1.Mechanism of active ingredient compatibility of Dimocarpus longan Lour. leaves in improving glucose and lipid metabolism disorders in type 2 diabetic mellitus rats
Yanli LIANG ; Shijia AN ; Fengsheng LI ; Jiani MAI ; Anqi HUO ; Jiali WEI ; Zejuan ZHANG ; Shuyan QIN ; Wenqing HUANG ; Jie LIANG
China Pharmacy 2026;37(13):1697-1703
OBJECTIVE To explore the mechanism of the active ingredient compatibility(quercetin, quercitrin and kaempferol at a mass ratio of 2∶9∶3)of Dimocarpus longan Lour. leaves(abbreviated as CDL) on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus (T2DM) rats. METHODS SD rats were randomly divided into blank control group, model group, metformin hydrochloride group (100 mg/kg), and CDL high-, medium- and low-dose groups (280, 140, 75 mg/kg), with 10 rats in each group. Rats in the blank control group were fed with standard chow, while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling, rats in each administration group were given corresponding drug solution, and rats in the blank control group and model group were intragastrically administered with equal volume of pure water, once a day, for consecutive 4 weeks. Fasting blood glucose (FBG) was detected at fixed time every week. The curves of oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were plotted, and the area under curve (AUC) was calculated. The pancreatic islet function indexes [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI)],blood lipid indexes [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group, the FBG, AUC of IPITT curve, AUC of OGTT curve, HOMA-IR, the levels of FINS, TC, TG and LDL-C, as well as the protein and mRNA expression of phosphatase and tensin homolog, forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group ( P <0.05). ISI, the levels of HDL-C and hepatic glycogen content, along with the protein and mRNA expression of PI3K, insulin receptor substrate-1, Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased ( P <0.05). In model group rats, the arrangement of hepatocytes was irregular, the overall structure of pancreatic lobules was disordered, and a large number of inflammatory cell infiltration was observed. Compared with the model group, most of the above quantitative indexes were significantly reversed in the CDL high-dose group ( P <0.05), and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders, elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.
2.Mechanism of active ingredient compatibility of Dimocarpus longan Lour. leaves in improving glucose and lipid metabolism disorders in type 2 diabetic mellitus rats
Yanli LIANG ; Shijia AN ; Fengsheng LI ; Jiani MAI ; Anqi HUO ; Jiali WEI ; Zejuan ZHANG ; Shuyan QIN ; Wenqing HUANG ; Jie LIANG
China Pharmacy 2026;37(13):1697-1703
OBJECTIVE To explore the mechanism of the active ingredient compatibility(quercetin, quercitrin and kaempferol at a mass ratio of 2∶9∶3)of Dimocarpus longan Lour. leaves(abbreviated as CDL) on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus (T2DM) rats. METHODS SD rats were randomly divided into blank control group, model group, metformin hydrochloride group (100 mg/kg), and CDL high-, medium- and low-dose groups (280, 140, 75 mg/kg), with 10 rats in each group. Rats in the blank control group were fed with standard chow, while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling, rats in each administration group were given corresponding drug solution, and rats in the blank control group and model group were intragastrically administered with equal volume of pure water, once a day, for consecutive 4 weeks. Fasting blood glucose (FBG) was detected at fixed time every week. The curves of oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were plotted, and the area under curve (AUC) was calculated. The pancreatic islet function indexes [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI)],blood lipid indexes [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group, the FBG, AUC of IPITT curve, AUC of OGTT curve, HOMA-IR, the levels of FINS, TC, TG and LDL-C, as well as the protein and mRNA expression of phosphatase and tensin homolog, forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group ( P <0.05). ISI, the levels of HDL-C and hepatic glycogen content, along with the protein and mRNA expression of PI3K, insulin receptor substrate-1, Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased ( P <0.05). In model group rats, the arrangement of hepatocytes was irregular, the overall structure of pancreatic lobules was disordered, and a large number of inflammatory cell infiltration was observed. Compared with the model group, most of the above quantitative indexes were significantly reversed in the CDL high-dose group ( P <0.05), and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders, elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.
3.Factors influencing daily blood donation attendance and their spatial heterogeneity at fixed donation sites in Nanjing
Zhanghui LI ; Wenbiao LIANG ; Wenjia HU ; Xian CHEN ; Wenqing YUAN ; Nizhen JIANG
Chinese Journal of Blood Transfusion 2026;39(7):908-916
Objective: To analyze the time-related factors influencing daily blood donation attendance at fixed donation sites in Nanjing and the heterogeneity among sites, and to provide evidence for optimizing site layout and operational management. Methods: Based on daily attendance data from 17 fixed donation sites in Nanjing for the full year of 2025, matched with contemporaneous meteorological and air quality data, a two-stage negative binomial generalized linear mixed model (NB-GLMM) was constructed. In the second stage, site-level static characteristics (number of scenic spots, daily operating hours, number of shopping malls, public transport stops, hospitals, universities, and residential buildings) were additionally incorporated. Model comparison was performed using Akaike information criterion (AIC). Significance of random effects was tested by likelihood ratio test, and site-specific random effects were extracted using empirical Bayes estimation. Robustness of the results was verified through residual diagnostics and multiple sensitivity analyses. Results: The first-stage model showed that rainfall was associated with lower attendance (IRR=0.943, P<0.001); holidays were associated with higher attendance (IRR=1.162, P<0.001); Saturdays and Sundays showed higher attendance than Mondays, with the strongest association on Sundays (IRR=1.195, P<0.001). Temperature exhibited a non-linear relationship (linear term P=0.051, quadratic term P=0.036). The joint results of the linear and quadratic terms for temperature suggested a nonlinear relationship between attendance and temperature. After introducing static characteristics in the second stage, the number of scenic spots (IRR=1.372, P=0.008) and daily operating hours (IRR=1.823, P<0.001) were found to be positively associated with attendance, while the numbers of shopping malls, public transport stops, hospitals, universities, and residential buildings showed no significant effects. Conclusion: Daily blood donation attendance at fixed sites in Nanjing is influenced by multiple factors including weather, day of the week, holidays, and site surroundings. Substantial heterogeneity exists among different sites; extended operating hours and more nearby scenic spots are associated with increased attendance.
4.Comparison of the Risk Stratification Systems of CHIC and New CCCG in the Prognostic Evaluation of Hepatoblastoma
Zhen LI ; Hong JIANG ; Wenqing WANG ; Yuanqi WANG ; Libin HUANG ; Juncheng LIU ; Hongman XUE
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(2):346-353
ObjectiveTo compare the Children's Hepatic tumors International Collaboration (CHIC) and the new Chinese Children's Cancer Group (CCCG) hepatoblastoma (HB) risk stratification systems in terms of their prognostic prediction efficacy and chemotherapy guidance value for Chinese children with HB, aiming to identify the risk stratification system more suitable for Chinese HB patients. MethodsThis retrospective study analyzed the clinical data of 403 pediatric patients with HB aged < 18 years who were initially diagnosed at The First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023. The prognostic predictive efficacy and chemotherapy-guided value of the CHIC and CCCG risk stratification systems was compared. Statistical analysis was performed using SPSS 27.0. Results①Using the new CCCG risk stratification, the 5-year event-free survival (EFS) rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 82.5% and 67.7% (P=0.002), respectively, and the 5-year overall survival (OS) rates were 91.5% and 85.1% (P=0.038). Using CHIC risk stratification, the corresponding 5-year EFS rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 80.3% and 68.5% (P=0.030), and the 5-year OS rates were 90.9% and 85.8% (P=0.151). ②Among children treated with the CCCG-HB-2016 protocol stratified by the new CCCG system, the 5-year EFS rates for the very low-risk (6 cases), low-risk (20 cases), intermediate-risk (61 cases), and high-risk (69 cases) groups were 100%, 94.1%, 94.7%, and 66.2% (P<0.001), respectively, and the 5-year OS rates were 100%, 100%, 96.5%, and 82.0% (P=0.017). Among children treated with the CCCG-HB-2016 protocol stratified by the CHIC system, the 5-year EFS rates for the very low-risk (32 cases), low-risk (22 cases), intermediate-risk (37 cases), and high-risk (54 cases) groups were 93.8%, 95.2%, 76.1%, and 66.8% (P=0.003), respectively, and the 5-year OS rates were 93.1%, 100%, 89.5%, and 85.6% (P=0.190). ③For patients receiving CCCG-HB-2016 risk-stratified chemotherapy, the P-values for EFS comparisons between the CHIC and new CCCG systems within the very low-risk, low-risk, intermediate-risk, and high-risk groups were 0.537, 0.879, 0.023, and 0.934, respectively. Among patients who received stratified chemotherapy according to the CCCG-HB-2016 regimen, the intermediate-risk group in the new CCCG risk stratification system exhibited a significant advantage in 5-year event-free survival (EFS) compared with the intermediate-risk group in the CHIC risk stratification system (94.7% vs. 76.1%). ConclusionCompared to the CHIC risk stratification, the new CCCG stratification may offer better prognostic prediction and guidance value for chemotherapy in Chinese HB patients, with the intermediate-risk group showing superior outcomes.
5.POEMS syndrome with hepatosplenomegaly as the initial manifestation: A report of two cases
Ye ZHANG ; Wenqing WANG ; Jing LI ; Qianrong BAI ; Jiayu LI ; Yan CHENG ; Miaomiao FANG ; Nana GAO ; Changxing HUANG
Journal of Clinical Hepatology 2025;41(1):127-132
POEMS syndrome is a rare condition associated with plasma cell disorders, and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease, the patients presented with lower limb weakness, hepatosplenomegaly, lymph node enlargement, ascites, hypothyroidism, positive M protein, and skin hyperpigmentation, and 18F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome, and the symptoms were relieved after immunomodulatory treatment.
6.Application of ASSR with different stimuli in hearing impaired children's hearing threshold assessment
Jialei ZHOU ; Fang CHEN ; Sihang GU ; Wenqing HUANG ; Xiaoyan LI
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(6):358-361
OBJECTIVE To investigate the application value of narrow-band CE-Chirp ASSR(NB CE-Chirp ASSR)and modulated acoustic ASSR in the assessment of hearing threshold in children with hearing impairment.METHODS Forty-eight children with sensorineural hearing loss were tested by pure tone audiometry(PTA),NB CE-Chirp ASSR and modulated acoustic ASSR.According to the results of pure tone audiometry,they were divided into mild to moderate group(48 ears)and severe to profound group(48 ears).The difference and correlation between pure tone hearing threshold and ASSR response threshold of different stimuli were compared between 500-4 000 Hz.RESULTS The absolute differences between the NB CE-Chirp ASSR response threshold and the PTA threshold in 48 children were all smaller than the differences between the modulated acoustic ASSR response threshold and the PTA threshold,and the differences were statistically significant(P<0.001).Under the same stimulus sound,the absolute difference between ASSR response threshold and pure tone hearing threshold in the mild to moderate group was higher than that in the severe to very severe group.The correlation coefficients between NB CE-Chirp ASSR threshold and pure tone hearing threshold are higher than those between modulated sound ASSR threshold and pure tone hearing threshold at 500-4 000 Hz.The test time of NB CE-Chirp ASSR[(20.92±9.33)min]was significantly shorter than that of modulated acoustic ASSR[(33.68±10.97)min](P=0.004).CONCLUSION NB CE-Chirp ASSR can more accurately assess the hearing threshold of children with different degrees of hearing loss than modulated acoustic ASSR.
7.Clinical study on Qigong Pills combined with IVF-ET technique in the treatment of PCOS infertility with phlegm-dampness type
Meiwei ZHANG ; Wenqing YIN ; Xiaoxia LI ; Yan ZHAO ; Lei WANG
International Journal of Traditional Chinese Medicine 2025;47(5):601-606
Objective:To explore the effects and safety of Qigong Pills in IVF-ET outcome of PCOS infertility patients with phlegm-dampness type.Methods:A randomized controlled trial study was carried out. In the Reproductive and Genetic Medicine Center of Dalian Women and Children Medical Center (Group) from January 2021 to December 2023, 60 patients with sputum and damp-induced PCOS infertility assisted by in-vitro fertilization and embryo transfer (IVF-ET) were enrolled and randomly divided into 2 groups by block randomization method, with 30 cases in each group. Patients in both groups took ethinylestradiol cyproterone tablets orally on the 2nd to 5th day of the 1st menstrual cycle before IVF-ET cycle, and received down-regulation treatment on the 18th to 20th day of menstruation. After confirming that the down-regulation standard was reached, Qigong Pills was added to the treatment group, and placebo was taken orally until the trigger day. Two groups of patients underwent transvaginal ultrasound-guided ovarian aspiration after injection of chorionic gonadotropin (hCG) for 24-36 h. The total amount of Gn, the days of Gn, the endometrial thickness of HCG, the number of eggs obtained, the rate of diprokaryotic (2PN) fertilization, the number of transferable embryos, the number of high-quality embryos, the rate of high-quality embryos, the incidence of OHSS and the clinical pregnancy rate were compared between the two groups.Results:Among the 60 patients, 28 cases in the final treatment group and 27 cases in the control group were included in the outcome index evaluation. During controlled hyperstimulation (COH), the total Gn [2 025 (1 575, 2 325) U vs. 2 700 (2 025, 3 150) U, Z=-3.67] and the number of Gn days of the treatment group [10 (8,11) d vs. 11 (9,13) d, Z=-2.31] were lower than those in control group ( P<0.001 or P<0.05). There was no statistical significance in endometrial thickness between 2 groups on HCG day ( P>0.05); the number of high-quality embryos [3 (3, 4) vs. 2 (2, 3), Z=0.11] and the rate of high-quality embryos [46.28% (87/188) vs. 35.19% (57/162), Z=4.42] in the treatment group were higher than those in the control group ( P<0.05). There was no statistical significance in the number of eggs obtained, the fertilization rate of 2PN and the number of transferable embryos between the two groups ( P>0.05). The incidence of OHSS was 3.6% (1/28) in the treatment group and 11.1% (3/27) in the control group, without statistical significance ( P=0.352). The clinical pregnancy rate was 53.6% (15/28) in the treatment group and 37.0% (10/27) in the control group, without statistical significance ( P=0.218). There was no significant difference in the safety indexes of liver and kidney function between 2 groups ( P>0.05). Conclusion:Qigong Pills combined with IVF-ET can effectively reduce the total amount of Gn and the number of days of treatment in PCOS infertility patients with phlegm-dampness type, increase the number and rate of high-quality embryos, and improve the outcome of IVF-ET, and it is safe and effective.
8.Distribution characteristics of food intolerance in children with autism spectrum disorders
Xiaoshuang ZHANG ; Jiajia ZHANG ; Hongfei DU ; Guohui LI ; Wenqing ZHANG ; Jing SU
Chinese Journal of Clinical Laboratory Science 2025;43(5):369-373
Objective To investigate the distribution of serum specific IgG antibodies against food in children with autism spectrum disorders(ASD),and provide experimental evidence for improving gastrointestinal symptoms of ASD children.Methods A retrospec-tive study was conducted on 411 children with ASD visited the Department of Psychology and Behavior of Hebei Children's Hospital from January 2021 to December 2022.Additionally,631 healthy children who underwent physical examination during the same period were collected as the healthy control group.Their venous blood samples were collected,and ELISA was used to detect the levels of 14 kinds of serum specific IgG antibodies against food.The distribution characteristics of food intolerance in children with different genders and ages were investigated.Results The total positive rate of specific IgG antibodies against food in children with ASD reached 91.84%(405/441).The top 3 positive rates of specific IgG antibodies were against egg(71.89%),milk(56.70%),and wheat(56.02%),respectively,which were significantly higher than those in the healthy control group(χ2=42.81,27.48,and 26.88,re-spectively,P<0.05).The comparative results of gender composition showed that the positive rate of specific IgG antibody against rice in female ASD children(15.96%)was significantly higher than that in male ASD children(4.90%,χ2=11.84,P<0.05).The posi-tive rates of specific IgG antibodies against egg and wheat in male and female ASD children were significantly higher than those in the healthy control group(χ2=19.44 and 4.42 for males,χ2=4.66 and 10.93 for females,P<0.05).The positive rate of specific IgG anti-body against milk in male ASD children was significantly higher than that in the healthy control group(χ2=12.62,P<0.05),while those against soybean and rice in female ASD children were also significantly higher than that in the healthy control group(χ2=7.00 and 5.42,P<0.05).There were significant differences in the positive rates of food intolerance to milk and soybean in ASD children with different ages(χ2=13.74 and 9.70,P<0.05)and they decreased with age.The positive rates of specific IgG antibody against wheat in ASD children aged 2-3 and 4-6 years were significantly higher than those in the healthy control group(χ2=5.78 and 4.55,P<0.05).The positive rate of specific IgG antibody against milk in ASD children aged 4-6 years was significantly higher than that in the healthy control group(χ2=7.57,P<0.05).Conclusion The highest positive rate of specific IgG antibodies against food in ASD chil-dren is against egg,which is not related to the patient's gender.Next are milk and wheat.The gastrointestinal issues and related food intolerance should be taken into account in the management of patients with ASD.
9.Safety and efficacy of different anastomotic techniques following proximal gastrectomy: a meta-analysis
Dongyang SONG ; Zehua WANG ; Jie WANG ; Jinjie ZHANG ; Shasha LI ; Kun ZHANG ; Guohua GAO ; Wenqing HU
Chinese Journal of Gastrointestinal Surgery 2025;28(10):1179-1193
Objective:This meta-analysis compares the postoperative outcomes of the double-flap technique (DFT) versus esophagogastrostomy (EG), jejunal interposition (JI), double-tract reconstruction (DTR), and gastric tube anastomosis (GTA) following proximal gastrectomy for gastric cancer.Methods:Prospective and retrospective studies published from database inception until June 2025 were retrieved from PubMed, Embase, Web of Science, Scopus, CNKI, and Wanfang databases. Studies reporting at least one predefined outcome with extractable data were included. Outcomes of interest consisted of incidence of gastroesophageal reflux, overall postoperative complications, anastomotic leakage, anastomotic stenosis, and digestive reconstruction time. Two investigators independently performed literature screening, data extraction, and quality assessment. Randomized controlled trials (RCTs) were evaluated with the Cochrane ROB 2.0 tool, retrospective cohort studies with the Newcastle-Ottawa Scale (NOS), and single-arm studies with the JBI critical appraisal tool. Dichotomous outcomes were pooled using risk ratios (RRs), and continuous variables were summarized with standardized mean differences (SMDs), using fixed- or random-effects models based on I2 statistics. Publication bias was assessed via funnel plots and Egger's test.Results:A total of 55 studies published between 2007 and 2025 were included, comprising 5 RCTs and 50 retrospective studies. Among 4,380 patients, 732 underwent EG, 454 GTA, 1,480 DTR, 468 JI, and 1,246 DFT. Quality assessment indicated that all except six retrospective cohort studies (rated as moderate quality) were of high quality or had low risk of bias. Among the five reconstruction methods, DFT showed the lowest incidence of gastroesophageal reflux (6.6%, 82/1,246) and overall postoperative complications (11.6%, 144/1,246). JI had the lowest rate of anastomotic leakage (1.3%, 6/468), followed by DFT (1.4%, 18/1,246), and DTR had the lowest rate of anastomotic stenosis (2.4%, 36/1,480), followed by DFT (7.5%, 94/1,246). DFT required the longest operative time for reconstruction ([141.2 ± 597.6] minutes), and DTR required the shortest ([50.1 ± 39.0] minutes). Compared to EG, DFT was associated with a significantly lower risk of gastroesophageal reflux (RR=0.13 ,95%CI: 0.03-0.55, P = 0.01), and no significant differences were observed in overall complications (RR=0.98, 95%CI: 0.55-1.74, P = 0.93), anastomotic leakage (RR = 0.81, 95%CI: 0.04-18.43, P = 0.90), or anastomotic stenosis (RR = 0.75, 95%CI: 0.09-6.39, P = 0.79). Compared to JI, DFT showed no significant differences in gastroesophageal reflux (RR = 0.36, 95%CI: 0.10-1.25, P=0.11), overall complications (RR=2.06, 95%CI: 0.30-14.11, P=0.46), anastomotic leakage (RR=2.05, 95%CI: 0.26-16.18, P=0.49), or anastomotic stenosis (RR=0.83, 95%CI: 0.10-7.17, P=0.87). Similarly, compared to DTR, DFT had a lower risk of overall complications (RR=0.70, 95%CI: 0.50-0.98, P=0.04) but a longer reconstruction time (SMD: 2.55, 95%CI: 0.31-4.79, P=0.03). No significant differences were found in gastroesophageal reflux (RR = 0.68, 95%CI: 0.35-1.30, P=0.24), anastomotic leakage (RR=0.59, 95%CI: 0.16-2.17, P=0.43), or anastomotic stenosis (RR=2.44 , 95%CI: 0.44-13.64, P=0.31). Compared to GTA, DFT was associated with a significantly lower risk of gastroesophageal reflux (RR = 0.53, 95%CI: 0.33-0.88, P=0.01), but again there were no significant differences in overall complications (RR = 0.69, 95%CI: 0.41-1.16, P=0.16), anastomotic leakage (RR = 0.25, 95%CI: 0.03-2.14, P=0.21), or anastomotic stenosis (RR=0.65, 95%CI: 0.24-1.76, P=0.40). No significant publication bias was detected in the analysis (Egger's test P>0.05). Conclusions:Among the five common anastomotic methods after proximal gastrectomy, DFT demonstrates superior anti-reflux efficacy, outperforming EG and GTA in particular in preventing gastroesophageal reflux. DFT also exhibits a lower overall complication risk compared with DTR but maintains anastomotic safety comparable with that of the other techniques.
10.Imaging poly(ADP-ribose) polymerase-1 (PARP1) in vivo with 18F-labeled brain penetrant positron emission tomography (PET) ligand.
Xin ZHOU ; Jiahui CHEN ; Jimmy S PATEL ; Wenqing RAN ; Yinlong LI ; Richard S VAN ; Mostafa M H IBRAHIM ; Chunyu ZHAO ; Yabiao GAO ; Jian RONG ; Ahmad F CHAUDHARY ; Guocong LI ; Junqi HU ; April T DAVENPORT ; James B DAUNAIS ; Yihan SHAO ; Chongzhao RAN ; Thomas L COLLIER ; Achi HAIDER ; David M SCHUSTER ; Allan I LEVEY ; Lu WANG ; Gabriel CORFAS ; Steven H LIANG
Acta Pharmaceutica Sinica B 2025;15(10):5036-5049
Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its 18F-isotopologue ([18F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [18F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [18F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

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