1.Expert consensus on the phase 0 clinical trials of positron-emitting radiopharmaceuticals (2025 edition)
Lu WANG ; Jinghao WANG ; Kuan HU ; Dongning YAO ; Benzhi CAI ; Chen SHI ; Baofeng YANG ; Rui WANG
China Pharmacy 2025;36(15):1825-1831
OBJECTIVE To provide a reference for standardizing the conduct of positron-emitting radiopharmaceuticals’ phase 0 clinical trials (hereinafter referred to as “phase 0 clinical trials”) and advancing the development of innovative drug by medical institutions. METHODS Initiated by the First Affiliated Hospital of Jinan University, a panel of experts consisting of pharmacy, clinical medicine and medical ethics from multiple institutions was established to investigate the current landscape, and discuss the necessary conditions, procedures, and other aspects for conducting phase 0 clinical trials in medical institutions by integrating relevant national policies, regulations and expert consensus. Finally, an agreement was reached to formulate this consensus. RESULTS & CONCLUSIONS Currently, most medical institutions have deficiencies in pharmaceutical care during the management of radiopharmaceuticals and the phase 0 clinical trials. In conjunction with the Expert Consensus on the Establishment of Nuclear Pharmacist Positions, this consensus explicitly defines the responsibilities of nuclear pharmacists in the phase 0 clinical trials on the basis of the Expert Consensus for the Application of Positron Emission Tomography Radioligands for Translational Study in the Phase 0 Clinical Trials (2020 edition), providing a guidance for high-quality participation of nuclear pharmacists from medical institutions in China in phase 0 clinical research. Additionally, in consideration of some constraints imposed by current relevant regulations, this consensus also proposes strategic recommendations, such as encouraging medical institutions to form a consortium, leading to the establishment of dedicated bases or industrial parks, holding significant implications to strengthen institutional capacity for advancing radiopharmaceutical innovation through phase 0 clinical trials.
2.Angiomatoid fibrous histiocytoma:a clinicopathologic study of fourteen cases
Baofeng YANG ; Libing FU ; Nan ZHANG ; Xingfeng YAO ; Jiatong XU ; Xiaoxing GUAN ; Jianwen WANG ; Lejian HE
Chinese Journal of Clinical and Experimental Pathology 2024;40(8):818-823
Purpose To study the clinical and pathological features of angiomatoid fibrous histocytoma(AFH)and to ex-plore its diagnosis,differential diagnosis and prognosis.Meth-ods The clinicopathological and follow-up data were analyzed in 14 cases of AFH,and the literatures were reviewed.Results There were 11 males and 3 females.The age ranged from 11 months to 12 years and 11 months,with average 5.9 years.3 cases were located in limbs,and 5 cases in trunk,5 cases in head and neck region,and 1 of intracranial tumor.Histological-ly,14 cases were composed of fibrous capsules and lymphocyte sheaths,and cell nucleus were vacuolar,forming fascicles with focal whirling and synteny.Intralesional pseudoangiomatous spaces were noted in 9 cases.Calcification was found in 2 ca-ses.2 cases showed high mitotic acticity(11/10 HPF).Scle-rosing and/or myxoid stroma was seen in 3 cases.Tumors were immunopositive for desmin(10/14),EMA(12/14),CD99(12/14),SMA(9/12),ALK(7/8),and the average of Ki67 index was 16%.7 cases harbored EWSR1 rearrangenent(part-ner gene not identified),2 cases had EWSR1-ATF1 fusion and 2 EWSR1-CREB1 fusion.Clinical follow-up information was a-vailable for 14 cases(average 46 months).All the 14 cases were alive without recurrence and metastasis.Conclusion AFH is a borderline or low-grade malignant tumor,often demon-strates indolent behavior in children,but rarely recurs and me-tastasizes.The diagnosis and differential diagnosis require a comprehensive analysis of clinical features,histopathologic changes,immunohistochemical finding and EWSR1 or FUS gene detection results.
3.Practice of Cybersecurity Risk Management in Large Hospitals Based on a Situational Awareness Platform
Baofeng SUN ; Weiyi ZHANG ; Yang YANG ; Yuhong LI
Journal of Medical Informatics 2024;45(10):81-85
Purpose/Significance To analyze the network security risk events monitored by the situational awareness platform of large hospitals,to find out the causes,and to put forward solutions and suggestions for improvement.Method/Process Taking the First Affiliated Hospital of Zhengzhou University as an example,the paper analyzes risk events on the situational awareness platform,screens the risky ter-minals on the hospital intranet,carries out rectification and reinforcement,analyzes the department distribution and causes of risky termi-nals,and puts forward suggestions for improvement.Result/Conclusion The number of risky terminals in medical and technical depart-ments is large,mainly due to the lack of management and the lack of full coverage of antivirus software.Through the rectification and rein-forcement of risky terminals,the number of network security risk events has been significantly reduced.Strengthening the hospital terminal security management,enhancing staff awareness of network security,and strengthening network security protection in different areas can ef-fectively reduce the incidence of hospital network security risk events and improve the hospital network security protection capability.
4.Development status of novel spectral imaging techniques and application to traditional Chinese medicine
Qi WANG ; Yong ZHANG ; Baofeng YANG
Journal of Pharmaceutical Analysis 2023;13(11):1269-1280
Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral tech-niques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.
5.Application value of joint friction sounds in diagnosing meniscus injury of the knee based on machine learning models
Bo HU ; Yang SHEN ; Shouyu CAO ; Baofeng GENG ; Feng LIN ; Xinnian GUO ; Jian QIN
Chinese Journal of Trauma 2023;39(12):1094-1100
Objective:To investigate the application value of joint friction sounds in diagnosing meniscus injury of the knee based on machine learning models.Methods:A case-control study was conducted to analyze the clinical data of 17 patients with meniscus injury of the knee (meniscus injury group) admitted to Sir Run Run Shaw Hospital Affiliated to Nanjing Medical University from August 2020 to October 2022, as well as 75 recruited healthy subjects without knee joint diseases (healthy group). The knee joint friction sounds of the subjects were collected in a relatively quiet environment (peak value below 40 dB). The sounds collected in a flexion-extension-flexion mode of exercise were split and divided randomly with a ratio of 4∶1 into the training set (125 segments from the meniscal injury group and 187 segments from the healthy group) and the test set (33 segments from the meniscal injury group and 47 segments from the healthy group). The sounds obtained in a sit-stand-sit mode of exercise were split and divided randomly with a ratio of 4∶1 into the training set (81 segments from the meniscal injury group and 164 segments from the healthy group) and the test set (20 segments from the meniscal injury group and 40 segments from the healthy group). Four machine learning models were built, including support vector machine with linear kernels, radial basis function support vector machine, random forest, and extremely randomized trees. The learning training of the model was performed on the training set, and its model performance was verified with the test set. The time required in a single collection of joint friction sound from the subjects and the interpretation of data analysis was recorded. Knee function of the subjects were scored according to the Lysholm Score before and at 1 day after the test. The accuracy rates of diagnosis of meniscus injury with friction sounds under the two modes of exercise were compared based on the test results to yield an optimal one. The effectiveness of the four models was compared to find the best machine learning model fitting the data frame of this study according to the test results such as accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC) obtained with the optimal mode of exercise. The diagnostic accuracy, misdiagnosis rate and missed diagnosis rate of joint friction sound for meniscal injury under the optimal machine learning model with the optimal mode of exercise were observed.Results:The time required in a single collection of joint friction sound ranged from 5 to 10 minutes [(7.1±1.3)minutes], when the time required for interpretation of data analysis was approximately 1 minute. The Lysholm Score before and after the test was (75.6±4.0)points and (77.7±3.7)points respectively in the meniscal injury group ( P>0.05), and (99.6±0.9)points and (99.5±1.0)points respectively in the healthy group ( P>0.05). The diagnosing accuracy rates for flexion-extension-flexion of exercise and sit-stand-sit modes of exercise were 0.775 and 0.817 under the support vector machine model with linear kernels; 0.813 and 0.900 under the radial basis function support vector machine model; 0.800 and 0.867 under the random forest model; 0.800 and 0.900 under the extremely randomized tree model. The accuracy rates for sit-stand-sit mode of exercise were all higher than those for flexion-extension-flexion mode of exercise. In the sit-stand-sit mode of exercise, the extremely randomized tree model had an accuracy rate of 0.900, sensitivity of 0.900, specificity of 0.950, F1 score of 0.900, and AUC of 0.942, which were higher than those under the remaining 3 models, showing better machine learning efficacy. Under the extremely randomized tree model in the sit-stand-sit mode of exercise, 22 (18 true positive and 4 false positive) were diagnosed as meniscal injury and 38 (36 true negative and 2 false negative) as healthy out of 60 segments in the test set (20 from the meniscal injury group and 40 from the healthy group). The diagnostic accuracy of joint friction sounds in diagnosing meniscus injury of the knee was 0.900, with the misdiagnosis rate of 0.100 and the missed diagnosis rate of 0.100. Conclusion:Diagnosis of meniscus injury of the knee with joint friction sounds can shorten time and enhance safety during the examination process. The diagnostic model using machine learning-based artificial intelligence is faster and more stable, which can be used as a diagnostic marker for such injury.
6.Effect of PSD-95 on long-term learning and memory impairment in neonatal rats induced by sevoflurane anesthesia
Baofeng YANG ; Jie WANG ; Changsheng LI ; Junpeng LIU ; Changhong MIAO ; Xihua LU
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(9):774-780
Objective:To investigate the effect of postsynaptic density-95(PSD-95)on long-term learning and memory impairment in neonatal rats induced by sevoflurane anesthesia.Methods:A total of 54 SD rats aged 7 days of SPF grade were randomly divided into 3 groups: control group (exposed to air), model group (exposed to 2.1% sevoflurane, 4 h/d, consecutive 3 days) and PSD-95 inhibitor group (inhaled sevoflurane+ intraperitoneal injection NA-1, consecutive 5 days), with 18 rats in each group.Morris water maze test and new object recognition test were used to detect the ability of visuospatial learning and memory and recognition memory of rats in each group.RT-qPCR was used to detect the mRNA levels of kalirin, Rac1 and PSD-95 in rat hippocampus.The expressions of kalirin, Rac1, PSD-95 and apoptosis related proteins Caspase-3, Bcl-2 and Bax in rat hippocampus were detected by Western blot.The expression levels of kalirin and Rac1 in hippocampus were detected by immunohistochemistry.SPSS 23.0 software was used for statistical analysis.Repeated measurement ANOVA and one-way ANOVA was used for comparing among groups.Results:Repeated measurement ANOVA showed that in the water maze test, the interaction between time and group of platform seeking latency and swimming distance of the three groups were significant ( Ftime×group=36.539, 41.548, both P<0.01). Simple effect analysis showed that the platform latency and swimming distance in the model group from day 2 to 6 were longer than those in the control group (platform latency from day 2 to 6: t=14.039, 17.147, 13.155, 13.831, 27.247, all P<0.01; swimming distance from day 2 to 6: t=10.122, 20.987, 7.267, 10.011, 8.121, all P<0.01). Compared with the model group, from day 2 to 6, the platform latencies of PSD-95 inhibitor group were prolonged( t=7.948, 14.768, 11.582, 12.832, 24.346, all P<0.01) and the swimming distances were increased( t=8.235, 24.325, 11.234, 12.031, 7.036, all P<0.01). The new object recognition test found that the new object exploration time in the model group was significantly longer than that in the control group ((21.30±2.27)s, (19.21±1.42)s, t=1.843, P<0.01), and the new object exploration time in the PSD-95 inhibitor group was significantly longer than that in the model group ((26.83±2.13)s, t=4.844, P<0.01). The difference index of novel objects in the model group was significantly lower than that in the control group ((0.41±0.12), (0.59±0.10), t=3.416, P<0.01), and the difference index of novel objects in the PSD-95 inhibitor group was significantly lower than that in the model group ((0.37±0.08), t=0.696, P<0.05). The qRT-PCR results showed that the expressions of Rac1, kalirin and PSD-95 mRNA in the model group were significantly lower than those in the control group ( t=9.969, 3.954, 6.561, P<0.05), and the expressions of Rac1, kalirin and PSD-95 mRNA in the PSD-95 inhibitor group were significantly lower than those of the model group ( t=2.132, 2.251, 3.502, all P<0.05). Immunohistochemistry results showed that the kalirin in the hippocampus CA1 area of the model group was significantly lower than that in the control group((8.18±1.94) vs (15.47±3.35), t=11.47, P<0.01), and kalirin in the PSD-95 inhibitor group was significantly lower than that in the model group((4.98±1.53), t=10.28, P<0.01); Rac1 in the model group was significantly lower than that in the control group ((3.72±1.53), (8.17±2.91), t=6.76, P<0.01), and the Rac1 in the PSD-95 inhibitor group(2.73±0.37) was significantly lower than the model group ( t=4.72, P<0.05). Western blot results showed that Caspase-3((1.37±0.16) vs (0.54±0.01), t=5.71, P<0.01) and Bax((1.87±0.31) vs (1.23±0.25), t=12.01, P<0.01) protein levels in the model group were significantly higher than those in the control group.Caspase-3 and Bax protein levels in the PSD-95 inhibitor group were significantly higher than those in model group (Caspase-3: (1.79±0.17), t=9.87, P<0.01; Bax: (2.19±0.21), t=16.19, P<0.01). The Bcl-2 protein level in the model group was significantly lower than that of the control group ((1.22±0.21) vs (1.96±0.38), t=11.92, P<0.01). And the Bcl-2 protein level in the PSD-95 inhibitor group (1.01±0.19) was significantly lower than that in the model group ( t=10.73, P<0.01). Conclusion:Sevoflurane anesthesia can damage the long-term learning and memory function and reduce the expression of PSD95 protein in neonatal rats.Inhibiting the expression of PSD95 can aggravate this damage, which may be related to the synaptic plasticity and apoptosis of neurons involved in PSD95.
7.Infant hand and forearm severe crush injury: A case of comprehensive microsurgery treatment
Qiqiang DONG ; Songjian ZHANG ; Shuqiang XIE ; Baofeng WANG ; Lei ZHANG ; Hongxin WANG ; Chaofan YANG ; Jianxi HOU
Chinese Journal of Microsurgery 2021;44(2):225-227
A case of a 3-year-old child suffered with severe crush injury to the right forearm and right hand on June, 2017. A comprehensive treatment was conducted with limb salvage, free flap repair and the repair of nerve, vessel and tendon for functional reconstructions followed by rehabilitation therapies. The function and appearance of the injured limb and hand recovered well 3 years after surgery.
8.HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/
Wei TIAN ; Jiatong LI ; Zhuo WANG ; Tong ZHANG ; Ying HAN ; Yanyan LIU ; Wenfeng CHU ; Yu LIU ; Baofeng YANG
Acta Pharmaceutica Sinica B 2021;11(6):1592-1606
HYD-PEP06, an endostatin-modified polypeptide, has been shown to produce effective anti-colorectal carcinoma effects through inhibiting epithelial-mesenchymal transition (EMT). However, whether HYD-PEP06 has similar suppressive effect on hepatocellular carcinoma (HCC) remained unknown. In this study, HYD-PEP06 inhibited metastasis and EMT but not proliferation
9.Berberine prevents primary peritoneal adhesion and adhesion reformation by directly inhibiting TIMP-1.
Xin LIU ; Yunwei WEI ; Xue BAI ; Mingqi LI ; Huimin LI ; Lei WANG ; Shuqian ZHANG ; Xia LI ; Tong ZHAO ; Yang LIU ; Rui GENG ; Hao CUI ; Hui CHEN ; Ranchen XU ; Heng LIU ; Yong ZHANG ; Baofeng YANG
Acta Pharmaceutica Sinica B 2020;10(5):812-824
Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.
10.The effect and possible mechanism of sevoflurane exposure on electroencephalographic seizures and long-term cognitive function in neonatal rats
Jie WANG ; Baofeng YANG ; Zhengbo YANG ; Ningtao LI ; Mingyang SUN ; Jiaqiang ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(3):215-220
Objective:To investigate the effect of sevoflurane anesthesia on electroencephalographic (EEG) seizures and long-term behavior and possible mechanism in neonatal rats.Methods:A total of 141 postnatal days 4-6 Sprague-Dawley rats (66 male, 75 female) were divided into 3 groups ( n=47 in each group) according to random number table method: control group, sevoflurane group, and NKCC1 inhibitor group, with 22 males and 25 females in each group. Rats in the control group were fed in normal cage without anesthesia; rats in the sevoflurane group were anesthetized with 2.1% sevoflurane for 6 hours; rats in the NKCC1 blocker group received intraperitoneal injection of 1.82 mg / kg bumetanide 30 minutes before anesthesia with 2.1% sevoflurane. The rats in the control group and sevoflurane group were injected subcutaneously with the same dose of DMSO at the same time when the NKCC1 blocker group received the drug intervention, so as to eliminate the influence caused by the solvent. The rats were observed for 30 minutes after recovery from anesthesia and then continued to breastfeed normally. Some of the new born rats received EEG monitoring from 9 to 11 days after being raised; the other rats received EPM and PPI respectively at 60 and 70 days after being raised. Results:The results of EEG showed that, compared with the control group, the number of epileptic waves((0.429±0.787), (1.571±0.787), t=2.753, P<0.01), the average duration of single epileptic wave ((1.575±2.349), (6.392±3.374), t=3.880, P< 0.01), the total duration increased significantly ((1.800±3.617), (10.957±6.028), t= 3.929, P<0.01) were all increased, the differences were statistically significant. Compared with sevoflurane group, the number of epileptic waves in EEG of male rats in NKCC1 blocker group decreased, the average duration of single epileptic wave decreased, and the total duration of epileptic wave shortened significantly, with statistical significance ((0.286±0.756), (0.925±1.733), (1.043±2.759), t=3.097, 4.404, 4.254, all P<0.01). There were no significant differences in female rat among the three groups (all P>0.05). Compared with male rats, the average duration of female rats in sevoflurane group decreased ((6.392±3.374), (2.515±2.992), t=3.044, P<0.01), the total duration shortened ((10.957±6.028), (3.270±5.883), t=2.626, P<0.01), the difference was statistically significant.The behavioral results showed that, compared with the control group, the open arm dwell time of male rats in sevoflurane group was significantly shorter ( P<0.05), and the panic response in PPI group was significantly lower ( P<0.05), the difference was statistically significant.Compared with the sevoflurane group, the open arm dwell time in NKCC1 blocker group was significantly longer ( P<0.05), and the panic response in PPI group was significantly increased.The difference was statistically significant ( P<0.05). The change trend in female rats of each group was similar to that of male rats, but there was no significant difference (all P>0.05). Comparison between male and female rats: compared with male rats in sevoflurane group, the female rats in sevoflurane group had a longer open arm stay time in EPM experiment ( P<0.05), the difference was statistically significant. Conclusion:Sevoflurane anesthesia for 6 hours can significantly increase the generation of epileptic waves in EEG of male newborn rats, and cause behavioral abnormalities in adult male rats, which may be related to NKCC1.And male rats are more vulnerable to the negative effects of sevoflurane anesthesia on brain nerve development.

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