1.Synthesis, preclinical evaluation and pilot clinical study of a P2Y12 receptor targeting radiotracer 18FQTFT for imaging brain disorders by visualizing anti-inflammatory microglia.
Bolin YAO ; Yanyan KONG ; Jianing LI ; Fulin XU ; Yan DENG ; Yuncan CHEN ; Yixiu CHEN ; Jian CHEN ; Minhua XU ; Xiao ZHU ; Liang CHEN ; Fang XIE ; Xin ZHANG ; Cong WANG ; Cong LI
Acta Pharmaceutica Sinica B 2025;15(2):1056-1069
As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an 18F-labeled PET tracer (QTFT) that targets the P2Y12, a receptor highly expressed on anti-inflammatory microglia. [18F]QTFT exhibited high binding affinity to the P2Y12 (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [18F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y12 antagonist. Furthermore, [18F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y12 in anti-inflammatory microglia. In a pilot clinical study, [18F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [18F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y12 overexpressed in anti-inflammatory microglia.
2.Association between remnant cholesterol and the risk of atherosclerotic cardiovascular disease in a community population in Shanghai
Yingqi DENG ; Minhua TANG ; Kexin ZHANG ; Xiaohua LIU ; Yanan WU ; Qian PENG ; Liping YI ; Jianhua SHI ; Yingfeng LU ; Yonggen JIANG ; Genming ZHAO
Chinese Journal of Epidemiology 2025;46(6):935-941
Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.
3.Research on the current status of penile erection hardness and its influencing factors in patients with non-obstructive azoospermia
Minhua LAI ; Yanshan LIN ; Fangliang ZOU ; Yang ZHANG ; Jing LONG ; Huaan XIA ; Lihong LIN ; Yunzhi DENG ; Ruiyun CHEN ; Jianhua YANG ; Yao XU ; Tianwen PENG
The Journal of Practical Medicine 2025;41(20):3276-3282
Objective To explore the current status of penile erection hardness and its influencing factors in patients with non-obstructive azoospermia.Methods From January to December 2024,450 patients with non-obstructive azoospermia were surveyed at the Reproductive Medicine Center of Hospital.A self-made general information questionnaire was used to collect their demographic data.The Erectile Hardness Scale(EHS)was employed to investigate the current status of their penile erection hardness,and a self-made questionnaire was utilized to explore the influencing factors.Results Among the 450 patients with non-obstructive azoospermia,during sexual intercourse,35.3%of the patients reported that their penile erection hardness could reach grade 4(normal state),54.5%reported that it only reached grade 3(sub-optimal state),9.3%reported that it only reached grade 2(slight penile erection),and 0.9%reported that it only reached grade 1(inability to achieve an erection).In the survey of satisfaction with sexual life quality,among the 450 patients,only 24.9%were very satisfied with their sexual life quality;57.3%were basically satisfied;9.6%considered it average;4.0%were dissatisfied;3.1%were very dissatisfied;and 1.1%had no sexual life.alcohol consumption(OR=2.393,95%CI:1.493~3.836),satisfaction with the quality of sexual life(OR=1.455,95%CI:1.118~1.894),educational attainment(OR=0.709,95%CI:0.549~0.917),and the sleep quality in the past month(OR=0.641,95%CI:0.452~0.907).Conclusions Clinical studies have shown that factors such as drinking habits,sexual life satisfaction,sleep quality,and educational attainment collectively influence the penile erection hardness in patients with non-obstructive azoospermia.Therefore,the medical team needs to customize personalized intervention plans and educational materials based on individual differences among patients.Through psychological counseling and lifestyle guidance,they can improve erectile function and the quality of sexual life,promote harmonious marital relationships,and enhance the overall life experience of the patients.
4.Association between remnant cholesterol and the risk of atherosclerotic cardiovascular disease in a community population in Shanghai
Yingqi DENG ; Minhua TANG ; Kexin ZHANG ; Xiaohua LIU ; Yanan WU ; Qian PENG ; Liping YI ; Jianhua SHI ; Yingfeng LU ; Yonggen JIANG ; Genming ZHAO
Chinese Journal of Epidemiology 2025;46(6):935-941
Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.
5.Research on the current status of penile erection hardness and its influencing factors in patients with non-obstructive azoospermia
Minhua LAI ; Yanshan LIN ; Fangliang ZOU ; Yang ZHANG ; Jing LONG ; Huaan XIA ; Lihong LIN ; Yunzhi DENG ; Ruiyun CHEN ; Jianhua YANG ; Yao XU ; Tianwen PENG
The Journal of Practical Medicine 2025;41(20):3276-3282
Objective To explore the current status of penile erection hardness and its influencing factors in patients with non-obstructive azoospermia.Methods From January to December 2024,450 patients with non-obstructive azoospermia were surveyed at the Reproductive Medicine Center of Hospital.A self-made general information questionnaire was used to collect their demographic data.The Erectile Hardness Scale(EHS)was employed to investigate the current status of their penile erection hardness,and a self-made questionnaire was utilized to explore the influencing factors.Results Among the 450 patients with non-obstructive azoospermia,during sexual intercourse,35.3%of the patients reported that their penile erection hardness could reach grade 4(normal state),54.5%reported that it only reached grade 3(sub-optimal state),9.3%reported that it only reached grade 2(slight penile erection),and 0.9%reported that it only reached grade 1(inability to achieve an erection).In the survey of satisfaction with sexual life quality,among the 450 patients,only 24.9%were very satisfied with their sexual life quality;57.3%were basically satisfied;9.6%considered it average;4.0%were dissatisfied;3.1%were very dissatisfied;and 1.1%had no sexual life.alcohol consumption(OR=2.393,95%CI:1.493~3.836),satisfaction with the quality of sexual life(OR=1.455,95%CI:1.118~1.894),educational attainment(OR=0.709,95%CI:0.549~0.917),and the sleep quality in the past month(OR=0.641,95%CI:0.452~0.907).Conclusions Clinical studies have shown that factors such as drinking habits,sexual life satisfaction,sleep quality,and educational attainment collectively influence the penile erection hardness in patients with non-obstructive azoospermia.Therefore,the medical team needs to customize personalized intervention plans and educational materials based on individual differences among patients.Through psychological counseling and lifestyle guidance,they can improve erectile function and the quality of sexual life,promote harmonious marital relationships,and enhance the overall life experience of the patients.
6.Observation of several physiological indexes of rhesus monkeys by implantable telemetry technology
Qijiong LU ; Minhua CHEN ; Cong XU ; Jun DENG ; Zhiwei XU ; Yaoxian XUAN
Chinese Journal of Comparative Medicine 2018;28(1):100-107
Objective To observe the changes of circadian characteristics and stress-response-related physiological parameters including respiration, blood pressure, electrocardiography and body temperature of conscious rhesus monkeys by implantable telemetry technique. Methods Surgery was performed on 8 rhesus monkeys (half male and half female, 3-5 years old) for implantation of a telemetry transmitter. After 3 weeks of recovery, the physiological parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus monkeys without binding were automatically recorded by a DSI telemetry system and the data were analyzed by the Ponemah software. Results Some electrocardiographic indexes showed significant differences at daytime and nighttime (P< 0. 05 or P< 0. 01) including mean heart rate (HR) ( 155. 0-122. 4 times/min), respiratory rate interval (RR-I) (410. 8-535. 7 ms), T-wave amplitude (T-A) (0. 181-0. 157 mV), PR interval (PR-I) (80. 4-87. 4 ms), QT interval (QT-I) (224. 8-263. 9 ms), and corrected QTcb interval (QTcb) (352. 3-366. 7 ms). The indexes of blood pressure and respiration at daytime were significantly higher than those at nighttime (P< 0. 01), including the mean systolic pressure (SYS) at daytime and nighttime (144. 6-131. 6 mmHg), diastolic pressure (DIA) (99. 8- 89. 9 mmHg), mean arterial pressure (MAP) (121. 5-110. 2 mmHg), tidal volume (TV) (64. 5-36. 6 mL), minute ventilation (MV) (1931. 9-920. 1 mL/min), and respiratory rate (RR) (32. 3-25. 4 times/min). Cleaning and feeding activities of the laboratory staff at 9: 00 a.m. and 2: 00 p.m. had a certain effect on the stress-responses in the monkeys. Conclusions The parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus macaques observed by implanted telemetry system show obvious circadian changes, which can truly reflect the changes of physiological indexes at daytime and nighttime, and avoid the stress in hungry monkeys caused by the feeding and cleaning activities of laboratory staff. This technique can improve the efficiency of drug safety pharmacology studies, reduce the number of animals used and meet the requirements of 3R principles.
7.The prognostic value of neutrophil to lymphocyte ratio on prostate cancer patients treated with maximal androgen blockade
Ning WANG ; Jianye LIU ; Minhua DENG ; Xiongjian ZHAO ; Jun GAO ; Yichuan ZHANG ; Jin TANG ; Zhi LONG ; Leye HE
Chinese Journal of Urology 2018;39(12):911-915
Objective To evaluate the prognostic value of pretreatment neutrophil to lymphocyte ratio (NLR) on prostate cancer patients treated with maximal androgen blockade (MAB).Methods The clinical data of 249 prostate cancer patients treated with MAB in our hospital from October 2007 to March 2017 were retrospectively analyzed.Among all the patients,the median age was 72 years old (ranged 48 to 89 years).The BMI was 14.5-31.8kg/m2 (median 23.0 kg/m2).The PSA was 1.00-758.21 ng/ml (median 60.04 ng/ml).216 patients' tumor invaded surrounding tissues;lymph node metastasis occurred in 157 patients;and distant organ metastasis occurred in the remaining 174 patients.The Gleason score was 3-10 (median 7).Copfimary end points were progression-free survival (PFS) and cancer-specific survival (CSS).The best cutoff value of NLR was calculated by receiver operating characteristic (ROC) curve.The prognostic analysis of NLR on prostate cancer patients treated with MAB was estimated using Cox proportional hazards models and Kaplan-Meier analysis.Results The ideal cutoff value of the pretreatment NLR was 2.29 (95% CI 0.603-0.737,P <0.001) determined by the ROC curve according to the survived and deceased cases at the end point of CSS,by which the 249 patients was divided into the high NLR group of 119 patients (47.8%) and the low NLR group of 130 patients (52.2%).High NLR was significantly associated with high Gleason score (P =0.019),higher clinical T stage (P =0.001),N stage (P < 0.001),M stage (P < 0.001) and more neutrophil count (P < 0.001).The median follow-up time was 29 months (ranged 5 to 124).During this period,115 patients died,and the whole fatality rate was 46.2%.40 patients died in low NLR group (30.8%),while the figures for the high NLR group were 75 (63.0%).Kaplan-Meier analysis demonstrated that patients with NLR ≥ 2.29 had a poor outcome both in PFS (P < 0.001) and CSS (P < 0.001).The multivariate Cox analysis showed that NLR,Gleason score,clinical TNM stage and ECOG score were independent predictors for PFS and CSS.Conclusion Pretreatment NLR could be an independent prognostic biomarker for PFS and CSS in prostate cancer patients undergoing MAB.
8.Advances in Classification and Research Methods of Lung Epithelial Stem and Progenitor Cells
DENG MINHUA ; LI JINHUA ; GAN YE ; CHEN PING
Chinese Journal of Lung Cancer 2017;20(2):130-137
Isolation and characterization of lung epithelial stem and progenitor cells and understanding of their specific role in lung physiopathology are critical for preventing and controlling lung diseases including lung cancer. In this re-view, we summarized recent advances in classification and research methods of lung epithelial stem and progenitor cells. Lung epithelial stem and progenitor cells were region-specific, which primarily included basal cells and duct cells in proximal airway, Clara cells, variant Clara cells, bronchioalveolar stem cells and induced krt5+ cells in bronchioles, type Ⅱ alveolar cells and type Ⅱ alveolar progenitor cells in alveoli. The research methods of lung epithelial stem and progenitor cells were mainly focused on lung injury models, lineage-tracing experiments, three dimensional culture, transplantation, chronic labeled cells and single-cell transcriptome analysis. Lastly, the potential relationship between lung epithelial stem and progenitor cells and lung cancer as well as lung cancer stem cell-targeted drug development were briefly reviewed.
9.Assessment of left atrial function in patients with rheumatic mitral stenosis by real time three-dimensional echocardiography
Minhua CHEN ; Shenglan GUO ; Shiyun QIN ; Ji WU ; Di ZHANG ; Yan DENG
Chongqing Medicine 2016;45(11):1499-1501
Objective To evaluate of left atrial(LA) function in patients with rheumatic mitral stenosis(MS) by real time three‐dimensional echocardiography (RT‐3DE) .Methods Thirty patients with MS and 50 healthy volunteers underwent RT‐3DE . The left atrial end‐diastolic volume (LAVmax ) ,end‐systolic volume (LAVmin ) and pre‐systolic volume (LAVpre ) were measured to calculate the total ,passive and active atrial stroke volume (TASV ,PASV ,AASV) ,left atrial expansion index (LAEI) ,left atrial to‐tal ,passive ,active ejection fraction (LAEF ,LAEFpassive ,LAEFactive ) .The volume data were corrected by body surface area (BSA) to gettheleftatrialend‐diastolicvolumeindex (LAVmaxI),end‐systolicvolumeindex(LAVminI),pre‐systolicvolumeindex(LAVpreI) and the total ,passive and active atrial stroke volume index (TASVI ,PASVI ,AASVI) .The correlations between the LA volume , stroke volume ,function indices and the mitral valve area (MVA) were analyzed .Results (1)LAVmaxI ,LAVminI and LAVpreI were significantly greater in patients with MS than the controls(all P<0 .05) .(2)There was no significant difference in TASVI ,PASVI and AASVI between the two groups(all P>0 .05) .(3) LAEI ,LAEF ,LAEFpassive and LAEFactive were significantly lower in patients with MS than the controls(all P<0 .05) .(4)There was a significant correlation between the LAVmax I ,LAVmin I ,LAVpre I ,LAEF , LAEFpassive and MVA (r= -0 .432 ,-0 .421 ,-0 .440 ,0 .352 ,0 .401 ,all P<0 .05) ,there was no correlation between the TAVSI , PASVI ,AASVI ,LAEI ,LAEFactive and MVA(all P>0 .05) .Conclusion LA function in patients with mitral stenosis decreased .RT‐3DE can be used to evaluate LA function in patients with MS and sinus rhythm .
10.Analysis of irrational drug use in adverse reaction reports of Chinese patent medicines
Xiaoling WU ; Minhua ZHOU ; Jianxiong DENG
Adverse Drug Reactions Journal 2014;(5):281-285
Objective To understand the effect of rational use of traditional Chinese patent medicines on medication safety. Methods By using cluster sampling method,the adverse drug reaction (ADR)reports about traditional Chinese patent medicines(including traditional Chinese medicine for injections)derived from the Center for ADR Monitoring of Guangdong from January 1st,2011 to December 31st,2011,were collected and retrospectively analyzed. The information of the patients' gender,ages, primary diseases,the suspected drugs causing ADR,drug combination,and the situation of ADR occurrence were collected. The situation of irrational drug use in these reports at 7 aspects such as indications, syndrome differentiation treatment,medication methods,dosage,combination of traditional Chinese patent medicines,concomitant use of the traditional Chinese medicines and the Western medicines,and suitability of medication were analyzed according to the protocol of evaluation standards of traditional Chinese patent medicine prescription and the rate of irrational drug use were calculated. Results A total of 283 reports in accordance with the inclusion criteria were collected,which comprised 283 patients. Of them,150 were male and 133 were female with ages from 2 months to 88 years and an average age was(44 ± 23)years. The primary diseases ranking at the top three were respiratory system disease( 71 patients ),nervous system disease(45 patients),and musculoskeletal system disease(42 patients). The traditional Chinese patent medicines involved in these reports were mainly antipyretic-detoxicating agents,blood activating and stasis removing agents,and reinforcing agents. The rates of irrational drug use associated with indications, medication methods,dosage,combination of traditional Chinese patent medicines,concomitant use of the traditional Chinese medicines and the Western medicines,and suitability of medication were 27. 2%(77/283), 6. 0%(17/283),7. 1%(20/283),5. 3%(15/283),6. 7%(19/283),0. 7%(2/283),respectively. Fifteen patients'medication(46. 8%)did not fit the syndrome differentiation classification among the 32 reports whose differentiation of syndromes could be identified. Conclusions The irrational drug use has marked effect on medication safety of traditional Chinese patent medicines and maybe one of the important factors in relation to adverse reactions induced by traditional Chinese patent medicines. In clinical use of traditional Chinese patent medicines,syndrome differentiation treatment should be the primary principle,medication beyond the indications should be avoided,more attention should be paid to usage and dosage of the drugs, and combination of function-similar traditional Chinese patent medicines and pharmacological action-similar traditional Chinese and Western medicines should be used cautiously.

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