ObjectiveTo evaluate the clinical efficacy and safety of acupuncture combined with levodopa in the treatment of Parkinson's disease（PD）. MethodsA total of 60 patients with PD were enrolled and randomly assigned to test group or control group， with 30 patients in each group. The control group received levodopa only， starting at 100 mg per dose， three times daily， with gradual increases not exceeding a maximum daily dose of 800 mg. The test group received acupuncture three times per week in addition to levodopa. Both groups were treated for 12 weeks. Assessments were conducted before treatment， after 6 and 12 weeks treatment， using the Unified Parkinson's Disease Rating Scale（UPDRS）， Wearing-Off Questionnaire-9（WOQ-9）， Montreal Cognitive Assessment（MoCA）， Mini-Mental State Examination（MMSE）， Depression Rating Scale（DRS）， Hamilton Depression Scale（HAMD）， Hamilton Anxiety Scale（HAMA）， PD Questionnaire-39（PDQ-39）， and Pittsburgh Sleep Quality Index（PSQI）. Repeated measures ANOVA was utilized to evaluate the effects of time， group， and their interaction on each index. Spearman correlation analysis was conducted to examine the relationships between combined treatment and outcome scores. Adverse events in both groups were recorded throughout the study. ResultsBoth groups showed significant improvements after 6 and 12 weeks treatment， with decreases in UPDRS total score， WOQ-9 total score， DRS score， HAMD score， HAMA score， PDQ-39 score， and PSQI score， and increases in MoCA and MMSE scores（P＜0.05）. Compared with the control group， the test group demonstrated significantly greater improvements in all the above indicators after 6 and 12 weeks （P＜0.05）. Repeated measures ANOVA showed significant time main effects， group main effects， and their interaction across all outcome measures（P＜0.01）. Spearman correlation analysis revealed that combined therapy was significantly negatively correlated with UPDRS， WOQ-9， DRS， HAMD， HAMA， PDQ-39， and PSQI scores， while positively correlated with MoCA and MMSE scores after 12 weeks of treatment（P＜0.05）. Both groups did not experience any serious adverse events and did not affect treatment. ConclusionAcupuncture combined with levodopa is more effective than levodopa alone in improving motor function， non-motor symptoms， cognitive function， depression and anxiety， quality of life， and sleep quality in patients with PD， with good safety.

Objective To evaluate the current situation of disease control in middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD) and analyze the relationship with disease cognition. Methods Among the 360 middle-aged and elderly COPD patients diagnosed and treated in our hospital from January 2022 to June 2024 were retrospectively selected as research subjects, and the COPD Assessment Test Questionnaire (CAT), COPD Patient Knowledge Questionnaire (BCKQ) and the hampion Health Belief Model Scale were used to evaluate disease control, disease cognition and health beliefs in COPD patients. The Pearson chi-square test was used to analyze the relationship between disease control level and disease cognition and health beliefs in older patients with COPD. Results A total of 360 middle-aged and elderly COPD patients, 112 were in the complete control group, 189 were in the partial control group, and 59 were in the uncontrolled group, the disease control rate was 83.61%. The differences in disease cognitive scores, severity cognition, susceptibility cognition, disorder cognition, benefit cognition, health motivation, self-efficacy score and total health belief scores in middle-aged and elderly COPD patients with different disease control conditions are statistically significant. The scores of the complete control group were higher than those of partial control group and uncontrolled group, and the scores of partial control group were higher than those of the uncontrolled group (P <0.05). The disease control level of middle-aged and elderly patients with COPD is positively correlated with disease cognitive level and health belief in all dimensions. The higher the disease control level, the higher the disease cognitive level and health belief in the patient . Conclusions Middle-aged and elderly COPD patients still have insufficient awareness of the disease, and the level of disease control needs to be improved. There is a significant correlation between disease cognition, health beliefs and the level of disease control, and the improved cognitive level may help to improve the disease management and control effect. For middle-aged and elderly COPD patients, the community can provide health education courses, personalized health guidance and self-management training to enhance their awareness of diseases, so as to improve the long-term management of COPD and the quality of life of patients.

Objective To evaluate the current situation of disease control in middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD) and analyze the relationship with disease cognition. Methods Among the 360 middle-aged and elderly COPD patients diagnosed and treated in our hospital from January 2022 to June 2024 were retrospectively selected as research subjects, and the COPD Assessment Test Questionnaire (CAT), COPD Patient Knowledge Questionnaire (BCKQ) and the hampion Health Belief Model Scale were used to evaluate disease control, disease cognition and health beliefs in COPD patients. The Pearson chi-square test was used to analyze the relationship between disease control level and disease cognition and health beliefs in older patients with COPD. Results A total of 360 middle-aged and elderly COPD patients, 112 were in the complete control group, 189 were in the partial control group, and 59 were in the uncontrolled group, the disease control rate was 83.61%. The differences in disease cognitive scores, severity cognition, susceptibility cognition, disorder cognition, benefit cognition, health motivation, self-efficacy score and total health belief scores in middle-aged and elderly COPD patients with different disease control conditions are statistically significant. The scores of the complete control group were higher than those of partial control group and uncontrolled group, and the scores of partial control group were higher than those of the uncontrolled group (P <0.05). The disease control level of middle-aged and elderly patients with COPD is positively correlated with disease cognitive level and health belief in all dimensions. The higher the disease control level, the higher the disease cognitive level and health belief in the patient . Conclusions Middle-aged and elderly COPD patients still have insufficient awareness of the disease, and the level of disease control needs to be improved. There is a significant correlation between disease cognition, health beliefs and the level of disease control, and the improved cognitive level may help to improve the disease management and control effect. For middle-aged and elderly COPD patients, the community can provide health education courses, personalized health guidance and self-management training to enhance their awareness of diseases, so as to improve the long-term management of COPD and the quality of life of patients.

ObjectiveTo identify the main chemical constituents of Anmeidan （AMD） and to explore the mechanism of AMD in regulating the extracellular signal-regulated kinase 1/2 （ERK1/2）/mitogen-activated protein kinase （MAPK）-interacting serine/threonine-protein kinase （MNK）/eukaryotic translation initiation factor 4E （eIF4E） signaling pathway to improve circadian rhythm disturbances in insomnia rats. MethodsThe main chemical constituents of AMD were identified using ultra-high-performance liquid chromatography-linear ion trap-electrostatic orbital trap mass spectrometry （UPLC-LTQ/Orbitrap/MS） in combination with reference standards. Sixty male Sprague-Dawley （SD） rats were randomly divided into control， model， melatonin， and AMD low-， medium-， and high-dose groups， with 10 rats in each group. Except for the control group， all rats were administered p-chlorophenylalanine via intraperitoneal injection to establish an insomnia model. The activity-rest rhythm of rats was assessed using the open field test and circadian rhythm test. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe structural changes in hypothalamic neurons. Immunofluorescence， real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot analysis were employed to detect mRNA and protein expression levels of ERK1/2， MNK， and eIF4E in the hypothalamus. ResultsA total of 50 chemical components， including flavonoids， phenylpropanoids， triterpenoid saponins， alkaloids， and lignans， were identified in AMD. Compared with the control group， the model group exhibited significantly increased total distance traveled， average speed， central area residence time， and cumulative rearing time （P<0.01）， as well as prolonged cumulative activity time and total activity time in both light and dark phases （P<0.01）. Hypothalamic neurons in the model group were sparsely arranged， reduced in number， and exhibited nuclear disappearance or nucleolar rupture， with a significantly increased apoptosis index （P<0.01）. The cytoplasm appeared turbid， Nissl body staining was lighter， and the Nissl body apoptosis index was significantly increased （P<0.01）. The mRNA expression levels of ERK1/2， MNK， and eIF4E were significantly decreased （P<0.01）， along with a significant reduction in protein expression levels of ERK1/2， phosphorylated ERK1/2 （p-ERK1/2）， MNK， phosphorylated MNK （p-MNK）， eIF4E， and phosphorylated eIF4E （p-eIF4E） （P<0.01）. Compared with the model group， the total distance， average speed， central area residence time and body upright cumulative time of the AMD high-dose group were significantly reduced （P<0.01）. The total distance， average speed and body upright cumulative time of the AMD medium-dose group were significantly reduced （P<0.01）. The cumulative time of light activity and total time of activity in each dose group of AMD were significantly shortened （P<0.01）. The cumulative time of dark activity in the high-dose group of AMD was prolonged （P<0.01）. The neurons in the middle and high dose groups of AMD were closely arranged， the number of neurons increased， and the apoptosis index of hypothalamic cells decreased significantly （P<0.05， P<0.01）. The cytoplasm of the low， middle and high dose groups of AMD was clear， the color of Nissl body became darker， and the apoptosis index of Nissl body decreased significantly （P<0.01）. The expression of ERK1/2， MNK and eIF4E mRNA and protein in the hypothalamus of the middle and high dose groups of AMD increased significantly （P<0.05， P<0.01）. ConclusionAMD primarily contains 50 chemical constituents， including flavonoids， phenylpropanoids， and triterpenoid saponins. It exhibits a "synergistic enhancement" effect through multiple components and multiple pathways to improve insomnia. AMD ameliorates circadian rhythm disturbances in p-chlorophenylalanine-induced insomnia rats by upregulating ERK1/2/MNK/eIF4E signaling pathway-related proteins.

Objective To investigate the effect of cinobufacini on inhibiting colorectal cancer metastasis by regula-ting the polarization of M2 macrophages.Methods THP-1 was induced into M0 type macrophages.The condi-tioned medium of HCT116 cells was collected to stimulate M0 type macrophages.The polarization of M2 type mac-rophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned me-dium of M0 type macrophages and HCT116-Mφ cells was collected to stimulate HCT116 cells.The ability of migra-tion and invasion was observed by wound healing assay and Transwell assay.The effect of cinobufacini on the via-bility of HCT116 cells was detected by CCK-8 assay.The conditioned medium of HCT116 and HCT116+cinobufa-cini was collected to stimulate M0 type macrophages.The polarization of M2 type macrophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned media of HCT116-Mφ cells and(HCT116+cinobufacini)-Mφ cells were collected to stimulate HCT116 cells.The changes of migration and inva-sion ability were observed by wound healing assay and Transwell assay.Results After stimulation of M0 type mac-rophages in HCT116 cell conditioned medium,the morphology of M0 macrophages turned into fusiform cells,the proportion of CD11b+CD206+cells increased,and the expression of M2 macrophage markers IL-10 and TGF-β in-creased.The migration and invasion ability of HCT116 cells were significantly enhanced after stimulation in the conditioned medium of HCT1 16-Mφ cells.After the addition of cinobufacini,not only the polarization proportion of M2 macrophages decreased,but also the metastatic effect mediated by M2 macrophages was inhibited.Conclusion HCT116 cells can induce the polarization of M2 macrophages,while cinobufacini can inhibit the tumor metastasis mediated by M2 macrophages by inhibiting the polarization of M2 macrophages.

Objective To investigate the role of bufalin(BU)in inhibiting M2-type macrophage-mediated colorec-tal cancer metastasis.Methods Human acute leukemia mononuclear cells(THP-1)were differentiated into M0 macrophages using phorbol ester induction(PMA)for 48 hours.The M0 macrophages were then treated with IL-4 and IL-13 medium.Surface markers and morphological changes were observed through ELISA,morphology,and RT-qPCR experiments.RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages.The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA.Additionally,the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell,Wound healing,RT-qPCR,and Western blot experiments.Subsequent-ly,bufalin was added to the conditioned medium and the changes in AKT/PI3K protein,migration,and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot,Transwell,Wound healing and RT-qPCR experiments.Results THP-1 were successfully differentiated into M2 macrophages.The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages,which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells.The migration and epithelial-mes-enchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin.Conclu-sion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells,thereby promoting their migration and epithelial-mesenchymal transition capacity.Moreover,bufalin exhibits inhibitory effects on this effect.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

Objective To study the expression of thyroid hormone receptor binding protein 4(TRIP4)and DNA damage inducing transcription factor 4(DDIT4)in glioma tissue and their relationship with clinical pathological characteristics and prognosis.Methods 94 glioma patients admitted to the First Hospital of Hebei Medical University from February 2018 to February 2019 were selected as the research subjects.The expression of TRIP4,DDIT4 proteins in tissues were detected by immunohistochemistry.The relationship between the expression of TRIP4,DDIT4 proteins in glioma tissues and clinical pathological characteristics were compared.The differences in survival prognosis of glioma patients with different levels of TRIP4,DDIT4 protein expression were analyzed by Kaplan-Meier survival curve.Univariate and multivariate COX regression analysis was conducted to analyze the factors affecting the survival prognosis of glioma patients.Results The positive rates of TRIP4(68.09%),DDIT4(65.96%)proteins in glioma tissues were higher than those in adjacent tissues(13.83%,10.64%),with statistically significant differences(χ2=57.212,60.866,all P<0.05).There was a significant positive correlation between TRIP4 and DDIT4 protein expression in glioma tissues(r=0.722,P<0.05).The positive rates of TRIP4(83.64%vs 46.15%,80.00%vs 51.28%)and DDIT4(80.00%vs 46.15%,76.36%vs 51.28%)proteins in glioma tissues with tumor diameter≥3cm,WHO grade Ⅲ were significantly higher than those in tissues with tumor diameter＜3cm,WHO grade Ⅰ～Ⅱ(χ2=6.393～14.754,P<0.05).The 3-year overall survival rates of the TRIP4 positive and negative expression groups were 37.50%(24/64)and 66.67%(20/30),respectively.The 3-year cumulative survival of the TRIP4 positive expression group was significantly lower than that in the TRIP4 negative expression group(Log-rank χ2=5.949,P=0.015).The 3-year overall survival rate of DDIT4 positive and negative expression group was 37.10%(23/62)and 70.00%(21/30),respectively.The 3-year cumulative survival of the DDIT4 positive expression group was significantly lower than that in the DDIT4 negative expression group(Log-rank χ2=7.642,P=0.006).Tumor diameter≥3cm(HR=1.614,P=0.000),WHO grade Ⅲ(HR=1.790,P=0.000),positive TRIP4(HR=1.665,P=0.000)and positive DDIT4(HR=1.476,P=0.000)were independent risk factors affecting the survival prognosis of glioma patients.Conclusion The expression of TRIP4 and DDIT4 protein in glioma tissue was increased.Both of them were related to tumor diameter and WHO grade,and are potential tumor markers for survival prognosis of glioma.

Objective:To summarize the clinical features of transient neonatal myasthenia gravis (TNMG).Methods:We retrospectively collected the clinical data of an neonate diagnosed with TNMG in the department of Neonatology at the Affiliated Hospital of North Sichuan Medical College. Literature was retrieved from databases including CNKI, VIP, Wanfang, the Chinese Medical Journal Full Text database, the Chinese biomedical literature database, PubMed, Embase, Web of Science, The Cochrane library, and Medline. Search terms were "neonatal"、"pregnancy"OR"pregnant"OR"maternal"、"myasthenia"OR "myasthenia gravis"、"transient myasthenia gravis"OR"transitory myasthenia gravis"OR"temporary myasthenia gravis"、"congenital myasthenia gravis"OR"geneogenous myasthenia gravis". Searching period was from establishment of database to May 31st 2023. We summarize the clinical characteristics, treatment, and prognosis of reported cases with TNMG.Results:This patient is a full-term male infant who experienced decreased muscle tone, weak crying, and difficulty breathing 10 min after birth. His mother had a history of myasthenia gravis for 13 years. On the second day of birth, his neostigmine test was positive. So he was diagnosed with TNMG and treated with respiratory support and intravenous human immunoglobulin. His symptoms were relieved at day 10 and resolved by day 20. No abnormalities were observed during follow-up up to 6 months of age. A total of 7 Chinese papers and 13 English papers were retrieved, reporting 39 cases in total including this patient. Mothers of 34 cases (87.2%) were diagnosed with MG before delivery, and the other 5 mothers (12.8%) were diagnosed with MG after delivery. The main clinical manifestations in neonates were reduced muscle tone (29 cases, 74.4%), weak crying (23 cases, 59.0%), dyspnea (20 cases, 51.3%), and feeding difficulties (18 cases, 46.2%). 33 cases (84.6%) developed symptoms within the first day after birth, 6 cases (15.4%) had symptoms between day 2 and day 4. Most patients had a disease course for 2-6 weeks (29 cases, 74.4%). 27 cases (69.2%) underwent neostigmine test, all were positive. 30 cases (76.9%) were treated with cholinesterase inhibitors, 5 cases (12.8%) received IVIG and 1 case (2.6%) received an exchange transfusion. Out of the 39 cases, 33 cases (84.6%) were cured and discharged, 6 cases (15.4%) died. The causes of death were pulmonary infection and respiratory failure. Among the 17 patients with follow-up records, except for 1 case who only followed up to 2 months old and had slightly worse head upright, the rest of the children had normal physical and neurological development.Conclusions:TNMG may occur in infants that were born to MG mothers, most of the patients with TNMG develop symptoms on the first day after birth, a few patients develop symptoms 3-4 d after birth. Neostigmine test, serum MG antibody test should be performed to assist diagnosis. Cholinesterase inhibitors and symptomatic support are the main treatment options. TNMG generally have a good prognosis after treatment.

OBJECTIVE To investigate the protective effect of Tibetan medicine Sanguo decoction on hyperlipidemic rats based on the Nrf2/HO-1 signaling pathway and its related mechanisms. METHODS Forty-eight male SD rats were randomly divided into six groups: the normal control group, the model control group, the simvastatin group(3.5 mg·kg−1), and the Tibetan medicine Sanguo decoction low, medium, and high dose groups(0.43 , 0.86 , 1.72 g·kg−1), with eight rats in each group. The normal control group was fed a basal diet, and the remaining groups were fed the H10060 high-fat diet to prepare a hyperlipidemic rat model. At the same time, each treatment group was given corresponding drugs by gavage once a day. The normal control group and model control group were given an equal volume of physiological saline(once a day) by gavage for 6 consecutive weeks. After 6 weeks, serum levels of lipids[totalcholesterol(TC), triglyceride(TG), low density lipoprotein(LDL) and high density lipoprotein(HDL)] and oxidative parameters[malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH)] were measured by reagent kit. Nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), Keap1, and quinone oxidoreductase(NQO1) protein expression in liver tissues were analyzed by Western blotting. The correlation of lipid and oxidative indices was investigated by person correlation. RESULTS Compared with the normal control group, the model control group showed a significant increase in body weight, significantly higher serum levels of TC, TG, LDL, and MDA, significantly lower serum levels of HDL, and significantly lower SOD and GSH activity. Compared with the model control group, each administration group showed a decrease in body weight and serum TC, TG, LDL, and MDA levels. In comparison with the model control group, the body weight was reduced, the serum levels of TC, TG, LDL, and MDA were significantly lower, the serum levels of HDL were significantly higher, and the SOD and GSH activities were significantly higher. Keap1 protein level expression was significantly up-regulated compared with the normal control group, and Nrf2, HO-1, and NQO1 protein level expression were significantly down-regulated in the model control group. Keap1 protein level expression was significantly down-regulated compared to the model control group, and Nrf2, HO-1, and NQO1 protein level expression were significantly up-regulated in the liver tissues of low and high doses of Sanguo decoction. The expressions of Nrf2, HO-1, and NQO1 were significantly up-regulated. Correlation analysis showed that TG was negatively correlated with SOD, HO-1, and NQO1, and positively correlated with Keap1, while TC was negatively correlated with SOD, HO-1, GSH, and Nrf2, and positively correlated with Keap1 and MDA. CONCLUSION The Tibetan medicine Sanguo decoction can improve body weight and blood lipid levels in hyperlipidemic rats, and the mechanism may be related to the regulation of the Nrf2/HO-1 signaling pathway and the improvement of oxidative stress.