1.Erk Signaling Pathway in Striatal D2-MSNs: an Essential Pathway for Exercise-induced Improvement in Parkinson’s Disease
Bo GAO ; Yi-Ning LAI ; Yi-Tong GE ; Wei CHEN
Progress in Biochemistry and Biophysics 2025;52(1):61-71
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D1-dopamine receptor (D1R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D2-dopamine receptor (D2R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D1R and D2R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.
2.Study progress of novel biomarkers for early prediction of polymyxin-associated acute kidney injury
Ge YANG ; Jun YANG ; Fang LIU ; Yongchuan CHEN ; Hong ZHANG
China Pharmacy 2025;36(2):251-256
Polymyxin is an essential antibiotic for treating multidrug-resistant Gram-negative bacterial infections; however, its significant nephrotoxicity greatly limits its clinical application. To enhance its safety and improve patient outcomes, the study of novel biomarkers for the early prediction of polymyxin-associated acute kidney injury is critically important. Novel biomarkers, such as cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-β-glucosaminidase, β2- microglobulin, have shown obvious advantages in the early prediction of polymyxin-associated acute kidney injury. Compared to traditional biomarkers, these biomarkers can provide sensitive and specific diagnostic information in the early stages of kidney injury, helping to optimize individualized treatment plans and reduce clinical risks. However, the high cost of detection and complex operation still limit their clinical promotion. Future research should focus on optimizing the detection technology of new biomarkers, simplifying the operation process and reducing costs, while conducting multi-center, large-scale randomized controlled trials to systematically evaluate the sensitivity and specificity of various novel biomarkers, in order to promote their application in the field of prediction of renal injury in clinical practice.
3.Study progress of novel biomarkers for early prediction of polymyxin-associated acute kidney injury
Ge YANG ; Jun YANG ; Fang LIU ; Yongchuan CHEN ; Hong ZHANG
China Pharmacy 2025;36(2):251-256
Polymyxin is an essential antibiotic for treating multidrug-resistant Gram-negative bacterial infections; however, its significant nephrotoxicity greatly limits its clinical application. To enhance its safety and improve patient outcomes, the study of novel biomarkers for the early prediction of polymyxin-associated acute kidney injury is critically important. Novel biomarkers, such as cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-β-glucosaminidase, β2- microglobulin, have shown obvious advantages in the early prediction of polymyxin-associated acute kidney injury. Compared to traditional biomarkers, these biomarkers can provide sensitive and specific diagnostic information in the early stages of kidney injury, helping to optimize individualized treatment plans and reduce clinical risks. However, the high cost of detection and complex operation still limit their clinical promotion. Future research should focus on optimizing the detection technology of new biomarkers, simplifying the operation process and reducing costs, while conducting multi-center, large-scale randomized controlled trials to systematically evaluate the sensitivity and specificity of various novel biomarkers, in order to promote their application in the field of prediction of renal injury in clinical practice.
4.STAR Guideline Terminology (I): Planning and Launching
Zhewei LI ; Qianling SHI ; Hui LIU ; Xufei LUO ; Zijun WANG ; Jinhui TIAN ; Long GE ; Yaolong CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):216-223
To develop a guideline terminology system and promote its standardization, thereby enhancing medical staff's accurate understanding and correct application of guidelines. A systematic search was conducted for guideline development manuals and method ological literature (as of October 25, 2024). After screening, relevant terms from the guideline planning and launching stages were extracted and standardized. The term list and definitions were finalized through discussion and evaluation at a consensus conference. A total of 36 guideline manuals and 14 method ological articles were included, and 27 core terms were identified. The standardization of guideline terminology is essential for improving guideline quality, facilitating interdisciplinary communication, and enhancing other related aspects. It is recommended that efforts to advance the standardization and continuous updating of the terminology system should be prioritized in the future to support the high-quality development of guidelines.
5.Short-term efficacy of oblique lateral interbody fusion combined with lateral plate fixation in treatment of single-level lumbar degenerative disease
Xiaoyin LIU ; Jianqun ZHANG ; Zhen CHEN ; Simin LIANG ; Zhiqiang WANG ; Zongjun MA ; Rong MA ; Zhaohui GE
Chinese Journal of Tissue Engineering Research 2025;29(3):531-537
BACKGROUND:Stand-alone oblique lateral interbody fusion has a high rate of complications of fusion segment sink.Oblique lateral interbody fusion with posterior fixation can provide stable support,but intraoperative position changes and double incisions weaken the advantages of this technique.Oblique lateral interbody fusion combined with lateral plate fixation can achieve one-stage decompression in the same incision,while the lateral internal fixation provides stable support. OBJECTIVE:To analyze the short-term efficacy of oblique lateral interbody fusion combined with lateral plate fixation in the treatment of single-level lumbar degenerative disease. METHODS:The clinical data of 34 patients with single-level lumbar degenerative disease treated with oblique lateral interbody fusion combined with lateral plate fixation were collected from May 2020 to October 2022.Among them,14 were males and 20 were females aged from 41 to 72 years at the mean age of(58.6±9.9)years.There were 11 cases of lumbar spondylolisthesis(Ⅰ°),7 cases of lumbar disc herniation with segmental instability,and 16 cases of lumbar spinal stenosis.Operation time,blood loss,and complications were recorded.Visual analog scale scores of lumbago,radiative pain of both lower limbs,and Oswestry disability index scores were evaluated before surgery,3 months after surgery,and the last follow-up.Dural sac cross-sectional area,intervertebral height,and intervertebral fusion were measured and observed. RESULTS AND CONCLUSION:(1)The 34 patients were followed up for 14-36 months,with an average of(21.3±5.2)months.(2)The operation time ranged from 50 to 92 minutes,with an average of(68.5±11.1)minutes.Intraoperative blood loss was 50-170 mL,with an average of(71.6±25.3)mL.(3)Compared with the preoperative results,the visual analog scale scores and Oswestry disability index scores were significantly decreased at 3 months after surgery and at the last follow-up(P<0.001),and the maximum Oswestry disability index scores were improved by nearly 50%.(4)Bone fusion was achieved in all patients during half-year follow-up.The overall complication rate was 21%(7/34),including 1 case of plate displacement,3 cases of cage subsidence,1 case of psoas weakness,and 2 cases of anterior thigh pain.(5)It is concluded that oblique lateral interbody fusion combined with lateral plate fixation for the treatment of lumbar degenerative diseases has the characteristics of less blood loss,short operation time,rapid postoperative recovery,and significant short-term clinical efficacy with the stable support to a certain extent.The long-term curative effect needs further follow-up observation.
6.Metabolomics analysis of the lumbar spine after alendronate sodium intervention in ovariectomized rats with osteoporosis
Xinfei CHEN ; Yahui DAI ; Bingying XIE ; Xiaobin HUANG ; Huimin HUANG ; Jingwen HUANG ; Shengqiang LI ; Jirong GE
Chinese Journal of Tissue Engineering Research 2025;29(11):2277-2284
BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis
7.Correlation between adult mosquito density and meteorological factors in Pudong New Area of Shanghai, China
Ge GE ; Yongting YUAN ; Lei FENG ; Hanzhao LIU ; Chen LIN ; Ruohua GU ; Juan GE ; Jun LIU
Shanghai Journal of Preventive Medicine 2025;37(2):105-108
ObjectiveTo learn the density and seasonal variation of adult mosquitoes in Pudong New Area of Shanghai, and to explore the influence of meteorological factors on the density of adult mosquitoes. MethodsFrom April to November in 2017‒2021, adult mosquito density in Pudong New Area was monitored every ten days a time by using CO2 trapping light method. Meteorological data were collected during the same time, and Pearson correlation analysis and multiple linear regression model were used to investigate the correlation between adult mosquito density and meteorological factors. ResultsThe seasonal variation of adult mosquito density showed a single-peak pattern, with the peak of 7.09 mosquitoes·(set·time)-1 in July. The adult mosquito density was positively correlated with the monthly average temperature, monthly maximum temperature, monthly minimum temperature, and monthly average relative humidity (r=0.813, 0.793, 0.820, 0.617, all P<0.05), but negatively correlated with monthly average air pressure (r=-0.738, P<0.05). The regression equation of the adult mosquito density and monthly minimum temperature in Pudong New Area of Shanghai was Y=0.066 X3-0.884, with a corrected R2 of 0.673, indicating a good model fitting. ConclusionThe overall seasonal variation of adult mosquito density in Pudong New Area showed a single-peak pattern. The density of adult mosquitoes was correlated with the monthly average temperature, monthly maximum temperature, monthly minimum temperature, monthly average relative humidity, and monthly average air pressure, and linearly correlated with monthly minimum temperature.
8.Analysis on current situation of drug use in Chinese aeromedical rescue
Aobo LI ; Wei WANG ; Yanrong ZHU ; Chunyan XIN ; Chen LI ; Xu GE
China Pharmacy 2025;36(9):1035-1039
OBJECTIVE To analyze the current situation of drug use in domestic aeromedical rescue, and provide references for the development of aeromedical rescue services and the rational use of drugs on board. METHODS All literature on aeromedical rescue in China were retrieved from the databases of SinoMed, CNKI, VIP, and Wanfang data up to September 1st, 2024. Extracting descriptive analysis were conducted on the literature screened by the inclusion and exclusion criteria. RESULTS A total of 36 literature were included. Aeromedical rescue cases had been reported in China since 1985, with a cumulative total of 5 370 cases reported. Prehospital rescue performed 861 cases, with 96.40% of them involving the use of at least 9 categories, totaling at least 10 different drugs, primarily emergency drugs. Interhospital rescue performed 4 509 cases, and 85.23% of them used over 48 kinds of drugs across 19 categories, mainly emergency drugs supplemented by specialty drugs. From the view of transportation, 5 166 air transfers were made by helicopters, of which 88.00% involved the use of drugs, and 204 cases by fixed-wing aircraft, of which 91.18% involved the use of drugs. CONCLUSIONS Drugs are frequently used in aeromedical rescue involving a wide variety of types in China. It is imperative to strengthen the focus on the equipment and rational use of drugs in aeromedical rescue, thereby facilitating the establishment of a standardized theoretical framework.
9.Influence evaluation of pharmaceutical quality control on medication therapy management services by the ECHO model
Kun LIU ; Huanhuan JIANG ; Yushuang LI ; Yan HUANG ; Qianying ZHANG ; Dong CHEN ; Xiulin GU ; Jinhui FENG ; Zijian WANG ; Yunfei CHEN ; Yajuan QI ; Yanlei GE ; Aishuang FU
China Pharmacy 2025;36(9):1123-1128
OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management (MTM) services for patients with coronary heart disease by using Economic, Clinical and Humanistic Outcomes (ECHO) model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 (pre-quality control implementation group, n=96) and June-August 2023 (post-quality control implementation group, n=164). Using propensity score matching analysis, 80 patients were selected from each group. The study subsequently compared the economic, clinical, and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching (P>0.05). Compared with pre-quality control implementation group, the daily treatment cost (16.26 yuan vs. 24.40 yuan, P<0.001), cost-effectiveness ratio [23.12 yuan/quality-adjusted life year (QALY) vs. 32.32 yuan/QALY, P<0.001], and the incidence of general adverse drug reactions (2.50% vs. 10.00%, P=0.049) of post-quality control implementation group were decreased significantly; the utility value of the EuroQol Five-Dimensional Questionnaire (0.74± 0.06 vs. 0.71±0.07, P=0.003), the reduction in the number of medication related problems (1.0 vs. 0.5, P<0.001), the medication adherence score ([ 6.32±0.48) points vs. (6.10±0.37) points, P=0.001], and the satisfaction score ([ 92.56±1.52) points vs. (91.95±1.56) points, P=0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups (1.25% vs. 3.75%, P=0.310). CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care, and the ECHO model can quantitatively evaluate the effect of MTM services, making pharmaceutical care better priced and more adaptable to social needs, thus being worthy of promotion.
10.STAR Guideline Terminology(Ⅱ): Clinical Question Formulation, Evidence Retrieval and Appraisal, and Recommendation Development
Di ZHU ; Haodong LI ; Zijun WANG ; Qianling SHI ; Hui LIU ; Yishan QIN ; Yuanyuan YAO ; Zhewei LI ; Hongfeng HE ; Jinhui TIAN ; Long GE ; Yaolong CHEN ;
Medical Journal of Peking Union Medical College Hospital 2025;16(3):756-764
To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development. A systematic search was conducted in guideline development manuals and relevant methodological literature, covering publications up to October 25, 2024. Terminology related to the three aforementioned stages of related to guideline development was extracted from the included literature, standardized, and refined through consensus meetings to finalize a comprehensive terminology list and definitions. A total of 30 guideline development manuals and 15 methodological articles were included, and 23 core terms were identified. It is recommended to develop a standardized and scientifically sound guideline terminology system with unified naming, clear definitions, and alignment with the linguistic environment and usage habits in China. At the same time, it is essential to strengthen terminology training for both guideline developers and users based on this system, in order to deepen their correct understanding and proper application of guideline terminology.

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