1.Effects of electroacupuncture on mitophagy in hippocampal neurons of mouse depression model
Zhiyun YU ; Wenmiao YANG ; Mingmin XU ; Zhiyan LI ; Chenchen YANG ; Junhan JIANG ; Yinan FENG ; Yu GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(9):1310-1323
Objective To explore the therapeutic effect and mechanism of electroacupuncture on depressive model mice based on the phosphatase and tensin homolog-induced kinase 1(PINK1)/Parkin pathway.Methods Specific pathogen-free grade male C57BL/6J mice were used.For experiment 1,60 mice were randomly divided into blank,model,sham electroacupuncture,and electroacupuncture groups using the random number table method,with 15 rats per group.For experiment 2,30 mice were randomly divided into normal,cyclosporine A(CsA),and electroacupuncture+CsA groups using the same method,with 10 rats per group.The chronic restraint stress(CRS)was used to establish a depression model.After successful modeling,CRS was continued to maintain model stability.After modeling,1 h before daily CRS stimulation,the electroacupuncture and electroacupuncture+CsA groups received electroacupuncture interventions at the"Baihui"(GV20)and"Zusanli"(ST36)acupoints,using continuous wave stimulation at a frequency of 2 Hz and an intensity of 1 mA for 20 min,once daily for 7 consecutive days.Mice in the sham electroacupuncture group received superficial needling at non-meridian,non-acupoint locations under the axilla 1 h before CRS,with the electroacupuncture device connected but not powered on once a day for 7 consecutive days.Mice in the CsA and electroacupuncture+CsA groups received an intraperitoneal injection of CsA solution(0.2 mg/g)30 min before electroacupuncture intervention,once daily for 7 consecutive days.In experiment 1,depressive-like behavior was assessed using the open field,tail suspension,and sucrose preference tests.The spontaneous excitatory postsynaptic currents(sEPSC)and spontaneous inhibitory postsynaptic currents(sIPSC)parameters of hippocampal neurons were evaluated using brain slice patch clamp techniques.Western blotting was conducted to measure the expression levels of mitochondrial autophagy-related proteins PINK 1,phosphorylated PINK1(p-PINK1),Parkin,microtubule-associated protein 1A/1B-light chain 3-Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),ubiquitin-binding protein(p62),and mitochondrial markers,including translocase of outer mitochondrial membrane 20(TOMM20),heat shock protein 60(HSP 60),and cytochrome c oxidase Ⅳ(COX Ⅳ).Immunofluorescence was used to detect PINK1 protein expression in the CA3 region of the hippocampus.Transmission electron microscopy was used to examine the ultrastructure of mitochondria in hippocampal neurons.On the basis of experiment 1,experiment 2 evaluated depressive-like behavior in mice using sucrose preference,open field,and tail suspension tests;Western blotting was used to detect the expressions of PINK1,p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,p62,TOMM20,HSP 60,and COX Ⅳ proteins of hippocampus in mice.The mitochondrial ultrastructure was observed in hippocampal neurons using transmission electron microscopy.Results In experiment 1,compared with the blank group,the model and sham electroacupuncture groups exhibited a decrease in sucrose consumption rate,a decrease in the time spent in the center area,a reduced proportion of distance moved in the center area,and an increase in immobility time of tail suspension(P<0.05).The sEPSC and sIPSC in hippocampal neurons decreased in both amplitude and frequency(P<0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus were reduced,whereas the p62 expression level was increased(P<0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus decreased(P<0.05).The number of healthy mitochondria in hippocampal neurons was reduced,with numerous damaged mitochondrial structures observed.Compared to the model and sham electroacupuncture groups,the electroacupuncture group showed an increased in the time spent in the center area,a higher proportion of distance moved in the center area,and an elevated sucrose consumption rate.In contrast,the immobility time in the tail suspension test decreased(P<0.05),whereas the amplitude and frequency of sEPSC and sIPSC in hippocampal neurons increased(P<0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus increased,whereas the p62 expression level decreased(P<0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus increased(P<0.05).Additionally,mitochondrial damage in hippocampal neurons was alleviated,and a notable presence of autophagosomes mitophagy lysosomes was observed.In experiment 2,compared with the normal group,the mice in the CsA and electroacupuncture+CsA groups showed a decrease in the time spent in the center area and the proportion of distance moved in the center area,a decrease in sucrose consumption rate,and an increase in the immobility time in the tail suspension test(P<0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COX Ⅳ expression levels in the hippocampus decreased,whereas p62 expression increased(P<0.05).Many damaged mitochondria were observed in hippocampal neurons.Conclusion Electroacupuncture may exert its antidepressant effects by promoting PINK1/Parkin pathway-mediated mitophagy to eliminate damaged mitochondria,thereby restoring the function of hippocampal neurons in depressive model mice.
2.Efficacy of stamp skin grafting combined with vacuum sealing drainage in the treatment of diabetic foot ulcers
Xing MAO ; Xiaobin CAI ; Binglin WU ; Shunping LIU ; Yinan LAN ; Xun JIANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(3):377-381
Objective:To investigate the clinical efficacy of stamp skin grafting combined with vacuum sealing drainage in the treatment of diabetic foot ulcers.Methods:A prospective study was conducted involving 80 patients with diabetic foot ulcers admitted to Lishui Central Hospital from January 2020 to December 2022. The patients were divided into an observation group and a control group, with 40 patients in each group, using a random number table method. The control group received treatment with vacuum-sealing drainage technology, while the observation group was treated with stamp skin grafting combined with vacuum sealing drainage. The two groups were compared based on several perioperative indicators, including wound healing time, length of hospital stay, number of dressing changes, and progress of granulation tissue growth. Pain levels were assessed using the Visual Analog Scale. Additionally, dorsalis pedis blood flow dynamics were evaluated, focusing on the diameter of the dorsalis pedis artery and arterial blood flow velocity. Foot function was assessed using the Maryland Foot Function Scale. The occurrence of postoperative complications was recorded.Results:The wound healing time and length of hospital stay in the observation group were (21.54 ± 5.32) days and (27.08 ± 5.97) days, respectively, which were significantly shorter than those in the control group [(26.69 ± 5.66) days, (31.49 ± 6.80) days, t = 4.19, 3.08, both P < 0.05]. The number of dressing changes in the observation group was (5.11 ± 1.14), which was significantly fewer than that in the control group [(8.07 ± 1.59), t = 9.56, P < 0.001]. The progress of granulation tissue growth in the observation group [(3.12 ± 0.64) mm] was faster that in the control group [(2.09 ± 0.48) mm, t = 8.14, P < 0.001]. At 1, 2, and 3 months post-surgery, the Visual Analog Scale scores for the observation group were (3.52 ± 0.65), (2.33 ± 0.42), and (1.40 ± 0.26), respectively, which were significantly lower than those in the control group [(3.96 ± 0.71), (2.74 ± 0.44), (1.78 ± 0.34), t = 2.89, 4.26, 5.615, all P < 0.05). At 3 months post-surgery, the diameter of the dorsalis pedis artery and arterial blood flow velocity in the observation group were (2.64 ± 0.44) mm and (36.42 ± 6.28) cm/s, respectively, which were greater than those in control group [(2.18 ± 0.41) mm, (30.97 ± 5.33) cm/s, t = 4.83, 4.18, both P < 0.001]. At 3 months post-surgery, the scores for pain, foot function, appearance, and range of motion in the observation group were (39.28 ± 6.70), (48.10 ± 7.22), (7.94 ± 1.54), and (12.15 ± 2.35), respectively, which were significantly higher than those in the control group [(33.46 ± 6.89), (43.08 ± 6.68), (5.38 ± 1.06), and (10.69 ± 2.16), t = 3.83, 3.22, 8.66, 2.89, all P < 0.05]. There was no statistically significant difference in the overall incidence of postoperative complications, including skin flap necrosis/dislocation, hematoma accumulation, infection, and ulcer recurrence, between the two groups ( P > 0.05). Conclusions:Stamp skin grafting combined with vacuum sealing drainage can significantly accelerate wound healing in patients with diabetic foot ulcers, reduce postoperative pain, improve dorsalis pedis blood flow dynamics, enhance foot function, and demonstrate good safety.
3.Implementation of US FDA boxed warning in drug labels from 2019 to 2024 and comparison with relevant situations in China
Yinan ZHANG ; Wenshuo JIANG ; Xiao ZHANG ; Yilong YAN ; Zhigang ZHAO
Adverse Drug Reactions Journal 2025;27(10):621-628
Objective:To investigate the implementation of boxed warning of drug labels in US Food and Drug Administration (FDA) from 2019 to 2024, and compared it with the relevant situations in China, in order to provide reference for the revision of drug labels and safe drug use.Methods:Data on boxed warning revisions in the US FDA "Drugs Safety Related Labeling Changes" Database from January 1, 2019 to December 31, 2024 were retrieved, and the revised contents were classified. The drug labels for newly marketed drugs in the United States during the same period were collected, the boxed warnings were recorded and summarized, and compared with the warning statements in drug labels of relevant drugs approved in China.Results:From 2019 to 2024, FDA revised boxed warnings in 209 drug labels. Among them, 22 items (10.53%) were newly added, 63 items (30.14%) were major updates, 115 items (55.02%) were minor updates, and 9 items (4.31%) were removed. A total of 293 new drugs were approved in the United States from 2019 to 2024, of which 69 (23.55%) had boxed warnings when they were approved, and 4 (1.37%) were added boxed warnings when they were revised in the labels. Up to December 31, 2024, 92 of the 293 new drugs had been approved in China. Compared with the labeling in the United States, some drugs lacked warning statements section in China, including zolpidem tartrate, dexzopiclone, zaleplon, montelukast sodium, denosumab, terlipressin, etc.Conclusions:The warning statements in some Chinese drug labels are inconsistent with the boxed warnings in the American drug labels. It is suggested that the revision of the boxed warning by US FDA should be regarded as one of the new sources of safety information to assess the risks of related drugs and determine whether it is necessary to revise the relevant drug labels in China.
4.Effects of electroacupuncture on mitophagy in hippocampal neurons of mouse depression model
Zhiyun YU ; Wenmiao YANG ; Mingmin XU ; Zhiyan LI ; Chenchen YANG ; Junhan JIANG ; Yinan FENG ; Yu GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(9):1310-1323
Objective To explore the therapeutic effect and mechanism of electroacupuncture on depressive model mice based on the phosphatase and tensin homolog-induced kinase 1(PINK1)/Parkin pathway.Methods Specific pathogen-free grade male C57BL/6J mice were used.For experiment 1,60 mice were randomly divided into blank,model,sham electroacupuncture,and electroacupuncture groups using the random number table method,with 15 rats per group.For experiment 2,30 mice were randomly divided into normal,cyclosporine A(CsA),and electroacupuncture+CsA groups using the same method,with 10 rats per group.The chronic restraint stress(CRS)was used to establish a depression model.After successful modeling,CRS was continued to maintain model stability.After modeling,1 h before daily CRS stimulation,the electroacupuncture and electroacupuncture+CsA groups received electroacupuncture interventions at the"Baihui"(GV20)and"Zusanli"(ST36)acupoints,using continuous wave stimulation at a frequency of 2 Hz and an intensity of 1 mA for 20 min,once daily for 7 consecutive days.Mice in the sham electroacupuncture group received superficial needling at non-meridian,non-acupoint locations under the axilla 1 h before CRS,with the electroacupuncture device connected but not powered on once a day for 7 consecutive days.Mice in the CsA and electroacupuncture+CsA groups received an intraperitoneal injection of CsA solution(0.2 mg/g)30 min before electroacupuncture intervention,once daily for 7 consecutive days.In experiment 1,depressive-like behavior was assessed using the open field,tail suspension,and sucrose preference tests.The spontaneous excitatory postsynaptic currents(sEPSC)and spontaneous inhibitory postsynaptic currents(sIPSC)parameters of hippocampal neurons were evaluated using brain slice patch clamp techniques.Western blotting was conducted to measure the expression levels of mitochondrial autophagy-related proteins PINK 1,phosphorylated PINK1(p-PINK1),Parkin,microtubule-associated protein 1A/1B-light chain 3-Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),ubiquitin-binding protein(p62),and mitochondrial markers,including translocase of outer mitochondrial membrane 20(TOMM20),heat shock protein 60(HSP 60),and cytochrome c oxidase Ⅳ(COX Ⅳ).Immunofluorescence was used to detect PINK1 protein expression in the CA3 region of the hippocampus.Transmission electron microscopy was used to examine the ultrastructure of mitochondria in hippocampal neurons.On the basis of experiment 1,experiment 2 evaluated depressive-like behavior in mice using sucrose preference,open field,and tail suspension tests;Western blotting was used to detect the expressions of PINK1,p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,p62,TOMM20,HSP 60,and COX Ⅳ proteins of hippocampus in mice.The mitochondrial ultrastructure was observed in hippocampal neurons using transmission electron microscopy.Results In experiment 1,compared with the blank group,the model and sham electroacupuncture groups exhibited a decrease in sucrose consumption rate,a decrease in the time spent in the center area,a reduced proportion of distance moved in the center area,and an increase in immobility time of tail suspension(P<0.05).The sEPSC and sIPSC in hippocampal neurons decreased in both amplitude and frequency(P<0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus were reduced,whereas the p62 expression level was increased(P<0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus decreased(P<0.05).The number of healthy mitochondria in hippocampal neurons was reduced,with numerous damaged mitochondrial structures observed.Compared to the model and sham electroacupuncture groups,the electroacupuncture group showed an increased in the time spent in the center area,a higher proportion of distance moved in the center area,and an elevated sucrose consumption rate.In contrast,the immobility time in the tail suspension test decreased(P<0.05),whereas the amplitude and frequency of sEPSC and sIPSC in hippocampal neurons increased(P<0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus increased,whereas the p62 expression level decreased(P<0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus increased(P<0.05).Additionally,mitochondrial damage in hippocampal neurons was alleviated,and a notable presence of autophagosomes mitophagy lysosomes was observed.In experiment 2,compared with the normal group,the mice in the CsA and electroacupuncture+CsA groups showed a decrease in the time spent in the center area and the proportion of distance moved in the center area,a decrease in sucrose consumption rate,and an increase in the immobility time in the tail suspension test(P<0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COX Ⅳ expression levels in the hippocampus decreased,whereas p62 expression increased(P<0.05).Many damaged mitochondria were observed in hippocampal neurons.Conclusion Electroacupuncture may exert its antidepressant effects by promoting PINK1/Parkin pathway-mediated mitophagy to eliminate damaged mitochondria,thereby restoring the function of hippocampal neurons in depressive model mice.
5.Efficacy of stamp skin grafting combined with vacuum sealing drainage in the treatment of diabetic foot ulcers
Xing MAO ; Xiaobin CAI ; Binglin WU ; Shunping LIU ; Yinan LAN ; Xun JIANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(3):377-381
Objective:To investigate the clinical efficacy of stamp skin grafting combined with vacuum sealing drainage in the treatment of diabetic foot ulcers.Methods:A prospective study was conducted involving 80 patients with diabetic foot ulcers admitted to Lishui Central Hospital from January 2020 to December 2022. The patients were divided into an observation group and a control group, with 40 patients in each group, using a random number table method. The control group received treatment with vacuum-sealing drainage technology, while the observation group was treated with stamp skin grafting combined with vacuum sealing drainage. The two groups were compared based on several perioperative indicators, including wound healing time, length of hospital stay, number of dressing changes, and progress of granulation tissue growth. Pain levels were assessed using the Visual Analog Scale. Additionally, dorsalis pedis blood flow dynamics were evaluated, focusing on the diameter of the dorsalis pedis artery and arterial blood flow velocity. Foot function was assessed using the Maryland Foot Function Scale. The occurrence of postoperative complications was recorded.Results:The wound healing time and length of hospital stay in the observation group were (21.54 ± 5.32) days and (27.08 ± 5.97) days, respectively, which were significantly shorter than those in the control group [(26.69 ± 5.66) days, (31.49 ± 6.80) days, t = 4.19, 3.08, both P < 0.05]. The number of dressing changes in the observation group was (5.11 ± 1.14), which was significantly fewer than that in the control group [(8.07 ± 1.59), t = 9.56, P < 0.001]. The progress of granulation tissue growth in the observation group [(3.12 ± 0.64) mm] was faster that in the control group [(2.09 ± 0.48) mm, t = 8.14, P < 0.001]. At 1, 2, and 3 months post-surgery, the Visual Analog Scale scores for the observation group were (3.52 ± 0.65), (2.33 ± 0.42), and (1.40 ± 0.26), respectively, which were significantly lower than those in the control group [(3.96 ± 0.71), (2.74 ± 0.44), (1.78 ± 0.34), t = 2.89, 4.26, 5.615, all P < 0.05). At 3 months post-surgery, the diameter of the dorsalis pedis artery and arterial blood flow velocity in the observation group were (2.64 ± 0.44) mm and (36.42 ± 6.28) cm/s, respectively, which were greater than those in control group [(2.18 ± 0.41) mm, (30.97 ± 5.33) cm/s, t = 4.83, 4.18, both P < 0.001]. At 3 months post-surgery, the scores for pain, foot function, appearance, and range of motion in the observation group were (39.28 ± 6.70), (48.10 ± 7.22), (7.94 ± 1.54), and (12.15 ± 2.35), respectively, which were significantly higher than those in the control group [(33.46 ± 6.89), (43.08 ± 6.68), (5.38 ± 1.06), and (10.69 ± 2.16), t = 3.83, 3.22, 8.66, 2.89, all P < 0.05]. There was no statistically significant difference in the overall incidence of postoperative complications, including skin flap necrosis/dislocation, hematoma accumulation, infection, and ulcer recurrence, between the two groups ( P > 0.05). Conclusions:Stamp skin grafting combined with vacuum sealing drainage can significantly accelerate wound healing in patients with diabetic foot ulcers, reduce postoperative pain, improve dorsalis pedis blood flow dynamics, enhance foot function, and demonstrate good safety.
6.Implementation of US FDA boxed warning in drug labels from 2019 to 2024 and comparison with relevant situations in China
Yinan ZHANG ; Wenshuo JIANG ; Xiao ZHANG ; Yilong YAN ; Zhigang ZHAO
Adverse Drug Reactions Journal 2025;27(10):621-628
Objective:To investigate the implementation of boxed warning of drug labels in US Food and Drug Administration (FDA) from 2019 to 2024, and compared it with the relevant situations in China, in order to provide reference for the revision of drug labels and safe drug use.Methods:Data on boxed warning revisions in the US FDA "Drugs Safety Related Labeling Changes" Database from January 1, 2019 to December 31, 2024 were retrieved, and the revised contents were classified. The drug labels for newly marketed drugs in the United States during the same period were collected, the boxed warnings were recorded and summarized, and compared with the warning statements in drug labels of relevant drugs approved in China.Results:From 2019 to 2024, FDA revised boxed warnings in 209 drug labels. Among them, 22 items (10.53%) were newly added, 63 items (30.14%) were major updates, 115 items (55.02%) were minor updates, and 9 items (4.31%) were removed. A total of 293 new drugs were approved in the United States from 2019 to 2024, of which 69 (23.55%) had boxed warnings when they were approved, and 4 (1.37%) were added boxed warnings when they were revised in the labels. Up to December 31, 2024, 92 of the 293 new drugs had been approved in China. Compared with the labeling in the United States, some drugs lacked warning statements section in China, including zolpidem tartrate, dexzopiclone, zaleplon, montelukast sodium, denosumab, terlipressin, etc.Conclusions:The warning statements in some Chinese drug labels are inconsistent with the boxed warnings in the American drug labels. It is suggested that the revision of the boxed warning by US FDA should be regarded as one of the new sources of safety information to assess the risks of related drugs and determine whether it is necessary to revise the relevant drug labels in China.
7.Stubborn Gout: Psychological and Behavioral Factors Affecting Physical Diseases
Jiarui LI ; Lixia CHEN ; Tao LI ; Yinan JIANG ; Shangzhu ZHANG ; Xi WANG ; Xulei CUI ; Han WANG ; Xiaoqing LI ; Jing WEI
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1204-1210
A middle-aged male came to Peking Union Medical College Hospital for treatment because of "pain for 10+ years, aggravated with emotional instability for 5 years". The patient's pain had a huge impact on life, with poor results even after repeated diagnosis and treatment in other hospitals. After multi-disciplinary discussion, it had been clarified that the pain was mainly caused by gout. The disease was heavily influenced by psychosocial factors. Therefore, the patient fits the diagnosis of "Psychological and Behavioral Factors Affecting Physical Diseases". The multi-disciplinary comprehensive management of the patient was carried out to identify and treat psychological factors affecting other medical conditions. After this mental treatment was performed, the patient's conditions significantly improved. The diagnosis and treatment of this patient demonstrates the importance of the multi-disciplinary treatment team for somatic symptoms (disorders).
8.Evaluation of machine learning prediction of altered inflammatory metabolic state after neoadjuvant therapy for breast cancer
Qizhen WU ; Qiming LIU ; Yezi CHAI ; Zhengyu TAO ; Yinan WANG ; Xinning GUO ; Meng JIANG ; Jun PU
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(9):1169-1181
Objective·To develop a machine learning approach for early identification of metabolic syndromes associated with inflammatory metabolic state changes in breast cancer patients after neoadjuvant therapy,using common laboratory and transthoracic echocardiography indices.Methods·Female patients with primary invasive breast cancer diagnosed at the Department of Breast Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,between September 2020 and September 2022,were included.General patient information,laboratory test results,and transthoracic echocardiography data were collected.After feature extraction,five machine learning algorithms,including random forest(RF),gradient boosting(GB),support vector machine(SVM),K-nearest neighbor(KNN),and decision tree(DT),were applied to construct a prediction model for the changes of the patients' metabolic state after neoadjuvant therapy,and the prediction performances of the five models were compared.Results·A total of 232 cases with valid clinical data were included,comprising 135 cases before neoadjuvant therapy and 97 cases after completing 4 cycles of neoadjuvant therapy.Feature extraction identified five key features:white blood cell count,hemoglobin,high-density lipoprotein(HDL),interleukin-2 receptor,and interleukin-8.In the multi-feature analysis,the area under the receiver operating characferistic curve(AUC)was higher in the combination of white blood cell count,hemoglobin and HDL compared to the combination of interleukin-2 receptor and interleukin-8(RF:0.928 vs 0.772,GB:0.900 vs 0.792,SVM:0.941 vs 0.764,KNN:0.907 vs 0.762,DT:0.799 vs 0.714).The RF,SVM,and GB models showed higher AUC(0.928,0.941,0.900)and accuracy(0.914,0.897,0.776).The SVM model exhibited superior accuracy in the training data compared to the RF and GB models(P=0.394,0.122 and 0.097,respectively).Conclusion·The SVM model can be used to establish a prediction model for identifying breast cancer patients at high risk of developing inflammatory metabolic state-related metabolic syndrome after neoadjuvant therapy by incorporating five common clinical indicators,namely,white blood cell count,hemoglobin,high-density lipoprotein,interleukin-2 receptor,and interleukin-8.SVM modeling may be useful for clinicians to establish individualized screening protocols based on a patient's inflammatory metabolic state.
9.Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor
Jia QI ; Zhou YINYIN ; Song LI ; Shi XIMENG ; Jiang XUAN ; Tao RUIZHI ; Wang AIYUN ; Wu YUANYUAN ; Wei ZHONGHONG ; Zhang YINAN ; Li XIAOMAN ; Lu YIN
Journal of Pharmaceutical Analysis 2024;14(7):1047-1062
Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.
10.Determination of glufosinate ammonium and three metabolites in urine by ultra performance liquid chromatography-tandem mass spectrometry
Yingru LING ; Zongli HUO ; Feng ZHANG ; Hao ZHANG ; Yinan CAO ; Xinnan WANG ; Dongxin JIANG ; Baoli ZHU
Journal of Environmental and Occupational Medicine 2024;41(6):701-706
Backgroud At present, there is no unified standard for the detection of glufosinate ammonium and three metabolites in urine, which affects the accurate assessment of occupational exposure risk to a certain extent. It is of great significance to establish a rapid and effective inspection method to ensure occupational safety and public health. Objective To establish an ultra performance liquid chromatography-tandem mass spectrometry for simultaneous determination of glufosinate ammonium and three metabolites in urine. Methods The effects of dilution solvents and dilution ratios on the response values of glufosinate ammonium and three metabolites were compared, and the retention capacities of solid phase extraction columns for targets as well as the effects of chromatographic columns and mobile phase systems on chromatographic peaks were analyzed. Samples were quantified by matrix effect matching external standard method. Accuracy of the method was evaluated by recovery rate of standard addition, and precision of the method was evaluated by relative standard deviation of intra-day and inter-day measurements. Urine samples of 30 health individuals were collected to evaluate the application of the method. Results The urine samples were diluted with 0.2 mL water and 0.6 mL acetonitrile, purified by HLB solid phase extraction columns, and separated by Dikma Polyamino HILIC columns, and gradient elution was carried out with 0.5 mmol·L−1 ammonium acetate and 0.1% ammonia water as mobile phase, which achieved a good peak shape and mass spectrum response. The linearities of the four target compounds were good in the range of 0.5-50 ng·mL−1, and the correlation coefficients (r) were all greater than 0.998. The detection limits were 0.56-2.86 μg·L−1, the quantification limits were 1.87-29.54 μg·L−1, and the recovery rates of standard addition ranged from 75.0% to 103.6%, The relative standard deviations of intra-batch and inter-batch were from 2.5% to 8.1% and from 4.3% to 9.3% respectively. The method was applied to detect 30 urine samples of subjects, and no target was detected. Conclusion The method is simple, rapid, sensitive, and accurate. It is suitable for the determination of glufosinate ammonium and its metabolites in human urine without derivatization.

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