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.Impact of body mass index on delayed extubation of patients with acute Stanford type A aortic dissection
Shumin WU ; Mingwei WANG ; Bolun SHI ; Xiangbo CAO ; Yanfeng LI ; Feng ZHANG ; Yangtao YU ; Hui WANG ; Faming HE
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(9):559-564
Objective:To investigate the impact of body mass index (BMI) on delayed extubation of patients with acute Stanford type A aortic dissection (ATAAD).Methods:A total of 400 ATAAD patients who were admitted to our hospital from October 2021 to October 2023 and underwent surgical treatment were selected as the research objects. According to BMI, they were divided into obese group (BMI≥28 kg/m 2, 119 cases) and non-obese group (BMI<28 kg/m 2, 281 cases). The differences of preoperative clinical characteristics, intraoperative and postoperative data between the two groups were compared. Starting from transferring to the ICU and ending with the first successful extubation, The risk factors of postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients were analyzed, and the predictive efficacy of related factors for postoperative invasive mechanical ventilation time ≥ 48 h in ATAAD patients was evaluated. Results:Compared with the non-obese group, the proportion of hypertension, diabetes, admission heart rate, admission systolic blood pressure, admission diastolic blood pressure and preoperative white blood cell count in the obese group were significantly increased, and the differences were statistically significant ( P<0.05). The cardiopulmonary bypass time, aortic cross-clamp time, operation time, red blood cell transfusion volume, invasive mechanical ventilation time, secondary operation rate and total hospitalization cost in the obese group were significantly higher than those in the non-obese group, and the differences were statistically significant ( P<0.05). Univariate logistic regression analysis showed that BMI, cardiopulmonary bypass time, ascending aortic cross-clamp time, operation time, age, hypertension, and red blood cell transfusion were related factors for postoperative invasive mechanical ventilation time ≥48 h in ATAAD patients ( P<0.05). Logistic multivariate regression analysis showed that increased BMI ( OR=1.213, P<0.05) and increased age ( OR=1.020, P<0.05) were independent risk predictors of postoperative invasive mechanical ventilation time≥48 h in ATAAD patients. Receiver operating characteristic curve ( ROC) analysis showed that the area under the ROC curve ( AUC) of BMI for predicting the duration of postoperative invasive mechanical ventilation in ATAAD patients≥48 h was 0.682 ( P<0.05), and the best predictive cut-off value was 25.64 kg/m 2. Conclusion:BMI≥28kg/m 2 increases the difficulty of surgery and the duration of invasive mechanical ventilation in ATAAD patients. BMI has a high predictive value for the duration of invasive mechanical ventilation in ATAAD patients after surgery ≥48 h, and effective intervention measures can be formulated to improve the treatment effect of patients.
3.Relationship between ITGA3 expression and immune cell infiltration in colorectal cancer
Xiao LIU ; Yanfeng XI ; Peng BU ; Guohai ZHAO ; Peiyu JIN ; Yuting FENG ; Wei CUI ; Jing XU
Chinese Journal of Clinical Oncology 2023;50(23):1196-1202
Objective:To explore the relationship between integrin ɑ3(ITGA3)expression and immune cell infiltration in colorectal cancer(CRC).Methods:Bioinformatic methods were used to analyze ITGA3 mRNA expression in pan-cancer and CRC tissues,as well as its associ-ation with CRC prognosis.The correlation between ITGA3 and tumor-infiltrating immune cells was also investigated.In total,233 cases of CRC diagnosed at Shanxi Provincial Cancer Hospital between January and December 2021 were included,and ITGA3,CD8,CD163,FOXP3,PD-L1,CTLA-4,and PD-1 expression in CRC tissues were determined by immunohistochemistry(IHC)to analyze the relationship between ITGA3 and infiltrating immune cells and immune checkpoints.Results:Bioinformatics analysis showed elevated ITGA3 mRNA levels in CRC.High ITGA3 expression was associated with PFS(P<0.05).Univariate and multifactorial analyses showed that age and stage were significantly cor-related with prognosis(P<0.05).In addition,ITGA3 upregulation was closely correlated with multiple immune cell infiltration levels in CRC.Furthermore,IHC results showed that ITGA3 expression in CRC tissues was significantly higher than that in adjacent normal tissues(P<0.05).ITGA3 expression was associated with lymph node metastasis(P<0.05)and correlated with the expression of immune markers,such as CD8+T-cells,PD-L1,and CTLA-4(P<0.05).Conclusions:ITGA3 is highly expressed in CRC,which is closely related to immune cell infiltration and may regulate the tumor immune microenvironment,which provides a new idea for clinical treatment and a potential new independent predictive marker.
4.Factors affecting microvascular complications among patients with type 2 diabetes mellitus
WU Yaxing ; LIU Hong ; FENG Jian ; YANG Guimao ; CHENG Xuebing ; XU Qian ; SUN Xiaodong ; REN Yanfeng
Journal of Preventive Medicine 2023;35(11):926-930
Objective :
To identify the factors affecting microvascular complications among patients with type 2 diabetes (T2DM), so as to provide insights into the management of microvascular complications of T2DM.
Methods:
T2DM patients hospitalized in the Department of Endocrinology of a tertiary hospital in Weifang City, Shandong Province from January 2021 to January 2022 were enrolled, and subjects' basic information, lifestyle and medical history were collected using questionnaire surveys. Fasting insulin, fasting blood glucose and glycated hemoglobin were measured, and factors affecting microvascular complications were identified among T2DM patients using a multivariable logistic regression model and a decision tree model.
Results:
Totally 1 003 T2DM inpatients were enrolled, including 515 men (51.35%) and 488 women (48.65%), and the prevalence of microvascular complications was 40.18%. Multivariable logistic regression analysis showed that age of 60 years and older (OR=2.510, 95%CI: 1.441-4.374), T2DM duration of 10 years and longer (OR=3.205, 95%CI: 2.242-4.581), fasting insulin of lower than 3.21 μIU/mL (OR=1.749, 95%CI: 1.239-2.469), using of agents or insulin to control blood glucose (OR=1.880, 95%CI: 1.143-3.092), glycated hemoglobin level of 7% and higher (OR=1.751, 95%CI: 1.172-2.615) as factors affecting microvascular complications among T2DM patients. Decision tree analysis identified course of T2DM as a major factor affecting the risk of microvascular complications among T2DM patients, and the prevalence of microvascular complications was 70.22% among T2DM patients with disease course of 10 years and longer and fasting insulin of lower than 3.21 μIU/mL or 16.32 μIU/mL and higher, 44.23% among T2DM patients with disease course of 5 to 10 years and at ages of 60 years and older, and 43.10% among T2DM patients with disease course of less than 5 years and fasting insulin of lower than 3.21 μIU/mL.
Conclusion
Advanced age, long course of T2DM, low fasting insulin and high glycated hemoglobin may increase the risk of microvascular complications among T2DM patients.
5.Clinical study of Baduanjin combined with mecobalamin tablets for the patients with type 2 diabetic peripheral neuropathy
Yi CHEN ; Yanfeng LI ; Yimiao GAN ; Wenlan GAO ; Feng TAO ; Yang SUN ; Xiao ZHENG
International Journal of Traditional Chinese Medicine 2022;44(1):38-42
Objective:To evaluate the efficacy of Baduanjin combined with mecobalamin tablets in the treatment of type 2 diabetic peripheral neuropathy. Methods:Eighty patients with type 2 diabetic peripheral neuropathy who met the inclusion criteria were randomly divided into two groups with 40 patients in each group ( n=40). The control group took oral mecobalamin tablets and self-management, and the treatment group were treated with Baduanjin on the basis of the control group. All patients were treated for 12 weeks. The clinical symptoms were evaluated by Toronto Clinical Scoring System (TCSS), and the motor nerve conduction velocity (MCV) of tibial nerve and the sensory conduction velocity (SCV) of superficial peroneal nerve were measured by EMG evoked potential instrument. The hemorheological indexes (whole blood low shear viscosity, whole blood high shear viscosity and plasma viscosity) were measured before and after treatment. The clinical efficacy was evaluated and adverse events were recorded. Results:In the course of treatment, 39 patients in each group completed the study with each one dropout. The total effective rate was 87.2% (34/39) in the treatment group and 64.1% (25/39) in the control group. There was significant difference between the two groups ( χ2=5.64, P=0.018). After treatment, the TCSS score of the treatment group was significantly lower than that of the control group ( t=-6.23, P<0.01), the tibial nerve MCV (43.06 ± 4.19 m/s vs. 39.55 ± 4.30 m/s, t=3.65), the superficial peroneal nerve SCV (43.23 ± 4.31 m/s vs. 39.92 ± 3.74 m/s, t=3.62) in the treatment group were significantly higher than the control group ( P<0.001), while the whole blood high shear viscosity, the whole blood low shear viscosity, and the plasma viscosity in the treatment group were significantly lower than the control group ( t value were -10.36, -14.21, -13.88, all Ps<0.001). During the treatment, no serious adverse events occurred in both groups. Conclusion:Baduanjin combined with mecobalamin tablets in the treatment of type 2 diabetic peripheral neuropathy can reduce blood viscosity, promote blood circulation, increase nerve conduction velocity, improve clinical symptoms and signs, and improve clinical efficacy.
6. Spatiotemporal heterogeneity of schistosomiasis in mainland China: Evidence from a multi-stage continuous downscaling sentinel monitoring
Yanfeng GONG ; Jiaxin FENG ; Zhuowei LUO ; Jingbo XUE ; Zhaoyu GUO ; Lijuan ZHANG ; Shang XIA ; Shan LV ; Jing XU ; Shizhu LI ; Yanfeng GONG ; Jiaxin FENG ; Zhuowei LUO ; Jingbo XUE ; Zhaoyu GUO ; Lijuan ZHANG ; Shang XIA ; Shan LV ; Jing XU ; Shizhu LI ; Yanfeng GONG ; Jiaxin FENG ; Zhuowei LUO ; Jingbo XUE ; Zhaoyu GUO ; Lijuan ZHANG ; Shang XIA ; Shan LV ; Jing XU ; Shizhu LI ; Yanfeng GONG ; Jiaxin FENG ; Zhuowei LUO ; Jingbo XUE ; Zhaoyu GUO ; Lijuan ZHANG ; Shang XIA ; Shan LV ; Jing XU ; Shizhu LI ; Yanfeng GONG ; Jiaxin FENG ; Zhuowei LUO ; Jingbo XUE ; Zhaoyu GUO ; Lijuan ZHANG ; Shang XIA ; Shan LV ; Jing XU ; Shizhu LI ; Shang XIA ; Shan LV ; Shizhu LI
Asian Pacific Journal of Tropical Medicine 2022;15(1):26-34
Objective: To determine the spatiotemporal distribution of Schistosoma (S.) japonicum infections in humans, livestock, and Oncomelania (O.) hupensis across the endemic foci of China. Methods: Based on multi-stage continuous downscaling of sentinel monitoring, county-based schistosomiasis surveillance data were captured from the national schistosomiasis surveillance sites of China from 2005 to 2019. The data included S. japonicum infections in humans, livestock, and O. hupensis. The spatiotemporal trends for schistosomiasis were detected using a Joinpoint regression model, with a standard deviational ellipse (SDE) tool, which determined the central tendency and dispersion in the spatial distribution of schistosomiasis. Further, more spatiotemporal clusters of S. japonicum infections in humans, livestock, and O. hupensis were evaluated by the Poisson model. Results: The prevalence of S. japonicum human infections decreased from 2.06% to zero based on data of the national schistosomiasis surveillance sites of China from 2005 to 2019, with a reduction from 9.42% to zero for the prevalence of S. japonicum infections in livestock, and from 0.26% to zero for the prevalence of S. japonicum infections in O. hupensis. Analysis using an SDE tool showed that schistosomiasis-affected regions were reduced yearly from 2005 to 2014 in the endemic provinces of Hunan, Hubei, Jiangxi, and Anhui, as well as in the Poyang and Dongting Lake regions. Poisson model revealed 11 clusters of S. japonicum human infections, six clusters of S. japonicum infections in livestock, and nine clusters of S. japonicum infections in O. hupensis. The clusters of human infection were highly consistent with clusters of S. japonicum infections in livestock and O. hupensis. They were in the 5 provinces of Hunan, Hubei, Jiangxi, Anhui, and Jiangsu, as well as along the middle and lower reaches of the Yangtze River. Humans, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the north of the Hunan Province, south of the Hubei Province, north of the Jiangxi Province, and southwestern portion of Anhui Province. In the 2 mountainous provinces of Sichuan and Yunnan, human, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the northwestern portion of the Yunnan Province, the Daliangshan area in the south of Sichuan Province, and the hilly regions in the middle of Sichuan Province. Conclusions: A remarkable decline in the disease prevalence of S. japonicum infection was observed in endemic schistosomiasis in China between 2005 and 2019. However, there remains a long-term risk of transmission in local areas, with the highest-risk areas primarily in Poyang Lake and Dongting Lake regions, requiring to focus on vigilance against the rebound of the epidemic. Development of high-sensitivity detection methods and integrating the transmission links such as human and livestock infection, wild animal infection, and O. hupensis into the surveillance-response system will ensure the elimination of schistosomiasis in China by 2030.
7.Historical Evolution of Boiling Method for Processing of Chinese Medicines
Ru GUO ; Yanhua CAO ; Xiao TAN ; Jintao FENG ; Yanfeng XIU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(24):229-236
Boiling is a common processing method of Chinese medicine. Based on the book of Summary of Processing Methods Data of Traditional Chinese Medicine in Past Dynasties, the authors consulted herbal books in all ages, combined with modern processing laws and regulations in various provinces and cities, the boiling methods and Chinese medicine varieties in ancient and modern times, judgment method of the endpoint of processing, as well as the study on boiling methods of representative Chinese medicines were compiled and analyzed. After sorting, it was found that the application of boiling methods began in the Han dynasty, enriched and developed in the Northern and Southern dynasties, Tang, Song and Yuan dynasties, and reached its heyday in the Ming and Qing dynasties. However, the number of modern boiling varieties decreased and mainly focused on toxic Chinese medicines or those that need to change or moderate their medicinal properties, indicating the development of boiling methods entered a stable period. The varieties of excipients used in the modern age mainly considered factors such as convenience of use and easy access, and the boiling degree, time and times were commonly used to judge the endpoint of boiling process. The main purposes of using boiling method for Chinese medicines were to remove impurities, remove non-medicinal parts, change or moderate the medicinal properties, and eliminate or reduce adverse reactions, which can provide a reference for carrying out the common research of boiling method for Chinese medicines.
8.Comparison of oncology efficacy and risk between combined hepatopplenectomy and conventional hepatectomy in patients with hepatocellular carcinoma complicated with hypersplenism
Jian XIN ; Weiwei FENG ; Yanfeng HE
Chinese Journal of Postgraduates of Medicine 2021;44(2):112-117
Objective:To compare the oncology effect and risk between hepatopplenectomy and conventional hepatectomy for hepatocellular carcinoma patients with hypersplenism, so as to provide guidance for clinical application.Methods:One hundred and eighteen patients with hepatic carcinoma with hypersplenism in the Private hospitals of Zhejiang Province Yiwu were studied retrospectively. Patients were divided into 2 groups according to different operation methods: combined hepatosplenectomy group and conventional hepatectomy group with 59 cases in each group. Blood routine, liver function, complication and tumor effect (local recurrence, distant metastasis and 1, 3, 5 years survival rate) was compared between two group.Results:There was no significant difference in operation time, intraoperative blood loss and hospitalization time between the two groups ( P>0.05). Compared with that of the control group, the clinical total effective rate of the combined group was significantly increased: 94.92% (56/59) vs. 79.66% (47/59), P<0.05; there was no significant difference in the incidence of complications between the two groups ( P>0.05); the two groups were followed up to August 1, 2019. The median survival time of the two groups was significantly higher than that of the open group (29 months vs 22 months) ( P<0.05); the local recurrence rate, distant metastasis rate, 1, 3 and 5-year survival rate between the two groups were statistically significant ( P<0.05). The platelet and white blood cells in the combined group were significantly higher than those in the control group after 7 days′ treatment: (264.48 ± 75.37) × 10 9/L vs. (153.53 ± 42.11) × 10 9/L, (7.86 ± 1.43) × 10 9/L vs. (3.48 ± 1.32) × 10 9/L, P<0.05. Compared with that of the control group, alanine aminotransferase and aspartate aminotransferase were significantly decreased: (49.42 ± 31.88) U/L vs. (84.22 ± 43.95) U/L, (36.50 ± 21.50) U/L vs. (49.98 ± 35.63) U/L, P<0.05. Conclusions:Compared with conventional hepatectomy for hepatocellular carcinoma patients with hypersplenism, combined hepatosplenectomy can effectively promote the increase of peripheral blood PLT and WBC and the recovery of liver function without increasing the risk of surgery, and the long-term follow-up results are more satisfactory, which has high clinical application value.
9.Expression of CDK6 and FOXM1 in peripheral T-cell lymphoma and their significance
Haonan FENG ; Xiaoxia SHAO ; Peng BU ; Fei ZHANG ; Yajing WANG ; Yanfeng XI ; Weina GUO
Chinese Journal of Pathology 2020;49(6):594-600
Objective:To investigate the expression of CDK6 and FOXM1 in peripheral T-cell lymphoma (PTCL), and its correlation with clinicopathologic features and patient prognosis.Methods:The Oncomine was used for data mining and analyzing the expression levels of CDK6 and FOXM1 in PTCL. Immunohistochemistry (IHC) of EnVision method was used to detect the expression of CDK6 and FOXM1 proteins in 166 cases of PTCL diagnosed at Shanxi Provincial Cancer Hospital from January 2016 to December 2018, and 30 cases of lymph node with reactive hyperplasia as control.Results:Among the PTCL patients, 104 were male and 62 were female, aged from 3 to 85 years, with an average age of 53 years. Analyses of the Oncomine 4.5 database showed that mRNA expression of CDK6 and FOXM1 in PTCL tissues was significantly higher than that in normal tissue ( P<0.05). IHC staining showed the positive rates of CDK6 and FOXM1 proteins in PTCL tissues were 27.7% (46/166) and 80.7% (134/166), respectively. The expression was mainly present in the nuclei of tumor cells, showing a diffuse, strongly positive pattern. The positive rates of CDK6 and FOXM1 proteins among the 30 cases of lymph-node reactive hyperplasia were 0 (0/30) and 30% (9/30), respectively. The expression of FOXM1 was mainly found in the lymphoid follicle germinal center, and not present in the T-zone cells. CDK6 protein, FOXM1 protein and the co-expression of CDK6 and FOXM1 proteins in PTCL were associated with higher Ann Arbor staging and international prognostication index score ( P<0.05), and inversely associated with overall survival ( P<0.05). Meanwhile, CDK6 protein expression was positively correlated with FOXM1 protein expression ( P<0.05). Conclusions:CDK6 and FOXM1 may be new targets for the diagnosis and treatment of PTCL. The overexpression of CDK6 may lead to enhanced function of the transcription factor FOXM1, while the overexpression of CDK6 and FOXM1 also promotes the development and progression of PTCL.
10.Analysis of TCR β chain CDR3 clonetype in HBV-infected patients with coexistence of HBsAg and HBsAb
Le CHANG ; Zheng ZENG ; Sa WANG ; Yanfeng HOU ; Zhiyan LI ; Zhenru Feng
Chinese Journal of Clinical Laboratory Science 2019;37(4):278-282
Objective:
To compare T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) in the patients with coexistence of HBsAg and HBsAb and other HBV infected patients.
Methods:
The clonotype and diversity of CDR3 in blood of group cases (positive HBsAg and HBsAb) (n=11), control 1 (negative HBsAg and positive HBsAb) (n=10) and control 2 (positive HBsAg and negative HBsAb) (n=10) were analyzed by high-throughput TCR sequencing with Illumina HiseqX10.
Results:
In the case group, the overlap rate of 6.28% (0.25%, 13.10%) was detected between any two samples, which was significantly lower than the overlap rate of 10.49% (6.20%,17.30%) seen in control 1 group (P=0.008). In control 2 group, the overlap rate of 2.60% (0.13%,13.69%) was significantly lower than control 1 group (P=0.001). There was no difference between case group and control 2 group. After pairwise comparison between the three groups, the frequency of clonotype TRBV7-2/TRBD1/TRBJ2-1 in case group was higher than that of control 1 group (P=0.029), the frequency of TRBV7-3/TRBD1/TRBJ2-7 in case group was lower than that of control 1 group (P=0.031). The difference of TRBV5-8 was significant in comparing case group with control 1 group (P=0.047). There were 14 clonotypes which had differences between case group and control 2 group in frequency. TRBV28was significant in comparing case group with control 2 group (P=0.028). For diversity, there was no difference among the three groups.
Conclusion
Clonotype TRBV7-2/TRBD1/TRBJ2-1, TRBV7-3/TRBD1/TRBJ2-7 and TRBV5-8 were associated with coexistence of HBsAg and HBsAb, but the diversity was not associated with TCR β chain CDR3.


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