1.Acute Inflammatory Pain Induces Sex-different Brain Alpha Activity in Anesthetized Rats Through Optically Pumped Magnetometer Magnetoencephalography
Meng-Meng MIAO ; Yu-Xuan REN ; Wen-Wei WU ; Yu ZHANG ; Chen PAN ; Xiang-Hong LIN ; Hui-Dan LIN ; Xiao-Wei CHEN
Progress in Biochemistry and Biophysics 2025;52(1):244-257
ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.
2.Shaoyaotang Restores Th17/Treg Cell Balance by Regulating Glucose Metabolism Reprogramming in Treatment of Ulcerative Colitis
Yiwen WANG ; Yiling XIA ; Erle LIU ; Shaijin JIANG ; Bo ZOU ; Dongsheng WU ; Youwei XIAO ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):78-85
ObjectiveTo investigate the effect of Shaoyaotang on T helper cell 17/regulatory T lymphocyte(Th17/Treg) cell balance in ulcerative colitis and decipher the intervention mechanism based on glucose metabolism reprogramming. MethodsThe mouse model of ulcerative colitis was established by the dextran sulfate sodium (DSS) method. Forty-eight C57BL/6 mice were randomly allocated into normal, model, Western drug control (mesalazine, 0.39 g·kg-1·d-1), Shaoyaotang (15.54 g·kg-1·d-1), inhibitor (2-deoxy-D-glucose, 2-DG, 100 mg·kg-1·d-1), and inhibitor (2-DG, 100 mg·kg-1·d-1) + Shaoyaotang (15.54 g·kg-1·d-1) groups. Mice were administrated with the corresponding drugs by gavage for 7 days. The general conditions and the colon injury degree were observed 24 h after the last administration. The expression of interleukin (IL)-10 and IL-17 in the colon tissue was detected by immunohistochemical staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were performed to determine the protein and mRNA levels, respectively, of hypoxia-inducing factor-1α (HIF-1α), lactate dehydrogenase (LDHA), and hexokinase 2 (HK2) in the colon tissue. Th17/Treg cell differentiation was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of lactic acid and glucose in the colon tissue and IL-10, IL-17, and IL-6 in the serum. ResultsCompared with the normal group, the model group showed decreases in body weight and disease activity index (DAI) (P<0.05), elevations in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and declines in the levels of of IL-10 and Treg cells (P<0.05). Compared with the model group, the drug administration groups showed increases in body weight and DAI (P<0.05), declines in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and rises in levels of IL-10 and Treg cells (P<0.05). Shaoyaotang+2-DG group had the most obvious effect. ConclusionShaoyaotang can relieve diarrhea and bloody stool in mice with ulcerative colitis by restoring the Th17/Treg cell balance via regulation of glucose metabolism reprogramming, thus playing a role in the treatment of ulcerative colitis.
3.Shaoyaotang Restores Th17/Treg Cell Balance by Regulating Glucose Metabolism Reprogramming in Treatment of Ulcerative Colitis
Yiwen WANG ; Yiling XIA ; Erle LIU ; Shaijin JIANG ; Bo ZOU ; Dongsheng WU ; Youwei XIAO ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):78-85
ObjectiveTo investigate the effect of Shaoyaotang on T helper cell 17/regulatory T lymphocyte(Th17/Treg) cell balance in ulcerative colitis and decipher the intervention mechanism based on glucose metabolism reprogramming. MethodsThe mouse model of ulcerative colitis was established by the dextran sulfate sodium (DSS) method. Forty-eight C57BL/6 mice were randomly allocated into normal, model, Western drug control (mesalazine, 0.39 g·kg-1·d-1), Shaoyaotang (15.54 g·kg-1·d-1), inhibitor (2-deoxy-D-glucose, 2-DG, 100 mg·kg-1·d-1), and inhibitor (2-DG, 100 mg·kg-1·d-1) + Shaoyaotang (15.54 g·kg-1·d-1) groups. Mice were administrated with the corresponding drugs by gavage for 7 days. The general conditions and the colon injury degree were observed 24 h after the last administration. The expression of interleukin (IL)-10 and IL-17 in the colon tissue was detected by immunohistochemical staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were performed to determine the protein and mRNA levels, respectively, of hypoxia-inducing factor-1α (HIF-1α), lactate dehydrogenase (LDHA), and hexokinase 2 (HK2) in the colon tissue. Th17/Treg cell differentiation was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of lactic acid and glucose in the colon tissue and IL-10, IL-17, and IL-6 in the serum. ResultsCompared with the normal group, the model group showed decreases in body weight and disease activity index (DAI) (P<0.05), elevations in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and declines in the levels of of IL-10 and Treg cells (P<0.05). Compared with the model group, the drug administration groups showed increases in body weight and DAI (P<0.05), declines in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and rises in levels of IL-10 and Treg cells (P<0.05). Shaoyaotang+2-DG group had the most obvious effect. ConclusionShaoyaotang can relieve diarrhea and bloody stool in mice with ulcerative colitis by restoring the Th17/Treg cell balance via regulation of glucose metabolism reprogramming, thus playing a role in the treatment of ulcerative colitis.
4.Construction Process and Quality Control Points of the Database for Facial Phenotypes and Clinical Data of Pediatric Growth and Development-related Diseases
Jiaqi QIANG ; Yingjing WANG ; Danning WU ; Runzhu LIU ; Jiuzuo HUANG ; Hui PAN ; Xiao LONG ; Shi CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):552-557
The growth and development of children is an important stage for health, and its monitoringand intervention are related to the long-term development of individuals. The construction of a standardized and multi-dimensional database of pediatric growth and development-related diseases is an important basis for realizing precise diagnosis and treatment and health management. Based on the needs of clinical practice, this study proposes to establish a specialized database of pediatric growth and development-related diseases that integrates facial phenotypes and clinical diagnosis and treatment information. This study elaborates on the construction process, including data sources, data collection content, and the operation and management of the database; and proposes key points for quality control, including the establishment of quality control nodes, database construction standards, and a full-process quality control framework. The above ensure the integrity, logic and effectiveness of the data, so that the database can provide an objective basis for the screening and diagnosis of pediatric growth and development-related diseases. On the basis of scientific data management and strict quality control, the database will help reveal the patterns of children's growth and development, and promote the level of children's health management.
5.Study on The Detection Method of Fat Infiltration in Muscle Tissue Based on Phase Angle Electrical Impedance Tomography
Wu-Guang XIAO ; Xiao-Peng ZHU ; Hui FENG ; Bo SUN ; Tong ZHAO ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2025;52(10):2663-2676
ObjectiveFat infiltration has been shown to be closely related to muscle mass loss and a variety of muscle diseases. This study proposes a method based on phase-angle electrical impedance tomography (ΦEIT) to visualize the electrical characteristic response caused by muscle fat infiltration, aiming to provide a new technical means for early non-invasive detection of muscle mass deterioration. MethodsThis study was divided into two parts. First, a laboratory pork model was constructed to simulate different degrees of fat infiltration by injecting1 ml or 2 ml of emulsified fat solution into different muscle compartments, and the phase angle images were reconstructed using ΦEIT. Second, a human experiment was conducted to recruit healthy subjects (n=8) from two age groups (20-25 years old and 26-30 years old). The fat content percentage ηfat of the left and right legs was measured by bioelectrical impedance analysis (BIA), and the phase angle images of the left and right calves were reconstructed using ΦEIT. The relationship between the global average phase angle ΦM and the spatial average phase angle ΦMi of each muscle compartment and fat infiltration was further analyzed. ResultsIn the laboratory pork model, the grayscale value of the image increased with the increase of ηfat and ΦM showed a downward trend. The results of human experiments showed that at the same fat content percentage, the ΦM of the 26-30-year-old group was about 20%-35% lower than that of the 20-25-year-old group. The fat content percentage was significantly negatively correlated with ΦM. In addition, the M2 (soleus) compartment was most sensitive to fat infiltration, and the spatial average phase angles of the M2 (soleus), M3 (tibialis posterior and flexor digitorum longus), and M4 (tibialis anterior, extensor digitorum longus, and peroneus longus) compartments all showed significant inter-group differences. ConclusionΦEIT imaging can effectively distinguish different degrees of fat infiltration, especially in deep, small or specially located muscles, showing high sensitivity, demonstrating the potential application of this method in local muscle mass monitoring and early non-invasive diagnosis.
6.Effect of Endoplasmic Reticulum Stress on Intestinal Mucosal Injury in Ulcerative Colitis and TCM Intervention Based on Theory of Sores Depending on Spleen-earth
Youwei XIAO ; Dongsheng WU ; Hui CAO ; Bo ZOU ; Yiqian YU ; Ruoru HUANG ; Qi CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):238-247
In recent years, as the incidence of ulcerative colitis (UC) is growing, intestinal mucosal injury has garnered increasing attention, and it is characterized by high recurrence, risk of inflammation-cancer transformation, and difficulty in repair. Intestinal mucosal injury in UC is centered on persistent inflammation and barrier dysfunction, with its pathological mechanisms involving endoplasmic reticulum stress (ERS)-mediated changes such as abnormal apoptosis, abnormal autophagy, and inflammatory responses. ERS induces apoptosis of intestinal epithelial cells, disrupts tight junction proteins, and exacerbates inflammatory responses through pathways such as protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 alpha (IRE1α), and activating transcription factor 6 (ATF6), ultimately causing intestinal mucosal injury. Traditional Chinese medicine (TCM) has a long history of research on UC. The theory of sores depending on spleen-earth holds that spleen deficiency is the fundamental cause of UC, while pathological products such as dampness-turbidity and blood stasis are the secondary manifestations. Dysfunction of the spleen-earth leads to insufficient production and transformation of Qi and blood, malnutrition of the intestinal mucosa, and invasion of external pathogens. In the active phase of UC, spleen deficiency is often accompanied by excessive pathogenic factors such as dampness-heat and heat-toxin, leading to acute intestinal mucosal damage. In the remission phase, however, it is mainly characterized by spleen deficiency and healthy Qi deficiency, accompanied by residual pathogens, resulting in weak intestinal mucosal repair. Studies have shown that the endoplasmic reticulum, as a key site for protein synthesis and folding, has functions highly similar to the TCM concept of the spleen governing transportation and transformation. From a TCM perspective, the endoplasmic reticulum can be regarded as the carrier of spleen transportation, and ERS is a microcosmic manifestation of spleen dysfunction, leading to intestinal mucosal injury. ERS impairs the structure and function of the endoplasmic reticulum, induces the generation of abnormal Qi, and triggers pathological changes, making inflammation difficult to be reduced and causing the aggravation of ERS, forming a vicious cycle of spleen deficiency-pathological products-intestinal injury. TCM has unique advantages in regulating ERS to prevent and treat intestinal mucosal injury. According to the theory of sores depending on spleen-earth and the modern medical understanding of ERS, this paper delves into the TCM and Western medicine pathogenesis of intestinal mucosal injury in UC. Furthermore, this paper discusses the roles of TCM active components and compound formulas in reducing intestinal mucosal injury in UC by regulating ERS under the guidance of the treatment principles of invigorating the spleen and replenishing Qi as the key and dispelling dampness and removing blood stasis as the supplementation, aiming to provide new ideas and methods for the prevention and treatment of UC.
7.Clinical trial of midazolam and propofol in the treatment of elderly patients undergoing mechanical ventilation after cardiopulmonary bypass cardiac surgery
En-Gang WU ; Sheng-Jun DONG ; Ning GAI ; Bao-Hui LIU ; Dian-Xiao LIU ; Feng WANG ; Kai-Qiang YANG ; Qian-Qian WANG
The Chinese Journal of Clinical Pharmacology 2024;40(7):963-967
Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88%,4.55%and 7.69%respectively,all with significant difference(all P<0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P>0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.
8.Effects of ropivacaine in cognitive dysfunction and synapses after tibial fracture in aged rats
Liang WU ; Xiao-Hui CHEN ; Ling LIN
The Chinese Journal of Clinical Pharmacology 2024;40(10):1478-1482
Objective To explore the effects of ropivacaine on cognitive dysfunction and synapses in aged rats after tibial fracture.Methods SD male rats were divided into sham operation group,model group and low,medium,high dose experimental groups.Sham operation group was incised and sutured under local anesthesia,and other four groups underwent open tibial fracture operation.Sham operation group and model group were given sevoflurane anesthesia,low,medium and high dose experimental groups were given 0.5,1.0,2.0 mg·kg-1 ropivacaine on the basis of sevoflurane anesthesia.Open field test and Morris water maze test were performed 7 days after operation;Longa score was evaluated;neurotransmitter levels were detected by kit;and Syn1 in hippocampus of rats was detected by immunohistochemistry.Western blot analysis was used to detected the expression of N-methyl-D-aspartate receptor 2B(NMDAR2B),calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ)and Syn1.Results The Longa scores of sham operation group,model group and low,medium,high dose experimental groups were 0,(3.50±0.71),(2.80±0.63),(2.20±0.63)and(0.90±0.32)points;the integrated optical density of Syn1 were 0.56±0.09,0.25±0.03,0.34±0.03,0.42±0.03 and 0.50±0.05;the expression of Syn1 protein were 1.08±0.12,0.42±0.05,0.55±0.07,0.72±0.06 and 0.86±0.05;the expression of NMDAR2B protein were 1.28±0.13,0.51±0.07,0.69±0.06,0.84±0.07 and 1.02±0.11;CaMK Ⅱ protein were 0.94±0.08,0.36±0.04,0.50±0.06,0.71±0.06 and 0.86±0.06.There were statistically significant differences between sham operation group and model group(P<0.05);there were significant differences in the above indexes between model group and low,medium,high dose experimental groups(all P<0.05).Conclusion Ropivacaine can improve cognitive dysfunction and synapses in aged rats after tibial fracture.
9.Effects of radiation on pharmacokinetics
Jie ZONG ; Hai-Hui ZHANG ; Gui-Fang DOU ; Zhi-Yun MENG ; Ruo-Lan GU ; Zhuo-Na WU ; Xiao-Xia ZHU ; Xuan HU ; Hui GAN
The Chinese Journal of Clinical Pharmacology 2024;40(13):1996-2000
Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.
10.Pharmacokinetics of JS026 and JS026-JS016 for single intravenous administration in healthy volunteers
Yan TIAN ; Hui-Jing YE ; Jing-Jing WANG ; Nan-Yang LI ; Juan MA ; Xi TAN ; Fan WU ; Jie WANG ; Shu-Yan YU ; Xiao-Jie WU ; Jin-Jie HE ; Jing ZHANG ; Wen-Hong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2251-2255
Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

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