OBJECTIVE To investigate the effect of Jianpi Yangzheng(JPYZ)formula regulating tumor-associated macrophage(TAM)exosomes on anoikis in gastric cancer and its mechanism.METHODS TAM model was established by inducing human mononuclear THP-1 cells in vitro;M0,TAM and TAM+JPYZ formula exosomes were extracted by ultracentrifugation and co-incuba-ted with gastric cancer cells.Flow cytometry was used to detect the effect of exosomes in each group on anoikis in gastric cancer cells.A BALB/c transplanted tumor mouse model was constructed,and the expression level of apoptotic proteins in transplanted tumors was detected by Western blot.Label-free mass spectrometry proteomics and bioinformatics were used to analyze the differential proteins in gastric cancer cells before and after intervention;Western blot and qPCR experiments were used to detect the expression level of dif-ferential protein isocitrate dehydrogenase 1(IDH1),and ubiquitination experiments were used to detect the ubiquitination level of IDH1;kits were used to detect the levels of α-ketoglutarate(α-KG),NADPH/NADP+,glutathione(GSH/GSSG)and reactive oxy-gen species(ROS)content.RESULTS The anoikis rate of gastric cancer cells was reduced after TAM exosomes intervention(P<0.05,P<0.01),while it was significantly increased after TAM+JPYZ exosomes intervention(P<0.05,P<0.01).In the in vivo mouse experiment,the ratio of Cleaved Caspase-3/Caspase-3 in the tumor of the TAM exosome group was reduced(P<0.05),while the ra-tio was significantly increased after TAM+JPYZ exosome intervention(P<0.05).Proteomic analysis showed that IDH1 was significant-ly different after intervention,and was related to tricarboxylic acid cycle metabolism.Compared with the M0 group,the IDH1 ubiquiti-nation level of gastric cancer cells in the TAM group with exosome intervention was increased,the levels of α-KG,NADPH/NADP+and GSH/GSSG were significantly increased,and the ROS content was reduced(P<0.05),while TAM+JPYZ exosomes could reverse the above phenomenon.CONCLUSION JPYZ Formula can regulate TAM exosomes to cause ubiquitin degradation of IDH1 in gas-tric cancer cells,reduce the level of tricarboxylic acid cycle metabolism in gastric cancer cells,promote ROS accumulation,induce anoikis in gastric cancer,and thus inhibit the development of gastric cancer.

Objective To observe the manifestations of isolated bicuspid aortic valve(i-BAV)in children using echocardiography.Methods Echocardiographic data of 79 children with i-BAV were retrospectively analyzed,and classification of i-BAV was performed.The patients were divided into complication group(n=50)and non-complication group(n=29)according to the existence of valve and/or aortic involvement or not,and echocardiographic parameters were compared between groups.Results After adjusting body surface area(BSA),in complication group,left ventricular end-systolic diameter/BSA was lower,while left ventricular myocardial mass index group was higher than those in non-complication group(both P＜0.05).Type 0 i-BAV was found in 22 cases,with lat subtype as the most common ones(18/22,81.82％),while Type Ⅰ was observed in 57 cases with L-R subtype as the most common ones(39/57,68.42％).The most common subtype in complication group was also Type Ⅰ L-R(31/50,62.00％),with incidence of valve involvement of 90.00％(45/50),mainly including mild aortic stenosis and/or incompetence(37/45,82.22％),and incidence of aorta involvement of 24.00％(12/50),all with type Ⅰ or Ⅱ aortic widening.Conclusion The most common subtype of i-BAV in children was type Ⅰ L-R,with mild valve damage as the main complication and possibility of left ventricular myocardial remodeling.

Objective:To investigate the effect of mindfulness-based cognitive therapy (MBCT) on mindfulness attention awareness, experiential avoidance, and cognitive fusion in individuals with general anxiety disorder(GAD).Methods:A total of 53 patients aged 18-60 years who met the GAD diagnostic criteria of DSM-5 were selected from the Seventh People's Hospital of Hangzhou from May 2021 to September 2022.After receiving routine treatment, patients were randomly assigned to two groups: MBCT group( n=26) for an 8-week mindfulness cognitive therapy and health education group( n=27) for an 8-week health education program. Participants were evaluated using the generalized anxiety disorder scale(GAD-7), acceptance and action questionnaire-2nd edition(AAQ-Ⅱ), cognitive fusion questionnaire(CFQ), and mindful attention awareness scale (MAAS) before and after the intervention.Data were analyzed using SPSS 26.0 software, with the chi-square test, independent sample t-test, and paired sample t-test. Results:(1)There was no significant difference in MAAS score between the two groups before the intervention (42.63±10.18, 47.67±9.52, t=-1.55, P=0.13). However, after the intervention, the MAAS score in MBCT group was significantly higher than that in the health education group(54.42±9.87, 47.83±7.59, t=-2.27, P=0.03). (2) No significant difference was observed in CFQ score between the two groups before the intervention (57.11±15.97, 53.50±12.01, t=-0.77, P=0.45). However, after the intervention, the CFQ score in the MBCT group was significantly lower than that in the health education group(38.32±10.31, 47.11±10.66, t=-2.51, P<0.01). (3) There was no significant difference in AAQ-Ⅱ scores between the two groups before the intervention(33.79±7.90, 30.00±7.23, t=1.52, P=0.14). After the intervention, the AAQ-Ⅱ score in the MBCT group was significantly lower than that in the health education group(21.89±8.69, 30.22±8.68, t=-3.51, P<0.01) . Conclusion:MBCT has a positive effect on enhancing mindfulness attention awareness, reducing cognitive fusion, and mitigating experiential avoidance in GAD patients.

Objective:To compare the efficacy of haplotype hematopoietic stem cell transplantation (HIDT) and sibling matched hematopoietic stem cell transplantation (MSDT) in the treatment of complete remission (CR) acute T-lymphoblastic leukemia (T-ALL) .Methods:We retrospectively analyzed the clinical characteristics and outcomes of 98 patients who underwent HSCT in Hebei Yanda Ludaopei hospital with HID ( n=81) or ISD ( n=17) between May 2012 and May 2016. Results:The incidence of grades 2-4 and 3-4 acute-versus-host disease 100 days after HSCT were 51.9% (95% Confidence interval [ CI] 42.0%-64.0%) vs 29.4% (95% CI 14.1%-61.4%) ( P=0.072) and 9.8% (95% CI 5.1%-19.1%) vs 11.8% (95% CI 3.2%-43.3%) ( P=1.000) for HIDT and MSDT. The 100-day cumulative incidences of CMV and EBV viremia were 53.1% (95% CI 43.3%-65.2%) vs 29.4% (95% CI 14.1%-61.4%) ( P=0.115) and 35.8% (95% CI 26.8%-47.9%) vs11.8% (95% CI 3.2%-43.3%) ( P=0.048) . The 5-year overall survival, leukemia-free survival, cumulative incidences of relapse, and no-relapse mortality were 60.5% (95% CI 5.4%-49.0%) vs 68.8% (95% CI 11.8%-40.0%) ( P=0.315) , 58.0% (95% CI 5.5%-46.5%) vs 68.8% (95% CI 11.8%-40.0%) ( P=0.258) , 16.1% (95% CI 9.8%-26.4%) vs 11.8% (95% CI 3.2%-43.3%) ( P=0.643) , 25.9% (95% CI 17.9%-37.5%) vs 19.4% (95% CI 6.9%-54.4%) ( P=0.386) for HIDT and MSDT, respectively. Conclusion:HID could be a valid alternative donor for patients with T-ALL in CR lacking an identical donor.

Objective:To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT.Methods:Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia.Results:A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95% CI 23.0%-70.6%) , 41.8% (95% CI 17.3%-64.9%) , 8.8% (95% CI 2.9%-26.4%) , and 51.1% (95% CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95% CI 12.7%-73.5%) and 75.0% (95% CI 51.4% -88.8%) ( P=0.017) , respectively. Conclusion:CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Objective:To explore the effects of quality control circle activity in the respiratory function exercise in patients with esophageal cancer.Methods:From June 2018 to June 2019, convenience sampling was used to select 96 patients with esophageal cancer admitted to the Cancer Hospital Affiliated to Zhengzhou University as the research object. According to the principle of computer randomization, patients were divided into experimental group and control group, with 48 cases in each group. Patients in control group were given nursing case based on enhanced recovery after surgery, and experimental group carried out quality control circle activity on the basis of the control group. The correct rate of breathing exercise and the ratio of forced expiratory volume in the first second to forced vital capacity (FEV 1/FVC) were compared between the two groups of patients. Results:After intervention, the correct rate of respiratory function exercise in experimental group was higher than that in control group, and the difference was statistically significant ( P<0.05) . The FEV 1/FVC of experimental group was higher than that of control group one day before discharge, and the difference was also statistically significant ( P<0.05) . Conclusions:Quality control circle activity applied to patients after esophageal cancer surgery can increase the correct rate of patients' respiratory function exercise and effectively improve the patient's lung function.

Objective:To investigate the predictive value of total cholesterol / high density lipoprotein cholesterol ratio (TC/HDL) for ischemic stroke in patients with coronary heart disease (CHD) .Methods:A total of 1 983 inpatients with CHD in the Affiliated Hospital of Jining Medical University from January 1, 2017 to December 31, 2017 were selected as subjects by cluster sampling method. The clinical data were collected and followed up prospectively for 2 years.Results:During the 2-year follow-up period, 36 cases of ischemic stroke occurred in patients with CHD, and the incidence rate was 1.82% (36/1 983) . There was a curvilinear relationship between TC/HDL and ischemic stroke in male patients with CHD, and the tipping point was 3.84.When TC / HDL was less than 3.84, TC / HDL was negatively correlated with the incidence of ischemic stroke. The incidence of ischemic stroke decreased by 72% for each additional unit of TC/HDL ( P=0.049) . When TC/HDL was over 3.84, there was no correlation between TC / HDL and the incidence of ischemic stroke ( P=0.267) . There was a curvilinear relationship between TC/HDL and ischemic stroke in female patients with CHD, and the tipping point was 2.81. When TC / HDL was less than 2.81, TC / HDL was negatively correlated with the incidence of ischemic stroke. The incidence of ischemic stroke decreased by 99% for each additional unit of TC/HDL ( P=0.019) . When TC/HDL was over 2.81, there was no correlation between TC / HDL and the incidence of ischemic stroke ( P=0.110) . Conclusions:TC/HDL has different thresholds in predicting ischemic stroke in CHD patients with different genders, which has a certain clinical significance in predicting the prognosis of patients with coronary heart disease.

Objective:To explore the range of medical reference value of thyroid hormone of pregnant women in early pregnancy in Jinan after adjustment of salt iodine content, so as to provide basis for clinical diagnosis and treatment of thyroid diseases of pregnant women in early pregnancy.Methods:A prospective study was conducted in 560 pregnant women in early pregnancy (0-13 weeks) who had underwent prenatal examination and thyroid function testing in Shandong Provincial Maternal and Child Health Care Hospital from January to December 2018. At the same time, 100 healthy non-pregnant women who were examined in the Health Examination Center of Shandong Provincial Maternal and Child Health Care Hospital were selected as the control population. Urine samples of pregnant women in early pregnancy were collected, and urinary iodine content was detected by arsenic cerium catalytic spectrophotometry. Venous blood samples were collected from pregnant women in early pregnancy and control population, the serum levels of free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were detected by electrochemiluminescence (ECL), and the medical reference values of FT 3, FT 4 and TSH were established. Results:The median urinary iodine of pregnant women in early pregnancy was 162.21 μg/L, which was in the appropriate level of iodine. After the adjustment of salt iodine content, the medical reference values of FT 3, FT 4 and TSH in pregnant women in early pregnancy were 3.86-6.15 pmol/L, 12.56-22.16 pmol/L and 0.01-3.48 mU/ L, respectively; and the medical reference values of FT 3, FT 4 and TSH in control population were 3.55-6.05 pmol/L, 9.93-20.58 pmol/L and 0.54-5.92 mU/L, respectively. Conclusions:The iodine nutrition of pregnant women in early pregnancy in Jinan is appropriate after the adjustment of salt iodine content. The medical reference values of FT 3, FT 4 and TSH in pregnant women in early pregnancy are different from those in the healthy non-pregnant women. Therefore, it is of clinical significance to establish a medical reference value range of thyroid hormone for pregnant women in early pregnancy.

Objective:To study the clinical results and prognostic factors for allo-HSCT of Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia (ALL) in complete remission (CR) in the era of tyrosine kinase inhibitors (TKI) . Methods:We performed a retrospective analysis of the clinical characteristics of 116 patients with Ph +ALL who underwent allo-HSCT while in CR. Results:The study population included 72 men and 44 women. The median patient age was 20 years (4-64 years) . The patients received sibling-identical donor ( n=21) , haplo ( n=77) , and unrelated donor ( n=18) HSCT. The overall survival (OS) rate at 5 years was 73.2% (95% CI 63.8% -80.5% ) . In particular, the 5-year OS can reach 87.5% when the time from diagnosis to transplant is <180 days. The 5-years DFS was 61.4% (95% CI 51.8% -69.7% ) , the 5-year molecular and morphology cumulative relapse incidence was 18.5% (95% CI 12.6% -27.3% ) , and the 5-year TRM was 19.9% (95% CI 13.8% -28.7% ) . A multivariate analysis showed that an age range of 15-39 years ( HR=2.730, P=0.044) , time from diagnosis to HSCT ≥ 180 days ( HR=4.534, P=0.010) , and Ⅲ-Ⅳgrade aGVHD ( HR=7.558, P=0.000) were significantly associated with an inferior overall survival. Limited cGVHD subgroup had better OS ( HR=0.300, P=0.034) . Sex, WBC count at diagnosis, type of BCR-ABL fusion genes, somatic gene mutations, CR 1 or >CR 1, MRD negative or positive, conditioning regimen based on TBI or Bu, conditioning intensity, donor source, GVHD prophylactic proposal using cyclosporine or tacrolimus, presence/absence of CMV viremia, and presence/absence of EBV viremia were not significantly different in terms of the OS and DFS. Conclusion:Factors influencing the overall survival of Ph + ALL patients who underwent allo-HSCT in CR in the TKI era include age, time form diagnosis to HSCT, and aGVHD severity.

Objective:To evaluate the association of TP53 mutations with the clinical outcomes of Ph-negative B-ALL following allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Total 300 patients with Ph-negative B-ALL who underwent allo-HSCT at the Hebei Yanda Ludaopei Hospital from May 2012 to May 2017 were retrospectively analyzed; their clinical characteristics, TP53 gene mutation type, and association between TP53 mutations and transplantation outcomes, including leukemia-free survival (LFS) , overall survival (OS) , non-relapse mortality (NRM) , relapse, and GVHD, were evaluated.Results:Total 23 patients had TP53 mutations; all the TP53 mutations affected P53’DNA-binding domain. The 5-year-LFS, OS, and RI were 34.8% and 62.3% ( P=0.001) , 41.9% and 65.1% ( P=0.020) , and 47.8% and 14.8% ( P=0.000) , respectively, for TP53 mutations and wild-type TP53 patients. However, there were no significant differences in NRM and GVHD. Multivariate analysis showed that TP53 mutations remained adverse prognostic factors for LFS, OS, and RI after allo-HSCT. Conclusion:Some patients with TP53 mutations can achieve long-term survival with allo-HSCT. TP53 mutations are adverse prognostic factors for Ph-negative B-ALL patients who undergo allo-HSCT.