Objective:To assess the efficacy and safety of azacitidine combined with lenalidomide in MDS patients and explore potential mechanisms of therapeutic response.Methods:Sixteen MDS patients with TP53 mutations received azacitidine plus lenalidomide at ZhongDa Hospital, Southeast University (January 2021–June 2025). Efficacy and safety were assessed, and TP53 mutation status was correlated with treatment response. Whole-transcriptome sequencing and bioinformatics were used to explore molecular biomarkers associated with therapeutic efficacy.Results:Sixteen patients (median age 69.5 years, range 52–82; 8 males, 8 females) were enrolled. According to the Molecular International Prognostic Scoring System (IPSS-M), 1, 2, and 13 patients were classified as median low, high, and very high risk, respectively. Among 16 TP53-mutated patients, 11 had biallelic mutations and 5 had monoallelic mutations. Overall response rate was 56.3% (9/16), composite complete remission rate (CRc) was 31.3% (5/16), and hematology improvement rate was 25% (4/16). Among TP53-mutated patients, the response rate was 56.3% (9/16), with variant allele frequency dropping from 65.6% to 16.5% in responders ( P=0.017). In patients with TP53 mutations and complex karyotype, response rate was 53.8% (7/13), with 57.1% (4/7) showing disappearance of CK post-treatment. The most common grade 3–4 nonhematologic adverse events were infections (9/16, 56.3% ), including pneumonia (4/16, 25.0% ), gastrointestinal infections (3/16, 18.8% ), perianal infections (1/16, 6.3% ) and sepsis (1/16, 6.3% ). High CBX8 expression may be linked to treatment response. Conclusion:Azacitidine plus lenalidomide is an effective and safe therapy for MDS, including patients with TP53 mutations and complex karyotypes. Treatment markedly reduces TP53 variant allele frequency in responders, and high CBX8 expression may predict therapeutic response.

Objective:To assess the efficacy and safety of azacitidine combined with lenalidomide in MDS patients and explore potential mechanisms of therapeutic response.Methods:Sixteen MDS patients with TP53 mutations received azacitidine plus lenalidomide at ZhongDa Hospital, Southeast University (January 2021–June 2025). Efficacy and safety were assessed, and TP53 mutation status was correlated with treatment response. Whole-transcriptome sequencing and bioinformatics were used to explore molecular biomarkers associated with therapeutic efficacy.Results:Sixteen patients (median age 69.5 years, range 52–82; 8 males, 8 females) were enrolled. According to the Molecular International Prognostic Scoring System (IPSS-M), 1, 2, and 13 patients were classified as median low, high, and very high risk, respectively. Among 16 TP53-mutated patients, 11 had biallelic mutations and 5 had monoallelic mutations. Overall response rate was 56.3% (9/16), composite complete remission rate (CRc) was 31.3% (5/16), and hematology improvement rate was 25% (4/16). Among TP53-mutated patients, the response rate was 56.3% (9/16), with variant allele frequency dropping from 65.6% to 16.5% in responders ( P=0.017). In patients with TP53 mutations and complex karyotype, response rate was 53.8% (7/13), with 57.1% (4/7) showing disappearance of CK post-treatment. The most common grade 3–4 nonhematologic adverse events were infections (9/16, 56.3% ), including pneumonia (4/16, 25.0% ), gastrointestinal infections (3/16, 18.8% ), perianal infections (1/16, 6.3% ) and sepsis (1/16, 6.3% ). High CBX8 expression may be linked to treatment response. Conclusion:Azacitidine plus lenalidomide is an effective and safe therapy for MDS, including patients with TP53 mutations and complex karyotypes. Treatment markedly reduces TP53 variant allele frequency in responders, and high CBX8 expression may predict therapeutic response.

Objective To evaluate the diagnostic value of ischemia-modified albumin(IMA)and the crea-tine kinase(CK)index in acute ischemic stroke(AIS).Methods According to the inclusion and exclusion cri-teria,totally 149 newly diagnosed and untreated AIS patients hospitalized in Henan Provincial People's Hospi-tal from October 2021 to October 2022 were selected as the AIS group.Additionally,156 healthy people who underwent the physical examination during the same period were selected as the control group.Activity levels of IMA,CK,creatine kinase-MB(CK-MB),lactate dehydrogenase(LDH)and hydroxybutyrate-dehydrogen-ase(HBDH)were measured using the Abbott C1600 biochemical analyzer,and the CK index(ratio of CK-MB to CK)was calculated.Relative risk factors were analyzed,receiver operating characteristics(ROC)curve was constructed,data were analyzed using SPSS27.0.1,graphs were plotted using GraphPad Prism 9.4.1,and differences in area under the curve(AUC)were compared using MedCalc(version 20.0.22).Results The AIS group exhibited significantly higher levels of IMA,CK-MB,and the CK index,and significantly lower levels of CK compared to the control group(all P＜0.05).Univariate logistic regression analysis revealed that both IMA and the CK index were risk factors for AIS(both P＜0.001).After adjusting for gender and age in a multivariate binary logistic regression analysis,IMA emerged as an independent risk factor for AIS(OR=1.901,95％CI:1.649-2.190,P＜0.001).IMA,CK-MB and CK index in the AIS group were significantly higher than those in the control group,and CK levels were significantly lower than those in the control group,and the differences were statistically significant(P＜0.05).Univariate Logistic regression analysis showed that IMA and CK index were risk factors for AIS(P＜0.001).After adjusting for sex and age in multivariate binary Logistic regression analysis,IMA was an independent risk factor for AIS(OR=1.901,95％CI:1.649-2.190,P＜0.001).The ROC curve demonstrated that AUC,the sensitivity and the specificity of sin-gle detection for IMA were 0.922,81.2％,and 90.4％,respectively.There was no significant difference compared to combined detection using IMA+CK index or IMA+CK index+CK(all P＞0.05).Conclusion IMA is an independent risk factor for AIS,which has strong diagnostic value and is worthy of clinical application.

Objective:To investigate the cytogenetic characteristics and influencing factors associated with first treatment response in primary childhood B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 49 children with primary B-ALL who were admitted to the First Hospital of Xiamen University from April 2019 to September 2021 were retrospectively collected, and the clinical characteristics, cytogenetic and molecular biology findings and other clinical indicators before and after treatment were obtained. Genotyping, clinical risk stratification after the first induction chemotherapy and chemotherapy regimen development were performed according to the pediatric ALL treatment specification (2018 version). The relationship between different genotypes and clinical indicators in children with B-ALL was analyzed, and the correlation between clinical risk stratification and each indicator was analyzed by Spearman rank correlation analysis.Results:The median age of 49 children was 3.0 years old (interquartile range: 3.2 years old), 32 cases (65.3%) were male and 17 cases (34.7%) were female, with a male-to-female ratio of 1.88∶1. Thirty-five cases (71.4%) had gene mutations before treatment and 14 cases (28.6%) had no mutations. Among the 35 cases with mutations, E2A-PBX1 was found in 5 cases (10.2%), including 1 case with Philadelphia chromosome (Ph)-like; IKZF1 deletion was found in 8 cases (16.3%), including 4 cases with Ph-like, 1 case with Ph-positive, and 1 case with MLL rearrangement; MLL rearrangement was found in 3 cases (6.1%); Ph-like alone was found in 12 cases (24.5%); TEL-AML1 was found in 6 cases (12.2%), including 2 cases with Ph-like; 1 case (2.0%) with Ph-positive alone. The clinical risk stratification showed that 7 cases (14.3%) had high risk, 28 cases (57.1%) had intermediate risk, and 14 cases (28.6%) had low risk. The proportions of patients with high and intermediate clinical risk before induction chemotherapy [20.0% (7/35) vs. 0.0% (0/14), 62.9% (22/35) vs. 42.9% (6/14)] and the proportion of patients with altered mutation status on day 33 of induction chemotherapy [42.9% (15/35) vs. 0.0% (0/14)] were higher in patients with mutations before induction chemotherapy than those in patients without gene mutations before treatment (all P < 0.01). The gene mutation or not before treatment was not correlated with gender, white blood cell count at first diagnosis, hormone sensitivity, minimal residual disease (MRD) from the 15th to the 19th day of induction chemotherapy, and MRD on the 33rd day of induction chemotherapy (all P > 0.05). Clinical risk stratification of children was associated with white blood cell count at first diagnosis ( r = 0.392, P = 0.005), neutrophil count ( r = 0.453, P = 0.001), lymphocyte count ( r = 0.418, P = 0.001), monocyte count ( r = 0.359, P = 0.017), blood uric acid level ( r = 0.378, P = 0.007), and proportion of bone marrow naive lymphocyte count before treatment ( r = 0.316, P = 0.027) and from 15th to the 19th day of induction chemotherapy ( r = 0.399, P = 0.005) and the 33rd day of induction chemotherapy ( r = 0.408, P = 0.028), proportion of children with bone marrow MRD ≥ 0.000 1 on the 33rd day of induction chemotherapy ( χ2 = 15.42, P < 0.001), and proportion of children with gene mutations before treatment ( χ2 = 9.10, P = 0.005). Conclusions:High levels of leukocytes, neutrophils, lymphocytes, monocytes, naive lymphocytes, blood uric acid, and naive lymphocytes from the 15th to the 19th day and the 33rd day of chemotherapy, MRD on the 33rd day of chemotherapy and genotype in children with B-ALL may be associated with poor response to treatment. Clinical risk stratification is associated with gene mutation status, and gene mutation may be an important indicator of treatment response in children with B-ALL.

Objective:To study the effects of Terra Flavausta on diarrhea mice with spleen yang deficiency based on metabonomics. Methods:Totally 30 mice were divided into normal group, model group and Terra Flavausta group according to random number table method. Mice in the model group and Terra Flavausta group were treated by the method of "diet disorder + clearing fire with herbs bitter in flavour and cold in property" to establish the diarrhea model of spleen yang deficiency. After successful modeling, Terra Flavausta group received Zaoxintu Decoction 12.0 g/kg for gavage, while normal group and model group were given equal volume of distilled water for gavage, for consecutive 7 d. The serum metabolites of each mouse were analyzed and identified based on UPLC-Q-Exective-MS. The differential metabolites were characterized by principal component analysis and orthogonal partial least squares discriminant analysis, and the potential biomakers were screened, and the KEGG pathway enrichment analysis was performed. Results:Totally 110 different metabolites were screened under the positive and negative ion mode. Terra Flavausta can effectively reverse the disorder of serum metabolism in diarrhea mice with spleen yang deficiency, and has a significant callback effect on 12 potential biomarkers related to diarrhea with spleen yang deficiency. KEGG pathway enrichment mainly involved HIF-1 signaling pathway, ascorbate and aldarate metabolism, platelet activation, etc. Conclusion:Terra Flavausta may play the effect of warming spleen and relieving diarrhea through down-regulation of L-ascorbic acid affecting HIF-1 signal pathway, ascorbic acid and aldose metabolism pathway, vitamin digestion and absorption pathway, up-regulation of prostaglandins G2 and H2 affecting platelet activation pathway, and down-regulation of jasmonic acid α linolenic acid metabolic pathway.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Objective:To analyze the clinicopathological characteristics, diagnosis and prognosis of meningioangiomatosis (MA), and to investige the possible origion of spindle cells.Methods:Seventeen cases of MA were collected at Xuanwu Hospital of Capital Medical University and the First Affiliated Hospital of Fujian Medical University, from June 2012 to March 2020. The clinical manifestations, radiologic, histopathologic, immunohistochemical features and patients′ outcome were analyzed. The presumed origin of spindle cells was evaluated by immunohistochemical staining.Results:Of the 17 patients, 9 were males and 8 were females. The age ranged from 3 to 56 years old. Thirteen patients presented with seizure as the initial symptom. The lesions were solitary and located in the cerebral cortex. Histopathologically, there were proliferation of small blood vessels and perivascular spindle cells in the cerebral cortex. The spindle cells had no obvious atypia, mitoses and necrosis. Four cases were combined with transitional meningioma. Immunohistochemically, the proliferative perivascular spindle cells were positive for vimentin in all cases, and focally positive for EMA and SSTR2. Ki-67 proliferation index was low. Neurofibrillary tangles were demonstrated by AT8. All 17 patients received surgical treatment and were followed up for one to 93 months. None had seizure attacks or tumor recurrence.Conclusions:MA is a rare slow-growing intracranial lesion, and the perivascular spindle cells could be derived from meningothelial cells, and MA is often associated with degeneration of the cerebral cortex and meningioma. The patients have good prognosis after surgical treatment.

Objective:To explore the influence of different mental status (evaluated by Likert scale) on the first success rate, image artifacts and examination time of cone beam CT (CBCT) in infants and young children.Methods:Prospective analysis of children aged 1-6 years (98 cases) who underwent CBCT examination, before the examination, the children were scored in seven aspects: activity, adaptability, attention, mood, gender, age and parents′ attitude, and the total score was calculated, The total score was used as the test variable, and the success rate of the first examination, the artifact of the image and whether the examination time was longer than 2 minutes were used as the state variable. Using SPSS 16.0 to draw the ROC curve, the area under curve (AUC), significance, maximum Yoden′s index and their corresponding diagnostic (evaluation) critical values were obtained.Results:The success rate of the first examination was 78.6%(77/98), the AUC was 0.949 ± 0.025, the significance P < 0.05, the maximum Yoden′s index was 0.766, the corresponding critical value of diagnosis (evaluation) was 15; the artifact-free rate was 67.3%(66/98), the AUC was 0.873±0.038, the significance P < 0.05, the maximum Yoden′s index was 0.549, and the corresponding critical value of diagnosis (evaluation) was 15; the proportion of examination time in 2 minutes was 80.6%(79/98), the AUC was 0.854 ± 0.039, the significant P < 0.05, the maximum Yoden′s index was 0.614, and the corresponding critical value of diagnosis (evaluation) was 14. Conclusions:The Likert scale scoring method based on Thomas′s temperament analysis theory has certain application value in the psychological evaluation of children before cone-beam CT examination. For children whose total score is greater than or equal to 14, sedation or psychological counseling should be carried out before examination in order to effectively improve the success rate of examination and reduce the occurrence rate of artifacts in images, further more to reduce radiation dosage and increase the examination circulation of CBCT in children.

Objective: To discuss the success rate and image quality in pediatric patients who used chloral hydrate before their cone beam computed tomography exam. Methods: 1752 patients aged 1 to 6 were selected for this retrospective study. They were divided into sedated group (219 cases) and non-sedated group (1 533 cases). The success rate and image quality were compared between two groups. Results: The sedated group had a higher success rate to non-sedated group: 99.5%(218/219) vs. 90.4% (1 386/1 533). The motion artifact in sedated group was lower than non- sedated group with I degree: 4.8% (15/314) vs. 20.1%(327/1 630) and II degree: 0.3%(1/314) vs. 12.2%(199/1 630). Conclusion Giving chloral hydrate to pediatric patients before their CBCT exam would improve both success rate and image quality, and reduce unnecessary radiation expose.

OBJECTIVETo investigate the synergistic effect between the N-terminus domain of the a2 isoform of vacuolar ATPase (a2NTD) and macrophage colony-stimulating factor (M-CSF) on modulating macrophage polarization and the impact of polarized macrophages on proliferation of gastric cancer cells.

METHODSPeripheral blood mononuclear cells were derived from healthy donor and induced into macrophages. Then macrophages were randomly divided into four groups: the control group (RPMI 1640), the experimental group I (M-CSF 100 μg/L), the experimental group II (a2NTD 500 μg/L) and the experimental group III (a2NTD 500 μg/L plus M-CSF 100 μg/L). After stimulation for 48 hours, double color immunofluorescence cytochemistry was adopted to detect the expression of cell membrane molecules on macrophages; ELISA was used to measure the secretion of cytokines IL-10 and IL-12; CCK-8 assay was used to evaluate the impact of macrophages on proliferation ability of gastric cancer cell strain SGC-7901.

RESULTSThe expression of CD68, also known as macrophage surface antigen, was detected on macrophage membrane in all four groups (+). The mean absorbance (A) was 0.092 ± 0.005 in control group, 0.095 ± 0.006 in group I, 0.094 ± 0.005 in group II, 0.094 ± 0.005 in group III, and no significant differences were observed among 4 groups (all P>0.05). Meanwhile, the expression of CD206, which mainly exists on M2 macrophage membrane, was hard to detect in control group (-) with A 0.025 ± 0.004; it was normal in groupI and group II (+) with A 0.191 ± 0.012 in group I and 0.197 ± 0.136 in group II (P=0.212), and it was up-regulated significantly in group III (+++) with A 0.285 ± 0.011. There were significant differences between either two groups except group I and group II (all P<0.01). Secretion of IL-10 in group I and group II [(85.65 ± 13.64) ng/L and (87.77 ± 14.25) ng/L] was significantly higher compared with control group [(71.67 ± 7.56) ng/L, P<0.01]. Secretion of IL-12 in group I and group II [(9.91 ± 1.50) ng/L and (10.15 ± 1.80) ng/L] was significantly lower compared with control group [(16.87 ± 1.10) ng/L, P<0.01]. Secretion of IL-10 in group III [(116.98 ± 14.27) ng/L] was the highest, and secretion of IL-12 [(5.31 ± 0.88) ng/L] was the lowest (all P<0.01). There was a synergistic effect between a2NTD and M-CSF on the secretion of both IL-10 and IL-12. Elevated proliferation of gastric cancer cell strain SGC-7901 was detected in all four groups, in which group III showed the greatest impact compared with other 3 groups (P<0.01).

CONCLUSIONSa2NTD and M-CSF show a synergistic effect in modulating macrophage phenotype and the secretion of IL-10 and IL-12. The polarized macrophage can significantly enhance proliferation of gastric cancer cell strain SGC-7901.

Cell Proliferation ; Humans ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Macrophage Colony-Stimulating Factor ; pharmacology ; Macrophages ; cytology ; Phenotype ; Stomach Neoplasms ; pathology ; Tumor Cells, Cultured ; Vacuolar Proton-Translocating ATPases ; pharmacology