1.N 6-Methyladenosine modification of circDcbld2 in Kupffer cells promotes hepatic fibrosis via targeting miR-144-3p/Et-1 axis.
Sai ZHU ; Xin CHEN ; Lijiao SUN ; Xiaofeng LI ; Yu CHEN ; Liangyun LI ; Xiaoguo SUO ; Chuanhui XU ; Minglu JI ; Jianan WANG ; Hua WANG ; Lei ZHANG ; Xiaoming MENG ; Cheng HUANG ; Jun LI
Acta Pharmaceutica Sinica B 2025;15(1):296-313
Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N 6-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.
2.Clinical effect of Tongluo Kaibi tablet combined with intra-articular injection of hyperosmolar glucose in the treatment of knee osteoarthritis
Jianhua WU ; Baolian YANG ; Xiaoming ZHU ; Xiaobo SUN
China Modern Doctor 2024;62(22):84-87
Objective To explore the efficacy of Tongluo Kaibi tablet combined with intra-articular injection of hypertonic glucose in the treatment of knee osteoarthritis(KOA).Methods A total of 82 patients with KOA admitted to Ganzhou Hospital of Traditional Chinese Medicine from January to December 2023 were selected and divided into control group and observation group according to random number table method,with 41 cases in each group.The control group was given diclofenac sodium oral administration+intra-articular injection of sodium hyaluronate,and the observation group was given Tongluo Kaibi tablet oral administration+intra-articular injection of hypertonic glucose.Both groups were treated for 8 weeks.The clinical efficacy,visual analogue scale(VAS)score,Lysholm knee joint score and inflammatory factor levels were compared between two groups.Results The total effective rate of observation group was significantly higher than that of control group(χ2=6.187,P<0.001).After 8 weeks of treatment,VAS score,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),matrix metalloproteinase 3(MMP-3)in both groups were significantly lower than before treatment,and Lysholm knee joint scores were significantly higher than before treatment(P<0.05).VAS score,TNF-α,IL-1β and MMP-3 levels in observation group were significantly lower than those in control group,and Lysholm knee joint score was significantly higher than that in control group(P<0.05).Conclusion Tongluo Kaibi tablet combined with intra-articular injection of hypertonic glucose can help KOA patients relieve knee pain,reduce the level of inflammatory factors and improve knee joint function,and the therapeutic effect is accurate.
3.Sphincter-preserving strategies for low rectal cancer in the era of immunotherapy
Chinese Journal of Digestive Surgery 2024;23(6):795-800
Total mesorectal excision is the standard surgical procedure for rectal cancer. Based on this, the intersphincteric resection and conformal sphincter-preserving operation have pushed the sphincter-preserving surgery for ultra-low rectal cancer to the limit. However, no matter what kind of surgery, patients still need to face stoma or anal dysfunction, which seriously affect the quality of life. The "watch and wait " strategy for patients who achieve clinical complete response after neoadjuvant chemoradiotherapy has provided novel therapeutic method for rectal cancer, making non-surgical treatment possible. Total neoadjuvant therapy has expanded the application of the watch and wait strategy and has been written to the guidelines. Meanwhile, the rise of immuno-therapy has changed the treatment pattern of tumors. It has been the first-line treatment for advanced colorectal cancer with mismatch repair deficiency or microsatellite instability-high. As for patients with proficient mismatch repair or microsatellite stability, researches focus on how to improve the effect of neoadjuvant radiotherapy combined with immunotherapy, so that more patients with low rectal cancer have the opportunity to achieve clinical complete response and enter the watch and wait procedure, which will achieve the purpose of preserving the anus or rectum. The authors elaborate on current status of sphincter-preserving strategies for low rectal cancer and the strategies in the era of immunotherapy, in order to provide references for treatment of low rectal cancer.
4.Preliminary exploration of prostate cancer screening mode based on the medical community model in primary hospitals
Liwei ZHENG ; Lingmin SONG ; Gang WANG ; Weizhi ZHU ; Liejun HOU ; Maomao LI ; Jianjun HUANG ; Kewen ZHOU ; Bin ZHENG ; Xiaoming XU ; Guobin WENG
Chinese Journal of Urology 2024;45(6):416-419
Objective:To explore the suitable prostate cancer screening mode under the medical community for primary hospitals.Methods:From April 2021 to April 2022, a total of 16007 male population ≥50 years from 9 branches of the medical community of the second hospital of Yinzhou participated in this study. They were divided into four groups according to age with group 1 of 50-59 years old, group 2 of 60-69 years old, group 3 of 70-79 years old, and group 4 of 80 years old and above. Serum tPSA was added to the routine physical examination, and the screening positive patients were referred to the referral hospital for further diagnosis and treatment under the mode of medical community. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 ng/ml and suspicious lesions should be scored according to PI-RADS V2. The ultrasound-guided transperineal targeted prostate biopsy was performed for those with PI-RADS ≥3 and those with PI-RADS < 3 but tPSA ≥10 ng/ml. The tPSA follow-up examinations were performed every 6 months for tPSA < 10 ng/ml and PI-RADS < 3 points and once a year for tPSA < 4 ng/ml.Results:Among the 16 007 male population ≥50 years, 2 007(12.54%) were found serum PSA ≥4 ng/ml, and 634(31.59%)were referred to the referral hospital through the medical community system. Combining tPSA and mpMRI, 271 patients underwent ultrasound-guided transperineal targeted prostate biopsy. Among them, 162 were finally diagnosed with PCa, with a biopsy positive rate of 59.78%. The detection rate of PCa in all the subjects was 1.01%. According to the pathological grade, 5(3.08%) were in ISUP group 1, 95(58.64%) in ISUP group 2-3, and 62(38.27%) in ISUP group 4-5. There were 102(62.96%), 39(24.07%) and 21(12.96%) with localized, locally advanced or metastatic PCa, respectively. The levels of tPSA in the four groups were (1.13±1.44)ng/ml, (1.77±3.45)ng/ml, (3.27±17.58)ng/ml, and (4.26±11.48)ng/ml, respectively, with statistically significant differences ( P<0.01). The positive number of biopsy in each group was 1 case(0.06%), 56 cases(0.79%), 81 cases(1.36%) and 24 cases(1.82%) respectively, with statistically significant differences ( P<0.01). The number of ISUP 4-5 grades in each group was 0, 17(30.35%), 29(35.80%), and 16(66.67%) respectively, with statistically significant differences ( P<0.01). Conclusions:Based on the medical community system, according to the tPSA screening results of the primary hospitals, it is feasible and effective to refer suspicious patients to the referral hospitals for mpMRI examination, and screen prostate cancer by ultrasound-guided transperineal prostate fusion biopsy.
5.Improved discharge survival in pre-hospital cardiac arrest patients: the Shenzhen Bao'an experience
Wenwu ZHANG ; Jinfeng LIANG ; Qingli DOU ; Jun XU ; Jinle LIN ; Conghua WANG ; Wuyuan TAO ; Xianwen HUANG ; Wenhua LIU ; Yujie LI ; Xiaoming ZHANG ; Cuimei XING ; Huadong ZHU ; Xuezhong YU
Chinese Journal of Emergency Medicine 2024;33(11):1518-1523
Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.
6.Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China
Yufei LUO ; Yuan WEI ; Xiaochen WANG ; Yi ZHANG ; Wenli ZHANG ; Bing WU ; Zhengxiong YANG ; Xiaojie DONG ; Ruiting HAO ; Yifu LU ; Xiaoshuang FU ; Ziyue ZHU ; Ying ZHU ; Yuebin LYU ; Dongqun XU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(6):839-846
Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.
7.Role of maternal–fetal immune tolerance in the establishment and maintenance of pregnancy
Jingjing WANG ; Tao HAN ; Xiaoming ZHU
Chinese Medical Journal 2024;137(12):1399-1406
Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal–fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal–fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal–fetal tolerance based on maternal–fetal crosstalk. Insights into maternal–fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.
8.Precise capture of circulating endometrial cells in endometriosis
Shang WANG ; Hongyan CHENG ; Honglan ZHU ; Xiaoming YU ; Xue YE ; Xiaohong CHANG
Chinese Medical Journal 2024;137(14):1715-1723
Background::Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods::Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People’s Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. Results::The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.Conclusion::The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.
9.Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China
Yufei LUO ; Yuan WEI ; Xiaochen WANG ; Yi ZHANG ; Wenli ZHANG ; Bing WU ; Zhengxiong YANG ; Xiaojie DONG ; Ruiting HAO ; Yifu LU ; Xiaoshuang FU ; Ziyue ZHU ; Ying ZHU ; Yuebin LYU ; Dongqun XU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(6):839-846
Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.
10.CT and MRI findings of extrapulmonary bronchogenic cyst and its differential analysis
Xiaoran LI ; Zhijun GAO ; Wenli ZHU ; Xiaoming FU
Journal of Practical Radiology 2024;40(11):1792-1795
Objective To investigate the distribution and imaging manifestations of extrapulmonary bronchogenic cyst(BC)and to make differential diagnosis.Methods The data of 32 patients with extrapulmonary BC confirmed by pathology were collected.The lesion location,CT and MRI findings were analyzed and summarized.All patients underwent plain CT scan,and 27 of them underwent enhanced CT scan.Three patients underwent MRI plain and enhanced scan.Results Of the 32 patients,24 cases were mediastinal BC including 20 cases in the anterior mediastinum and other 4 cases in the posterior mediastinum.8 cases were ectopic BC,including 2 cases in the upper chest wall,4 cases in the gastric cardia,1 case in the greater curvature of the stomach,and 1 case in the left adre-nal gland.All lesions were single with clear boundary.The lesions were mainly round in shape(22 cases),and a few were flat/"D"shape(10 cases).There were no significant differences in the included signs between mediastinal BC and ectopic BC(P>0.05).Nodular calcification of cyst wall was found in 2 cases.There were 4 cases with CT value<20 HU and other 28 cases with CT value≥20 HU.The enhanced CT scan in 27 cases showed non-or mild enhancement.MRI showed hypointensity on T1WI in 2 cases,isointensity on T1WI in 1 case,hyperintensity on T2WI in 3 cases,and obvious enhancement on T1WI enhanced scan in 1 case.In addition,30 cases(93.7%)were misdiagnosed as thymic cyst(8 cases),thymoma(12 cases),neurogenic tumor(4 cases),ganglioneuroma(4 cases)and gastric stromal tumor(2 cases).Conclusion Extrapulmonary BC is rare,and most of the lesions are located near the central axis of the body with no obvious enhancement and sometimes cyst wall calcification,which has certain value for clinical diagnosis.

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