1.Photodynamic enhancement of PROTAC prodrug activation in hypoxic tumors.
Zhongliang FU ; Chunrong YANG ; Yuchen YANG ; Meichen PAN ; Hongwei HOU ; Jinghong LI
Acta Pharmaceutica Sinica B 2025;15(9):4945-4960
Proteolysis-targeting chimeras (PROTACs) have emerged as a promising therapeutic strategy for targeted protein degradation. However, the clinical application of PROTACs may be hindered by off-target toxicity resulting from non-tissue-specific protein degradation and ingenious prodrug strategies may open new avenues to addressing this concern. Herein, we propose a light-induced positive feedback strategy to use photodynamic therapy (PDT) to improve the activation efficiency of PROTAC prodrugs, monitor PROTAC release, and combine PROTAC to induce tumor cell apoptosis. In the hypoxic tumor microenvironment, the azo bond in AZO-PRO selectively cleaves, triggering the release of the potent protein degrader PRO and the multifunctional photosensitizer. Once activated, the fluoresce signal of the photosensitizer dramatically recovers, allowing monitoring of prodrug activation. Additionally, upon irradicating the tumor site using near-infrared (NIR) laser, PDT exacerbates tumor hypoxia, further promoting AZO-PRO activation. Our work introduces a novel approach to efficiently track and activate PROTAC prodrugs, enhance their antitumor efficacy, and mitigate off-target systemic toxicity.
2.Efficacy of Tanzhuo Decoction in the treatment of early diabetic nephropathy in patients with type 2 diabetes mellitus and its effect on cystatin C, C-reactive protein, urinary albumin excretion rate, and creatinine clearance rate
Hongwei YU ; Zhongliang PAN ; Shaorong FAN ; Guoqiang XU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(2):218-222
Objective:To investigate the efficacy of Tanzhuo Decoction in the treatment of early diabetic nephropathy in patients with type 2 diabetes mellitus and its effect on cystatin C (Cys-C), C-reactive protein (CRP), urinary albumin excretion rate (UAER), and creatinine clearance rate (CCr). Methods:Eighty patients with type 2 diabetes mellitus complicated by early diabetic nephropathy who received treatment at Maanshan Hospital of Traditional Chinese Medicine from 2019 to 2021 were included in this randomized controlled study. They were divided into a control group ( n = 40) and a treatment group ( n = 40) using the random number table method. Patients in the control group received conventional therapy including blood glucose and blood pressure control, while those in the treatment group received Tangzhuo Decoction in addition to the same treatment as that given to the control group. Both groups of patients were treated for 30 days. The clinical efficacy as well as pre- and post-treatment Cys-C, CRP, UAER, and CCr were compared between the two groups. Results:The total response rate in the treatment group was 92.5% (37/40), which was significantly higher than 75.0% (30/40) in the control group ( χ2 = 4.50, P < 0.05). After treatment, Cys-C, CRP, and UAER in the treatment group were (2.04 ± 0.08) mg/L, (3.97 ± 1.71) mg/L, and (91.18 ± 18.68) μg/min, respectively, which were significantly decreased compared with those before treatment ( t = 12.14, 5.59, 4.73, all P < 0.05). After treatment, CCr in the treatment group was (56.3 ± 5.01) mL/min, which was significantly increased compared with that before treatment ( t = -8.56, P < 0.05). After treatment, Cys-C, CRP, and UAER in the control group were (2.17 ± 0.04) mg/L, (4.66 ± 1.47) mg/L, and (103.93 ± 22.62) μg/min, respectively, which were significantly decreased compared with those before treatment ( t = 4.05, 5.00, 2.24, all P < 0.05). After treatment, CCr in the control group was (45.9 ± 4.9) mL/min, which was significantly increased compared with that before treatment ( t = -3.98, P < 0.05). There were significant differences in Cys-C, UAER, and CCr between the treatment and control groups ( t = -7.42, -2.29, 7.82, all P < 0.05). Conclusion:Tanzhuo Decoction for the treatment of early diabetic nephropathy in patients with type 2 diabetes mellitus has a definite effect. It can effectively reduce levels of Cys-C and UAER, reduce inflammatory reactions, improve kidney function, and delay the progression of kidney injury.
3.Predictive value of ADD3 and MMP14 in peripheral blood of patients with acute ST segment elevation myocardial infarction for acute heart failure
Xu QIU ; Zhongliang DONG ; Haichuan CAO ; Xiaoming XU ; Zhengmao PAN
International Journal of Laboratory Medicine 2024;45(24):2956-2960,2966
Objective To investigate the predictive value of adductor 3(ADD3)and matrix metalloprotein-ase 14(MMP14)in peripheral blood of patients with acute ST segment elevation myocardial infarction(STE-MI)for acute heart failure(AHF).Methods A total of 98 STEMI patients admitted to the inpatient depart-ment of the Department of Cardiology of the hospital from November 2019 to October 2022 were selected as the STEMI group.STEMI patients were divided into AHF group(30 cases)and non AHF group(68 cases)according to whether AHF occurred within 48 hours of onset,and 63 healthy volunteers who urderwent the physical examination in the hospital were selected as control group.The levels of ADD3 and MMP14 in pe-ripheral blood was detected,and their relationship with AHF in STEMI patients and the value in predicting AHF were analyzed.Results The level of ADD3 in peripheral blood in STEMI group was lower than that in the control group(P<0.05),and MMP14 level was higher than that in the control group(P<0.05).The level of ADD3 in peripheral blood in AHF group was lower than that in non AHF group(P<0.05),and the level of MMP14 was higher than that in non AHF group(P<0.05).The level of ADD3 in peripheral blood of STEMI patients was negatively correlated with cardiac troponin Ⅰ(cTnI),creatine kinase isoenzyme(CK-MB),brain natriuretic peptide(BNP),and Killip grading(P<0.05),and the level of MMP14 was positively correlated with cTnI,CK-MB,BNP,and Killip grading(P<0.05).Killip grade Ⅳ,high BNP level and high MMP14 level were risk factors for complications of AHF in STEMI patients(P<0.05),and high ADD3 level was a protective factor(P<0.05).The area under the curve of the combination of ADD3,MMP14 and BNP for predicting AHF in STEMI patients was 0.890,which was greater than 0.704,0.702,0.750 of individual indicators alone(P<0.05).Conclusion ADD3 level in peripheral blood of STEMI patients is decreased and MMP14 level is increased,which is associated with complication of AHF.ADD3 and MMP14 are expected to be biological indicators of AHF in STEMI patients.
4.Application of endoscopic complete areola approach in the resection of parathyroid adenoma
Xiaoyang LI ; Yi JIANG ; Jian YU ; Zhe LIN ; Zhongliang PAN
Chinese Journal of Endocrine Surgery 2022;16(2):255-256
The most common cause of primary hyperparathyroidism (PHPT) is parathyroid adenoma. Surgery is the most effective method to treat PHTP. The data of 10 patients who underwent endoscopic complete areola approach for parathyroid adenoma resection in our hospital from Jan. 2018 to Oct. 2021 were reviewed. It is considered that this method is feasible and has certain advantages compared with traditional surgery.
5. Epidemiological characteristics of pre-hospital mortality due to acute myocardial infarction from 1999 to 2016 in Tianjin city
Guohong JIANG ; Dezheng WANG ; Hui ZHANG ; Xiaodan XUE ; Yi PAN ; Chong WANG ; Ying ZHANG ; Zhongliang XU
Chinese Journal of Preventive Medicine 2020;54(1):99-103
To explore the epidemiological characteristics, trends and relevant factors of pre-hospital mortality due to acute myocardial infarction (AMI) from 1999 to 2016 in Tianjin city, based on mortality surveillance information and household registration population information. Standardized mortality rates were calculated using the year 2000 world standard population. From 1999 to 2016, the research result showed that the pre-hospital crude mortality rates of AMI were 39.47/100 000 to 90.64/100 000 and the standardized mortality rates were 30.92/100 000 to 53.90/100 000. The proportion of pre-hospital AMI deaths was 73.96%-81.92% (
6.Medical computer-aided detection method based on deep learning.
Pan TAO ; Zhongliang FU ; Kai ZHU ; Lili WANG
Journal of Biomedical Engineering 2018;35(3):368-375
This paper performs a comprehensive study on the computer-aided detection for the medical diagnosis with deep learning. Based on the region convolution neural network and the prior knowledge of target, this algorithm uses the region proposal network, the region of interest pooling strategy, introduces the multi-task loss function: classification loss, bounding box localization loss and object rotation loss, and optimizes it by end-to-end. For medical image it locates the target automatically, and provides the localization result for the next stage task of segmentation. For the detection of left ventricular in echocardiography, proposed additional landmarks such as mitral annulus, endocardial pad and apical position, were used to estimate the left ventricular posture effectively. In order to verify the robustness and effectiveness of the algorithm, the experimental data of ultrasonic and nuclear magnetic resonance images are selected. Experimental results show that the algorithm is fast, accurate and effective.
7.Left ventricle segmentation in echocardiography based on adaptive mean shift.
Kai ZHU ; Zhongliang FU ; Pan TAO ; Shuo ZHU
Journal of Biomedical Engineering 2018;35(2):273-279
The use of echocardiography ventricle segmentation can obtain ventricular volume parameters, and it is helpful to evaluate cardiac function. However, the ultrasound images have the characteristics of high noise and difficulty in segmentation, bringing huge workload to segment the object region manually. Meanwhile, the automatic segmentation technology cannot guarantee the segmentation accuracy. In order to solve this problem, a novel algorithm framework is proposed to segment the ventricle. Firstly, faster region-based convolutional neural network is used to locate the object to get the region of interest. Secondly, -means is used to pre-segment the image; then a mean shift with adaptive bandwidth of kernel function is proposed to segment the region of interest. Finally, the region growing algorithm is used to get the object region. By this framework, ventricle is obtained automatically without manual localization. Experiments prove that this framework can segment the object accurately, and the algorithm of adaptive mean shift is more stable and accurate than the mean shift with fixed bandwidth on quantitative evaluation. These results show that the method in this paper is helpful for automatic segmentation of left ventricle in echocardiography.
8.Influence of social network on quality of life of elderly stroke patients in communities
Xin CHEN ; Zhongliang BAI ; Shengsheng TAO ; Xinxiang PAN ; Xia QIN ; Zhi HU
Chinese Journal of Behavioral Medicine and Brain Science 2018;27(11):1011-1015
Objective To explore the influence of social network on the quality of life of elderly stroke patients in communities. Methods The general situation questionnaire, the stroke impact scale ( SIS) and social network scale for the elderly were used to investigate the community elderly stroke patients. Results The total score of social network was(39. 82±5. 87). The scores of social participation,social con-tact and social support were(11. 79±1. 61),(14. 90±3. 31) and (13. 13±3. 19). Results of univariate a-nalysis showed there were statistically significant differences ( P<0. 05) in quality of life among stroke pa-tients of different ages (F=7. 803),educational level (F=2. 664),family income (F=4. 754),smoking (F=5. 467),alcohol consumption (F=7. 058),physical exercise (F=10. 393),body mass index (t=4. 841) and hypertension (t=-2. 862). Multiple linear regression results showed that 3 times or more exercises per week ( B=5. 689),normal body mass index (B=6. 613),high degree of social support (B=0. 710),social partici-pation (B=1. 421) and social contact (B=1. 372) were protective factors for the quality of life of stroke pa-tients. Age 80 years and above (B=-10. 426),frequent smoking (B=-9. 005),frequent drinking (B=-8. 419) and hypertension ( B=-5. 224) were risk factors for quality of life. Conclusion The elderly stroke patients should quit smoking and alcohol,strengthen exercise,maintain a normal body mass index and avoid overweight and obesity in daily life. While promoting health-related behaviors,more attention should be paid to the promotion effect of social network on treatment,rehabilitation and overall quality of life of stroke patients.
9.A preliminary study on clinical significance and method of using carbon nanoparticles in endoscopic treatment of papillary thyroid microcarcinoma
Shangrui RAO ; Zhonglin WANG ; Yi WANG ; Zhongliang PAN ; Zhe LIN ; Jian YU
Chinese Journal of Endocrine Surgery 2018;12(4):291-293
Objective To explore the value and method of using carbon nanoparticles in endoscopic treatment of papillary thyroid microcarcinoma.Method 74 cases were randomly divided into two groups,34 cases in experimental group which were injected with carbon nanoparticles,and 40 cases in the control group without any injection.All cases were analyzed in terms of the tumor size,the number of lymph nodes and parathyroid gland injury.Results All patients underwent the operation smoothly.The postoperative pathological specimens result showed there was no statistical difference of carcinoma size between the two groups.The number of lymph nodes dissected was 177 in the control group and 220 in the experimental group (the rate of lymph node black staining rate was 89%).In the experimental group,the average number of lymph node detected in each patient was 6.47±2.13,more than 4.42±1.91 in the control group.The number of parathyroid glands found in the experimental group was 3 and 11 in the control group,and the difference had no statistical significance.Postoperative temporary laryngeal recurrent nerve injury occurred to 2 cases in each group,and no statistical difference was found.Conclusion Using carbon nanoparticles in endoscopic treatment of papillary thyroid microcarcinoma can increase the detection rate of lymph node,and to some extent,reduce the parathyroid injury.It has a certain clinical significance,However,care should be taken to avoid contamination of the mirror field of view.
10. Comparative study of endoscopic via areola approach versus open conventional thyroidectomy in papillary thyroid carcinomapatients
Zhonglin WANG ; Shangrui RAO ; Zhe LIN ; Jian YU ; Zhongliang PAN
Chinese Journal of Postgraduates of Medicine 2018;41(8):691-695
Objective:
To evaluate and compare the surgery prognosis of the papillary thyroid carcinoma (PTC) patients who underwent conventional and endoscopic thyroidectomies via areola.
Methods:
From January 2012 to December 2017, 887 patients with PTC underwent thyroidectomy. The A group of 693 patients underwent traditional thyroidectomy, and B group of 194 patients underwent endoscopic thyroidectomy. Clinicopathologic characteristics, surgical methods, pathological features and complications were analyzed and compared between two groups.
Results:
The mean age of A group was older than B group: (45.2 ± 11.5) years vs. (34.9 ± 9.4) years,

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