1.Aging and perioperative brain health: Mechanisms, management, and future.
Peilin CONG ; Qian CHEN ; Qianqian WU ; Jing WANG ; Xinwei HUANG ; Qian ZHANG ; Zheping CHEN ; Huanghui WU ; Yuxin ZHANG ; Mengfan HE ; Zhouxiang LI ; Li TIAN ; Lize XIONG
Chinese Medical Journal 2025;138(19):2381-2398
Globally, over 300 million surgeries are performed each year, and more than 50% of surgeries involve patients aged 65 and older. Aging poses significant challenges to perioperative brain health, as the deterioration of brain structure and function increases susceptibility to postoperative neurological complications. Protecting perioperative brain health remains a worldwide clinical challenge. With senescence, the brain undergoes a progressive decline in homeostasis across various molecular, cellular, and regional functions. Anesthetics and surgical stimuli may accelerate the disruption of brain homeostasis and exacerbate age-related neurodegeneration. This review provides a framework for understanding how anesthesia and surgery can affect brain health in the aging population and contribute to postoperative neurological complications, with a particular focus on perioperative neurocognitive disorder.
2.Disease-modifying treatment for post-stroke epilepsy
Journal of Apoplexy and Nervous Diseases 2025;42(8):685-692
Post-stroke epilepsy (PSE) is one of the most common complications of stroke and represents a leading cause of secondary epilepsy in adults. Its development follows a well-defined temporal sequence, progressing through stroke onset, latent phase remodeling, and eventual seizure manifestation. PSE is classified into early- and late-onset types based on the timing of seizures. The former is associated with acute injury, while the latter involves chronic reorganization of neural networks. During the latent phase, the brain exhibits pathological changes such as disrupted synaptic plasticity, inflammatory activation, oxidative stress accumulation, and blood-brain barrier disruption, offering a critical window for therapeutic intervention. However, conventional antiseizure medications, which primarily inhibit abnormal neuronal discharges, are insufficient to reverse the underlying pathogenesis and show limited preventive efficacy. Against this backdrop, the concept of disease-modifying treatment (DMT) has gained traction. DMT underscores mechanistic, targeted, and early-stage interventions that prioritize core processes such as inflammation, synaptic remodeling, ferroptosis, and miRNA regulation. Due to its predictability and ease of modeling, PSE serves as an ideal platform for DMT research. Emerging strategies encompass small-molecule drugs, stem cell transplantation, epigenetic modulation, and neuromodulation, some of which have shown promising results in animal models. This review systematically summarizes the pathogenesis of PSE and recent advances in DMT approaches, providing a theoretical foundation and practical guidance for clinical interventions.
3.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.
4.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.
5.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.
6.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.
7.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.
8.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.
9.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.
10.Analysis on rate of adverse pregnancy outcomes in HIV-infected pregnant women and influencing factors in some regions of China, 2017-2023
Xinwei LI ; Ailing WANG ; Yanli CAO ; Qinghua QIN ; Jiarui ZHENG ; Xiaohua XIE ; Maimaitiming AIBIBAI ; Lingling GUAN ; Xiaoyan WANG ; Dongxu HUANG ; Qian WANG
Chinese Journal of Epidemiology 2025;46(1):125-130
Objective:To understand the incidence of adverse pregnancy outcome in HIV-infected pregnant women and influencing factors in China and provide reference for the improvement of the health status of HIV-infected pregnant women and their newborns.Methods:Based on a mother-child cohort of HIV-infected pregnant women and children (PMTCT-MC-2005) established in Guangxi Zhuang Autonomous Region, Yunnan Province and Xinjiang Uygur Autonomous Region, this study enrolled pregnant women with or without HIV infection as study subjects from January 2017 to June 2023, a total of 1 646 pregnant women (558 HIV-infected and 1 088 HIV-uninfected) were included, and 34 cases with missing data were excluded. The χ2 test was used to analyze the difference in the incidence adverse pregnancy outcome between two groups, and used logistic regression model to identify the influencing factors of adverse pregnancy outcome in HIV-infected pregnant women. Results:A total of 1 612 pregnant women were included in the study, in whom 541 were infected with HIV and 1 071 were not infected with HIV. The incidence of adverse pregnancy outcome was 18.8% (303/1 612), the incidence of adverse pregnancy outcome was 33.1% (179/541) in the HIV-infected pregnant women and 11.6% (124/1 071) in the pregnant women without HIV infection. The results of multivariable logistic regression analysis showed that the influencing factors of adverse pregnancy outcome were age <35 years at delivery (a OR=0.64, 95% CI: 0.43-0.95) compared with the age ≥35 years and the duration of antiviral treatment over 10 years (a OR=0.43, 95% CI: 0.23-0.79) compared with less than one year. Conclusions:The incidence of adverse pregnancy outcome in HIV-infected pregnant women was high in some regions of China during 2017-2023. It is necessary for HIV-infected women to get pregnancy at appropriate time based on antiretroviral treatment effect and strengthen self-care to reduce the incidence of adverse pregnancy outcome.

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