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.Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries (version 2025)
Fulin TAO ; Jinlei DONG ; Gang WANG ; Xianzhong MA ; Guanglin WANG ; Jiandong WANG ; Zhanying SHI ; Wei FENG ; Shiwen ZHU ; Gang LYU ; Guangyao LIU ; Dahui SUN ; Yuqiang SUN ; Ming LI ; Weixu LI ; Yan ZHUANG ; Kaifang CHEN ; Dapeng ZHOU ; Qishi ZHOU ; Zhangyuan LIN ; Chengla YI ; Longpo ZHENG ; Jianzhong GUAN ; Zhiyong HOU ; Shuquan GUO ; Xiaodong GUO ; Xiaoshan GUO ; Xiaodong QIN ; Hua CHEN ; Shicai FAN ; Dongsheng ZHOU ; Lianxin LI
Chinese Journal of Trauma 2025;41(8):709-720
Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.
3.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
4.Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries (version 2025)
Fulin TAO ; Jinlei DONG ; Gang WANG ; Xianzhong MA ; Guanglin WANG ; Jiandong WANG ; Zhanying SHI ; Wei FENG ; Shiwen ZHU ; Gang LYU ; Guangyao LIU ; Dahui SUN ; Yuqiang SUN ; Ming LI ; Weixu LI ; Yan ZHUANG ; Kaifang CHEN ; Dapeng ZHOU ; Qishi ZHOU ; Zhangyuan LIN ; Chengla YI ; Longpo ZHENG ; Jianzhong GUAN ; Zhiyong HOU ; Shuquan GUO ; Xiaodong GUO ; Xiaoshan GUO ; Xiaodong QIN ; Hua CHEN ; Shicai FAN ; Dongsheng ZHOU ; Lianxin LI
Chinese Journal of Trauma 2025;41(8):709-720
Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.
5.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
6.Effects of early-life 6:2 Cl-PFESA exposure on hippocampal AMPA receptor gene expression in offspring mice
Ruiwen WANG ; Yaping YAO ; Jingshuang CAI ; Fulin QU ; Xiaoxia JIN
Journal of Environmental and Occupational Medicine 2024;41(5):552-559
Background The compound 6:2 chlorinated polyfluorinated ether sulfonic acids (6:2 Cl-PFESA) has been demonstrated abilities of strong bioaccumulation and placental barrier penetration, and it can also cross the blood-brain barrier. However, the mechanism of its neurodevelopmental toxicity in offspring induced by early-life exposure is still unknown. Objective To explore effects of 6:2 Cl-PFESA on the growth and the α-amino-3-hydroxy-5-methylisoxazole-4-propionic (AMPA) receptor gene expression in the hippocampus of offspring mice by establishing a 6:2 Cl-PFESA exposure animal model. Methods Thirty Kunming pregnant mice were randomly divided into five groups: control group, and 2, 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups. The treatment groups were exposed to designed doses of 6:2 Cl-PFESA through drinking water from the first day of gestation until the end of lactation. The pups were weaned on postnatal day (PND) 21, and continued to be exposed to 6:2 Cl-PFESA through drinking water. Birth weight and body length of the offspring were recorded. Offspring mice were anesthetized and sacrificed respectively on PND7, PND21, and PND35, then their hippocampus was peeled from harvested brain tissue. The ultrastructure of hippocampus was observed via transmission electron microscopy; and the expression of AMPA receptors GluR1, GluR2, and GluR3 in the hippocampus was evaluated by real-time reverse transcription polymerase chain reaction. The learning and memory ability of the PND35 mice was measured by Morris water maze test before they were sacrificed. Results The birth weights and the lengths of the pups in the 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups were (2.23±0.36), (1.92±0.20), (1.88±0.31) g, and (33.73±0.98), (32.91±1.30), (32.52±2.07) mm, respectively, which were lower than those in the control group, (2.78±0.35) g and (36.46±2.34) mm (P<0.05), respectively. The results of Morris water maze showed that the escape latencies in the orientation navigation experiment on the 4th day in the 250 μg·L−1 6:2 Cl-PFESA exposure group and on the 5th day in the 10, 50, and 250 μg·L−1 6:2 Cl-PFESA exposure groups were longer than those in the control group (P<0.05). In the space exploration experiment, the times of crossing platform in the 50 and 250 μg·L−1 6:2 Cl-PFESA exposure groups were decreased when compared with the control group (P<0.05), and the time of staying in the target quadrant of the 250 μg·L−1 6:2 Cl-PFESA exposure groups were also decreased (P<0.05). Via transmission electron microscopy, compared with the control group, the postsynaptic density was decreased and the synaptic cleft width was widened on PND35 in the 250 μg·L−1 6:2 Cl-PFESA exposure group. The mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups exposed to 250 μg·L−1 6:2 Cl-PFESA during different developmental stages were significantly lower than those in the control group (P<0.05). Except for the 2 μg·L−1 6:2 Cl-PFESA exposure group on PND7, the 6:2 Cl-PFESA exposure inhibited the mRNA expression levels of GluR1, GluR2, and GluR3 in the hippocampus of pups at different developmental stages (P<0.05). Among them, the 6:2 Cl-PFESA exposure during early development resulted in the highest decrease in the expression levels of GluR1 and GluR2 mRNA in the hippocampus of pups on PND7; GluR3 mRNA expression level in the hippocampus of the exposed pups on PND21 showed the maximum inhibitory effect; the expression levels of GluR1, GluR2, and GluR3 mRNA all showed the least decrease in the hippocampus of the exposure groups on PND35. Conclusion Early-life exposure to 6:2 Cl-PFESA may affect the growth and development of offspring mice, alter the hippocampal synaptic structure, and influence the learning and memory abilities, which may be related to their inhibitory effects on the expression levels of AMPA receptor subunits GluR1, GluR2, and GluR3 genes in the hippocampus of offspring mice at various developmental stages.
7.Minimally invasive technique for tibial plateau bicondylar fracture repair using the double reverse traction repositor
Zhimeng ZHAO ; Fulin TAO ; Dawei WANG ; Lin LI ; Dongsheng ZHOU ; Lianxin LI
Chinese Journal of Orthopaedics 2023;43(22):1509-1516
Objective:To assess the efficacy of a minimally invasive technique for repairing tibial plateau bicondylar fractures utilizing the double reverse traction repositor.Methods:A retrospective analysis was performed of the data of 31 patients (Schatzker V 17 cases, Schatzker VI 14 cases) who had been admitted to trauma center of Shandong provincial hospital affiliated to Shandong first medical university for tibial plateau bicondylar fractures from January 2017 to January 2022. There were 21 males and 10 females, aged from 18 to 67 years (average, 32.4±6.5 years). The intervention strategy comprised the use of a double reverse traction repositor and was augmented by precise screw fixation. A comprehensive set of parameters were measured, including time interval between injury and operation, operation time, blood loss, hospital stay, fracture healing time, incision complications. Postoperative assessments were made immediately and at the 12-month mark, including the evaluation of articular step-off height, medial tibial plateau angle, and posterior tibial slope angle. The evaluation also included thTime interval between injury and operation ranged from 5 to 11 days, with an average of 6.1±1.3 days. The surgical procedures varied in length from 70 to 160 minutes, averaging at 109.2±15.6 minutes. The volume of blood loss was noted to be between 90 to 380 ml, averaging at 176.5±20.8 ml. Hospitalization spanned from 10 to 15 days, with an average stay of 12.2 ±0.8 days. Over a follow-up duration of 12 to 20 months, averaging at 13.5±1.1 months, all patients achieved fracture union within a period of 11 to 20 weeks, with an average time of 14.6±1.5 weeks. The postoperative articular step-off was recorded at 0.45±0.13 mm immediately after surgery and 0.58±0.21 mm at the one-year follow-up. Similarly, the medial tibial plateau angle and posterior tibial slope angle showed marginal changes from the immediate postoperative period to the 12-month evaluation. Knee joint mobility at the one-year mark ranged impressively from 0° to 135°, with an average of 125.6°±2.1°. Functional outcomes as reflected by Rasmussen scores ranged from 18 to 28 points, with an average of 25.4±1.7 points. Pain, as assessed by the VAS, had a low score range of 0 to 2 points, averaging at 0.7±0.2 points. Notably, there were no postoperative complications associated with the incisions, such as fat liquefaction, infection, skin necrosis, or exposure of internal fixations. Additionally, no cases of delayed union or fixation failure were observed. Six patients had traumatic arthritis 1 year after operation.Conclusion:The minimally invasive double reverse traction repositor technique for tibial plateau bicondylar fracture repair is effective, warranting its broader application in orthopedic surgery.
8.Simultaneous determination of 5 kinds of pentacyclic triterpenoids in Chaenomeles speciosa by quantitative analysis of multi-components by single-marker
Tingting ZHANG ; Haoning HU ; Pingyuan LI ; Yongmei HUANG ; Junzhi WANG ; Haiming TANG ; Yonghong YIN
China Pharmacy 2022;33(20):2477-2480
OBJECTIVE To establish a method for simultan eous determination of 5 kinds of pentacyclic triterpenoids as 3-O- acetyl-pomolic acid in Chaenomeles speciosa ,and to analyze the difference in the contents of C. speciosa from different producing areas by different processing technologies . METHODS HPLC method was adopted . The determination was performed on COSMOSIL 5 C18-MS-Ⅱ column with mobile phase consisted of acetonitrile -0.005 mol/L ammonium dihydrogen phosphate solution (pH value adjusted to 6.5 with phosphoric acid )(70∶30,V/V)at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelength was set at 210 nm,and sample size was 20 μL. The contents of the other four pentacyclic triterpenoids were calculated according to quantitative analysis of multi -components by single -marker(QAMS)using oleanolic acid as internal reference . The results were compared with those determined by external standard method . The total content of oleanolic acid and ursolic acid ,the total content of 5 components in C. speciosa from different producing areas and different processing technologies were compared . RESULTS The linear range of 3-O-acetyl-pomolic acid ,betulinic acid ,oleanolic acid ,ursolic acid and 3-O-acetyl ursolic acid were 4.06-81.2,2.12-42.4,9.62-192.3,7.77-155.4,4.21-84.1 μg/mL,respectively(R2>0.999). RSDs of precision ,reproducibility and stability (24 h)tests were all lower than 3%. The average recoveries were 98.29%-101.38% (RSDs<3%,n=6). The mass fraction of 3-O-acetyl-pomolic acid ,betulinic acid ,ursolic acid and 3-O-acetyl ursolic acid measured by QAMS w ere 0.023%-0.060%,0.044%-0.528%,0.101%-0.368%,0.067%-0.221%,respectively;the deviations from the results measured by external standard method were all within 8%. The total content of oleanolic acid and ursolic acid, the total content of 5 components in C. speciosa processed by fresh -cut technology from the same producing area were higher than those in C. speciosa processed by traditional technology ,and the total content of 5 components in C. speciosa from Chongqing Qianjiang were significantly higher than those from other producing areas (P<0.05). CONCLUSIONS QAMS method is established for the simultaneous determination of 3-O-acetyl-pomolic acid ,betulinic acid ,oleanolic acid ,ursolic acid and 3-O-acetyl ursolic acid in C. speciosa. Established method is simple ,rapid and accurate . The total content of 5 components in C. speciosa produced in Chongqing Qianjiang is higher ,and the total content of C. speciosa processed by fresh -cut technology from the same origin is higher than C. speciosa processed by traditional technology .
9.Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway
Fulin TAO ; Yuanyuan ZHOU ; Mengwen WANG ; Chongyang WANG ; Wentao ZHU ; Zhili HAN ; Nianxia SUN ; Dianlei WANG
The Korean Journal of Physiology and Pharmacology 2022;26(2):95-111
Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.
10. Huatanjiangqi capsule regulates Nrf2/HDAC2 and improves glucocorticoid resistance of 16HBE cells
Mengwen WANG ; Chongyang WANG ; Fulin TAO ; Wentao ZHU ; Zhili HAN ; Nianxia SUN ; Dianlei WANG ; Yan GUO ; Zegeng LI ; Dianlei WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(12):1360-1369
AIM: To explore the effect of Huatanjiangqi capsule medicated serum (HTJQ) on the resistance of human bronchial epithelial cells (16HBE) to glucocorticoid (GC) stimulated by cigarette smoke extract (CSE). METHODS: After 16HBE cells were treated with HTJQ, the effects of different concentrations of HTJQ on the viability of 16HBE cells were determined by CCK-8 method. 16HBE cells were pretreated with HTJQ, and then cultured with dexamethasone (DEX) and lipopolysaccharide (LPS) for 24 hours, the effect of HTJQ on glucocorticoid (GC) resistance of 16HBE cells was determined by Enzyme-linked immunosorbent assay (ELISA). The effects of HTJQ, sulforaphane (SFN) and glutathione (GSH) on the expression of NF-E2-related factors 2 (Nrf2), Heme oxygenase-1 (HO-1) and histone deacetylase 2 (HDAC2) in 16HBE cells stimulated by CSE were measured by Western blot, and the effects of HTJQ, SFN and GSH on interleukin-8 (IL-8) in 16HBE cells were measured by ELISA. RESULTS: HTJQ promoted the proliferation of 16HBE cells at 1 h, 2 h and 4 h, the results of ELISA and Western blot showed that CSE induced GC resistance and decreased the expression of Nrf2, HO-1 and HDAC2 in 16HBE cells, HTJQ significantly decreased IL-8 and improved GC sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). In addition, HTJQ significantly up-regulated the level of GSH in 16HBE cells (P<0.01). Nrf2 agonists SFN and GSH significantly improved the glucocorticoid sensitivity of 16HBE cells (P<0.01), and up-regulated the expression of Nrf2, HO-1 and HDAC2 (P<0.01). CONCLUSION: HTJQ improves the GC resistance of 16HBE cells by up-regulating the expression of Nrf2/HDAC2 protein and the level of intracellular GSH.

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