Objective:To investigate, for multi-sensitized allergic rhinitis (AR) patients allergic to dust mites combined with other allergens (pollen, mold, animal dander, etc.), whether the single dust mite subcutaneous immunotherapy (SCIT) can improve the specific symptoms caused by other allergens in the patients, and to analyze the relationship between the effectiveness of symptom improvement in these patients and the type, quantity and severity of the allergens.Methods:A multicenter retrospective study was conducted to collect mul-sensitized AR patients from allergy or respiratory departments of 5 hospitals who received house dust mite allergen preparation SCIT for 12 to 36 months and met other inclusion and exclusion criteria from February to July 2024. General clinical data were collected and the perennial or seasonal symptoms before and after treatment were evaluated with visual analogue scale (VAS) to assess whether there was an perennial or allergen-specific symptom improvement (VAS score decrease ≥30%), by which the patients were divided into effective group and ineffective. R software was used to analyze the differences between groups by using Fisher′s exact test and Mann-Whitney U test. Results:A total of 62 patients were enrolled, and the treatment were effective in 39 of them, with an effective rate of 62.9%. For allergen-specific symptoms, the median age of the effective group was higher than that of the ineffective group (12 years old vs. 8 years old, P=0.039), and the effective rate in dust mite specific immunoglobin E (sIgE) grade ≤5 group was higher than that in sIgE grade >5 group (81.6% vs. 45.5%, P=0.008), and the effective rate of mold sIgE grade ≤2 group was higher than that of sIgE grade >2 group (83.3% vs. 28.6%, P=0.045), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). For perennial symptoms, the effective rate in the mold grade ≤2 group was higher than that in the sIgE grade >2 group (91.3% vs. 28.6%, P=0.010), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). There was no significant correlation between the treatment effectiveness of perennial or allergen-specific symptoms and the number of combined allergens, the grade of skin test, and the difference between the grade of combined allergens and that of dust mites ( P>0.05). Conclusion:Among the patients with multi-sensitized AR allergic to dust mites included in this study, single dust mite SCIT is effective in some of them, and for allergen-specific symptoms, the effective group was elder, and dust mite sIgE grade 6 and mold sIgE grade ≥2 was related to the low effective rate of SCIT. The present results are insufficient for selecting single or multiple AIT in any type of multi-sensitized patients.

Objective:To investigate, for multi-sensitized allergic rhinitis (AR) patients allergic to dust mites combined with other allergens (pollen, mold, animal dander, etc.), whether the single dust mite subcutaneous immunotherapy (SCIT) can improve the specific symptoms caused by other allergens in the patients, and to analyze the relationship between the effectiveness of symptom improvement in these patients and the type, quantity and severity of the allergens.Methods:A multicenter retrospective study was conducted to collect mul-sensitized AR patients from allergy or respiratory departments of 5 hospitals who received house dust mite allergen preparation SCIT for 12 to 36 months and met other inclusion and exclusion criteria from February to July 2024. General clinical data were collected and the perennial or seasonal symptoms before and after treatment were evaluated with visual analogue scale (VAS) to assess whether there was an perennial or allergen-specific symptom improvement (VAS score decrease ≥30%), by which the patients were divided into effective group and ineffective. R software was used to analyze the differences between groups by using Fisher′s exact test and Mann-Whitney U test. Results:A total of 62 patients were enrolled, and the treatment were effective in 39 of them, with an effective rate of 62.9%. For allergen-specific symptoms, the median age of the effective group was higher than that of the ineffective group (12 years old vs. 8 years old, P=0.039), and the effective rate in dust mite specific immunoglobin E (sIgE) grade ≤5 group was higher than that in sIgE grade >5 group (81.6% vs. 45.5%, P=0.008), and the effective rate of mold sIgE grade ≤2 group was higher than that of sIgE grade >2 group (83.3% vs. 28.6%, P=0.045), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). For perennial symptoms, the effective rate in the mold grade ≤2 group was higher than that in the sIgE grade >2 group (91.3% vs. 28.6%, P=0.010), and there was no statistically significant correlation between the other allergen grades and the effective rate ( P>0.05). There was no significant correlation between the treatment effectiveness of perennial or allergen-specific symptoms and the number of combined allergens, the grade of skin test, and the difference between the grade of combined allergens and that of dust mites ( P>0.05). Conclusion:Among the patients with multi-sensitized AR allergic to dust mites included in this study, single dust mite SCIT is effective in some of them, and for allergen-specific symptoms, the effective group was elder, and dust mite sIgE grade 6 and mold sIgE grade ≥2 was related to the low effective rate of SCIT. The present results are insufficient for selecting single or multiple AIT in any type of multi-sensitized patients.

Objective To investigate the value of stress hyperglycemia ratio(SHR)in predicting symptomatic intracranial hemorrhage(sICH)after successful recanalization of endovascular ther-apy(EVT)in patients with non-diabetic acute large vascular occlusive(LVO)stroke.Methods A total of 150 non-diabetic patients with acute stroke due to LVO admitted in our hospital from June 2022 to June 2024 were recruited,and all of them underwent EVT and obtained successful recanalization.According to whether sICH occurred 24 h after surgery,they were divided into a sICH group(15 cases)and a non-sICH group(135 cases).They were also assigned into a poor prognosis group(55 cases)and a good prognosis group(95 cases)according to the prognosis in 3 months after surgery.The general clinical data were compared between groups,and multivariate logistic regression analysis was used to identify the influencing factors for sICH and prognosis after successful EVT recanalization in the non-diabetic acute stroke patients.ROC curves were plotted to analyze the predictive value of SHR in sICH and prognosis after successful EVT reca-nalization in the patients.Results Significantly larger proportion of embolic occlusion,higher NIHSS score at admission and SHR were observed in the sICH group than the non-SICH group(66.67％vs 37.04％,P＜0.05;20.15±3.68 vs 15.62±3.10,P＜0.01;1.25±0.25 vs 1.01±0.28,P＜0.01).The poor prognosis group had obviously larger female ratio,advanced age,higher NIHSS score at admission,larger proportion of previous stroke history and higher SHR than the good prognosis group(49.09％vs 29.47％,P＜0.05;75.41±5.38 years old vs 72.56±5.63 years old,P＜0.01;18.65±3.71 vs 16.27±3.21,P＜0.01;32.73％vs 14.74％,P＜0.05;1.16±0.23 vs 1.02±0.25,P＜0.01).Multivariate logistic regression analysis showed that embolic occlusion,NIHSS score at admission and SHR were risk factors for sICH after successful EVT recanaliza-tion in non-diabetic acute stroke due to LVO(OR=2.038,95％CI:1.138-4.234,P=0.000;OR=2.026,95％CI:1.173-4.317,P=0.000;OR=1.996,95％CI:1.101-4.027,P=0.000),while gender,age,NIHSS score at admission,previous stroke history,and SHR were risk factors for poor prognosis in the patients(OR=2.004,95％CI:1.085-3.407,P=0.000;OR=2.075,95％CI:1.138-4.067,P=0.000;OR=2.010,95％CI:1.208-4.106,P=0.000;OR=2.034,95％CI:1.137-4.821,P=0.000;OR=2.038,95％CI:1.138-4.234,P=0.000).ROC curve analysis showed that the AUC value of SHR in predicting sICH and prognosis of the non-diabetic patients with acute stroke due to LVO after successful EVT recanalization was 0.797 and 0.823,with a sensitivity of 80.00％and 81.82％,and a specificity of 82.22％and 80.00％,respectively.Conclusion SHR can affect sICH and prognosis after successful EVT recanalization in non-diabetic acute LVO stroke patients,and it has a certain predictive value for sICH and poor prog-nosis of the patients.

Objective To investigate the value of stress hyperglycemia ratio(SHR)in predicting symptomatic intracranial hemorrhage(sICH)after successful recanalization of endovascular ther-apy(EVT)in patients with non-diabetic acute large vascular occlusive(LVO)stroke.Methods A total of 150 non-diabetic patients with acute stroke due to LVO admitted in our hospital from June 2022 to June 2024 were recruited,and all of them underwent EVT and obtained successful recanalization.According to whether sICH occurred 24 h after surgery,they were divided into a sICH group(15 cases)and a non-sICH group(135 cases).They were also assigned into a poor prognosis group(55 cases)and a good prognosis group(95 cases)according to the prognosis in 3 months after surgery.The general clinical data were compared between groups,and multivariate logistic regression analysis was used to identify the influencing factors for sICH and prognosis after successful EVT recanalization in the non-diabetic acute stroke patients.ROC curves were plotted to analyze the predictive value of SHR in sICH and prognosis after successful EVT reca-nalization in the patients.Results Significantly larger proportion of embolic occlusion,higher NIHSS score at admission and SHR were observed in the sICH group than the non-SICH group(66.67％vs 37.04％,P＜0.05;20.15±3.68 vs 15.62±3.10,P＜0.01;1.25±0.25 vs 1.01±0.28,P＜0.01).The poor prognosis group had obviously larger female ratio,advanced age,higher NIHSS score at admission,larger proportion of previous stroke history and higher SHR than the good prognosis group(49.09％vs 29.47％,P＜0.05;75.41±5.38 years old vs 72.56±5.63 years old,P＜0.01;18.65±3.71 vs 16.27±3.21,P＜0.01;32.73％vs 14.74％,P＜0.05;1.16±0.23 vs 1.02±0.25,P＜0.01).Multivariate logistic regression analysis showed that embolic occlusion,NIHSS score at admission and SHR were risk factors for sICH after successful EVT recanaliza-tion in non-diabetic acute stroke due to LVO(OR=2.038,95％CI:1.138-4.234,P=0.000;OR=2.026,95％CI:1.173-4.317,P=0.000;OR=1.996,95％CI:1.101-4.027,P=0.000),while gender,age,NIHSS score at admission,previous stroke history,and SHR were risk factors for poor prognosis in the patients(OR=2.004,95％CI:1.085-3.407,P=0.000;OR=2.075,95％CI:1.138-4.067,P=0.000;OR=2.010,95％CI:1.208-4.106,P=0.000;OR=2.034,95％CI:1.137-4.821,P=0.000;OR=2.038,95％CI:1.138-4.234,P=0.000).ROC curve analysis showed that the AUC value of SHR in predicting sICH and prognosis of the non-diabetic patients with acute stroke due to LVO after successful EVT recanalization was 0.797 and 0.823,with a sensitivity of 80.00％and 81.82％,and a specificity of 82.22％and 80.00％,respectively.Conclusion SHR can affect sICH and prognosis after successful EVT recanalization in non-diabetic acute LVO stroke patients,and it has a certain predictive value for sICH and poor prog-nosis of the patients.

OBJECTIVE To study the repair effect of ephedrine on lipopolysaccharide （LPS）-induced microglia function injury and its mechanism. METHODS Human microglia cells （HMC3） were used as research objects to investigate the effects of different concentrations of ephedrine （75， 150， 300， 600 μg/mL） on the viability and apoptosis of HMC3 cells. HMC3 cells were divided into control group （without drug intervention）， LPS group （1 μg/mL）， ephedrine group （1 μg/mL LPS+300 μg/mL ephedrine）， BAY11-7082 group [1 μg/mL LPS+5 μmol/L nuclear factor-κB （NF-κB） pathway inhibitor BAY11-7082]， inhibitor group （1 μg/mL LPS+300 μg/mL ephedrine+5 μmol/L BAY11-7082） and activator group （1 μg/mL LPS+300 μg/mL ephedrine+1 μmol/L NF-κB pathway activator Prostratin）. After 24 hours of drug treatment， cell migration， the levels of soluble interleukin-6（sIL-6）， interleukin-10（IL-10）， superoxide dismutase（SOD）and malondialdehyde（MDA）， and the expressions of NF-κB pathway-related proteins were all detected. RESULTS The viability of HMC3 cells could be increased significantly by 300 μg/mL ephedrine， while the apoptotic rate was decreased significantly （P＜0.05）. Compared with the control group， the number of migrating cells was increased significantly in the LPS group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were increased significantly， while the levels of IL-10 and SOD were decreased significantly （P＜0.05）. Compared with the LPS group， the above indexes were reversed significantly in the ephedrine group and BAY11-7082 group （P＜0.05）. Compared with the ephedrine group， the number of migrating cells was decreased significantly in the inhibitor group； the levels of sIL-6 and MDA， the phosphorylation of NF-κB protein were decreased significantly， while the levels of IL-10 and SOD were increased significantly （P＜0.05）. The above indexes were reversed significantly in the activator group （P＜0.05）can repair cell injury by inhibiting LPS induced apoptosis， migration， inflammation and oxidant stress of HMC3 cells， the mechanism of which may be associated with inhibiting the activity of the NF-κB signaling pathway.

Objective To investigate the relationship between the ratio of soluble hemoglobin scavenger receptor 163 protein(sCD163)/soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)in plasma and prognosis in patients with spontaneous acute cerebral hemorrhage(ACH).Methods From August 2020 to August 2022,90 patients with ACH admitted to the Department of Neurosurgery,Harison International Peace Hospital,Hengshui City were regarded as the research group.According to the Glasgow outcome scale,patients with ACH were separated into the poor prognosis group(n=38)and the good prognosis group(n=52).Another 45 healthy examinee who underwent physical examination were used as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to detect plasma sCD163 and sTWEAK levels,and the sCD163/sTWEAK ratio was calculated.Pearson method was applied to analyze the correlation between plasma sCD163,sTWEAK levels,sCD163/sTWEAK ratio and clinical data.Logistic regression was applied to analyze influencing factors of poor prognosis in patients with ACH.Receiver operating characteristic(ROC)was applied to analyze the predictive value of sCD163/sTWEAK ratio for poor prognosis of patients with ACH.Results The plasma levels of sCD163,sTWEAK and sCD163/sTWEAK ratio were obviously higher in the research group than those in the control group(P＜0.05).The plasma levels of sCD163,sTWEAK and sCD163/sTWEAK ratio were obviously lower in the good prognosis group than those in the poor prognosis group(P＜0.05).Hematoma volume,National Institutes of Health Stroke Scale(NIHSS)scores,hypertension and subtentorial hemorrhage were lower in the good prognosis group than those in the poor prognosis group,and low density lipoprotein cholesterol(LDL-C)was higher in the good prognosis group than that in the poor prognosis group(P＜0.05).Correlation analysis showed that plasma sCD163,and sTWEAK levels and the sCD163/sTWEAK ratio were positively correlated with bleeding site,hematoma volume,NIHSS score,white blood cell count,platelet count and neutrophil/lymphocyte ratio(NLR)(P＜0.05).Results of Logistic regression analysis showed that sCD163,sTWEAK,sCD163/sTWEAK ratio,hematoma volume,bleeding site and NIHSS score were influencing factors for poor prognosis in patients with ACH(P＜0.05).Results of receiver operating characteristic showed that the AUC of sCD163/sTWEAK ratio in evaluating poor prognosis of patients with ACH was 0.850,and the sensitivity and specificity were 86.84%and 69.23%.Conclusion The sCD163/sTWEAK ratio has a high level in the plasma of patients with ACH,which is associated with poor prognosis and has important value in predicting the prognosis of patients with ACH.

Objective:To compare the clinicopathological differences between elderly and non-elderly patients with idiopathic membranous nephropathy(IMN).Methods:Patients diagnosed with IMN via renal biopsy at Beijing Huairou Hospital, Beijing Changping Hospital of Traditional Chinese Medicine, and Beijing Hospital of Traditional Chinese Medicine from January 2017 to August 2021 were retrospectively enrolled.They were classified into the elderly group(≥65 years)and the non-elderly group(<65 years), and the clinicopathological differences between the two groups were compared.Results:A total of 207 IMN patients were included in the study, with a male to female ratio of 1.7∶1.0.There were 56 patients in the elderly group, aged(68.2±3.1)years, and 151 patients in the non-elderly group, aged(48.2±6.2)years.Compared with the non-elderly group, the elderly group had a longer time from onset to renal biopsy and a higher proportion of patients with renal insufficiency and hypertension( P<0.05). The elderly group had a lower eGFR, lower serum albumin, higher serum cholesterol, and higher low-density lipoprotein than the non-elderly group( P<0.05). The proportions of patients with glomerulosclerosis, renal tubular atrophy, and interstitial fibrosis in the elderly group were higher than in the non-elderly group( P<0.05). The positive rates of glomerular PLA2R antigen staining in the two groups were 90.6%(29/32)and 91.0%(111/122), respectively, and there was no statistically significant difference between the two groups.IgG4 deposition represented the most common IgG subtype, with 93.8%(30/32)in the elderly group and 94.3%(115/122)in the non-elderly group.There was no statistical significance between the two groups( P>0.05). Conclusions:Compared with non-elderly IMN patients, a higher proportion of elderly IMN patients has renal insufficiency, hypertension and chronic renal pathology.The glomerular deposition of pathogenic antigens in elderly IMN patients was similar to that in non-elderly IMN patients, suggesting no difference in pathogenesis between the two groups.The clinicopathological differences between the two groups may be related to age and complications.

Objective:To analyze the characteristics of sleep disorders in patients with Parkinson disease (PD) and to explore the relationship between respiratory events and rapid eye movement sleep with hypotonia.Methods:Thirty-nine PD patients compared with 75 controls matched with gender, age and body mass index(BMI) were collected in the Dalian Municipal Central Hospital from January 1, 2019 to September 31, 2019. Both groups underwent polysomnography monitoring. The characteristics of sleep disorders were analyzed and discussed.Results:Apnea and hypopnea index (AHI) during total sleep, AHI during non-rapid eye movement(NREM) sleep, AHI during rapid eye movement (REM) sleep, obstructive apnea index, mixed apnea index, central apnea index, total apnea index, hypopnea index, the time with pulse oximetry <90% and oxygen desaturation index in the PD group were lower than those in the control group: 3.70(0.80, 20.00) /h vs. 17.30(7.30, 28.20)/h, 2.30(0.70, 13.90)/h vs. 15.20(4.90, 27.50)/h, 2.30(0.00, 29.80)/h vs. 16.90(5.70, 39.50)/h, 0.30(0.00, 5.10)/h vs. 3.10(0.50, 7.80)/h, 0.00(0.00, 0.20)/h vs. 0.20(0.00, 0.60)/h, 0.00(0.00, 0.30)/h vs. 0.30(0.00, 0.80)/h, 0.70(0.00, 6.00)/h vs. 3.90(0.80, 10.70)/h, 1.70(0.50, 8.90)/h vs. 8.70(2.70, 14.90)/h, 0.00(0.00, 0.40)min vs. 0.20(0.00, 1.70)min, 4.10(1.10, 18.40)% vs. 16.50(9.30, 30.80)%, and the differences were statistically significant ( P<0.05). The mean pulse oximetry and minimum pulse oximetry in the PD group were higher than those in the control group: 96.00(95.00, 97.00)% vs. 95.00(94.00, 96.00)%, 89.00(82.00, 91.00)% vs. 85.00(81.00, 89.00)%, and the differences were statistically significant ( P<0.05). PD group was divided into PD with RSWA group (PD + RSWA) and PD without RSWA group (PD-RSWA) according to whether there was atonia or not. AHI during REM sleep in the PD+RSWA group was lower than that in the PD-RSWA group: 0.00(0.00, 5.40)/h vs. 5.75(0.52, 34.57)/h, and the difference was statistically significant ( P<0.05). Conclusions:PD has a protective effect on nocturnal respiratory events, which may be due to the increased muscle tone of upper airway.

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Animals ; Brain ; CRISPR-Cas Systems/genetics* ; Dependovirus/genetics* ; Haplorhini ; Phenotype ; Protein Kinases/genetics*

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.