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.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
3.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
4.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
5.4 Weeks of HIIT Modulates Metabolic Homeostasis of Hippocampal Pyruvate-lactate Axis in CUMS Rats Improving Their Depression-like Behavior
Yu-Mei HAN ; Chun-Hui BAO ; Zi-Wei ZHANG ; Jia-Ren LIANG ; Huan XIANG ; Jun-Sheng TIAN ; Shi ZHOU ; Shuang-Shuang WU
Progress in Biochemistry and Biophysics 2025;52(6):1468-1483
ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) Smax+1 min (50%-55%) Smax, 3-5 cycles, Smax is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.
6.Four Weeks of HIIT Modulates Lactate-mediated Synaptic Plasticity to Improve Depressive-like Behavior in CUMS Rats
Yu-Mei HAN ; Zi-Wei ZHANG ; Jia-Ren LIANG ; Chun-Hui BAO ; Jun-Sheng TIAN ; Shi ZHOU ; Huan XIANG ; Yong-Hong YANG
Progress in Biochemistry and Biophysics 2025;52(6):1499-1510
ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, Smax) alternated with one minute at low speed (50%-55% Smax), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.
7.The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.
Xiaoxuan ZHONG ; Xiang WEI ; Yan XU ; Xuehai ZHU ; Bo HUO ; Xian GUO ; Gaoke FENG ; Zihao ZHANG ; Xin FENG ; Zemin FANG ; Yuxuan LUO ; Xin YI ; Ding-Sheng JIANG
Acta Pharmaceutica Sinica B 2024;14(2):712-728
Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
8.Functional near infrared imaging of college students on speech fluency tasks in traumatized
ZHENG Minxiao, ZHU Dongmei, WEI Qiang, XIANG Nian, QIU Min, XIAO Qiang, LI Xiaonan, ZHANG Yan
Chinese Journal of School Health 2024;45(3):375-378
Objective:
The study aims to explore the neural mechanism of cognitive differences in college students with posttraumatic stress disorder under verbal fluency task based on functional near infrared spectroscopy (fNIRS), so as to provide neuroimaging support for the evaluation, diagnosis and treatment of posttraumatic stress disorder(PTSD).
Methods:
Posttaumatic Stress Disorder Checklist Combat(PCL-C) was used to screen the subjects, including 21 students in PTSD group (PCL-C≥38) and 30 students in control group from September to Novenber in 2020. A 53 channel near infrared spectroscopy device was used to collect cerebral blood oxygen signals under the verbal fluency task, and correlation analysis, Mann Whitney U test and independent sample t test were performed on the results.
Results:
The difference in the total average score of PCL-C Scale between PTSD group and the control group(46.38±6.96,25.57±6.09) was statistically significant ( t=11.33, P <0.05). Correlation analysis showed that Avg-HbO in left dorsolateral prefrontal lobe was negatively correlated with PCL-C Score ( r=-0.37, P <0.05). Mann Whitney U test showed that in the left dorsolateral prefrontal lobe (Ch6), the Avg-HbO change in PTSD group [0.19(-0.09, 0.86)mmol/(L〖KG*7〗·mm)] was significantly lower than the control group [0.79( 0.37 , 1.47)mmol/(L ·mm)] ( Z=2.16, P <0.05), which was statistically significant.
Conclusions
The degree of PTSD was negatively correlated with the index of oxygenated hemoglobin in the left dorsolateral prefrontal lobe, and the oxygenated hemoglobin content in the PTSD group was lower than that in the normal group. In the future, fNIRS may be used to collect blood oxygen signals from the left dorsolateral prefrontal lobe in cognitive tasks to provide imaging evidence for the identification of PTSD.
9.Discussion on the pathogenesis of colorectal polyp from "damp pathogen causing diseases"
Zikuan SUN ; Xiaolan SU ; Yanran BAN ; Zhuozhi GONG ; Kaixuan ZHANG ; Lang XIANG ; Mengxi YAO ; He YAN ; Wei WEI
International Journal of Traditional Chinese Medicine 2024;46(3):288-292
The clinical manifestations of colorectal polyps are consistent with the characteristics of dampness, stickiness and heaviness. The TCM constitutions in the prone population are mostly related to dampness. The pathological changes of intestinal flora imbalance, intestinal micro inflammation, neuroendocrine immune network and abnormal aquaporin in colorectal polyps are consistent with the research results of modern mechanism of dampness pathogen. This article believed that the TCM pathogenesis of colorectal polyps caused by damp pathogen is the accumulation of spleen deficiency and dampness caused by improper diet, poor emotion and other factors, and the interweaving of various diseases and pathogens to form tangible foreign bodies. According to the pathogenic characteristics of damp pathogen and the pathogenic factors of colorectal polyps, the influence of damp pathogen on the pathogenesis of colorectal polyps was discussed, in order to provide an effective TCM theoretical basis for the diagnosis and treatment of colorectal polyps in clinic.
10.Data Mining of Medication Rules of Chinese Herbal Prescriptions for Oral Use in the Treatment of Venomous Snake Bites
Song-Jie ZHANG ; Dian-Hong LI ; Wei-Cai CAI ; Qing-Xiang WU ; Jian-Liang LIN ; Man-Guang LIANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):251-256
Objective Data mining method was used to analyze the Chinese herbal prescriptions for oral use in treating venomous snake bites collected from the major domestic literature databases and the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions),so as to explore their potential prescription and medication rules,and to provide references for the treatment of venomous snake bites in the primary hospitals.Methods The Chinese herbal prescriptions for oral use in treating venomous snake bites were retrieved from the CNKI,VIP and Wanfang databases,and the ancient formulas for treating venomous snake bites were screened in the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions).Excel software was used to extract the relevant information of the formulas,and R language was used to analyze the medication frequency,properties,flavors and meridian tropism of the herbs as well as their association rules and clustering analysis.Results A total of 187 prescriptions for oral use in treating venomous snake bite were obtained,involving 284 Chinese herbal medicines.The top 15 Chinese herbal medicines in decreasing sequence of medication frequency were Lobeliae Chinensis Herba,Rhei Radix et Rhizoma,Angelicae Dahuricae Radix,Glycyrrhizae Radix et Rhizoma,Paridis Rhizoma,Rehmanniae Radix,Coptidis Rhizoma,Scutellariae Radix,Lonicerae Japonicae Flos,Paeoniae Radix Rubra,Moutan Cortex,Hedyotis Diffusae Herba,Imperatae Rhizoma,Plantaginis Herba,and Scutellariae Barbatae Herba.The flavor of herbs in the prescription for the treatment of venomous snakebite was usually bitter,pungent and sweet,and their property was relatively cold.Most of the herbs had the meridian tropism of the liver meridian and lung meridian.The core prescription mainly composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,and Paridis Rhizoma was obtained after association rule analysis and cluster analysis.Conclusion The herbs for the treatment of venomous snake bites often have the actions of clearing heat and removing toxins,and the prescription is usually composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,Paridis Rhizoma together with the compatibility of medicines for clearing heat and cooling blood,extinguishing wind and arresting convulsion,clearing heat and promoting urination.


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