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.

Background and Aims:Cholangiocarcinoma,a rare malignant tumor,is difficult to diagnose and often detected at an advanced stage,limiting treatment options to palliative care.Conventional chemotherapy drugs have poor efficacy against cholangiocarcinoma,making the search for new treatments critical.This study was conducted to investigate the effects of Huai'erjunzhi on the malignant biological behavior of human cholangiocarcinoma cells and its relationship with the TGF-β/Smad pathway,aiming to provide a theoretical basis for the use of Huai'erjunzhi in cholangiocarcinoma treatment. Methods:Human normal liver cells(L-02)and human cholangiocarcinoma cells(HuCCT1)were incubated with different concentrations of Huai'erjunzhi for various durations.Cell proliferation was assessed,and the half-maximal inhibitory concentration(IC50)was calculated.HuCCT1 cells were divided into a negative control group(no intervention),a positive control group(15 mg/L cisplatin),and different Huai'erjunzhi intervention groups(1/5 IC50,2/5 IC50,and IC50 based on preliminary experimental results).Scratch and Transwell assays were used to measure cell migration and invasion,while Western blot was employed to detect the expression of proteins related to the TGF-β/Smad pathway in HuCCT1 cells. Results:Only high concentrations of Huai'erjunzhi(＞312.5 mg/L)significantly inhibited the proliferation of L-02 cells.Huai'erjunzhi significantly inhibited the proliferation of HuCCT1 cells at concentrations above 5 mg/L in a concentration-dependent manner(all P＜0.05),with IC50 values of 138.52 mg/L at 24 h,99.41 mg/L at 48 h,and 113.52 mg/L at 72 h.Compared with the negative control group,the positive control group and the three Huai'erjunzhi intervention groups(20,40,and 100 mg/L)exhibited reduced migration distance,decreased invasive cell numbers,lower expression of TGF-β1,Smad2,Smad3,Smad4,N-cadherin,Snail,and Slug,and increased expression of E-cadherin(all P＜0.05).Compared with the positive control group,these changes in the Huai'erjunzhi groups were less pronounced but showed a clear concentration-dependent relationship(all P＜0.05). Conclusion:Huai'erjunzhi can potentially inhibit the malignant biological behavior of HuCCT1 cells by inhibiting the TGF-β/Smad pathway.

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.

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

Objective:To investigate the demand and influencing factors of home care social support services for the elderly with dementia in urban areas, and provide a decision-making basis for improving home care social support services for the elderly with dementia.Methods:This was a cross-sectional study. From March 2021 to March 2022, 386 family caregivers of elderly people with dementia were randomly selected from tertiary hospitals in four central urban areas of Wuhan by stratified sampling method. A questionnaire was used to investigate the current situation and attributes of the demand for home care social support services for the elderly with dementia in urban areas. The importance of the demand for home care social support services for the elderly with dementia in urban areas was calculated by the Better-Worse coefficient method and sensitivity formula method. The optimal scale regression model was used to analyze the influencing factors and influencing forces of independent variables on service demand.Results:The score of social support service demand for home care was (88.6 ± 29.71) points. The Better coefficient of demand for all social support services was greater than the absolute value of the Worse coefficient. One requirement (pressure ulcer prevention and treatment guidance) was a one-dimensional attribute, and the remaining 29 items were charm attributes. The top 6 items in importance ranking were 2 items of informational support (pressure ulcer prevention and treatment guidance; telephone counselling guidance for family caregivers), 1 items of instrumental support (financial assistance for family caregivers) and 3 items of social companionship support(cultural recreation/physical activity activities, door-to-door accompaniment, accompany the elderly to social activities). Optimal scale regression model test: all four models of social support service demand were statistically significant ( F values were 2.75-4.23, all P <0.01). The gender, education level, number of children of the elderly with dementia, age,education level, self rated physical condition of family caregivers, the average monthly income of families, and the relationship between family caregivers and the elderly with dementia were the influencing factors of self-esteem support (all P<0.05). The educational level, marital status, type of dementia of the elderly with dementia, educational level, self rated physical condition of family caregivers, the average monthly income of the family, and the relationship between family caregivers and the elderly with dementia were the influencing factors of informational support (all P <0.05). The educational level and type of dementia of the elderly with dementia, the educational level, self rated physical condition of family caregivers, and the average monthly income of families were the influencing factors of social companionship support (all P <0.05). The type of dementia of the elderly with dementia, the self rated physical condition of family caregivers, the average monthly income of families, and the relationship between family caregivers and elderly relatives were the influencing factors of instrumental support (all P <0.05). Five times for caregiver human resources, 3 times for family economic resources and 3 times for the elderly with dementia, and 1 time for relatives resource factors were the top 3 times of independent variable influence force entered the ranking. Conclusions:The demand for social support services for home care of the elderly with dementia is low, with the characteristics of expectant tendency and centralized demand. The provision of home-based care social support services should give priority to meeting the needs of "pressure ulcer prevention and treatment guidance", and provide financial assistance, counseling and guidance, social companionship and other services as much as possible. Caregiver human resources are the key factors affecting home care social support services, family economic resources and the elderly with dementia are important factors, it is recommended to fully tap the potential of relatives resources and community resources.

Objective:To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy.Methods:Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging ( M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results:Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time.Conclusions:Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

Objective:To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy.Methods:Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging ( M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results:Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time.Conclusions:Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

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.

The clinical features and genetic variants of the patient with sitosterolemia who was referred to Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine from June 2019 to January 2020 were retrospectively analyzed.The patient was treated with Ezetimibe tablets combined with diet control, and the follow-up was performed regularly.Besides, a relevant literature review was conducted.A 7-year and 5-month-old boy was referred to the hospital for " repeated thrombocytopenia for 7 months" with normal serum cholesterol.The whole exome sequencing showed that compound heterozygous mutations (p.Arg446*, p.Gln251*) in ABCG5 gene were inherited from their parents respectively.Hence, he was diagnosed with sitosterolemia.After 29 days of treatment with Ezetimibe tablets combined with diet control, the patient′s platelets returned to normal values without obvious adverse reactions related to drugs.Children with sitosterolemia may present with rare thrombocytopenia, and the therapeutic effects of Ezetimibe tablets combined with diet control are favorable.