1.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.
2.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.
3.Construction and Application of An Animal Model of Respiratory Syncytial Virus Infection Based on Humanized IGF1R Mice
Xiaowei YANG ; Dan XIE ; Shuran LI ; Lei BAO ; Zihan GENG ; Xian LIU ; Mengyao CUI ; Yaxin WANG ; Shan CAO ; Xiaolan CUI ; Jing SUN ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):48-53
ObjectiveTo construct an animal model of respiratory syncytial virus(RSV)-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect (CPE), and 50% tissue culture infective dose(TCID50) was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group, the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor (IGF1R) mice was evaluated by measuring organ indices, peripheral blood lymphocyte percentages, pulmonary pathology and imaging, and pulmonary viral load. Additionally, ten BALB/c mice served as normal group, and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group, ribavirin group (82.5 mg·kg-¹·d-¹), and high and low dose groups of Lianhua Qingwen (3.3 mg·kg-¹·d-¹ , 1.65 mg·kg-¹·d-¹), with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention, and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group, large solid and diffuse ground-glass shadows were seen, and the lung volume was significantly increased (P<0.01). The lung index was significantly increased (P<0.01), and both the spleen index and thymus index were significantly decreased (P<0.01). The percentages of CD3+ and CD4+T cells were significantly decreased (P<0.05), and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue, which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached, with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV, the expression of viral nucleic acids in the lung tissue of the mice was significantly increased, with significant differences compared with the normal group (P<0.01). The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced, with significant differences compared with the normal group (P<0.01). ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC, and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed, which is suitable for the evaluation of anti-RSV drugs.
4.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.
5.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.
6.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.
7.Construction and Application of An Animal Model of Respiratory Syncytial Virus Infection Based on Humanized IGF1R Mice
Xiaowei YANG ; Dan XIE ; Shuran LI ; Lei BAO ; Zihan GENG ; Xian LIU ; Mengyao CUI ; Yaxin WANG ; Shan CAO ; Xiaolan CUI ; Jing SUN ; Shanshan GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):48-53
ObjectiveTo construct an animal model of respiratory syncytial virus(RSV)-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect (CPE), and 50% tissue culture infective dose(TCID50) was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group, the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor (IGF1R) mice was evaluated by measuring organ indices, peripheral blood lymphocyte percentages, pulmonary pathology and imaging, and pulmonary viral load. Additionally, ten BALB/c mice served as normal group, and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group, ribavirin group (82.5 mg·kg-¹·d-¹), and high and low dose groups of Lianhua Qingwen (3.3 mg·kg-¹·d-¹ , 1.65 mg·kg-¹·d-¹), with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention, and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group, large solid and diffuse ground-glass shadows were seen, and the lung volume was significantly increased (P<0.01). The lung index was significantly increased (P<0.01), and both the spleen index and thymus index were significantly decreased (P<0.01). The percentages of CD3+ and CD4+T cells were significantly decreased (P<0.05), and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue, which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached, with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV, the expression of viral nucleic acids in the lung tissue of the mice was significantly increased, with significant differences compared with the normal group (P<0.01). The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced, with significant differences compared with the normal group (P<0.01). ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC, and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed, which is suitable for the evaluation of anti-RSV drugs.
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.Three-dimensional classification and clinical treatment of posterior cruciate ligament tibial avulsion fracture based on CT.
Guang-Kai REN ; Yu-Hang TIAN ; Ming-Yu CUI ; Bao-Ming YUAN ; Yan-Bing WANG ; Chuan-Gang PENG ; Ming LI ; Dan-Kai WU
China Journal of Orthopaedics and Traumatology 2025;38(4):389-395
OBJECTIVE:
A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study.
METHODS:
From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test.
RESULTS:
A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency.
CONCLUSION
The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans
;
Male
;
Female
;
Posterior Cruciate Ligament/surgery*
;
Adult
;
Tibial Fractures/classification*
;
Tomography, X-Ray Computed
;
Middle Aged
;
Retrospective Studies
;
Fractures, Avulsion/classification*
;
Imaging, Three-Dimensional
;
Young Adult
10.Five new meroterpenoids from Rhododendron anthopogonoides and their anti-inflammatory activity.
Mengtian LI ; Norbu KELSANG ; Yongqin ZHAO ; Wensen LI ; Feng ZHOU ; PEMA ; Lu CUI ; Xianjie BAO ; Qian WANG ; Xin FENG ; Minghua YANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):881-887
Five meroterpenoids, rhodonoids K-M (1-2), daurichromene E (3), and grifolins A-B (4-5), together with seven known compounds (6-12), were isolated from Rhododendron anthopogonoides. The chemical structures of these compounds were elucidated through comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) data. Their absolute configurations were determined by comparing experimental electronic circular dichroism (ECD) spectra with computed values. Notably, compounds 1 and 3 demonstrated significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. These compounds markedly suppressed the mRNA expressions of inflammatory factors, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) while also down-regulating the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).
Mice
;
Rhododendron/chemistry*
;
Animals
;
Anti-Inflammatory Agents/isolation & purification*
;
RAW 264.7 Cells
;
Terpenes/isolation & purification*
;
Molecular Structure
;
Tumor Necrosis Factor-alpha/immunology*
;
Cyclooxygenase 2/immunology*
;
Nitric Oxide Synthase Type II/immunology*
;
Macrophages/immunology*
;
Interleukin-6/immunology*
;
Lipopolysaccharides
;
Interleukin-1beta/immunology*

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