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.

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.

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 7^th 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 1^st， 3^rd， 6^th， 8^th， and 10^th 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 10^th 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.

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.

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.

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 7^th 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 1^st， 3^rd， 6^th， 8^th， and 10^th 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 10^th 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.

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.

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.

OBJECTIVE: To explore the effectiveness of primary interventional revascularization combined with secondary perforator composite flap in the treatment of peripheral arterial disease (PAD) accompanied by soft tissue defects around the ankle. METHODS: Between January 2022 and January 2025, 12 patients with PAD and soft tissue defects around the ankle were admitted. Among them, there were 9 males and 3 females; their ages ranged from 52 to 82 years, with an average of 68.9 years. The causes of injury included 4 cases of traffic accident, 5 cases of falls, 1 case of falling from height, 1 case of foreign body puncture injury, and 1 case of electric shock injury. The infection duration ranged from 1 month to 35 years, with a median duration of 3.5 months. The wound size ranged from 5.5 cm×3.0 cm to 15.0 cm×9.0 cm. The ankle-brachial index (ABI) was 0.32±0.12. The visual analogue scale (VAS) score for pain was 3.3±0.5. Preoperative vascular stenosis assessment was performed in all patients, with primary intervention to dredge large and medium-sized arteries, followed by secondary repair of the wound using a perforator composite flap. The flap size ranged from 6.5 cm×4.0 cm to 16.0 cm×10.0 cm. The donor sites were sutured directly or repaired with skin grafts. After two stages of treatment, the effectiveness was evaluated by measuring ABI, observing flap survival and wound healing, assessing VAS scores, and American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: All 12 cases completed two stages of treatment; all patients were followed up after the second-stage treatment, with a follow-up period ranging from 7 to 28 months, with an average of 16.8 months. After the first-stage treatment, the skin temperature around the ankle was significantly higher than that before treatment, and the ABI increased to 0.71±0.07, with a significant difference ( t=9.918, P<0.001). After the second-stage treatment, the blisters on the distal end of the skin flap occurred in 3 cases. The flaps survived and the wounds healed, with a healing time ranging from 10 to 14 days (mean, 11.8 days). The incisions at the donor site healed by first intention, and the skin grafts survived. The VAS score was 0.5±0.5 at 3 weeks, which was significantly lower than that before treatment ( t=13.675, P<0.001). No infection recurrence occurred during follow-up. At 6 months after the second-stage treatment, the AOFAS score of the ankle joint ranged from 92 to 97, with an average of 94.7, all reaching excellent. CONCLUSION Interventional revascularization combined with perforator composite flap for staged treatment of PAD with ankle soft tissue defects can obtain good effectiveness, by unclogging the main blood vessels, improving lower limb blood supply, and improving the survival rate of the skin flap.
Humans ; Male ; Female ; Middle Aged ; Aged ; Peripheral Arterial Disease/surgery* ; Soft Tissue Injuries/surgery* ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Aged, 80 and over ; Ankle/blood supply* ; Treatment Outcome ; Ankle Brachial Index ; Skin Transplantation/methods*

Objective: To investigate the effects of usnic acid(UA) on proliferation, cell cycle, apoptosis and autophagy of lung cancer cells A549 and NCI-H358. Methods: The CCK-8 method was used to detect the inhibitory effect of UA on two kinds of lung cancer cells proliferation. Flow cytometry was used to detect the cell cycle arrest effect of UA on two types of lung cancer cells. The fluorescence amount of UA-induced reactive oxygen species(ROS) in two kinds of lung cancer cells were detected by DCFH-DA probe assay and flow cytometry. Western blot was used to detect the expression of apoptosis related proteins Bax, Caspase-3, Cleaved-Caspase-3, and autophagy related proteins LC3-Ⅰ and LC3-Ⅱ in two types of lung cancer cells after treatment with UA and UA+ROS inhibition. Results: (1) Usnic acid reduced the survival rates of two types of cells and had a stronger ability to inhibit the proliferation of A549 cells than NCI-H358 cells.(2) Usnic acid blocked A549 cells in the G0/G1phase, while NCI-H358 cells in the G2/M and S phases.(3) Usnic acid induced an increase in ROS content in two types of cells. Compared to A549, NCI-H358 cells showed a greater increase in ROS, and the ROS inhibitor reduced the intracellular ROS increase induced by UA.(4) Usnic acid induced high expression of apoptosis-related proteins Bax and Cleaved Caspase-3 and increased the ratio of autophagy-related proteins LC3-Ⅱ/LC3-Ⅰ in both lung adenocarcinoma cells, and its pro-apoptotic and autophagic effects were stronger in A549 than in NCI-H358. After ROS inhibition, the expression levels of Bax and Cleaved Caspase-3 and the LC3-Ⅱ/LC3-Ⅰ ratio of both lung adenocarcinoma cells decreased, and the decrease was greater in NCI-H358 cells. Conclusion Usnic acid inhibits the proliferation of lung cancer A549 and NCI-H358 cells, induces cell cycle arrest, and induces apoptosis and autophagy in cancer cells. The inhibitory and killing effect of UA on A549 cells is stronger than that on NCI-H358 cells. In this case, the induced cell ROS are involved in the action of UA in two types of lung cancer cells. In contrast to A549 cells,ROS might play a more significant role in mediating the apoptosis and autophagy induced by usnic acid in NCI-H358 cells.