Yanfeng WU ; Huiyong SHEN ; Jinteng LI
Acta Pharmaceutica Sinica B 2025;15(8):4064-4077
Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.
2.Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia.
Mingya LIU ; Feifei QI ; Jue WANG ; Fengdi LI ; Qi LV ; Ran DENG ; Xujian LIANG ; Shasha ZHOU ; Pin YU ; Yanfeng XU ; Yaqing ZHANG ; Yiwei YAN ; Ming LIU ; Shuyue LI ; Guocui MOU ; Linlin BAO
Protein & Cell 2025;16(2):148-155
3.Study on the therapeutic effect of Xuefu Zhuyu Capsule combined with sacubitril valsartan on patients with dilated cardiomyopathy
Zhenhuan CHEN ; Yuan LIU ; Xiantao HUANG ; Yanfeng LIU ; Yu TAO ; Hengli LAI ; Qiuling LIU
Chongqing Medicine 2024;53(4):512-516
Objective To study the therapeutic effect of Xuefu Zhuyu Capsule combined with sacubitril valsartan on dilated cardiomyopathy.Methods A total of 70 patients with dilated cardiomyopathy who were hospitalized in the Hospital from January to December 2020 were selected as the research objects and random-ly divided into control group and experimental group,with 35 cases in each group.The control group was only treated with sacubitril valsartan,and the experimental group was treated with Xuefu Zhuyu Capsule combined with sacubitril valsartan.According to the patient's blood pressure and renal function,sacubitril valsartan was titrated from a small dose to the maximum dose.Xuefu Zhuyu Capsule was uesd 2.4 g each time,twice a day,and the treatment time was three months.The symptoms of heart failure,glycosylated hemoglobin(HbA1c),low density lipoprotein(LDL),total cholesterol(TC),triglyceride(TG),ALT,AST,N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular end-systolic diameter(LVEDd),left ventricular end-dias-tolic diameter(LVEDs),ejection fraction(EF)and the incidence of arrhythmia were observed in the two groups after treatment.Results After treatment,the level of NT-proBNP in the experimental group was sig-nificantly lower than that in the control group(P<0.05).There was no significant difference in LDL,TC,TG,LVEDd,LVEDs and EF between the two groups(P>0.05).The incidence of atrial tachycardia and ven-tricular premature beat in the experimental group was higher than that in the control group(P<0.05).Con-clusion Xuefu Zhuyu Capsule combined with sacubitril valsartan can significantly improve the symptoms of patients with heart failure and reduce the level of NT-proBNP,but it may increase the proportion of patients with atrial tachycardia and ventricular premature beats.
4.Evolution and innovation of preservation fluid for donor liver
Guotao YU ; Yanfeng YIN ; Chuntao YAN ; Guangxu ZOU ; Huangyan ZHANG ; Li MA ; Zongqiang HU
Organ Transplantation 2024;15(1):131-137
Organ preservation fluid could mitigate cold ischemia injury and maintain normal function of the grafts. At present, how to reduce a series of injury caused by cold ischemia of donor liver and improve the preservation quality of grafts are the hot and challenging spots in this field. Currently, preservation fluid in clinical practice has not achieved ideal preservation effect, especially for the protection of marginal donor organs. In the context of severe donor shortage, the key solution is still to explore the optimal preservation protocol for donor liver to prevent grafts from cold ischemia injury. In this article, the mechanism of donor liver injury during cold ischemia, the classification and evolution of donor liver preservation fluid were summarized, the development direction and challenges of donor liver preservation fluid were discussed, aiming to provide novel ideas and references for the research and development of donor liver preservation fluid.
5.Neuro-pathological study of intrathalamic neurovirulence test of poliomyelitis vaccine in rhesus macaques
Pin YU ; Yanfeng XU ; Yunlin HAN ; Wenjie ZHAO ; Chuan QIN
Chinese Journal of Comparative Medicine 2024;34(6):47-53
Objective To study the effect and pathological mechanisms of the neuro-immune response to viral encephalomyelitis caused by virulence reversion following the intrathalamic neurovirulence test for poliomyelitis vaccine in rhesus macaques.Methods Stock solutions(≥7000 lgCCID50/L)of inactivated polio vaccines(Vero cells)of type I,type Ⅱ,and type Ⅲ Sabin strains and 10-1 dilution of each type of polio vaccine were given to macaques,which were subjected to a intrathalamic neurovirulence test.Using immunohistochemical method,the pathological changes caused by polio,as determined by the distribution of CD 155 and CD4+receptor T lymphocytes,CD20+B lymphocytes,and CD68+microglia,were detected.Results Lesions were observed on the virulence-reverted polio cases.Inflammatory cell infiltration,neuronal degeneration and necrosis,satellite phenomena,perivascular cuffing,and glial cell proliferation were observed in the spinal cord.The inflammatory cells in the perivascular cuffing and proliferative glial nodules were mainly CD4+T lymphocytes,CD20+B lymphocytes,and CD68+microglia.There was no significant difference in the distribution of the poliovirus receptor CD 155 in the neurons and glial cells of monkeys with and without polio,and no expression was observed in their vascular endothelial cells.Conclusions Polio caused by virulence reversion of the intrathalamic neurovirulence test is viral encephalomyelitis.
6.Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study
Xinhua CHEN ; Hexin LIN ; Yuehong CHEN ; Xiaodong WANG ; Chaoqun LIU ; Huilin HUANG ; Huayuan LIANG ; Huimin ZHANG ; Fengping LI ; Hao LIU ; Yanfeng HU ; Guoxin LI ; Jun YOU ; Liying ZHAO ; Jiang YU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):694-701
Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.
7.Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study
Xinhua CHEN ; Hexin LIN ; Yuehong CHEN ; Xiaodong WANG ; Chaoqun LIU ; Huilin HUANG ; Huayuan LIANG ; Huimin ZHANG ; Fengping LI ; Hao LIU ; Yanfeng HU ; Guoxin LI ; Jun YOU ; Liying ZHAO ; Jiang YU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):694-701
Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.
8.Relationship between heart rate variability, deceleration capacity and cardiovascular metabolic diseases in children and adolescents with normal weight obesity
Bo YU ; Kun SHI ; Xiaojuan ZHOU ; Xiaoyan WANG ; Lingxia FAN ; Feifei SI ; Yanfeng YANG
Chinese Journal of Applied Clinical Pediatrics 2024;39(6):450-454
Objective:To investigate the relationship between heart rate variability(HRV), deceleration capacity(DC) and cardiovascular metabolic disease(CMD) in children and adolescents with normal weight obesity(NWO).Methods:A total of 200 children and adolescents aged 6-17 who underwent normal physical examination in Chengdu Women′s and Children′s Central Hospital from December 2022 to June 2023 were included in this retrospective case-control study.They were divided into the NWO group, normal weight lean(NWL) group, and overweight-obesity(OW-OB) group according to their body mass index(BMI) and body fat percentage(BF%).Fifty children were enrolled into the NWO group; fifty-one children were enrolled into the NWL group; and 99 children were enrolled into the OW-OB group.All the subjects received 24-hour heart monitoring, and their HRV indexes, such as the standard deviation of N-N interval in normal sinus(SDNN), the standard deviation of the mean value N-N intervals every 5-minute(SDANN), the mean of the standard deviations of all N-N intervals for each 5-minute segment of 24 hours(SDNNindex), the root mean square of successive N-N interval difference(rMSSD), the proportion of N-N 50(the successive N-N interval differences>50 ms) in the total number of N-N intervals(pNN50), and DC were automatically calculated.Blood pressure, fasting blood glucose and blood lipids were measured, and the cardiometabolic risk score(CRS) was obtained through the accumulation of relevant factors.The general data, SDNN, SDANN, SDNNindex, rMSSD, pNN50, DC and CRS of the three groups were compared by variance analysis.Spearman correlation and multivariate Logistic regression were used to analyze the risk factors affecting CRS.Results:There was no significant difference in age, gender and other general information among the three groups(all P>0.05).SDNN in the NWO, NWL, and OW-OB groups were(120.88±16.36) ms, (129.07±16.36) ms, and(109.29±16.38) ms, respectively( F=26.231, P<0.001); SDANN were(64.44±11.61) ms, (66.25±8.34) ms, and(61.70±6.85) ms, respectively( F=5.048, P=0.007); rMSSD were(27.02±3.87) ms, (27.51±5.92) ms, and(25.12±6.78) ms, respectively( F=3.328, P=0.038); pNN50 were(12.62±4.04)%, (13.39±2.26)%, and(11.22±2.93)%, respectively( F=9.099, P<0.001); DC were(4.83±0.20) ms, (4.94±0.33) ms, and(4.63±0.28) ms, respectively( F=23.496, P<0.001)and CRS was 0.94±0.87, 0.69±0.19 and 1.57±1.07, respectively( P<0.01).The differences between the three groups were statistically significant.Spearman correlation analysis showed that BMI( r=0.211, P=0.003) and BF%( r=0.558, P<0.001) were significantly positively correlated with CRS, while SDNN( r=-0.258, P<0.001) and DC( r=-0.499, P<0.001) were significantly negatively correlated with CRS.Multivariate Logistic regression analysis showed that BF%(95% CI: 0.098-0.265, P<0.001) and DC(95% CI: -3.962--1.391, P<0.001) were independent risk factors for predicting CMD. Conclusions:Increased BF% and decreased DC are independent risk factors for CMD.Analysis of body composition and HRV in children and adolescents can help to identify potentially high-risk groups more accurately, intervene early, and reduce the risk of CMD.
9.Application progress of speckle tracking imaging in the diagnosis and evaluation of congenital heart disease
Bo YU ; Kun SHI ; Xiaoyan WANG ; Lingxia FAN ; Yanfeng YANG
Chinese Pediatric Emergency Medicine 2024;31(10):788-792
The early diagnosis of congenital heart disease is very important. Ultrasound is widely used in the early diagnosis and evaluation of congenital heart disease because of its advantages of non-radiation, non-invasive property and portability.Speckle tracking imaging has the advantages of being free from angle, efficient and accurate, which makes up for some shortcomings of traditional echocardiography. It greatly improves the diagnosis accuracy of fetal congenital heart disease, especially congenital heart disease with outflow tract obstruction.Myocardial strain index and left ventricular torsion can more accurately evaluate myocardial function,help to judge prognosis, choose the time of operation and assist perioperative management. Blood speck tracking helps identify different blood flow patterns and may become an important diagnostic tool for the diagnosis and treatment of congenital heart disease.
10.Highlights and cutting-edge advances from the 2024 Korean International Gastric Cancer Week(KINGCA WEEK 2024)
Longfei GOU ; Hao CHEN ; Yanfeng HU ; Jiang YU ; Haijun DENG
Chinese Journal of General Surgery 2024;33(10):1705-1713
From September 26 to 28,2024,the 11th Korean International Gastric Cancer Week(KINGCA WEEK 2024),a prestigious academic conference in the field of gastric cancer,was held in Seoul.Organized by the Korean Gastric Cancer Association,the conference featured one main venue,18 sub-venues,and 16 thematic symposiums,including 100 invited presentations and four keynote speeches,attracting 788 experts and scholars from around the world.Additionally,the conference set 16 themes and received 425 submissions from 24 countries,including Republic of Korea,China,Japan,and the United States.After a review process,365 submissions were accepted,which included eight plenary oral presentations,78 oral reports,and 279 poster presentations.The conference covered many hot topics in gastric cancer diagnosis and treatment,with a particular focus on surgical-related areas such as treatment strategies for metastatic gastric cancer,an international consensus meeting on the conversion therapy for stage Ⅳgastric cancer,future research directions of the Korean Laparoendoscopic Gastrointestinal Surgery Study Group,the development of new surgical instruments and equipment,and key issues in lymph node dissection,resection,and reconstruction during minimally invasive gastric cancer surgeries.Furthermore,our team was invited to present two oral reports on"the application of artificial intelligence in minimally invasive gastric cancer surgery".This report aims to detail the dynamics and hotspots related to surgical treatment for gastric cancer,providing valuable references and insights for domestic surgical peers.

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