OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective:To explore the effects of early electroacupuncture(EA)intervention on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway-related protein expression and oligodendrocytes in mice with amyotrophic lateral sclerosis(ALS),and uncover the potential molecular mechanisms underlying the improvement of motor function in ALS mice by early EA intervention.Methods:ALS mice carrying the SOD1G93A gene were randomly divided into a model group and an EA group,with 10 mice in each group;10 littermate mice with a negative SOD1G93A genotype served as the control group.In the EA group,Baihui(GV20),Tianzhu(BL10),and Tianshu(ST25)were selected with needles retained for 10 min,5 consecutive days per week,with 2 days of rest.One week constituted a course of treatment,and a total of 3 consecutive courses were performed.The other groups were grasped and fixed similarly,but without intervention.Motor function was assessed using the open field test(OFT)and Morris water maze(MWM).Subsequently,hematoxylin-eosin staining was used to observe neuron morphology in the M1 region of the cerebral cortex.Immunofluorescence was performed to detect the positive cell rate of TAR DNA-binding protein 43(TDP-43),and double immunofluorescence staining was used to observe the positive cell rate and cell states of ionized calcium-binding adaptor molecule 1(Iba-1)and myelin basic protein(MBP)in the M1 region of the cerebral cortex.Western blotting was used to detect the relative expression levels of TDP-43,tumor necrosis factor(TNF)-α,HMGB1,and TLR4 proteins.Results:Compared to the control group,the model group exhibited a reduced total movement distance in the OFT,and an increased escape latency,as well as fewer platform crossings in the MWM,with statistically significant differences(P<0.01).In the model group,the number of degenerated and necrotic neurons in the M1 region of the ALS mouse cerebral cortex increased,with significant nuclear shrinkage and cytoplasmic vacuolization;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex increased(P<0.01),and the relative expression level of TDP-43 protein in the cerebral cortex showed a significant increase(P<0.01);the Iba-1 positive cell percentage increased,while the MBP positive cell percentage decreased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins increased(P<0.05).Compared to the model group,the EA group showed an increased total movement distance(P<0.01),and a reduced escape latency,and more platform crossings in the MWM,with statistically significant differences(P<0.05).In the EA group,neurons showed improvement,with reduced degeneration and necrosis,and larger,clearer nuclei;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex decreased(P<0.05),and the relative expression level of TDP-43 protein also decreased(P<0.05);the percentage of Iba-1 positive cells in the M1 region of the cerebral cortex decreased,while the percentage of MBP positive cells increased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins decreased(P<0.05).Conclusion:EA intervention can suppress microglial activation,improve the state of oligodendrocytes,and reduce abnormal TDP-43 aggregation in the M1 region of the cerebral cortex in ALS model mice;its mechanism of action may be related to the HMGB1/TLR4 signaling pathway.

Objective:To observe the high-risk histopathological feature (HRF) and their correlation with prognosis in children with intraocular retinoblastoma (RB) in the intraocular stage after failed eyepreserving treatment and enucleation surgery.Methods:A single-center retrospective case study. From August 2018 to January 2023, 64 children (64 eyes) with advanced intraocular RB who were diagnosed in Department of Ophthalmology of Beijing Children's Hospital and underwent enucleation surgery after failed eye-preserving treatment were included in the study. The median follow-up time was 51 months. The gender of the children patients, the age of visit and enucleation, International Intraocular Retinoblastoma Classification (IIRC), the initial chemotherapy regimen (hereinafter referred to as "chemotherapy"), the time of enucleation surgery, pathological results, post-enucleation treatment methods and prognosis were collected. The Mann-Whitney U test was used for comparison between groups. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used for comparison between groups. Results:Among 64 cases and 64 eyes, 37 were male and 27 were female. The age of seeking medical treatment was 20 (11-31) months. The age at which the surgery was performed was 29 (16-40) months. The number of eyes in IIRC stage D and E was 16 and 48 respectively. The initial chemotherapy regimens simply applied (hereinafter referred to as "alone") intravenous systemic chemotherapy (IVC) and ophthalmic artery infusion chemotherapy (IAC) in 40 cases and 11 cases, 13 cases of IVC+IAC. All patients with positive HRF received systemic adjuvant chemotherapy after surgery. There were 37 eyes (57.8%, 37/64) positive for HRF. There was no statistically significant difference in the positive rate of HRF between children in IIRC stage D and stage E ( χ2=0.021, P=0.884). Among the 37 eyes with HRF, the numbers of eyes with extensive choroidal invasion, posterior lamina cribrosa optic nerve invasion, scleral invasion and optic nerve stump involvement were 17 (45.9%, 17/37), 16 (43.2%, 16/37), 3 (8.1%, 3/37) and 3 (8.1%, 3/37), respectively. During the follow-up period, there were 5 cases (7.8%, 5/64) of extraocular metastasis of the tumor and death, all of which were stage E and had HRF. Among them, the initial treatment plan was IAC for 4 cases, one case of IVC. The survival rates of children among the IVC, IAC or IVC+IAC regimens were 97.5% (39/40), 63.6% (7/11), and 100.0% (13/13), respectively. The comparison of survival rates among different chemotherapy regimens showed statistically significant differences ( χ2=14.233, P<0.001). The results of survival analysis showed that the cumulative survival rate of those with extensive choroidal invasion, posterior lamina cribrosa optic nerve infiltration, and those who received IAC was significantly lower than that of those without extensive choroidal invasion, posterior lamina cribrosa optic nerve infiltration, and those who received IVC+IAC and IVC ( P<0.05). Conclusions:Eye-preserving treatment for children with advanced intraocular RB may increase the positive rate of HRF and the risk of extraocular metastasis. The IVC+IAC eye-protecting treatment plan can improve the survival rate of children.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

Objective To observe the effects of electroacupuncture on RhoA/ROCK2 signaling pathway in cerebral cortex of mice with amyotrophic lateral sclerosis(ALS);To explore the mechanism of electroacupuncture in improving the motor function of ALS mice.Methods The male hSOD1G93A mice were divided into model group and electroacupuncture group,and wild-type male mice in the same litter were set as blank group,with 12 mice in each group.After the mice were 60 days old,"Baihui"and both side of"Tianzhu","Tianshu"were selected for electroacupuncture for 10 min per day,5 days of continuous treatment and 2 days off for 3 weeks.Rotating rod experiment and open field experiment were used to evaluate the motor function of mice,the damage of neurons in cerebral cortex was observed by Nissl staining,Western blot was used to detect the expressions of Tar DNA binding protein-43(TDP-43),tumor necrosis factor(TNF)-α,interleukin(IL)-1β,RhoA and ROCK2 protein in cerebral cortex.Immunofluorescence staining was used to detect the positive expressions of ion calcium binding adapter molecule 1(Iba-1)and glial fibrillary acidic protein(GFAP)in cerebral cortex.Results Compared with the blank group,the incubation period of rod turning and the total distance of open field movement in the model group were reduced(P<0.01),the neuron damage was obvious in the cerebral cortex,with Nissl body shrinkage and reduction in quantity(P<0.01),the relative expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 protein increased(P<0.01),and the positive expression of Iba-1 and GFAP increased(P<0.01).Compared with the model group,the incubation period of rod turning and the total distance of open field movement increased in electroacupuncture group(P<0.05),the damage of neuron in cerebral cortex was reduced,the number of Nissl bodies increased(P<0.05),the expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 decreased(P<0.05),and the positive expression of Iba-1 and GFAP reduced(P<0.05).Conclusion Electroacupuncture can improve motor function in ALS model mice,and the mechanism may be related to the inhibition of RhoA/ROCK2 signaling pathway activity and then relieve neuroinflammation.

OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

Objective To observe the effects of electroacupuncture on RhoA/ROCK2 signaling pathway in cerebral cortex of mice with amyotrophic lateral sclerosis(ALS);To explore the mechanism of electroacupuncture in improving the motor function of ALS mice.Methods The male hSOD1G93A mice were divided into model group and electroacupuncture group,and wild-type male mice in the same litter were set as blank group,with 12 mice in each group.After the mice were 60 days old,"Baihui"and both side of"Tianzhu","Tianshu"were selected for electroacupuncture for 10 min per day,5 days of continuous treatment and 2 days off for 3 weeks.Rotating rod experiment and open field experiment were used to evaluate the motor function of mice,the damage of neurons in cerebral cortex was observed by Nissl staining,Western blot was used to detect the expressions of Tar DNA binding protein-43(TDP-43),tumor necrosis factor(TNF)-α,interleukin(IL)-1β,RhoA and ROCK2 protein in cerebral cortex.Immunofluorescence staining was used to detect the positive expressions of ion calcium binding adapter molecule 1(Iba-1)and glial fibrillary acidic protein(GFAP)in cerebral cortex.Results Compared with the blank group,the incubation period of rod turning and the total distance of open field movement in the model group were reduced(P<0.01),the neuron damage was obvious in the cerebral cortex,with Nissl body shrinkage and reduction in quantity(P<0.01),the relative expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 protein increased(P<0.01),and the positive expression of Iba-1 and GFAP increased(P<0.01).Compared with the model group,the incubation period of rod turning and the total distance of open field movement increased in electroacupuncture group(P<0.05),the damage of neuron in cerebral cortex was reduced,the number of Nissl bodies increased(P<0.05),the expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 decreased(P<0.05),and the positive expression of Iba-1 and GFAP reduced(P<0.05).Conclusion Electroacupuncture can improve motor function in ALS model mice,and the mechanism may be related to the inhibition of RhoA/ROCK2 signaling pathway activity and then relieve neuroinflammation.

Objective:To explore the effects of early electroacupuncture(EA)intervention on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway-related protein expression and oligodendrocytes in mice with amyotrophic lateral sclerosis(ALS),and uncover the potential molecular mechanisms underlying the improvement of motor function in ALS mice by early EA intervention.Methods:ALS mice carrying the SOD1G93A gene were randomly divided into a model group and an EA group,with 10 mice in each group;10 littermate mice with a negative SOD1G93A genotype served as the control group.In the EA group,Baihui(GV20),Tianzhu(BL10),and Tianshu(ST25)were selected with needles retained for 10 min,5 consecutive days per week,with 2 days of rest.One week constituted a course of treatment,and a total of 3 consecutive courses were performed.The other groups were grasped and fixed similarly,but without intervention.Motor function was assessed using the open field test(OFT)and Morris water maze(MWM).Subsequently,hematoxylin-eosin staining was used to observe neuron morphology in the M1 region of the cerebral cortex.Immunofluorescence was performed to detect the positive cell rate of TAR DNA-binding protein 43(TDP-43),and double immunofluorescence staining was used to observe the positive cell rate and cell states of ionized calcium-binding adaptor molecule 1(Iba-1)and myelin basic protein(MBP)in the M1 region of the cerebral cortex.Western blotting was used to detect the relative expression levels of TDP-43,tumor necrosis factor(TNF)-α,HMGB1,and TLR4 proteins.Results:Compared to the control group,the model group exhibited a reduced total movement distance in the OFT,and an increased escape latency,as well as fewer platform crossings in the MWM,with statistically significant differences(P<0.01).In the model group,the number of degenerated and necrotic neurons in the M1 region of the ALS mouse cerebral cortex increased,with significant nuclear shrinkage and cytoplasmic vacuolization;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex increased(P<0.01),and the relative expression level of TDP-43 protein in the cerebral cortex showed a significant increase(P<0.01);the Iba-1 positive cell percentage increased,while the MBP positive cell percentage decreased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins increased(P<0.05).Compared to the model group,the EA group showed an increased total movement distance(P<0.01),and a reduced escape latency,and more platform crossings in the MWM,with statistically significant differences(P<0.05).In the EA group,neurons showed improvement,with reduced degeneration and necrosis,and larger,clearer nuclei;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex decreased(P<0.05),and the relative expression level of TDP-43 protein also decreased(P<0.05);the percentage of Iba-1 positive cells in the M1 region of the cerebral cortex decreased,while the percentage of MBP positive cells increased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins decreased(P<0.05).Conclusion:EA intervention can suppress microglial activation,improve the state of oligodendrocytes,and reduce abnormal TDP-43 aggregation in the M1 region of the cerebral cortex in ALS model mice;its mechanism of action may be related to the HMGB1/TLR4 signaling pathway.

Objective:To observe the effect of electroacupuncture(EA)on microglia and cortical excitability in hSOD1G93A mice and to explore the potential central mechanisms of EA intervention to improve motor func-tion in amyotrophic lateral sclerosis(ALS)mice.Method:The present study includes 2 parts.① Sixteen hSOD1G93A mice were randomly divided into model group and EA group(n=8 per group).Eight hSOD1G93A-negative mice were used as the blank group.The EA group was applied to the Baihui,bilateral Tianzhu and bilateral Tianshu acupoints(10 minutes/session,5 sessions/week,for 3 weeks).After 3 weeks of EA,hind limb functional neurologic score and open field test were used to evaluate the changes in motor function of mice.The concentrations of IL-1β and IL-6 were de-tected by ELISA.Immunofluorescence staining and flow cytometry were employed to observe the rate of Iba-1 positive cells and cell phenotypes in the cerebral cortex.②Twenty-one hSOD1G93A mice and seven wild-type mice were included.The Chemical genetic excitatory virus[rAAV-CaMKIIa-hM3D(Gq)-EGFP-WPRE-hGH poly A]was injected into the primary motor cortex(M1)area of the mice.After 21 days,four mice(3 SOD1G93A and 1 wild-type)were randomly selected for fluorescent microscopy to confirm viral expression.The remaining hSOD1G93A mice were randomly divided into 3 groups:model,EA group,and chemogenetic excitatory virus(intraperitoneal injection of clozapine-N-oxide[CNO])combined with EA group,with 6 mice per group.The rate of c-Fos positive cells in the cerebral cortex was observed by immunofluorescence.The open field experiment was used to evaluate the changes in motor function of mice.Result:Compared with the blank group,the model group showed significantly reduced total distance in the open-field test and increased neurologic scores(P＜0.01),elevated serum IL-1β and IL-6 levels,increased corti-cal Iba-1 and c-Fos expression(P＜0.01),and higher proportions of M1 and M2 microglia(P＜0.01,P＜0.05).Compared with the model group,the total distance of open field movement was prolonged and the neurologi-cal score decreased in the EA group(P＜0.01,P＜0.05).The contents of serum IL-1β and IL-6,the expression of Iba-1、c-Fos in cerebral cortex were decreased in the EA group(P＜0.01,P＜0.05),with an increased propor-tion of M2 microglia(P＜0.05);the rate of c-Fos positive cells decreased in the virus+EA group,and the total distance of open field movement was prolonged.Conclusion:EA intervention can improve motor function in ALS mice.The underlying mechanism may be re-lated to suppress the activity of microglia,reduce the expression of inflammatory cytokines and further to de-crease the excitability of M1 cortical neurons.

Objective:To observe the effect of electroacupuncture(EA)on microglia and cortical excitability in hSOD1G93A mice and to explore the potential central mechanisms of EA intervention to improve motor func-tion in amyotrophic lateral sclerosis(ALS)mice.Method:The present study includes 2 parts.① Sixteen hSOD1G93A mice were randomly divided into model group and EA group(n=8 per group).Eight hSOD1G93A-negative mice were used as the blank group.The EA group was applied to the Baihui,bilateral Tianzhu and bilateral Tianshu acupoints(10 minutes/session,5 sessions/week,for 3 weeks).After 3 weeks of EA,hind limb functional neurologic score and open field test were used to evaluate the changes in motor function of mice.The concentrations of IL-1β and IL-6 were de-tected by ELISA.Immunofluorescence staining and flow cytometry were employed to observe the rate of Iba-1 positive cells and cell phenotypes in the cerebral cortex.②Twenty-one hSOD1G93A mice and seven wild-type mice were included.The Chemical genetic excitatory virus[rAAV-CaMKIIa-hM3D(Gq)-EGFP-WPRE-hGH poly A]was injected into the primary motor cortex(M1)area of the mice.After 21 days,four mice(3 SOD1G93A and 1 wild-type)were randomly selected for fluorescent microscopy to confirm viral expression.The remaining hSOD1G93A mice were randomly divided into 3 groups:model,EA group,and chemogenetic excitatory virus(intraperitoneal injection of clozapine-N-oxide[CNO])combined with EA group,with 6 mice per group.The rate of c-Fos positive cells in the cerebral cortex was observed by immunofluorescence.The open field experiment was used to evaluate the changes in motor function of mice.Result:Compared with the blank group,the model group showed significantly reduced total distance in the open-field test and increased neurologic scores(P＜0.01),elevated serum IL-1β and IL-6 levels,increased corti-cal Iba-1 and c-Fos expression(P＜0.01),and higher proportions of M1 and M2 microglia(P＜0.01,P＜0.05).Compared with the model group,the total distance of open field movement was prolonged and the neurologi-cal score decreased in the EA group(P＜0.01,P＜0.05).The contents of serum IL-1β and IL-6,the expression of Iba-1、c-Fos in cerebral cortex were decreased in the EA group(P＜0.01,P＜0.05),with an increased propor-tion of M2 microglia(P＜0.05);the rate of c-Fos positive cells decreased in the virus+EA group,and the total distance of open field movement was prolonged.Conclusion:EA intervention can improve motor function in ALS mice.The underlying mechanism may be re-lated to suppress the activity of microglia,reduce the expression of inflammatory cytokines and further to de-crease the excitability of M1 cortical neurons.