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:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

In the central nervous system (CNS), the myelin sheath, a specialized membrane structure that wraps around axons, is formed by oligodendrocytes through a highly coordinated spatiotemporal developmental program. The process begins with the directed differentiation of neural precursor cells into oligodendrocyte precursor cells (OPCs), followed by their migration, proliferation, differentiation, and maturation, ultimately leading to the formation of a multi-segmental myelin sheath structure. Recent single-cell sequencing research has revealed that this process involves the temporal regulation of over 200 key genes, with a regulatory network composed of transcription factors such as Sox10 and Olig2 playing a central role. The primary function of the myelin sheath is to accelerate nerve signal transmission and protect nerve fibers from damage. Its insulating properties not only increase nerve conduction speed by 50-100 times but also ensure the long-term functional integrity of the nervous system by maintaining axonal metabolic homeostasis and providing mechanical protection. The pathological effects of myelin sheath injury exhibit a cascade amplification pattern: acute demyelination leads to action potential conduction block, while chronic lesions may cause axonal damage and neuronal death in severe or long-term cases, ultimately resulting in irreversible neurological dysfunction with neurodegenerative characteristics. Multiple sclerosis (MS) is a neurodegenerative disease characterized by chronic inflammatory demyelination of the CNS. Clinically, the distribution of lesions in MS exhibits spatial heterogeneity, which is closely related to differences in the regenerative capacity of oligodendrocytes within the local microenvironment. Emerging evidence suggests that astrocytes form a dynamic “neural-immune-metabolic interface” and play a multidimensional regulatory role in myelin development and regeneration by forming heterogeneous populations composed of different subtypes. During embryonic development, astrocytes induce the targeted differentiation of OPCs in the ventricular region through the Wnt/β-catenin pathway. In the mature stage, they secrete platelet-derived growth factor AA (PDGF-AA) to establish a chemical gradient that guides the precise migration of OPCs along axonal bundles. Notably, astrocytes also provide crucial metabolic support by supplying energy substrates for high-energy myelin formation through the lactate shuttle mechanism. In addition, astrocytes play a dual role in myelin regulation. During the acute injury phase, reactive astrocytes establish a triple defense system within 72 h: upregulating glial fibrillary acidic protein (GFAP) to form scars that isolate lesions, activating the JAK-STAT3 regeneration pathway in oligodendrocytes via leukemia inhibitory factor (LIF), and releasing tumor necrosis factor-stimulated gene-6 (TSG-6) to inhibit excessive microglial activation. However, in chronic neurodegenerative diseases, the phenotypic transformation of astrocytes contributes to microenvironmental deterioration. The secretion of chondroitin sulfate proteoglycans (CSPGs) inhibits OPC migration via the RhoA/ROCK pathway, while the persistent release of reactive oxygen species (ROS) leads to mitochondrial dysfunction and the upregulation of complement C3-mediated synaptic pruning. This article reviews the mechanisms by which astrocytes regulate the development and regeneration of myelin sheaths in the CNS, with a focus on analyzing the multifaceted roles of astrocytes in this process. It emphasizes that astrocytes serve as central hubs in maintaining myelin homeostasis by establishing a metabolic microenvironment and signaling network, aiming to provide new therapeutic strategies for neurodegenerative diseases such as multiple sclerosis.

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (I_Na.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC₅₀) values of Mel on transient sodium current (I_Na.T) and specific I_Na.L opener 2 nmol·L^-1 sea anemone toxins II (ATX II) increased I_Na.L were 686.615 and 7.37 μmol·L^-1, respectively. Mel did not affect L-type calcium current (I_Ca.L), transient outward current (I_to), and AP. In addition, 16 μmol·L^-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking I_Na.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Objective To investigate the neuroprotective effect of 7,8-dihydroxyflavone(7,8-DHF)on cerebral hemorrhage in mice by regulating the tyrosine kinase receptor B(TrkB)/brain derived neurotrophic factor(BDNF)signal pathway.Methods C57BL/6 mice were injected with bacterial collagenase V Ⅱ to establish cerebral hemorrhage model.The mice were randomly grouped into model group,control group(5 mg·kg-1 7,8-DHF),experimental group(1 mg·kg-1 K252a),and combined group(5 mg·kg-1 7,8-DHF+1 mg·kg-1 K252a),mice injected with normal saline were used as sham-operation group,with 10 mice in each group.After the treatment,the mice were scored for neurological function by Garcia method,brain water contents of the brain tissue were detected by the dry and wet weight method,the blood brain barrier permeability was examined using the Evans blue method,the neuronal apoptosis was detected by TUNEL method,and the protein expression levels of TrkB,phosphorylated TrkB(p-TrkB)and BDNF were detected by Western blot.Results The neurological function scores of control,experimental,combined,model and sham-operation groups were(15.47±1.55),(7.23±0.73),(10.55±1.06),(10.45±1.05)and(16.12±1.62)points;the brain water contents were(62.88±2.19)％,(83.77±3.11)％,(72.71±2.59)％,(72.88±2.61)％and(59.64±2.06)％;the Evans blue contents were(3.26±0.36),(16.23±1.63),(8.78±0.88),(9.47±0.95)and(1.02±0.11)μg·g-1;neuronal apoptosis rates were(9.82±0.99)％,(39.88±3.99)％,(22.15±2.24)％,(25.71±2.58)％and(6.46±0.65)％;p-TrkB/TrkB ratios were 1.01±0.11,0.21±0.03,0.48±0.05,0.49±0.05 and 1.03±0.11;the protein expression levels of BDNF were 1.15±0.12,0.18±0.02,0.46±0.05,0.42±0.05 and 1.18±0.12,respectively.The above indexes of sham-operation,control and experimental groups were compared with those of model group,and the above indexes of control and experimental groups were compared with those of combined group,the differences were statistically significant(all P＜0.05).Conclusion 7,8-DHF has neuroprotective effect on mice with intracerebral hemorrhage,and its mechanism may be related to the activation of TrkB/BDNF signal pathway.

Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.

Objective To observe the clinical efficacy and safety of rituximab injection in the treatment of patients with phospholipase A2 receptor-associated membranous nephropathy(PLA2R-MN).Methods The PLA2R-MN patients were randomly divided into control group and treatment group.The control group received oral prednisone tablets,initial dose of 40-60 mg·d-1,gradually reduced the dose according to the patients'condition after 2 months,cyclophosphamide injection 0.6 g per time,intravenous infusion,once every 2 weeks,for 6 consecutive times,then adjusted to 1.0 g per time,intravenous infusion,once a month;the treatment group received 375 mg·m-2 rituximab injection intravenous infusion,once a week,for 4 consecutive weeks,on the basis of the control group treatment.Both groups of patients were treated for 6 months.The clinical efficacy,24 h urine protein quantification,serum creatinine(SCr),glomerular filtration rate(eGFR),urinary microalbumin(UAlb),urinary creatinine(UCr)and adverse drug reactions were compared between two groups.Results Fifty-three patients were enrolled in the treatment group,2 cases dropped out,and 51 cases were finally included in the statistical analysis.Fifty-three patients were enrolled in the control group,2 cases dropped out,and 51 cases were finally included in the statistical analysis.After treatment,the total effective rate of the treatment group and the control group were 92.16％(47 cases/51 cases)and 76.47％(39 cases/51 cases),and the difference was statistically significant(P＜0.05).After treatment,the 24 h urine protein quantification of the treatment and control groups were(0.86±0.30)and(1.04±0.27)g·24 h-1;SCr levels were(103.37±18.80)and(120.55±19.94)μmol·L-1;eGFR levels were(65.89±8.17)and(55.87±9.36)mL·min-1·1.73 m-2;UAlb levels were(47.45±13.52)and(98.21±25.50)mg·L-1;UCr were(1.55±0.42)and(1.96±0.51)mg·g-1,respectively,and the differences were all statistically significant(all P＜0.05).The adverse drug reactions of two groups were mainly nausea,vomiting,liver function damage,skin itching,infection,hair loss,etc.The total incidences of adverse drug reactions in the treatment and control groups were 43.14％and 37.25％,without significant difference(P＞0.05).Conclusion Rituximab injection has a definite clinical efficacy in the treatment of PLA2R-MN patients,which can significantly improve the renal function of patients,and does not increase the incidence of adverse drug reactions.

The Philippines has an increasingly aging population thereby increasing the demand for healthcare and support from families. Studies showed that the family is the main caregiver of elderly parents/adults as dictated by the Filipino culture of filial piety and respectful behavior towards older people. However, this caring culture is now slowly declining, and Filipino older adults also experience abuse, exploitation, and other forms of neglect from their families. This special article described that the declining caring culture was due to deteriorating family values and societal influences brought about by modernization. This paper also highlights the crucial role of the family and the community in inculcating the preservation of this valued caring Filipino culture, especially among the youth. In cases where senior citizens are being abused and neglected by their families, the state steps in to safeguard the welfare and protection of Filipino senior citizens. Enacted and promulgated laws ensure social justice and protection of human dignity among Filipino older adults as well as the provision of socioeconomic and health needs. In conclusion, the preservation of a caring culture through educating the youth coupled with the implementation of enacted and promulgated laws of the country ensures the quality of aging life among Filipino older adults.

Pregnancy is a critical period in every woman's life. The health of both the mother and her unborn child is at stake, with poor access to needed prenatal care services. Obtaining prenatal care is affected by the pregnancy literacy of the expectant mother. However, the assessment tool for health literacy among Filipino pregnant women is limited. This paper aimed to examine existing maternal health literacy instruments. Hopefully, an adopted tool can be found for assessing prenatal health literacy. After examining existing maternal health literacy tools, 18 questions were suggested that can be further modified before they are used for Filipino pregnant women to assess their prenatal health literacy.
Human ; Female ; Prenatal Care ; Pregnant Women