ObjectiveTo explore the possible mechanisms of electroacupuncture at Fengchi （GB 20）， Waiguan （TE 5）， and Yanglingquan （GB 34） in treating chronic migraine from the perspective of nociceptive sensitization. MethodsForty SPF-grade SD rats were randomly divided into blank group， model group， electroacupuncture group， electroacupuncture + agonist group， and inhibitor group， with 8 rats in each group. Except for the blank group， rats were injected intraperitoneally with nitroglycerin to establish a chronic migraine rat model. After successful modeling， the electroacupuncture group received electroacupuncture at bilateral "Fengchi" （GB 20）， "Waiguan" （TE 5）， and "Yanglingquan" （GB 34） for 30 minutes each session. The electroacupuncture + agonist group received the same electroacupuncture treatment and additional injection of protein kinase C （PKC） agonist Phorbol 12-myristate 13-acetate （1.0 ng/μl， 25 μl） via the infraorbital foramen. The inhibitor group received PKC inhibitor Chelerythrine Chloride （1.0 ng/μl， 10 μl） via the infraorbital foramen. The blank group， model group， and inhibitor group underwent restraint for 30 minutes without other interventions. All groups were continuously intervened for 5 days. After the intervention， the nociceptive thresholds （mechanical and thermal pain） of the periorbital area and hind paw were measured. The expression levels of transient receptor potential vanillic acid subtype 1 （TRPV1）， phosphorylated TRPV1 （p-TRPV1）， PKC proteins， Trpv1， Pkc mRNA， and the average fluorescence intensity of transient receptor potential vanillic acid subtype 1 （TRPV1） and PKC in the trigeminal ganglion were detected using Western Blot， real-time fluorescence quantitative PCR， and immunofluorescence methods. ResultsCompared with the blank group， the mechanical and thermal pain thresholds of the periorbital area and hind paw were reduced in the model group， and the protein levels of TRPV1， PKC， p-TRPV1， as well as the mRNA expression of Trpv1 and Pkc， and the average fluorescence intensity of TRPV1 and PKC in the trigeminal ganglion significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， the electroacupuncture group exhibited increased mechanical and thermal pain thresholds in the periorbital and hind paw areas， and decreased protein levels of TRPV1， PKC， p-TRPV1， mRNA expression of Trpv1 and Pkc， and average fluorescence intensity of TRPV1. In the electroacupuncture + agonist group， the average fluorescence intensity of TRPV1 in the trigeminal ganglion decreased. The inhibitor group exhibited increased mechanical pain thresholds in the periorbital area and thermal pain thresholds in the hind paw， along with decreased protein levels of TRPV1， PKC， p-TRPV1， and the average fluorescence intensity of TRPV1 and PKC （P＜0.05 or P＜0.01）. Compared with the electroacupuncture group， the electroacupuncture + agonist group showed an increase in the protein levels of TRPV1， PKC， p-TRPV1， and the mRNA expression of Trpv1 （P＜0.05 or P＜0.01）. ConclusionElectroacupuncture at the "Fengchi" （GB 20）， "Waiguan" （TE 5）， and "Yanglingquan" （GB 34） acupoints can increase the mechanical and thermal pain thresholds in chronic migraine rats and alleviate nociceptive sensitization. The mechanism may be related to the inhibition of PKC/TRPV1 pathway.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

ObjectiveTo investigate the possible mechanism of electroacupuncture at Fengchi （GB 20）， Yanglingquan （GB 34） and Waiguan （TE 5） for acute migraine attacks by peroxisome proliferator-activated receptor γ/ nuclear transcription factor-κB pathway in the trigeminal neurovascular system. MethodsForty SD rats were randomly divided into blank group， model group， electroacupuncture group， electroacupuncture plus inhibitor group， and agonist group， 8 rats in each group. Except for the blank group， rats were injected with inflammation decoction intracranial catheter to establish rat models of acute migraine. Thirty minutes after modelling， the electroacupuncture group was given 0.9% NaCl solution by intraperitoneal injection and then electroacupuncture at "Fengchi" （GB 20）， "Yanglingquan" （GB 34）， and "Waiguan" （TE 5） for 30 mins； the electroacupuncture plus inhibitor group was given PPARγ inhibitor T0070907 （1.5 mg/kg） and eclectroacupuncture as the above for 30 mins； the agonist group was given PPARγ inhibitor pioglitazone hydrochloride （10 mg/kg） for 30 mins. Rats in the blank group and the model group were injected intraperitoneally with 0.9% NaCl solution and then bound and restrained for 30 mins. Behavioural scores were evaluated before modelling， 30 mins after modelling （pre-intervention） and post-intervention； after the last behavioural test， PPARγ， NF-κB p65 mRNA content in rat dura mater was detected by real-time fluorescence quantitative PCR； protein expression of PPARγ， NF-κB p65， interleukin 6 （IL-6）， tumour necrosis factor α （TNF-α） in spinal trigeminal nucleus of rats was detected by protein blotting； immunofluorescence double-labelling method was used to detect the fluorescence intensity of PPARγ， NF-κB p65 in spinal trigeminal nucleus of rats. ResultsCompared with the blank group at the same time， the behavioural scores of rats in the remaining groups increased after modelling and after intervention （P＜0.01）. Compared with the model group at the same time， the beha-vioural scores of rats in the electroacupuncture group， electroacupuncture plus inhibitor group， and agonist group decreased after the intervention （P＜0.01）. Compared with the electroacupuncture group at the same time， beha-vioural scores reduced in the agonist group and elevated in the electroacupuncture plus inhibitor group after intervention （P＜0.01）. Compared with the blank group， expression of PPARγ and NF-κB p65 mRNA elevated in the dura mater of rats in the model group， and expression of PPARγ， NF-κB p65， IL-6， and TNF-α protein enhanced in spinal trigeminal nucleus， and the fluorescence intensity of PPARγ and NF-κB p65 enhanced （P＜0.01）. Compared with the model group， PPARγ mRNA expression in dura mater elevated and NF-κB p65 mRNA expression reduced in each intervention group， PPARγ protein expression in spinal trigeminal nucleus enhanced， and NF-κB p65， IL-6， and TNF-α protein expression weakened； in the electroacupuncture group and the agonist group， PPARγ fluorescence intensity enhanced， and the fluorescence intensity of NF-κB p65 weakened in each intervention group （P＜0.05 or P＜0.01）. Compared with the electroacupuncture group， in the electroacupuncture plus inhibitor group， PPARγ mRNA， protein expression and fluorescence intensity reduced， NF-κB p65 mRNA， protein expression and fluorescence intensity elevated， and IL-6 and TNF-α protein expression enhanced； in the agonist group， PPARγ mRNA and protein expression elevated， NF-κB p65 mRNA and protein expression reduced， and IL-6 and TNF-α protein expression decreased （P＜0.05 or P＜0.01）. ConclusionElectroacupuncture at "Fengchi" （GB 20）， "Yanglingquan" （GB 34） and "Waiguan" （TE 5） can can reduce the symptoms of acute migraine attacks in rats， and its mechanism may be related to the up-regulation of PPARγ expression and the reduction of NF-κB expression， thus inhibiting the neurogenic inflammatory response.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.

Objective To develop an oxybutynin nanotransdermal formulation with high skin permeability based on cubsomes carrier.Methods The oxybutynin loaded cubsomes(OXY-CS)was prepared by ultrasonic method.Using particle size,polydispersity index and encapsulation efficiency as evaluation indexes,stirring temperature,stirring time,stirring speed,ultrasound time,ultrasound power,glycerol monooleate/poloxamer 407 ratio(GMO/F127),carrier(GMO+F127)/drug ratio and drug concentration were optimized.The effects of drug concentration,permeation promoter and gel matrix type on skin permeability were investigated using cumulative permeation and skin retention as evaluation indicators.Results The prepared OXY-CS had small particle size and high encapsulation efficiency at stirring temperature of 50℃,stirring time of 30 min,stirring speed of 1 000 r/min,ultrasound time of 10 min,ultrasound power of 100 W,GMO/F127 ratio of 2∶1,carrier/drug ratio of 3∶1 and drug concentration of 1％,respectively.OXY-CS had high cumulative penetration and skin retention at concentration ≥ 3％.The addition of a permeation promoter to OXY-CS did not increase the cumulative penetration of the drug.The skin permeability of oxybutynin cubsomes gel made with carbomer was significantly better than those of other gel matrices.Conclusion In this study,oxybutynin is made into a topical cubsomes gel,which is expected to reduce the incidence of adverse effects associated with oral administration.

Objective:To investigate the medical narrative competence of pediatric staff, and analyze its influencing factors and correlation with psychological resilience, and to discuss strategies to improve narrative competence.Methods:From January 11 to February 25, 2022, by convenience sampling, we sampled pediatric personnel and those on refresher training at Children's Hospital, Zhejiang University School of Medicine for a questionnaire survey involving general information, the narrative competence scale, and the 14-item resilience scale. With the use of SPSS 26.0, the narrative competence of different populations was compared, and factors affecting narrative competence were determined through Pearson correlation analysis and multiple regression analysis.Results:A total of 361 valid questionnaires were included in this study, and there was significant differences in the narrative competence score between different ages, professional titles, working years, income levels, and whether they wrote parallel charts ( P<0.05). The total score of narrative competence of pediatric staffs was (147.13±18.76), and positively correlated with the total resilience score and the score of each dimension ( P≤0.001). The regression analysis showed that writing parallel charts and resilience could explain 53.10% of the variation in narrative competence ( P<0.001). Conclusions:Pediatric staff's narrative competence is at low or intermediate levels. Parallel chart writing and resilience training can improve narrative competence and promote a harmonious doctor-patient relationship.

Female ; Humans ; Anti-Mullerian Hormone ; Sexual Development ; Peptide Hormones

Objective To explore the clinical value of anti-Müllerian hormone(AMH)to optimize endocrine therapy for peri-menopausal early breast cancer.Methods Two hundred and four patients of pre-menopausal breast cancer aged 45-55 years old between 2020 and 2023 were enrolled,and AMH≤0.1 ng/mL was considered as cut-off value for menopause.Switching from selective estrogen receptor modulator(SERM)to aromatase inhibitor aromatase inhibitor(AI)and initial endocrine therapy regimens were based on AMH,follicle-stimulating hormone(FSH)and estradiol(E2).Results Pre-chemotherapy AMH level was significantly negatively correlated with FSH level(P<0.001).Among 100 cases who were amenorrhea for one year during SERM treatment,42 cases did not have AMH testing.Fourteen out of the 42 cases switched to AI within one year,and ovarian function recovery(OFR)occurred in 2 cases after AI switching.Fifteen cases with AMH>0.1 ng/mL did not switch to AI within one year.Forty among 43 cases with AMH≤0.1 ng/mL switched to AI,after a significantly shorter median SERM treatment duration(3.15 months vs.8.14 months,P<0.001)and a significantly lower OFR rate(0 vs.12.5%,P=0.023)compared with those who did not test AMH but switched to AI.AMH≤0.1 ng/mL was an independent risk factor of transition to menopause shortly in peri-menopausal patients(OR=35.857,P<0.001).Among 104 cases with AMH tested before adjuvant chemotherapy,69 cases had AMH>0.1 ng/mL.Thirty-one out of the 69 cases were treated with ovarian function suppression(OFS)initially and 38 with SERM initially.Thirty-five cases with AMH≤0.1 ng/mL were all treated with SERM initially,with a higher rate of switching to AI(71.4%vs.23.7%,P<0.001)and a shorter SERM treatment duration(6.52 months vs.13.56 months,P=0.016)compared with the 38 cases(AMH>0.1 ng/mL)treated initially with SERM.After a median 30-month follow-up,no recurrence was observed in these thirty-five cases treated with SERM initially and AMH≤0.1 ng/mL,just like in OFS group.And they had a tendency of improved survival outcome compared with those treated with SERM initially and AMH>0.1 ng/mL(Log Rank P=0.076).Conclusion AMH could evaluate and predict menopause accurately,resulting in optimizing endocrine therapy for peri-menopausal patients effectively and safely.