OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

Objective To investigate the prognostic value of optic nerve sheath diameter(ONSD)measured by critical care ultrasound combined with serum biomarkers[S100 calcium-binding protein β(S100β)and neuron-specific enolase(NSE)]in patients with severe traumatic brain injury.Methods A total of 103 adult severe traumatic brain injury patients admitted to the intensive care unit of this hospital from A-pril 1,2023,to April 1,2024 were enrolled.All patients underwent invasive intracranial pressure monitoring after admission,alongside bedside critical care ultrasound measurement of ONSD at 3 mm behind the globe and serum biomarker testing.Baseline data and Glasgow outcome scale(GOS)scores at 90 days after dis-charge were recorded.Patients were divided into the survival and the non-survival groups based on GOS scores.Receiver operating characteristic(ROC)curve analysis and area under the curve(AUC)were used to evaluate the predictive performance of ONSD and serum biomarkers for poor prognosis in severe traumatic brain injury patients.Results Ninety-six patients were ultimately included,with 52(54.1％)in the survival group and 44(45.9％)in the non-survival group.Significant differences were observed in blood glucose,Glas-gow coma scale(GCS)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,ONSD,NSE,and S100β levels(P＜0.05)between the two groups.Multivariate analysis identified ONSD(OR=4.962,95％CI:3.473-6.254),NSE(OR=2.704,95％CI:1.987-3.033),S100β(OR=2.983,95％CI:1.843-4.571),and APACHE Ⅱ score(OR=3.726,95％CI:2.837-4.592)as independent predictors of mortality in severe traumatic brain injury patients(P＜0.05).The combination of ONSD,NSE,and S100β yielded an AUC of 0.840 for predicting poor prognosis,with a specificity of 88.3％and sensitivity of 98.6％.Conclusion ONSD and serum brain injury biomarkers(NSE,S100β)are associated with in-hospital prognosis in severe traumatic brain injury patients.Their combined detection can effectively predict a poor outcome.

Idiopathic pulmonary fibrosis （IPF） can be classified as pulmonary collateral disease，and its pathogenesis is mainly characterized by the loss of Qi meridian nourishment，the loss of Yin meridian nourishment，and the formation of blood stasis in the blood vessels. Qi Yin deficiency is the pathological basis that runs through IPF，and obstruction of meridians and collaterals is a key element in the development of the disease. The dysfunction of "spleen being in charge of the defensive function" is closely related to the formation of the pathological pattern of "lung deficiency and collateral stasis" in IPF. The term "spleen being in charge of the defensive function" originated from the Yellow Emperor's Inner Canon. If the spleen is healthy，the Qi will be filled with vitality. Positive energy is stored inside，evil cannot be dried up. Its concept is quite similar to the immune defense function in modern medicine. If the principle of "spleen being in charge of the defensive function" is lost，the key structure and function of the IPF alveolar epithelial barrier may be abnormal，and it can interact with various innate immune cells to promote inflammation and fibrosis processes. Therefore，this article explains the imbalance of immune homeostasis in IPF alveolar epithelium from two aspects：the barrier function of alveolar epithelial cells（AECs） and their interaction with innate immune cells. And based on the theory of "spleen being in charge of the defensive function"，using traditional Chinese medicine for strengthening the spleen and nourishing Qi to treat IPF from the perspective of the spleen. This not only strengthens the scientific connotation of "spleen being in charge of the defensive function" in the pathogenesis of IPF，but also provides new research directions and ideas for its future clinical prevention and treatment.

Guided by the pathogenesis of"structure-activity imbalance of lung collaterals",this paper proposes that structure-activity imbalance of lung collaterals is the initial factor of idiopathic pulmonary fibrosis(IPF)and elucidates the pathogenesis of abnormal changes in biomechanical properties of IPF.It is postulated that the changes of biomechanical properties of lung tissue are closely related to the injury of lung qi collaterals,the abnormal mechanical stress are closely related to the injury of lung blood collaterals,and the biomechanical response of intrapulmonary resident cells is closely related to the structure-activity imbalance of lung collaterals,which ultimately leading to abnormal increase in lung tissue stiffness and progressive scarring formation in lung tissue.Integrating traditional pathogenesis concepts with microscopic pathological changes,and the in-depth exploration of the correlation between the structure-activity imbalance of lung collaterals and the biomechanical properties of IPF can provide direction for exploring IPF medical-engineering cross research,which are of great significance for enriching the syndrome and treatment system of lung collateral diseases.

Objective To explore the value of peripheral blood monocyte subsets and their CD169 expression levels in the diagnosis of common respiratory viral infections and the immune mechanism of the infection in children.Methods A total of 125 children with re-spiratory viral infections(virus infection group),71 children with bacterial respiratory infections(bacteria infection group),and 35 healthy children(healthy control group)admitted to the Third Affiliated Hospital of Zhengzhou University from February 2022 to Octo-ber 2023 were included in this study.The counts of peripheral blood monocytes and lymphocytes were detected by hematologic analyzer.The proportions of lymphocyte subsets,monocyte subsets,and the expression levels of CD169 were detected by a flow cytometry.Mono-cyte subsets were classified into three types:classical monocytes(CM),intermediate monocytes(IM),and non-classical monocytes(NCM).ANOVA and Kruskal-Wallis H tests were used to screen for differentially expressed indicators among the three groups,and the receiver operator characteristic(ROC)curve was used to evaluate their diagnostic performance.Paired t-tests were used to analyze the differences in the indicators between the first day and the seventh day of hospitalization in the virus group.Spearman rank correlation a-nalysis was used to explore the relationship between CD 169 expression levels in monocyte subsets and the quantity of lymphocyte sub-sets.Results Statistically significant differences in the expression levels of CD169 in monocytes of CM,IM,and NCM types were ob-served in peripheral blood between the children's respiratory viral infection group and the healthy control group(all P＜0.01).In con-trast,no statistically significant differences in CD169 expression levels were found in monocytes of CM and IM type between the respira-tory viral infection group and the bacterial infection group(all P＞0.05).The differences in CD 169 expression levels among the groups were statistically significant in the NCM subset(P=0.008).The area under the ROC curve(AUC)of CD169 expression level in NCM type monocytes for diagnosing respiratory viral infections was 0.897(P＜0.01),with a cutoff point of ≥ 62.75％,sensitivity of 68.60％,and specificity of 91.80％.The quantity and proportion of CM,IM,and NCM type monocytes did not show statistically signif-icant differences between the respiratory viral infection group and the bacterial infection group(all P＞0.05).However,there were sig-nificant differences in the quantity and proportion of CM and IM type monocytes,as well as the proportion of NCM type monocytes,be-tween the virus infection group and the healthy control group(all P＜0.05).The proportions of CM,IM,and NCM type monocytes,the quantity of IM type monocytes,and the CD169 expression levels of monocyte subsets showed statistically significant differences between the first day and the seventh day after admission(all P＜0.05).There were no statistically significant differences in the quantity of CM and NCM type monocytes between the first day and the seventh day after admission(all P＞0.05).The expression levels of CD169 in peripheral blood CM,IM,and NCM type monocytes were negatively correlated with the number of CD8+T cells with correlation coeffi-cients of-0.65,-0.63,and-0.66,respectively(all P＜0.01).Conclusion The expression level of CD169 in NCM type monocytes could be used as an auxiliary diagnostic marker for the children with respiratory viral infection.The changes of monocyte subsets during respiratory viral infection course in children may involve that more CM type monocytes differentiate into IM type monocytes,and some IM type monocytes do not differentiate into NCM type monocytes in proportion.IM and NCM type monocytes may play important roles in the early stage of respiratory viral infections in children.CD169 serves as a marker of monocyte activation.

Guided by the pathogenesis of"structure-activity imbalance of lung collaterals",this paper proposes that structure-activity imbalance of lung collaterals is the initial factor of idiopathic pulmonary fibrosis(IPF)and elucidates the pathogenesis of abnormal changes in biomechanical properties of IPF.It is postulated that the changes of biomechanical properties of lung tissue are closely related to the injury of lung qi collaterals,the abnormal mechanical stress are closely related to the injury of lung blood collaterals,and the biomechanical response of intrapulmonary resident cells is closely related to the structure-activity imbalance of lung collaterals,which ultimately leading to abnormal increase in lung tissue stiffness and progressive scarring formation in lung tissue.Integrating traditional pathogenesis concepts with microscopic pathological changes,and the in-depth exploration of the correlation between the structure-activity imbalance of lung collaterals and the biomechanical properties of IPF can provide direction for exploring IPF medical-engineering cross research,which are of great significance for enriching the syndrome and treatment system of lung collateral diseases.

Objective To explore the value of peripheral blood monocyte subsets and their CD169 expression levels in the diagnosis of common respiratory viral infections and the immune mechanism of the infection in children.Methods A total of 125 children with re-spiratory viral infections(virus infection group),71 children with bacterial respiratory infections(bacteria infection group),and 35 healthy children(healthy control group)admitted to the Third Affiliated Hospital of Zhengzhou University from February 2022 to Octo-ber 2023 were included in this study.The counts of peripheral blood monocytes and lymphocytes were detected by hematologic analyzer.The proportions of lymphocyte subsets,monocyte subsets,and the expression levels of CD169 were detected by a flow cytometry.Mono-cyte subsets were classified into three types:classical monocytes(CM),intermediate monocytes(IM),and non-classical monocytes(NCM).ANOVA and Kruskal-Wallis H tests were used to screen for differentially expressed indicators among the three groups,and the receiver operator characteristic(ROC)curve was used to evaluate their diagnostic performance.Paired t-tests were used to analyze the differences in the indicators between the first day and the seventh day of hospitalization in the virus group.Spearman rank correlation a-nalysis was used to explore the relationship between CD 169 expression levels in monocyte subsets and the quantity of lymphocyte sub-sets.Results Statistically significant differences in the expression levels of CD169 in monocytes of CM,IM,and NCM types were ob-served in peripheral blood between the children's respiratory viral infection group and the healthy control group(all P＜0.01).In con-trast,no statistically significant differences in CD169 expression levels were found in monocytes of CM and IM type between the respira-tory viral infection group and the bacterial infection group(all P＞0.05).The differences in CD 169 expression levels among the groups were statistically significant in the NCM subset(P=0.008).The area under the ROC curve(AUC)of CD169 expression level in NCM type monocytes for diagnosing respiratory viral infections was 0.897(P＜0.01),with a cutoff point of ≥ 62.75％,sensitivity of 68.60％,and specificity of 91.80％.The quantity and proportion of CM,IM,and NCM type monocytes did not show statistically signif-icant differences between the respiratory viral infection group and the bacterial infection group(all P＞0.05).However,there were sig-nificant differences in the quantity and proportion of CM and IM type monocytes,as well as the proportion of NCM type monocytes,be-tween the virus infection group and the healthy control group(all P＜0.05).The proportions of CM,IM,and NCM type monocytes,the quantity of IM type monocytes,and the CD169 expression levels of monocyte subsets showed statistically significant differences between the first day and the seventh day after admission(all P＜0.05).There were no statistically significant differences in the quantity of CM and NCM type monocytes between the first day and the seventh day after admission(all P＞0.05).The expression levels of CD169 in peripheral blood CM,IM,and NCM type monocytes were negatively correlated with the number of CD8+T cells with correlation coeffi-cients of-0.65,-0.63,and-0.66,respectively(all P＜0.01).Conclusion The expression level of CD169 in NCM type monocytes could be used as an auxiliary diagnostic marker for the children with respiratory viral infection.The changes of monocyte subsets during respiratory viral infection course in children may involve that more CM type monocytes differentiate into IM type monocytes,and some IM type monocytes do not differentiate into NCM type monocytes in proportion.IM and NCM type monocytes may play important roles in the early stage of respiratory viral infections in children.CD169 serves as a marker of monocyte activation.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload. METHODS: Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca²⁺-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method. RESULTS: Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05). CONCLUSION EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture ; Male ; Animals ; Rats, Sprague-Dawley ; Learning ; Memory ; Signal Transduction ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Memory Disorders/therapy* ; Brain-Derived Neurotrophic Factor/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Dementia, Vascular/therapy*

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Objective To invesitgate the epidemiological characteristics of common allergens in 10 664 patients with allergic diseases in Zhengzhou area.Methods A total of 10 664 patients visited our hospital and underwent serum allergen screening during January 2013 and August 2021 were selected,and their serum sIgE results were retrospectively analyzed.Results The total positive rate of sIgE to allergens in 10 664 patients was 69.82%.The positive rate of sIgE to inhalant allergens was significantly higher than that to in-gestive allergens(χ2=99.15,P＜0.01).The top three inhalant allergens were grass and tree combination,dust mite combination,and cockroach.The top three ingestive allergens were egg protein,milk,and seafood combination.The positive rate of sIgE to ingestive al-lergens in males was significantly higher than that in females(χ2=8.18,P＜0.01).The highest positive rate of sIgE to ingestive aller-gens was found in the early childhood period(χ2=125.92,P＜0.05).The highest positive rate of sIgE to inhalant allergens was found in the school-age and preschool periods(χ2=283.76,P＜0.01).The proportions of sIgE to cockroach and house dust mite showed a de-creasing trend year by year,while the proportions of sIgE to milk,peanut,lamb,and seafood combination showed an increasing trend year by year.Conclusion The top three inhalant and ingestive allergens in Zhengzhou area are grass and tree combination,dust mite,cockroach and egg protein,milk,seafood combination,respectively.In recent years,the allergies to milk,peanut,lamb,and seafood should be paid attention.