1.Relationship between the SUV max of primary lesion on 18F-FAPI-42 PET/CT imaging and the clinicopathological characteristics of patients with gastric cancer
Lilan FU ; Fei XIE ; Ye DONG ; Yanjiang HAN ; Jinmei ZHONG ; Caixia XIAO ; Ganghua TANG ; Hubing WU ; Wenlan ZHOU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(6):331-336
Objective:To explore the relationship between 18F-fibroblast activation protein inhibitor (FAPI)-42 SUV max of primary gastric cancer and clinicopathological factors of patients. Methods:Fifty-one patients (31males, 20 females, age: 51(47, 65) years) with gastric cancer who underwent 18F-FAPI-42 PET/CT before surgical resection in Nanfang Hospital, Southern Medical University from February 2022 to January 2023 were analyzed retrospectively. The clinicopathological factors that might affect tumor SUV max (including gender, age, tumor location, pathological type, histological grade, Lauren classification, vascular and(or) neural invasion, programmed cell death-ligand 1 (PD-L1) expression, pathologic(p)T stage, pN stage and pTNM stage) were evaluated by the univariate analysis (Mann-Whitney U test or Kruskal-Wallis rank sum test) and multivariate analysis (multiple linear regression analysis). Results:The sensitivity of 18F-FAPI-42 PET/CT in the diagnosis of patients with primary gastric cancer was 82.35% (42/51). The diagnostic sensitivities for early gastric cancer (T1) and locally advanced gastric cancer (T2-T4) were 59.09%(13/22) and 100%(29/29), respectively. The SUV max of primary lesion was 4.90(1.71, 12.51). The univariate analysis showed that SUV max of primary gastric cancer was related to tumor location ( z=-2.00, P=0.046), pT stage ( H=36.94, P<0.001), pN stage ( z=-3.89, P<0.001), pTNM stage ( H=31.49, P<0.001) and vascular and(or) nerve invasion ( z=-5.22, P<0.001), but not related to pathological type, histological grade, Lauren typing, and PD-L1 expression ( z values: from -1.78 to -0.09, all P>0.05). pT stage was found to be a significant independent factor for SUV max in primary gastric lesion by multivariate analysis ( t=2.52, P=0.015). Conclusions:The 18F-FAPI-42 SUV max of primary tumor was related to tumor location, pT stage, pN stage, pTNM stage, and vascular and(or) nerve invasion; pT stage is an independent factor affecting tumor SUV max. The ability of 18F-FAPI-42 PET/CT to detect gastric cancer is mainly affected by pT stage.
2.Data-driven engineering framework with AI algorithm of Ginkgo Folium tablets manufacturing.
Lijuan MA ; Jing ZHANG ; Ling LIN ; Tuanjie WANG ; Chaofu MA ; Xiaomeng WANG ; Mingshuang LI ; Yanjiang QIAO ; Yongxiang WANG ; Guimin ZHANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2023;13(5):2188-2201
Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.
3.Effects and mechanism of pterostilbene on wound healing in diabetic skin ulcer model rats
Yakun LIU ; Gang LI ; Juan YAN ; Huizhi XU ; Yanjiang WU ; Shuai YOU ; Jingya NIU ; Hongjian LI ; Binggui ZHANG
China Pharmacy 2023;34(16):1967-1971
OBJECTIVE To explore the effects of pterostilbene (PTE) on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group; after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back, model rats were randomly divided into model group, PTE low-dose group (40 mg/kg), PTE high-dose group (80 mg/kg), PTE high-dose+PP2 group (80 mg/kg PTE+2 mg/kg SRC inhibitor PP2), with 10 rats in each group. On the second day after modeling, the rats in each drug group were intraperitoneally injected with corresponding drug solutions, while the rats in control group and model group were intraperitoneally injected with normal saline, once a day, for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration; the contents of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in the serum of rats were detected; the pathological changes of wound granulation tissue were observed, and the expressions of SRC/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group, the wound healing rate, serum content of VEGF, the phosphorylation levels of SRC, MEK1/2 and ERK1/2 were decreased significantly (P<0.05), while serum contents of IL- 1β, IL-6 and TNF-α were increased significantly (P<0.05); there was obvious infiltration of inflammatory cells in the wound granulation tissue, and the number of new blood vessels decreased. Compared with model group, above indexes of PTE low-dose and high-dose groups were improved significantly (P<0.05), and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes (P<0.05). CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats, the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.
4.Preclinical evaluation and pilot clinical study of 18FAlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts.
Kongzhen HU ; Junqi LI ; Lijuan WANG ; Yong HUANG ; Li LI ; Shimin YE ; Yanjiang HAN ; Shun HUANG ; Hubing WU ; Jin SU ; Ganghua TANG
Acta Pharmaceutica Sinica B 2022;12(2):867-875
In recent years, fibroblast activation protein (FAP) has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands. Herein, we aimed to design a novel 18F-labeled FAP tracer ([18F]AlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The [18F]AlF-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32 ± 6% (n = 8). Among A549-FAP cells, [18F]AlF-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer [18F]FAPI-42, [18F]AlF-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of [18F]AlF-P-FAPI (7.0 ± 1.0% ID/g) compared to patent tracers [18F]FAPI-42 (3.2 ± 0.6% ID/g) and [68Ga]Ga-FAPI-04 (2.7 ± 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, [18F]AlF-P-FAPI and [18F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that [18F]AlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies.
5.Preparation and Quality Evaluation of Pogostone Transfersomes
Lina MA ; Zhimin WU ; Chang YANG ; Shujuan GUO ; Liping CHEN ; Yanjiang QIAO ; Xinyuan SHI
China Pharmacy 2019;30(1):50-54
OBJECTIVE: To prepare pogostone transfersomes, and to evaluate its quality. METHODS: Film dispersion method was used to prepare pogostone transfersomes. Using the accumulative penetration volume (Qn) and accumulative penetration ratio (PR) of pogostone as evaluation indexes, the types of surfactant, formulation were screened in respects of the dosage of surfactant and the dosage of pogostone. The pogostone transfersomes were prepared with optimal formulation; the morphology, particle size distribution and Zeta potential were observed and the entrapment efficiency was measured. RESULTS: The optimal formulation was as follows as the sodium cholate was selected as surfactant; the dosage of sodium cholate was 0.25 g; the dosage of pogostone was 15 mg. The optimal pogostone transfersomes were ivory-white suspension; average particle size was (115.6±3.65) nm (RSD=3.20%,n=3); PDI was 0.185±0.008 (RSD=4.30%, n=3); Zeta potential was (-13.76±0.225) mV (RSD=1.70%,n=3); entrapment efficiency of pogostone was (46.01±0.40)% (RSD=0.87%,n=3); Qn was (378.76±0.61) μg/cm2 (RSD=0.20%,n=3); PR was (89.02±0.96)% (RSD=1.10%,n=3). CONCLUSIONS: Prepared pogostone transfersomes are in line with quality requirements, which can provide reference for the further study of new dosage form of pogostone.
6.Efficient lung cancer-targeted drug delivery a nanoparticle/MSC system.
Xusheng WANG ; Haiyan CHEN ; Xiaowei ZENG ; Wenpeng GUO ; Yu JIN ; Shan WANG ; Ruiyun TIAN ; Yanjiang HAN ; Ling GUO ; Jimin HAN ; Yaojiong WU ; Lin MEI
Acta Pharmaceutica Sinica B 2019;9(1):167-176
Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered MSC accumulated in the lung. Both MSC/A549 cell experiments and MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.
7.New sensor technologies in quality evaluation of Chinese materia medica: 2010-2015.
Xiaosu MIAO ; Qingyu CUI ; Honghui WU ; Yanjiang QIAO ; Yanfei ZHENG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2017;7(2):137-145
New sensor technologies play an important role in quality evaluation of Chinese materia medica (CMM) and include near-infrared spectroscopy, chemical imaging, electronic nose and electronic tongue. This review on quality evaluation of CMM and the application of the new sensors in this assessment is based on studies from 2010 to 2015, with prospects and opportunities for future research.
8.Establishment of a diagnostic model for charactering solitary pulmonary nodule based on 18F-FDGPET/CT and clinical data
Wenjuan LIU ; Quanshi WANG ; Hubing WU ; Yanjiang HAN ; Wenlan ZHOU ; Hongsheng LI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(3):211-215
Objective To establish a diagnostic model based on 18F-FDG PET/CT and clinical data and assess its diagnostic potency for characterizing SPN.Methods From November 2004 to May 2014,164 patients with SPN who underwent 18F-FDG PET/CT scan were retrospectively analyzed.The patients'clinical factors (age,gender,history of smoking and history of malignancy),information on CT (diameter,location and spiculated edge of the lesion) and metabolic information on PET imaging were collected to establish a diagnostic model by using the binary logistic regression.Then,the optimal operating point (OOP)of the established model was set.The diagnostic potencies of the established model and PET were assessed by ROC curve.Results Malignancy was diagnosed in 104 of 164 SPN patients.The rest 60 patients had benign diseases.The factors of age,spiculation(0:no spiculation,1:obvious spiculation) and metabolic information(0:≤ mediastinal blood pool,1:>mediastinal blood pool) were demonstrated to be useful for the establishment of the model (x2 =5.486,16.240,33.855,all P<0.05).However,the factors of gender,history of smoking,the diameter and location of lesions showed no influence for the model (x2 =2.452,0.453,0.127,0.390,all P>0.05) and rejected from the model established.The history of malignancy was excluded from statistical analysis because there were only 2 patients with history of malignancy.The established model was as follows:P=1/(1+e-Z),z=-5.512+0.061xage+2.208xspiculation+3.767×metabolic increase.The ROC AUC of the established model and PET using two-point scoring scale (TPSS) for charactering SPN were 0.92(95% CI:0.87-0.96)and 0.80(95% CI:0.73-0.86).The model had higher diagnostic efficacy compared with TPSS (z=4.369,P<0.05).When P=0.796 7 was set as an OOP,the diagnostic sensitivities of the model and PET for charactering SPN were 91.3% (95/104) and 94.2% (98/104) respectively,and no significant difference was found between them (x2 =0.800,P>0.05).However,significant difference was found between the diagnostic specificities of them (80.0% (48/60) vs 65.0% (39/60);x2 =7.111,P<0.05).Conclusions A new diagnostic model for characterizing SPN based on the information from 18FFDG PET,thin-section CT and clinical data is successfully established.Its sensitivity for diagnosis of lung cancer is high,and its specificity is superior to PET using with TPSS.This model has a potential value for clinical application.
9.Can radical parametrectomy be omitted in occult cervical cancer after extrafascial hysterectomy?
Huai-Wu LU ; Jing LI ; Yun-Yun LIU ; Chang-Hao LIU ; Guo-Cai XU ; Ling-Ling XIE ; Miao-Fang WU ; Zhong-Qiu LIN
Chinese Journal of Cancer 2015;34(9):413-419
BACKGROUNDOccult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP.
METHODSA total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed.
RESULTSOf the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence.
CONCLUSIONSPerioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.
Adult ; Cervical Intraepithelial Neoplasia ; Combined Modality Therapy ; Female ; Humans ; Hysterectomy ; Lymph Node Excision ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Unknown Primary ; Postoperative Complications ; Retrospective Studies ; Risk Factors ; Uterine Cervical Neoplasms
10.Value of 18F-FDG PET/CT in the evaluation of treatment response and prognosis for patients with recurrent uterine cervical cancer
Dandan CHEN ; Hubing WU ; Quanshi WANG ; Yanjiang HAN ; Wenlan ZHOU ; Hongsheng LI ; Ying TIAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(3):168-172
Objective To investigate the value of 18F-FDG PET/CT in the evaluation of treatment response and prognosis for patients.with recurrent uterine cervical cancer.Methods Forty-five patients with recurrent uterine cervical cancer underwent 18F-FDG PET/CT before and after treatment from October 2004 to December 2014,and their PET/CT results were retrospectively analyzed.Treatment response was categorized as complete metabolic response (CMR),partial metabolic response (PMR),stable metabolic disease (SMD) and progressive metabolic disease (PMD) according to PET response criteria in solid tumors (PERCIST).Kaplan-Meier survival analysis was used.The difference of progression-free survival (PFS) between patients with and without PMD was compared by x2 test.The PFS difference among patients with different SUVmax on pretreatment PET/CT was also compared byx2 test.Results After treatment,22.2% (10/45) of patients were categorized as CMR,22.2%(10/45) as PMR,4.4%(2/45) as SMD and 51.1% (23/45) as PMD by post-treatment 18F-FDG PET/CT.Thirty-two patients had long-term (6-64 months) clinical follow-up.The PFS was 1-64 months and the median PFS was 5 months.The patients without PMD had a significantly better PFS than those with PMD(12.2 vs 4.2 months,x2 =7.223,P<0.01).Patients with lesion SUVmax<7.5 on pretreatment PET/CT had a better PFS than those with SUVmax ≥7.5 (16.3 vs 5.9 months,x2 =5.415,P<0.05).Conclusion 18F-FDG PET/CT is useful forthe evaluation of treatment response and prognosis in patients with recurrent cancer of the uterine cervix.

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