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

This paper summarizes Li Fei's academic insights and clinical experience in treating intractable facial paralysis.Li Fei posits that prolonged illness inevitably leads to deficiency and stasis,and thus,the treatment of intractable facial paralysis should first focus on identifying the etiology and syndrome differentiation,resolving stasis and unblocking stagnation,and regulating qi and blood,with particular emphasis on the relaxation of the meridian sinew system.The meridian sinew system,affiliated with the meridian and collateral,serves as the framework through which qi and blood nourish muscles,tendons,and joints,playing a crucial role in facial paralysis treatment.Guided by the theory of the meridian sinew system,Li Fei employs syndrome-based treatment,integrating the anatomy of facial expression muscles.His approach includes needle-knife therapy to release adhesions and break stasis,acupuncture to harmonize qi and blood,and intradermal needle therapy for sustained stimulation.Through these methods,the meridian sinew system is relaxed,qi and blood are regulated,and facial muscles are nourished,leading to gradual recovery from facial paralysis.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

Objective:To investigate the neuroprotective effect of hesperidin combined with enriched environment on ferroptosis in collagenase-induced intracerebral hemorrhage(ICH) mouse model as well as the ferroptosis mechanism.Methods:ICH model was established by injecting collagenase Ⅶ into caudate putamen nucleus. Ninty C57BL/6J mice were randomly divided into 6 groups according to a random number table: sham group, intracerebral hemorrhage group, enriched environment group, hesperidin group, enriched environment and hesperidin group (combination group), and combination group + Nrf2 specific inhibitor ML385 (inhibitor group), with 15 mice in each group. The mice in inhibitor group, intracerebral hemorrhage group, enriched environment group, hesperidin group and combination group were injected with 0.5 μL collagenase type Ⅶ solution (0.075 U/μL, dissolved with 0.9% NaCl solutin) for ICH modeling, and the mice in sham group were injected with 0.9% normal saline. The hesperidin group, combination group, and inhibitor group were given hesperidin solution (dissolved in 0.5% carboxymethyl cellulose sodium) by gavage within 6 hours after the modeling surgery. The sham group, intracerebral hemorrhage group, and enriched environment group were given equal volumes of 0.5% carboxymethyl cellulose sodium solution by gavage. The inhibitor group was intraperitoneally injected with Nrf2 specific inhibitor ML385 (30 mg/kg, dissolved in 5% DMSO), while the other groups were intraperitoneally injected with an equal volume of 5% DMSO. Both gastric perfusion and intraperitoneal injection were completed within 6 hours after the end of modeling operation, once a day for 14 days. After the postoperative recovery of the mice, the enriched environment group, combination group, and inhibitor group were placed in enriched environment cages, while the sham group, intracerebral hemorrhage group, and hesperidin group were placed in regular cages. After all intervention were completed, all mice were evaluated using the modified neurological severity score (mNSS). Then the mice were subjected to brain water content detection, Prussian blue staining, ELISA detection of changes in malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase 4 (Gpx4), PCR and Western blot detection of nuclear factor E2 related factor 2 (Nrf2) and Gpx4 at the mRNA level and protein level. The GraphPad Prism 9 software was used for statistical analysis. ANOVA was used for multi-group comparison, and Tukey test was used for multiple comparisons.Results:(1) There was a statistically significant difference in mNSS scores among the 6 groups ( F=66.35, P<0.001). The mNSS score of the intracerebral hemorrhage group(8.00±1.46) was higher than that of the sham group(0.86±0.83)( P<0.05). The mNSS scores of the enriched environment group (6.47±1.13) and hesperidin group (6.13±1.25) were lower than that of the intracerebral hemorrhage group, but higher than that of the combination group (4.53±1.30)(all P<0.05). (2) There was a statistically significant difference in the percentage of brain water content among the 6 groups ( F=33.29, P<0.001). The percentage of brain water content in the intracerebral hemorrhage group was higher than that in the sham group.The percentage of brain water content in the enriched environment group and hesperidin group were lower than that in the intracerebral hemorrhage group, but higher than that in the combination group (all P<0.05). (3) The result of Prussian blue staining showed that iron deposition in the intracerebral hemorrhage group was higher than that in the sham group, while the iron depositions in the enriched environment group and hesperidin groups were lower than that in the intracerebral hemorrhage group, but higher than that in the combination group(all P<0.05). (4) There were statistically significant differences in the expression levels of Nrf2 and Gpx4 mRNA and protein among the 6 groups ( F=27.73, 31.24, 26.79, 13.79, all P<0.001). The mRNA and protein levels of Nrf2 and Gpx4 in the combination group were higher than those in the enriched environment group, hesperidin group, but higher than those in the inhibitor group(all P<0.05). (5) The results of ELISA showed that the levels of MDA, Gpx4, ROS, and SOD in the brain tissues of 6 groups were statistically significant ( F=111.20, 21.53, 29.45, 22.75, all P<0.001). Among them, the MDA and ROS in the combination group ((14.05±0.57) nmol/mL, (75.46±3.40) ng/mL) were lower than those in the enriched environment group ((18.17±2.51) nmol/mL, (97.23±3.43) ng/mL), hesperidin group ((17.24±0.68) nmol/mL, (90.02±9.46) ng/mL) and the inhibitor group ((17.08±0.64) nmol/mL, (101.07±3.38) ng/mL), while Gpx4 and SOD ((340.40±31.21) pg/mL, (62.55±2.81) ng/mL) were higher than those in the enriched environment group ((267.81±27.17) pg/mL, (50.47±8.38) ng/mL), hesperidin group ((271.55±34.36) pg/mL, (50.55±8.19) ng/mL) and the inhibitor group ((235.65±72.54)pg/mL, (52.67±3.56)ng/mL)(all P<0.05). Conclusion:Enriched environment and hesperidin can inhibit ferroptosis after ICH by activating the Nrf2/GPX4 pathway, exerting neuroprotective effects on ICH mouse models, and the combined treatment of the enriched environment and hesperidin has a more significant effect.

Aim To investigate the effect of Toddalia asiatica(TA)on bone destruction in rheumatoid ar-thritis(RA)and its possible mechanism by network pharmacology and in vitro experiments.Methods The active components and targets of TA against RA bone damage were analyzed by network pharmacology.Mo-lecular docking was performed by using AutoDock and PyMOL software pairs.MC3T3-e1 cells were cultured in vitro,and the effect of Toddalia asiatica alcohol ex-tract(TAAE)on cell viability was detected by CCK-8,and appropriate drug concentration and intervention time were screened.The osteoblast model was induced by osteogenic induction medium,and the osteogenic differentiation was detected by ALP staining,activity detection and alizarin red staining.The expression of pathway-related proteins Wnt3a and β-catenin was de-tected by Western blot,and the pathway inhibitor DKK-1 was used to further verify whether TAAE regulated osteoblast differentiation through the Wnt/β-catenin signaling pathway.Results A total of 158 anti-RA bone destruction targets and 56 core targets were se-lected.The enrichment of KEGG signaling pathway mainly included cancer pathway,phosphatidylinositol 3-kinase/protein kinase B signaling pathway and cAMP signaling pathway.The results of CCK-8 showed that 1 g·L-1 TAAE could significantly improve cell survival rate.The results of ALP staining and ALP activity de-tection showed that TAAE could significantly increase the staining positive rate and ALP activity of cells in-duced by osteogenic induction medium.Western blot showed that TAAE could increase the expression of Wnt3a and β-catenin.The expression of these proteins decreased after DKK-1 inhibitors were used.Conclu-sion TAAE can regulate osteoblast differentiation through Wnt/β-catenin signaling pathway to treat os-teodestruction in rheumatoid arthritis.

Objective To observe the effects of modified Poge Jiuxin decoction combined with acupuncture in the treatment of septic cardiomyopathy(SIC),and explore its possible mechanism.Methods Totally 72 patients with SIC admitted to Chengdu First People's Hospital from January 2022 to June 2023 were enrolled.The patients were divided into control group and treatment group according to random number table method,with 36 cases in each group.Patients in control group received basic treatment for SIC.On this basis,the treatment group was administrated with modified Poge Jiuxin decoction[includes Prepared Aconite 30 g(earlier decocted),Red Ginseng 30 g(another stew),Cornel Meat 60 g,Dried Ginger 30 g,Raw Keel 30 g(earlier decocted),Raw Oyster 30 g(earlier decocted),Magnet 30 g(earlier decocted),Poria Cocos 90 g,Plantain Seeds 30 g(in bag),Roasted Licorice 60 g,Musk 0.5 g(artificial)],one dose a day,100 mL in 3 meals a day.Acupuncture at bilateral Zusanli,Guangyuan,Neiguan,Sanyinjiao and Qihai points,twice a day.Both groups were treated for 7 days.The changes of C-reactive protein(CRP),procalcitonin(PCT),cardiac tropomin I(cTnI),N-terminal pro-B type natriuretic peptide(NT-proBNP)and lactic acid(Lac)were observed before and after treatment,acute physiology and chronic health evaluationⅡ(APACHEⅡ)and sequential organ failure assessment(SOFA)were calculated,left ventricular ejection fraction(LVEF),left ventricle fractional shortening(LVFS),and mitral orifice early/late diastolic blood flow velocity ratio(E/A ratio)were measured with echocardiography,the heart rate(HR),mean arterial pressure(MAP),mechanical ventilation time,vasoactive drug use time,in the intensive care unit(ICU)stay time,the incidence of multiple organ dysfunction syndrome(MODS)and 28-day mortality were recorded.Results After treatment,the indexes of inflammation(CRP,PCT),myocardial markers(cTnI,NT-proBNP),hemodynamics and perfusion(HR,Lac),illness severity score(APACHEⅡ,SOFA)and the 28-day mortality in the two groups were significantly reduced,while LVEF and MAP were significantly increased compared to before treatment.The improvement of various indexes in the treatment group were better than those in the control group[CRP(mg/L):22.18±9.46 vs.68.45±13.46,PCT(μg/L):1.16±0.59 vs.4.35±1.28,LVEF:0.48±0.06 vs.0.41±0.05,cTnI(μg/L):0.60±0.14 vs.0.98±0.30,NT-proBNP(ng/L):204.35±26.54 vs.240.12±56.12,HR(bmp):88.75±10.05 vs.98.57±10.56,MAP(mmHg,1 mmHg≈0.133 kPa):82.10±5.08 vs.73.46±3.55,Lac(mmol/L):0.75±0.28 vs.1.60±0.36,APACHEⅡscore:10.46±1.80 vs.15.50±2.16,SOFA score:2.60±1.24 vs.6.76±1.60,all P<0.05].After treatment,LVFS and E/A ratio in the two groups increased significantly compared to those before treatment,however,there was no significant difference between the treatment group and the control group after treatment[LVFS:(25.12±3.46)%vs.(22.61±3.88)%,E/A ratio:1.16±0.46 vs.0.96±0.32,both P>0.05].The vasoactive drug use time and ICU stay time were shortened in the treatment group than those in the control group[vasoactive drug use time(days):9.62±3.05 vs.10.48±3.40,ICU stay time(days):12.51±2.04 vs.13.72±1.14,both P<0.05],the incidence of MODS and the 28-day mortality were lower than those of the control group[38.89%(14/36)vs.52.77%(9/36),44.44%(16/36)vs.47.22%(17/36)],but there were no statistical differences(both P>0.05).Conclusion Modified Poge Jiuxin decoction combined with acupuncture can effectively improve the prognosis of patients with SIC,and its mechanism may be related to inhibition of inflammatory reaction and improvement of cardiac function.

Objective To investigate clinical characteristics and the risk factors of sepsis-induced myocardial dysfunction(SIMD),and to provide evidence for the diagnosis,treatment and prevention of SIMD.Methods The clinical data of 284 patients with sepsis(≥18 years old)admitted to the department of critical care medicine of Chengdu Integrated Traditional Chinese Medicine&Western Medicine Hospital/Chengdu First People's Hospital from January 2020 to December 2022 were retrospectively analyzed.This includes gender,age,chronic underlying diseases,the mean arterial pressure(MAP),heart rate(HR),laboratory test results,disease severity score,the proportion of requiring mechanical ventilation,vasoactive drugs treatment and renal replacement therapy,length of intensive care medicine(ICU)stay and the 28-day mortality.Patients were divided into SIMD group and non-SIMD group according to the occurrence of SIMD,allowing for an analysis of the clinical characteristics of two groups of patients.Univariate and multivariate Logistic regression analyses were used to identify the risk factors of SIMD,and receiver operator characteristic curve(ROC curve)were plotted to analyze the predictive value of each risk factor for the occurrence of SIMD.Results A total of 284 septic patients were included,including 136 cases(47.89％)in the SIMD group and 148 cases(52.11％)in the non-SIMD group.Compared with the non-SIMD group,the levels of age,N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac tropomin I(cTnI),lactic acid(Lac)at admission to ICU,the proportion of vasoactive drugs treatment,acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)and sequential organ failure assessment(SOFA)in the SIMD group were significantly higher than those in the non-SIMD group[age(years):75.92±2.35 vs.55.02±1.68,NT-proBNP(ng/L):3 037.00±544.50 vs.2 493.92±630.21,cTnI(μg/L):0.12±0.07 vs.0.06±0.03,Lac in ICU(mmol/L):4.46±1.21 vs.2.98±1.02,the proportion of vasoactive drugs treatment:40.44％(55/136)vs.21.62％(32/148),APACHEⅡ score:24.25±1.02 vs.20.95±0.85,SOFA score:7.41±4.69 vs.6.21±2.81,all P<0.05],but the 24-hour Lac clearance rate of the SIMD group was significantly lower than that of the non-SIMD group[(13.80±7.01)％vs.(25.41±8.90)％,P<0.05].Multivariate Logistic regression analysis showed that age≥75 years,24-hour Lac clearance rate and NT-proBNP≥3 000 ng/L were the independent factors of SIMD in patients with sepsis[odds ratio(OR)and 95％confidence interval(95％CI)were 5.990(2.143-16.742),0.348(0.155-0.786)and 2.708(1.093-6.711),P values were 0.001,0.011 and 0.031].ROC curve analysis showed that age,24-hour Lac clearance rate,NT-proBNP had predictive value for the development of SIMD[area under the curve(AUC)were 0.637,0.811,0.743,95％CI were 0.573-0.701,0.761-0.860,0.687-0.800,all P<0.05].Conclusions SIMD occurs more frequently in patients with sepsis.Increased age,elevated NT-proBNP,and reduced 24-hour Lac clearance rate are independent risk factors of SIMD,warranting clinical attention.