1.Bacterial extracellular vesicles for gut microbiome-host communication and drug development.
Dingfei QIAN ; Peijun XU ; Xinwei WANG ; Chong DU ; Xiao ZHAO ; Jiaqi XU
Acta Pharmaceutica Sinica B 2025;15(4):1816-1840
As the intricate interplay between microbiota and the host garners increasing research attention, a significant parallel surge has emerged in the investigation of intestinal bacterial extracellular vesicles (BEVs). Most intestinal bacteria secrete BEVs, which harbor specific cargo molecules and exhibit diverse functions, encompassing interactions among bacteria themselves and between bacteria and the host. These interactions can either bolster host health or contribute to various pathologies. By integrating the characteristics of BEVs, we summarized the current research landscape, delving into the intricate interplay between BEVs and different diseases. Furthermore, we offer a succinct overview of the challenges faced in BEVs-based research, encompassing separation, detection, engineering for drug purposes, clinical diagnostics, safety, and future study. In essence, these summaries may serve as invaluable guides for BEVs as communication tools between the gut microbiome and host, ultimately propelling the discovery of novel studies and drug discovery.
2.Combination of cerebral small vessel disease and cerebral artery stenosis predicts risk for coronary atherosclerosis
Xian XU ; Xinwei CHANG ; Linsong LIU ; Jian ZHAO ; Guanzhong LIU ; Jing LI ; Xinjiang WANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(10):1292-1297
Objective To predict the risk of coronary atherosclerosis using cerebral small vessel disease and cerebral artery stenosis in order to assist early identification of coronary artery disease(CHD).Methods A retrospective analysis was conducted on 130 patients(aged≥65 years)who underwent cerebral MRI,magnetic resonance angiography(MRA),and coronary computed tomo-graphy angiography in the Chinese PLA General Hospital between January 2019 and December 2024.Based on coronary computed tomography angiography results,the patients were categorized into an asymptomatic CHD group(56 cases)and a non-CHD group(74 cases).Cerebral MRI and MRA were used to assess white matter hyperintensity,enlarged perivascular spaces,lacunar infarcts,cerebral microbleeds(CMB)scores,total score of cerebral small vessel disease and degree of cerebral artery stenosis.Multivariate logistic regression analysis was employed to identify the clinical and radiological indicators related to CHD.Then a predictive model was constructed,and then its performance in early predicting CHD was evaluated.Results Blood glucose,low-density lipoprotein cholesterol,CMB score≥ 1,and≥50%stenosis of the posterior cerebral artery were independent risk factors for CHD(P<0.05).The combined predictive model integrating clinical indicators,cerebral small vessel disease,and cerebral artery stenosis demonstrated the best performance,with an AUC value of 0.867(95%CI:0.807-0.927),outperforming the clinical model and the clinical-cerebral small vessel disease model.Conclusion cerebral small vessel dis-ease and cerebral artery stenosis are closely related to coronary atherosclerosis.The predictive model integrating clinical features and cerebrovascular disease imaging markers provides impor-tant reference for early screening of CHD.
3.Advances in the minimally invasive McKeown procedure in the management of esophageal cancer
Zhichao LIU ; Xinwei YANG ; Xuesong ZHAO ; Li JING ; Linjing GUO ; Xiaoliang YAN
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(4):248-256
Esophageal cancer is the eighth most common malignant tumor in the world, and China is a country with high incidence of esophageal cancer. Currently, The treatment options for resectable esophageal cancer is multidisciplinary comprehensive treatment based on surgery. In recent years, minimally invasive esophageal cancer surgery has been increasingly used in clinical practice, especially McKeown minimally invasive esophagectomy(MIE) has become the most minimally invasive esophagectomy currently used in China. But how effective is the McKeown MIE for esophageal cancer compared to the open McKeown and other minimally invasive esophageal cancer procedures? A detailed comprehensive description is not yet available. In this paper, We will summarize the clinical studies related to McKeown MIE and traditional open McKeown, Ivor-Lewis MIE, Sweet operation and robot-assisted McKeown MIE, and systematically analyze them, so as to clarify the value of McKeown MIE surgery in the treatment of esophageal cancer.
4.Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults (version 2025)
Zhengwei XU ; Liming CHENG ; Qixin CHEN ; Jian DONG ; Shunwu FAN ; Zhong FANG ; Shiqing FENG ; Haoyu FENG ; Haishan GUAN ; Weimin JIANG ; Dianming JIANG ; Yong HAI ; Lijun HE ; Yuan HE ; Bo LI ; Jianjun LI ; Feng LI ; Li LI ; Weishi LI ; Chunde LI ; Qi LIAO ; Baoge LIU ; Xiaoguang LIU ; Yong LIU ; Xuhua LU ; Shibao LU ; Bin LIN ; Wei MEI ; Chao MA ; Renfu QUAN ; Limin RONG ; Jiacan SU ; Honghui SUN ; Yuemin SONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Jiwei TIAN ; Qiang WANG ; Xinwei WANG ; Zhe WANG ; Zheng WANG ; Liang YAN ; Guoyong YIN ; Jie ZHAO ; Yue ZHU ; Xiaobo ZHANG ; Xuesong ZHANG ; Zhongmin ZHANG ; Rongqiang ZHANG ; Dingjun HAO ; Yanzheng GAO ; Baorong HE
Chinese Journal of Trauma 2025;41(1):19-32
Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.
5.Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures (version 2025)
Bolong ZHENG ; Wei MEI ; Yanzheng GAO ; Liming CHENG ; Jian CHEN ; Qixin CHEN ; Liang CHEN ; Xigao CHENG ; Jian DONG ; Jin FAN ; Shunwu FAN ; Xiangqian FANG ; Zhong FANG ; Shiqing FENG ; Haoyu FENG ; Haishan GUAN ; Yong HAI ; Baorong HE ; Lijun HE ; Yuan HE ; Hua HUI ; Weimin JIANG ; Junjie JIANG ; Dianming JIANG ; Xuewen KANG ; Hua GUO ; Jianjun LI ; Feng LI ; Li LI ; Weishi LI ; Chunde LI ; Qi LIAO ; Baoge LIU ; Xiaoguang LIU ; Xuhua LU ; Shibao LU ; Bin LIN ; Chao MA ; Xuexiao MA ; Renfu QUAN ; Limin RONG ; Honghui SUN ; Tiansheng SUN ; Yueming SONG ; Hongxun SANG ; Jun SHU ; Jiacan SU ; Jiwei TIAN ; Xinwei WANG ; Zhe WANG ; Zheng WANG ; Zhengwei XU ; Huilin YANG ; Jiancheng YANG ; Liang YAN ; Feng YAN ; Guoyong YIN ; Xuesong ZHANG ; Zhongmin ZHANG ; Jie ZHAO ; Yuhong ZENG ; Yue ZHU ; Rongqiang ZHANG
Chinese Journal of Trauma 2025;41(9):805-818
Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.
6.IFN-γ inhibits human liver cancer cell migration and stem cell differentiation via the Akt/JNK-IL-8 signaling pathway
Yue ZHANG ; Lu ZHENG ; Xinwei XU ; Yuting MA ; Chengwen ZHAO ; Xinyu WANG ; Feng GU ; Yongqiang CHEN
Chinese Journal of Microbiology and Immunology 2025;45(7):587-594
Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.
7.Therapeutic Effect of Cranial Painkiller Pills' Extract Powder in Treatment of Trigeminal Neuralgia Induced by Injection of Talci Pulvis into Infraorbital Foramen of Model Rats Based on OTULIN-regulated Neuroinflammation
Shuran LI ; Xinwei WANG ; Jing SUN ; Dan XIE ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Jingsheng ZHANG ; Yaxin WANG ; Xihe CUI ; Xinying LI ; Bing HAN ; Tianjiao LU ; Xiaolan CUI ; Liying LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):21-28
ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis, evaluate its potential clinical application value, and compare the therapeutic effect with that of Cranial Painkiller granules, so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis, and the rats were randomly divided into the normal group, model group, carbamazepine group (60 mg·kg-1), Cranial Painkiller granules group (2.70 g·kg-1), and low, medium, and high dosage groups of Cranial Painkiller pills' extract powder (1.35, 2.70, 5.40 g·kg-1) according to the basal mechanical pain thresholds, and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling, and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin (HE) staining was used to detect pathological changes in the trigeminal ganglion, and enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory factors interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels in rat serum, as well as neuropeptide substance P (SP) and β-endorphin (β-EP) levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3, ASC, Caspase-1, and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group, the pain threshold of rats in the model group showed a continuous significant decrease (P<0.01). The pathological damage of brain tissue was significant (P<0.01), and the inflammatory levels of IL-1, IL-6, IL-8, and TNF-α in serum were significantly elevated (P<0.01). The level of the SP in the brain tissue was significantly elevated (P<0.01), and the level of β-EP was significantly reduced (P<0.01), while the level of OTULIN was significantly reduced, and NLRP3, ASC, and Caspase-1 protein levels were significantly elevated (P<0.01). After administration of the drug, compared with the model group, the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased (P<0.01). The inflammatory levels of IL-1, IL-6, IL-8, and TNF-α and SP levels significantly decreased (P<0.01), and the β-EP levels were significantly elevated (P<0.01), while the levels of OTULIN protein were significantly elevated (P<0.05, P<0.01), and the levels of NLRP3, ASC proteins were decreased (P<0.01)in high dose Cranial Painkiller pills' extract powder. Meanwhile, compared with those in the model group, the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement (P<0.05, P<0.01). ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis, and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.
8.Therapeutic Effect of Jidesheng Sheyao Tablets on VZV-induced Skin Vesicles in Guinea Pigs and Postherpetic Neuralgia in Rats
Rui XIE ; Shanshan GUO ; Zihan GENG ; Lei BAO ; Ronghua ZHAO ; Shuran LI ; Qiyue SUN ; Xinwei WANG ; Jingsheng ZHANG ; Xihe CUI ; Xiaolan CUI ; Jing SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):38-47
ObjectiveThis paper aims to investigate the therapeutic effects of Jidesheng Sheyao tablets on varicella-zoster virus (VZV) and its associated postherpetic neuralgia (PHN) to provide experimental evidence for the clinical application and secondary development of Jidesheng Sheyao tablets. MethodsFifty-six guinea pigs were randomly divided into seven groups according to their body weight, namely the normal group, the model group, the positive control group, the high-dose group, medium-dose group, and low-dose group of Jidesheng Sheyao tablets (1.92, 0.96, 0.48 g·d-1), and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets (0.96 g·d-1 + 1.2 g·kg-1·d-1). The skin on the back of the guinea pigs in each group was depilated and then abraded with sandpaper. Except for the normal group, 200 μL of VZV solution was dropped on the damaged parts of the back of the guinea pigs in the other groups, and the infection lasted for 2 consecutive days. The drug administration started 2 hours after the infection on the first day and lasted for 7 days. The pathological changes of the back of the guinea pigs in each group were observed every day starting from the second day after the infection. On the 7th day, the guinea pigs were sacrificed by CO2 anesthesia. The locally infected skin was taken, and the viral DNA nucleic acid load was detected by real-time polymerase chain reaction (Real-time PCR). The pathological histology examination was carried out after hematoxylin-eosin (HE) staining. Seventy rats were randomly divided into seven groups according to their body weight, namely the normal group, the model group, the positive control group, the high-dose group, medium-dose group, and low-dose group of Jidesheng Sheyao tablets (1.08, 0.54, 0.27 g·d-1), and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets (0.54 g·d-1 + 1.2 g·kg-1·d-1). The rats in each group (except the normal group) were subcutaneously inoculated with 50 μL of VZV suspension between the web of the first and second fingers of the left forelimb. The skin on the back of the rats was depilated, and the drug administration started 2 hours after the infection and lasted for 10 days. The mechanical withdrawal threshold of the paws of the rats was detected by a Von Frey filament algometer before inoculation and on the 1st, 3rd, 6th, 8th, and 10th days after inoculation, and the thermal withdrawal reflex latency of the paws of the rats was detected by a hot and cold plate algometer. On the 10th day after the virus inoculation, the rats were anesthetized after the behavioral examination, and the dorsal root ganglia of the spinal cord and spinal cord segments were taken. The contents of substance P (SP), neurokinin (NK), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the dorsal root ganglia of the spinal cord and spinal cord were detected by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with those in the normal group, the guinea pigs in the model group had obvious skin herpes lesions (P<0.01). The viral nucleic acid load was high (P<0.01), and there were disorganized subcutaneous cellular structures and obvious infiltration of inflammatory cells and cell necrosis (P<0.01). The mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats were significantly decreased (P<0.05), and the contents of NK, SP, TNF-α, and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats were significantly increased (P<0.01). Compared with the model group, the high-dose and medium-dose groups of topical administration of Jidesheng Sheyao tablets and the group of oral administration combined with topical application could significantly improve the lesions such as skin redness and herpes of the guinea pigs caused by VZV infection (P<0.01), reduce the VZV viral nucleic acid load in the skin tissues of the guinea pigs (P<0.01), alleviate the degree of inflammatory cell infiltration and skin cell necrosis in the skin tissue (P<0.05), significantly increase the mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats (P<0.05), and decrease the contents of NK, SP, TNF-α, and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats (P<0.01). ConclusionJidesheng Sheyao tablets demonstrated significant therapeutic effects on VZV-induced skin infections and postherpetic neuralgia (PHN), providing a promising candidate for the prevention and treatment of VZV infections.
9.Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
Shuran LI ; Yaxin WANG ; Jing SUN ; Lei BAO ; Zihan GENG ; Dan XIE ; Ronghua ZHAO ; Yanyan BAO ; Qiyue SUN ; Jingsheng ZHANG ; Xinwei WANG ; Xinying LI ; Xihe CUI ; Xiaowei YANG ; LIUXIAN ; Mengyao CUI ; Qingshan LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):54-60
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang (SWDK) on cognitive dysfunction in mice suffering from Alzheimer's disease (AD) and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group, total ginsenoside group(0.04 g·kg-1), high-, medium-, and low-dose groups of SWDK (32.60, 16.30, 8.15 g·kg-1), with 10 mice in each group, and ten wild-type mice of the same age were used as the normal group, male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin (HE) staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin (SYP) and postsynaptic dense substance 95 (PSD95) in mice serum were detected by enzyme-linked immunosorbent assay (ELISA). The positive expression of brain-derived neurotrophic factor(BDNF) in the dentate gyrus (DG) region of mouse brain tissue was observed by immunohistochemistry (IHC). The protein levels of BDNF, Wnt family member 3A(Wnt3a), and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice, the model group of mice had significantly more complex swimming routes and lower swimming speed (P<0.01), significantly lower percentage of time spent in the target quadrant (P<0.01), and a significantly lower percentage of freezing time (P<0.05). The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95(P<0.01) in the serum of mice were reduced, and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice were obviously reduced (P<0.05, P<0.01). Compared with the model group, the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes, the high- and medium- dose SWDK groups significantly higher swimming speeds (P<0.01), significantly higher percentage of time spent in the target quadrant (P<0.01), obviously higher percentage of Freezing time (P<0.05), and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP (P<0.05, P<0.01), PSD95 (P<0.01), increased BDNF-positive cells in the DG region of brain tissue, and obviously elevated levels of BDNF, Wnt3a, and β-catenin proteins in the hippocampus of mice (P<0.05, P<0.01). ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice, and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway, which promotes BDNF expression and thereby enhances synaptic plasticity, allowing neuronal signaling to be restored.
10.Therapeutic Effect of Cranial Painkiller Pills' Extract Powder in Treatment of Trigeminal Neuralgia Induced by Injection of Talci Pulvis into Infraorbital Foramen of Model Rats Based on OTULIN-regulated Neuroinflammation
Shuran LI ; Xinwei WANG ; Jing SUN ; Dan XIE ; Ronghua ZHAO ; Lei BAO ; Zihan GENG ; Qiyue SUN ; Jingsheng ZHANG ; Yaxin WANG ; Xihe CUI ; Xinying LI ; Bing HAN ; Tianjiao LU ; Xiaolan CUI ; Liying LIU ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):21-28
ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis, evaluate its potential clinical application value, and compare the therapeutic effect with that of Cranial Painkiller granules, so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis, and the rats were randomly divided into the normal group, model group, carbamazepine group (60 mg·kg-1), Cranial Painkiller granules group (2.70 g·kg-1), and low, medium, and high dosage groups of Cranial Painkiller pills' extract powder (1.35, 2.70, 5.40 g·kg-1) according to the basal mechanical pain thresholds, and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling, and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin (HE) staining was used to detect pathological changes in the trigeminal ganglion, and enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory factors interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels in rat serum, as well as neuropeptide substance P (SP) and β-endorphin (β-EP) levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3, ASC, Caspase-1, and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group, the pain threshold of rats in the model group showed a continuous significant decrease (P<0.01). The pathological damage of brain tissue was significant (P<0.01), and the inflammatory levels of IL-1, IL-6, IL-8, and TNF-α in serum were significantly elevated (P<0.01). The level of the SP in the brain tissue was significantly elevated (P<0.01), and the level of β-EP was significantly reduced (P<0.01), while the level of OTULIN was significantly reduced, and NLRP3, ASC, and Caspase-1 protein levels were significantly elevated (P<0.01). After administration of the drug, compared with the model group, the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased (P<0.01). The inflammatory levels of IL-1, IL-6, IL-8, and TNF-α and SP levels significantly decreased (P<0.01), and the β-EP levels were significantly elevated (P<0.01), while the levels of OTULIN protein were significantly elevated (P<0.05, P<0.01), and the levels of NLRP3, ASC proteins were decreased (P<0.01)in high dose Cranial Painkiller pills' extract powder. Meanwhile, compared with those in the model group, the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement (P<0.05, P<0.01). ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis, and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

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