Objective To investigate the protective effect and mechanism of heat acclimation(HA)on electromagnetic field(EMF)induced hippocampus neuron injury in mice.Methods Forty healthy BALB/c male mice(18～22 g,7 weeks old)were randomly divided into 4 groups(n=10):Control group(Con),HA group(34℃,30 d),EMF group(2 450 MHz,20 min/d,4 weeks)and HA+EMF group(HA preconditioning+EMF).Sucrose preference test was performed to evaluate sucrose preference levels of mice in each group.Tail suspension test and forced swimming test were utilized to observe the immobility time.Morris water maze test was conducted to determine the learning and memory capabilities.Pathological changes in the hippocampus were observed with HE staining.Immunohistochemical assay for Iba1(marker of microglia),CD68(marker of pro-inflammatory phenotype)and CD206(marker of anti-inflammatory phenotype)were used to detect the number and activation phenotype of microglia in the hippocampus.ELISA was applied to measure the levels of TNF-α,IL-1β,TGF-β and IL-10 in the hippocampus of each group.Western blotting was performed to determine the protein levels of HSP70 in the hippocampus.Results As compared with the Con group,the EMF group showed a decreased preference for sucrose(P<0.05),prolonged immobile time in the tail suspension test(P<0.01)as well as in the forced swimming test(P<0.01),extented escape latency on the 7th day(P<0.01),and a decreased time of crossing the platform(P<0.05).EMF exposure resulted in that the hippocampal neurons were in disordered arrangement,loose structure and irregular morphology,with swollen cytoplasm and condensed nuclei,swollen and more microglial cells in the hippocampus(P<0.01),and enhanced relative fluorescence intensity of CD68(P<0.01),but not in CD206 fluorescence intensity(P=0.885).All these findings suggested that activated microglia predominantly exhibited a pro-inflammatory M1 phenotype during this phase.In the hippocampus,the levels of TNF-α and IL-1β were significantly increased,while the levels of IL-10 and TGF-β were significantly decreased(P<0.01).HA treatment reversed the conditions induced by EMF exposure,including better preference for sucrose(P<0.01),shorten immobile time in tail suspension test(P<0.05)and forced swimming test(P<0.01),less escape latency on the 7th day(P<0.01),and improved hippocampal cell injuries.Compared with the Con group,there were more microglial cells in the hippocampus in the HA+EMF group,with increased relative fluorescence intensity of M2 phenotype marker CD206(P<0.01)and decreased CD68 fluorescence intensity(P<0.01).HA treatment also significantly decreased the expression of TNF-α and IL-1β levels(P<0.01),increased the expression of IL-10 and TGF-β(P<0.01),and elevated the protein level of HSP70(P<0.01)when compared with the EMF group.Conclusion HA may ameliorate EMF-induced hippocampus neurons injury in mice by altering the phenotype of activated microglia and inhibiting inflammatory responses.

Alcoholic liver disease(ALD), a major cause of chronic liver disease worldwide, poses a serious threat to human health. Despite the availability of various drugs for treating ALD, their efficacy is often uncertain, necessitating the search for new therapeutic approaches. Traditional Chinese medicine polysaccharides have garnered increasing attention in recent years due to their versatility, high efficiency, and low side effects, and they have demonstrated significant potential in preventing and treating ALD. Emerging studies have suggested that these polysaccharides exert their therapeutic effects through multiple mechanisms, including the inhibition of oxidative stress and the regulation of lipid metabolism, gut microbiota, and programmed cell death. This review summarizes the recent research progress in the pharmacological effects and regulatory mechanisms of traditional Chinese medicine polysaccharides in treating ALD, aiming to provide a scientific basis and theoretical support for their application in the prevention and treatment of ALD.
Humans ; Liver Diseases, Alcoholic/metabolism* ; Polysaccharides/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Oxidative Stress/drug effects* ; Medicine, Chinese Traditional ; Gastrointestinal Microbiome/drug effects* ; Lipid Metabolism/drug effects*

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Objective To investigate the clinical effect of LUO's Nephropathy Recipe Ⅲ(composed of Sargassum,Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Rehmanniae Radix Praeparata,calcined Ostreae Concha,Houttuyniae Herba,Schizonepetae Spica,etc.)combined with conventional western medicine in treating stage 3-5 non-dialysis chronic kidney disease(CKD)of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type.Methods A total of 180 patients with stage 3-5 non-dialysis CKD of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type were randomly divided into observation group and control group,with 90 cases in each group.The control group was given conventional western medicine for symptomatic treatment,and the observation group was treated with LUO's Nephropathy RecipeⅢon the basis of treatment for the control group.The course of treatment for the two groups covered one month.Before and after treatment,the levels of serum inflammatory factors,renal function indicators and urine protein parameters in the two groups were observed.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate in the observation group was 95.56%(86/90)and that in the control group was 81.11%(73/90).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammatory factors of transforming growth factor β1(TGF-β1),monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function indicators of blood urea nitrogen(BUN),serum creatinine(Scr),blood uric acid(UA),and cystatin C(Cys-C)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of 24-hour urine protein quantification and urine microalbumin in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.44%(4/90),which was significantly lower than that of 15.56%(14/90)in the control group,and the difference was statistically significant between the two groups(P＜0.05).Conclusion LUO's Nephropathy Recipe Ⅲ combined with conventional western medicine exerts satisfactory efficacy in treating stage 3-5 non-dialysis CKD patients with spleen-kidney deficiency with turbidity-toxin-stasis obstruction syndrome type,and the therapy can significantly alleviate the inflammatory response,improve the renal function,decrease the urinary protein excretion of the patients,with high safety profile.

Objective To investigate the effect of microglial derived extracellular vesicles on neuronal damage in the context of heat stress.Methods After BV2 microglial cells were exposed to heat stress,the supernatant was collected and subjected to ultracentrifugation at different speeds to obtain large and small vesicles,respectively.Nano Particle Tracking and Zeta Potential Distribution Analyzer was used to measure and analyze the size distribution of the large vesicles and small vesicles.Western blotting was used to detect the expression of specific vesicle surface markers,TSG101,CD63 and flotillin-1.Microglial extracellular vesicles were labeled with PKH67 dye and then co-cultured with N2a cells to examine the uptake by capacity the neurons.After large and small vesicles derived from microglia after heat stress stimulation were co-cultured with N2a cells,respectively,CCK-8 assay,lactate dehydrogenase (LDH)assay,Trypan blue staining and TUNEL assay were employed to evaluate heat stress induced neuronal damage.Results The small vesicles were in a particle size of 30～120 nm,and highly expressed TSG101 and CD63,whereas the large vesicles,in a size of 90～1000 nm,highly expressed flotillin-1.The BV2-derived extracellular vesicles could be taken up by N2a cells and were proved to be involved in the modulation of N2a cell injury caused by heat stress.CCK-8 assay showed that both large and small vesicles of microglial cells inhibited the viability of N2a cells after heat exposure (P<0.05).The results of LDH assay,Trypan blue staining and TUNEL assay showed that both large (P<0.05)and small vesicles (P<0.01)significantly enhanced the LDH release,blue stain intensity and apoptosis of N2a cells after heat exposure,and the release,intensity and apoptosis were stronger in the cells treated with small vesicles than those group of large vesicles.Conclusion Microglia aggravate heat stress-induced neuronal damage through releasing extracellular vesicles.

Objective To observe area of coagulation necrosis after microwave ablation(MWA)of rabbit liver showed on contrast-enhanced ultrasound(CEUS)in comparison with pathological findings.Methods Twenty-five healthy male experimental rabbits were equally randomly divided into L0,M0,H0,M7 and M14 groups.MWA was achieved with different power and time,and then CEUS and pathological examinations were performed,respectively.Four target areas of rabbit liver were ablated under 20 W for 1 min in L0 group,under 30 W for 1 min in M0 group and under 30 W for 3 min in H0 group,and the ablated areas were observed on the same day after MWA,while 2 target areas of rabbit liver were ablated under 30 W for 1 min in M7 and M14 groups,and the ablated areas were observed 7 days and 14 days after MWA,respectively.The ablated foci and ablated foci+edema band(inflammatory reaction band,IRB)showed on CEUS and pathology were compared,and their differences and changes with time going were analyzed.Results On the day of ablation,the extent of ablation foci,ablation foci+IRB as well as IRB in L0,M0 and H0 groups showed on CEUS were all larger than pathological findings under light microscopy(all P＜0.05),and the difference value of the length of the ablation foci between 2 methods increased sequentially among group L0,M0 and H0(all adjusted P＜0.05).Seven days after ablation,the area of ablation foci measured with CEUS in M 7 group was slightly larger than that measured with pathology(adjusted P=0.045),but no significant difference of the length nor the short diameter was found(both adjusted P＞0.05).Fourteen days after ablation,no significant difference of the length,the short diameter nor the area of ablation foci was detected between 2 methods in M14 group(all adjusted P＞0.05).The length,short diameter and area of ablation foci in M0 group measured with CEUS or pathology were all smaller than those in M 7 and M14 groups(all adjusted P＜0.05),while no significant difference was found between the latter 2 groups(all adjusted P＞0.05).Conclusion On the day of MWA of rabbit liver with different power and time settings,the areas of ablation foci,ablation foci+IRB and IRB showed on CEUS were larger than pathological findings.The range of ablation foci showed on CEUS 7 days after ablation was basically in line with pathology,indicating that CUES should be reexamined 7 days after ablation to evaluate the actual extent of coagulation and necrosis of ablation foci.

Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100％,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P＞0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.

Objective To observe the impact of cold circulation liquid temperature on ablation focus morphology of microwave ablation(MWA)for in vitro porcine liver tissue.Methods Twenty in vitro fresh porcine liver blocks were randomly divided into ice water circulation group(group A)and normal temperature circulation group(group B),respectively.Ten target ablations in each subgroups in group A and group B,i.e.A1 and B1(50 W,1 min),A2 and B2(50 W,5 min),A3 and B3(60 W,1 min),A4 and B4(60 W,5 min),A5 and B5(70 W,1 min)as well as A6 and B6(70 W,5 min)subgroups were performed using different ablation power(50,60,70 W)and ablation time(1,5 min),respectively.Then the morphology indexes of ablation foci,including longitudinal diameter(LD),transverse diameter(TD),roundness index(RI)and volume(V)were compared between subgroups in group A and B,also among subgroups within group A and B.Results Under the same ablation power and time,LD of ablation foci in subgroups of group A were all smaller than those of group B(all P＜0.05).Significant differences of RI of ablation foci were found between A1 and B1,A2 and B2,A4 and B4,A5 and B5 as well as A6 and B6 subgroups(all P＜0.05),but not between A3 and B3 subgroups(P＞0.05).However,the main effect of cold circulation liquid temperature on ablation focus TD(F=1.125)nor V(F=3.332)was not significant(both P≥0.05).Under the same cold circulation liquid temperature,significant differences of the morphology indexes of ablation foci were detected between A1 and A2,A3 and A4 as well as A5 and A6 subgroups,also between corresponding subgroups in group B(all P＜0.05).Conclusion During MWA for in vitro porcine liver tissue under constant ablation power and time,taken ice water as the cold circulation liquid was benefit to ablation focus shaped spherically.With the extension of ablation time,the larger the ablation focus,the higher the RI.