Artificial intelligence technologies, particularly large language models and generative artificial intelligence, which have advanced rapidly in recent years, are profoundly reshaping the technological landscape of innovative drug discovery and development. This article systematically reviews representative achievements made by Chinese researchers in AI-assisted drug design from 2022 to 2025. These advances cover multiple key stages, including target discovery, virtual screening, molecular generation, drug property prediction, synthetic route planning, and database construction. The review highlights China’s rapid progress in achieving core technological breakthroughs and translating artificial intelligence technologies into practical applications in drug discovery and development.

Acupuncture treatment of chronic pain combined with depression (CPDC) is the result of a multi-target, multi-pathway approach. Acupuncture can treat CPDC by inhibiting the activation of glial cells, regulating the release of inflammatory mediators, regulating the expressions of neurotransmitters, changing the plasticity of neural synapses, regulating related epigenetic effects, regulating the microbiota-brain-gut axis, inhibiting nerve cell apoptosis, and antagonizing oxidative stress. The mechanism of its effect mainly involves anti-inflammatory related signaling pathways, regulation of neural synapse-related signaling pathways, and exerts its therapeutic effect through hippocampus, cerebral cortex, and amygdala.

Objective To observe the effects of wheat grain moxibustion on the hippocampal ERK/CREB-BDNF/TrkB signaling pathway and neurotransmitters in rats with perimenopausal depressive disorder(PDD);To explore its mechanism in treating PDD.Methods Totally 24 female SD rats were randomly divided into sham-operation group,model group,Western medicine group and wheat grain moxibustion group,with 6 rats in each group.The PDD rat model was established by bilateral ovariectomy and chronic unpredictable mild stress.The wheat grain moxibustion group received moxibustion at the"Zhongwan","Xiawan","Qihai","Guanyuan"acupoints,with a conical moxa cone for intervention,6 cones per acupoint;the Western medicine group was given fluoxetine hydrochloride solution 1.8 mg/kg by gavage,once a day,for consecutive 21 d.Before and after modeling and after intervention,the body mass,sucrose water preference rate and immobility time in the forced swimming test of the rats were recorded;Transmission electron microscopy was used to observe the synaptic structure in hippocampal tissue;ELISA was used to detect the expressions of 5-HT,GABA and Glu in hippocampal tissue;Western blot was used to detect the expressions of ERK,p-ERK,CREB,p-CREB,BDNF and TrkB proteins in hippocampal tissue.Results Compared with the sham-operation group,the body mass and sucrose water preference rate of the model group decreased,and the immobility time in the forced swimming test was prolonged(P<0.01);the number of synaptic vesicles in hippocampus decreased,the thickness of the postsynaptic density decreased,the aggregation of transduction-related proteins decreased,the synaptic cleft increased;the contents of 5-HT and GABA in hippocampal tissue decreased,the content of Glu increased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins decreased(P<0.01).Compared with the model group,the body mass and sucrose water preference rate of the rats in Western medicine group and wheat grain moxibustion group increased,and the immobility time in the forced swimming test was shortened(P<0.01);the area of the postsynaptic density in the hippocampus increased,the synaptic cleft reduced,the contents of 5-HT and GABA in hippocampal tissue increased,the content of Glu decreased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins increased(P<0.01).Conclusion Wheat grain moxibustion can effectively alleviate depressive-like behavior in PDD rats,and its mechanism may be related to regulating neurotransmitter expressions and mediating the ERK/CREB-BDNF/TrkB signaling pathway,thereby regulating hippocampal neuroplasticity.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Objective To observe the effects of wheat grain moxibustion on the hippocampal ERK/CREB-BDNF/TrkB signaling pathway and neurotransmitters in rats with perimenopausal depressive disorder(PDD);To explore its mechanism in treating PDD.Methods Totally 24 female SD rats were randomly divided into sham-operation group,model group,Western medicine group and wheat grain moxibustion group,with 6 rats in each group.The PDD rat model was established by bilateral ovariectomy and chronic unpredictable mild stress.The wheat grain moxibustion group received moxibustion at the"Zhongwan","Xiawan","Qihai","Guanyuan"acupoints,with a conical moxa cone for intervention,6 cones per acupoint;the Western medicine group was given fluoxetine hydrochloride solution 1.8 mg/kg by gavage,once a day,for consecutive 21 d.Before and after modeling and after intervention,the body mass,sucrose water preference rate and immobility time in the forced swimming test of the rats were recorded;Transmission electron microscopy was used to observe the synaptic structure in hippocampal tissue;ELISA was used to detect the expressions of 5-HT,GABA and Glu in hippocampal tissue;Western blot was used to detect the expressions of ERK,p-ERK,CREB,p-CREB,BDNF and TrkB proteins in hippocampal tissue.Results Compared with the sham-operation group,the body mass and sucrose water preference rate of the model group decreased,and the immobility time in the forced swimming test was prolonged(P<0.01);the number of synaptic vesicles in hippocampus decreased,the thickness of the postsynaptic density decreased,the aggregation of transduction-related proteins decreased,the synaptic cleft increased;the contents of 5-HT and GABA in hippocampal tissue decreased,the content of Glu increased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins decreased(P<0.01).Compared with the model group,the body mass and sucrose water preference rate of the rats in Western medicine group and wheat grain moxibustion group increased,and the immobility time in the forced swimming test was shortened(P<0.01);the area of the postsynaptic density in the hippocampus increased,the synaptic cleft reduced,the contents of 5-HT and GABA in hippocampal tissue increased,the content of Glu decreased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins increased(P<0.01).Conclusion Wheat grain moxibustion can effectively alleviate depressive-like behavior in PDD rats,and its mechanism may be related to regulating neurotransmitter expressions and mediating the ERK/CREB-BDNF/TrkB signaling pathway,thereby regulating hippocampal neuroplasticity.

Objective To observe the effects of wheat grain moxibustion for"Huantiao"on sciatic nerve function,pathological morphology of sciatic nerve stem and expressions of TLR4/MyD88/NF-κB signaling pathway expression in spinal cord tissue of rats with sciatic nerve injury(SNI);To explore the possible mechanism of wheat grain moxibustion for the treatment of SNI.Methods Totally 24 SD male rats were randomly divided into blank group,sham-operation group,model group and wheat grain moxibustion group,with 6 rats in each group.The model group and the wheat grain moxibustion group used a rat model with sciatic nerve clamping injury.From the 7th day after modeling,the rats were treated with moxibustion on the affected side of"Huantiao"for 6 strokes each time,once a day,for consecutive 10 days.The sciatic nerve function index(SFI)of rats on the 7th day after modeling and after intervention were observed,mechanical withdraw threshold(MWT)in rats were measured using a fiber optic pain gauge,ELISA was used to detect NO and iNOS content in spinal cord tissue,HE staining was used to observe the morphology of sciatic nerve stem,the expression of TLR4,NF-κBp65,p-NF-κBp65,MyD88,IκBα and p-IκBα in spinal cord tissue were detected by Western blot.Results Compared with the sham-operation group,the SFI and MWT of the rats in the model group significantly decreased(P<0.01),the arrangement of nerve fibers in sciatic nerve stem was disordered,with a significant increase in the number of Schwann cells and a large number of vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα protein in spinal cord tissue significantly increased(P<0.01).Compared with the model group,the SFI and MWT of the rats in the wheat grain moxibustion group increased significantly(P<0.01),the damage of sciatic nerve stem was reduced,with orderly cell arrangement,a decrease in the number of Schwann cells,and a decrease in axonal demyelination and cellular vacuolar degeneration,the content of NO,iNOS and the expression of TLR4,p-NF-κBp65,MyD88,p-IκBα in spinal cord tissue significantly decreased(P<0.05).Conclusion Wheat grain moxibustion for"Huantiao"can down-regulate TLR4,p-NF-κBp65,MyD88 and p-IκBα protein expressions in spinal cord tissue of SNI rats,reduce the secretion of NO and iNOS,thereby relieve pain and damaged nerve tissue inflammation response.

Objective To observe the effects of electroacupuncture(EA)at"Hegu"and"Taichong"on the expressions of cytochrome C(Cyt-C)and Caspase-9 in the hippocampus of rats with chronic pain and depression comorbidity(CPDC);To explore its potential mechanism for the treatment of CPDC.Methods A total of 60 SD rats were randomly divided into sham-operation group,model group,medication group and EA group,with 15 rats in each group.The CPDC model was induced by twice injection of complete Freund's adjuvant into the plantar of the left hind paw.EA group was applied to bilateral"Hegu"and"Taichong"for 20 min,the medication group were treated with duloxetine suspension 10 mg/kg by gavage for 14 days.The mechanical paw withdrawal threshold and thermal withdrawal latency were measured on day 7,14,21 and 28 after the first injection,tail suspension test and sucrose preference test were performed on day 14 and 28,Nissl staining was used to observe hippocampal neurons and the number of Nissl body,the protein expressions of Cyt-C and Caspase-9 in hippocampal tissue were detected by Western blot and immunohistochemistry.Results Compared with the sham-operation group,the mechanical paw withdrawal threshold and thermal withdrawal latency of the model group significantly decreased(P<0.01),the tail suspension immobility time increased(P<0.01),the percentage of sucrose preference decreased(P<0.01),the neurons were thinly arranged,the neurons were damaged and lost,and the number of Nissl body were less(P<0.01),the apoptotic rate of hippocampal neurons increased(P<0.01),the expression of Cyt-C,Caspase-9 and cleaved-Caspase-9/Caspase-9 ratio in hippocampal tissue increased(P<0.01).Compared with the model group,the mechanical paw withdrawal threshold and thermal withdrawal latency of the EA group and medication group significantly increased(P<0.01),the tail suspension immobility time decreased(P<0.01),the percentage of sucrose preference increased(P<0.01),the loss of neurons in hippocampus was reduced,the cells were arranged neatly,and the nucleoli were clear,the number of Nissl body increased(P<0.01),the apoptotic rate of hippocampal neurons decreased(P<0.01),and the expression of Cyt-C,Caspase-9 and cleaved-Caspase-9/Caspase-9 ratio in hippocampal tissue decreased(P<0.01).Conclusion EA at"Hegu"and"Taichong"can alleviate pain and depression in CPDC rats,which may be related to inhibiting the expressions of Cyt-C and Caspase-9 in hippocampal tissue and inhibiting the apoptosis of hippocampal neurons,thus playing a neuroprotective effect.

Objective:To investigate the effect of dihydroartemisinin (DHA) and gasdermin E(GSDME) on the proliferation, metastasis and pyroptosis of laryngeal cancer cells as well as its related mechanisms.Methods:Human laryngeal squamous cell cancer Hep-2 cells were taken and divided into 4 groups: the blank group (untreated Hep-2 cells), DHA group (Hep-2 cells treated with 50 μmol/L DHA), GSDME-siRNA group (Hep-2 cells transfected with GSDME-siRNA), and DHA+GSDME-siRNA group (Hep-2 cells treated with 50 μmol/L DHA and transfected with GSDME-siRNA). Methyl thiazolyl tetrazolium (MTT) method was used to detect the effect of DHA on the proliferation ability of Hep-2 cells, and the cell proliferation inhibition rate and half inhibitory concentration ( IC50) were calculated. Flow cytometry was used to detect the pyroptosis rate, Transwell assay was used to detect cell invasion ability and Western blot was used to detect the relative expression levels of GSDME, caspase-3, hexokinase Ⅱ (HK-Ⅱ), cyclophilin D, and voltage-dependent anion channel (VDAC) proteins. Results:The cell proliferation inhibition rates of Hep-2 cells treated with 10, 20, 40, 80, 160 μmol/L DHA for 48 h were higher than those treated with the corresponding concentration for 24 h (all P < 0.05). The IC50 values of Hep-2 cells treated by DHA for 24 h and 48 h were 57.20 μmol/L and 43.50 μmol/L, respectively, and thus 50 μmol/L DHA was selected for subsequent experiments. The pyroptosis rate was (6.5±0.8)%, (22.7±2.5)%, (3.1±0.6)% and (7.0±1.0)%, respectively in the blank group, DHA group, GSDME-siRNA group, and DHA+GSDME-siRNA group, and the difference was statistically significant ( F = 221.20, P < 0.05). The number of invasive cells was (153±14), (95±10), (205±16), and (148±16), respectively in the blank group, DHA group, GSDME-siRNA group, and DHA+GSDME-siRNA group, and the difference was statistically significant ( F = 56.89, P < 0.05). The results of Western blot showed that the relative expression levels of GSDME and caspase-3 in DHA group were higher than those in the blank group (both P < 0.05); the relative expression levels of GSDME and caspase-3 in GSDME-siRNA group were lower than those in DHA group (both P < 0.05); the relative expression levels of GSDME and caspase-3 in DHA+GSDME-siRNA group were higher than those in GSDME-siRNA group (both P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in DHA group were lower than those in the blank group (all P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in GSDME-siRNA group were higher than those in DHA group (all P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in DHA+GSDME-siRNA group were lower than those in GSDME-siRNA group (all P < 0.05). Conclusions:Dihydroartemisinin can increase the pyroptosis of laryngeal cancer cells and reduce cell proliferation and metastasis ability. The mechanism may be related to the inhibition of mitochondrial HK-Ⅱ expression.

Objective To observe the effects of plantar injection of complete Freund's adjuvant(CFA)on pain-depressive behavior and changes in hippocampal monoamine neurotransmitters in rats to establish an animal model of related comorbidity.Methods Sixteen male,8-week-old,SPF-grade healthy SD rats were randomly divided into model and control groups with eight rats in each group.In the model group,rats were anesthetized and injected with 100 μL CFA in the left hind paw to induce the comorbid chronic inflammatory pain and depression model.In the control group,rats were injected with the same volume of saline.Pain thresholds were measured using the Von Frey hair and thermal radiation instrument,and depression-like behaviors were assessed using the open field test(OFT),tail suspension test(TST),and forced swim test(FST).Enzyme-linked immunosorbent assays were used to measure 5-hydroxytryptamine(5-HT),dopamine(DA),and norepinephrine(NE)in rat hippocampal tissue.Histological changes in the hippocampal area were observed by hematoxylin-eosin(HE)staining.Results Compared with the control group,the mechanical withdrawal threshold and thermal withdrawal latency in the model group were significantly decreased at 3,7,and 14 days(P<0.01).The total distance in the OFT was significantly reduced at 7 and 14 days(P<0.01),and the time spent in the center zone was significantly decreased at 14 days(P<0.01).Immobility time in the TST was significantly increased at 14 days(P<0.01),and the immobility time in the FST was significantly increased at 7 and 14 days(P<0.05,P<0.01).5-HT,DA,and NE contents in hippocampal tissue of the model group rats were significantly reduced compared with those in the control group(P<0.01),and hippocampal tissue in the model group showed pathological changes,including irregular neuronal shapes,loose and disordered arrangement,increased intercellular space,some unclear cell nuclei,and some neuronal contraction and apoptosis.Conclusions Injection of 100 μL CFA into the footpad causes pain hypersensitivity,depression-like behavior,significant reductions in monoaminergic neurotransmitters in the hippocampus,and histological changes in the hippocampus,effectively simulating the manifestations of comorbid pain and depression,and is an experimental model to study the pathological mechanisms of comorbid chronic inflammatory pain and depression.