ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Eosinophil extracellular traps (EETs), an important pathway of eosinophil to exert its effects, are composed of DNA fibers, histone and eosinophil granule proteins. Recently, many researches have shown that EETs play an important role in the genesis and development of respiratory diseases including asthma, allergic bronchopulmonary aspergillosis and chronic obstructive pulmonary disease. EETs can directly damage airway epithelial cells, promote airway inflammation and airway hypersecretion, increase the stickiness of secretions and induce the generation of autoantibody, helping eosinophils and their products participate in a cascade of events leading to inflammation and disease. Researches on EETs can also be helpful in investigating new targets for the treatment of chronic airway diseases.

The data of a case of congenital subglottic stenosis (C-SGS) who underwent slide laryngotracheoplasty in the Center for Respiratory Intervention, Children′s Hospital Affiliated to Shandong University in December 2021 was analyzed retrospectively.The patient was a girl aged 2 months and 15 days.She visited the hospital 23 days after tracheotomy due to dyspnea for more than 2 months.The bronchoscopy and annular cartilage B ultrasound results suggested subglottic stenosis and no scar hyperplasia.Based on the medical history, the child was diagnosed with C-SGS.Slide laryngotracheoplasty was performed 2 weeks after admission, and the tracheotomy tube was removed after surgery.The child was followed up 2 months after surgery, and she recovered well with no dyspnea.The study results suggest that early and safe slide laryngotracheoplasty after definite diagnosis can provide immediate and sufficient airway space for C-SGS patients, and protect their voice and swallowing function.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To explore the clinical typing, diagnostic method and treatment plan of congenital tracheal stenosis (CTS) combined with communicating bronchopulmonary foregut malformation (CBPFM) in children.Methods:The clinical data of 2 children with CTS and CBPFM who were treated in the Center for Respiratory Intervention of Children′s Hospital Affiliated to Shandong University in May 2021 and January 2022 were retrospectively analyzed.Studies were retrieved from domestic and foreign databases, so as to summarize the clinical characteristics of CTS complicated with CBPFM and investigate the typing method of CBPFM.Results:One patient was a 4-year-old girl, who sought the medical advice due to " recurrent cough and asthma for more than 4 years" . She was diagnosed with typeⅡ CBPFM at the right side and CTS.Surgical thoracoscopic right pneumonectomy plus oesophageal repair was performed.The other patient was a 7-month-and-2-day-old female, who visited the hospital for " difficult eating, dyspnea and purple lip cyanosis for 7 months" . This patient was diagnosed with typeⅡ CBPFM at the left side and CTS.Slide tracheoplasty and left pneumonectomy+ oesophageal repair were performed successively.Eight English and one Chinese studies were collected.Twenty-one children with CBPFM and 12 children with CTS and CBPFM were included.Eleven CTS cases with sufficient diagnostic evidence were complicated with typeⅠA and typeⅡCBPFM.Conclusions:CTS and CBPFM can lead to severe wheezing and dyspnea.Clinicians should enhance their awareness and be more cautious.There may be a potential link between CTS and typeⅠA and typeⅡCBPFM, and further investigation is required.

Objective:To study the risk factors of hypotension after ligation of patent ductus arteriosus (PDA) in very/extremely low birth weight infants (VLBWI/ELBWI).Method:From March 2016 to January 2021, preterm infants with birth weight <1 500 g receiving bedside PDA ligation in the neonatal intensive care unit (NICU) of our hospital were enrolled in the study. According to the occurrence of hypotension within 72 hours after ligation, the infants were assigned into non-hypotension group and hypotension group. The general status and perioperative conditions of the two groups were analyzed. Multivariate Logistic regression was used to analyze the risk factors of hypotension.Result:A total of 44 cases were enrolled, including 33 in non-hypotension group and 11 in hypotension group. Univariate analysis showed that hypotension group had significantly more cases with body weight <1 100 g during surgery and receiving preoperative high frequency oscillatory ventilation (HFOV) than non-hypotension group ( P<0.05). Multivariate Logistic regression analysis showed that weight <1 100 g during surgery ( OR=12.045, 95% CI 1.351~107.394, P=0.026) and receiving preoperative HFOV ( OR=27.832, 95% CI 1.363~568.292, P=0.031)were independent risk factors of hypotension. Conclusion:Hypotension is one of the common complications of PDA ligation in VLBWI/ELBWI. The infant's body weight during ligation and receiving preoperative HFOV are independent risk factors of hypotension.

To compare the effects of endogenous 3-nitrotyrosine and non-natural 4-nitrophenylalanine in PD-L1 vaccine on the differentiation of T cell subsets, two immunogenic amino acids were introduced into the same site of PD-L1 vaccine. Two PD-L1 mutants with 3-nitrotyrosine and 4-nitrophenylalanine were obtained, respectively, using genetic code expansion technology. Mice were immunized with these two mutants, and their effects on the differentiation of T cell subsets in spleen were analyzed. The results of flow cytometry showed that the introduction of 4-nitrophenylalanine in PD-L1 vaccine could promote the polarization of Th1 cells while reducing the proportion of Treg cells; the introduction of 3-nitrotyrosine had no effect on the polarization of Th1 cells, while significantly increasing the proportion of Treg and Th17 cells. The introduction of both into PD-L1 vaccine could promote the response of CD8+ T cells in spleen, and the response of PD-L1 mutant containing 4-nitrophenylalanine was stronger. In summary, the non-natural 4-nitrophenylalanine is more suitable for the design of tumor vaccines as compared with endogenous 3-nitrotyrosine.