BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

PURPOSE: To investigate the regulatory role of nerve injury-induced protein 1 (NINJ1) in the anti-inflammatory function of human umbilical cord mesenchymal stem cells (hUC-MSCs) co-stimulated by interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). METHODS: hUC-MSCs were expanded in vitro using standard protocols, with stem cell characteristics confirmed by flow cytometry and multilineage differentiation assays. The immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR, lymphocyte proliferation suppression assays, and Cell Counting Kit-8 viability tests. Transcriptome sequencing, Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 expression. Functional roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays, Annexin V/Propidium Iodide apoptosis analysis, macrophage co-culture models, and cytokine Enzyme-Linked Immunosorbent Assay. Therapeutic efficacy was validated in a cecal ligation and puncture-induced septic mouse model: 80 mice were randomly allocated into 4 experimental groups (n=20/group): sham group (laparotomy without cecal ligation); phosphate-buffered saline-treated group (cecal ligation and puncture (CLP) + 0.1 mL phosphate-buffered saline); hUC-MSCs (small interfering RNA (siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation (IT))-treated group (CLP + hUC-MSCs transfected with scrambled siRNA); and hUC-MSCs (siNINJ1-IT)-treated group (CLP + hUC-MSCs with NINJ1-targeting siRNA). RESULTS: hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria, confirming their stem cell identity. IFN-γ/TNF-α co-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs, accompanied by the reduction of cellular viability, while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and interleukin-1β. This co-stimulation significantly elevated NINJ1 expression in hUC-MSCs, whereas genetic silencing of NINJ1 effectively suppressed pro-inflammatory cytokine production and attenuated damage-associated molecular patterns release through inhibition of programmed plasma membrane rupture. Furthermore, the NINJ1 interference potentiated the ability of cytokine-pretreated hUC-MSCs to suppress LPS-induced pro-inflammatory responses in RAW264.7 macrophages. In cecal ligation and puncture-induced sepsis model, NINJ1-silenced hUC-MSCs exhibited enhanced therapeutic efficacy, manifested by reduced systemic inflammation and multi-organ damage. CONCLUSION Our findings shed new light on the immunomodulatory functions of cytokine-primed MSCs, offering groundbreaking insights for developing MSC-based therapies against inflammatory diseases via interfering the expression of NINJ1.
Mesenchymal Stem Cells/drug effects* ; Animals ; Interferon-gamma/pharmacology* ; Tumor Necrosis Factor-alpha/pharmacology* ; Humans ; Mice ; Umbilical Cord/cytology* ; Cells, Cultured ; Apoptosis ; Male

Objective:To investigate the effects of Kanglaite injection combined with chemotherapy on quality of life and myelosuppression in patients with non-small cell lung cancer (NSCLC).Methods:The clinical data of 60 patients with NSCLC who received treatment at Zhejiang Jinhua Guangfu Tumor Hospital from August 2018 to February 2022 were retrospectively analyzed. These patients were divided into an experimental group and a control group, with 30 patients in each group according to the treatment methods used. The patients in the experimental group received the Kanglaite injection in combination with chemotherapy using gemcitabine and cisplatin, whereas the patients in the control group were treated solely with chemotherapy with gemcitabine and cisplatin. The quality of life was evaluated using the Karnofsky Performance Status score. Before and after treatment, a comparison was made between the two groups in terms of Karnofsky Performance Status score, the incidence of adverse reactions (such as myelosuppression), and clinical efficacy.Results:After treatment, the disease control rate and objective response rate in the experimental group were 86.67% (26/30) and 60.00% (18/30), respectively, which were significantly higher than 60.00% (18/30) and 30.00% (9/30) in the control group ( χ2 = 4.18, 4.31, both P < 0.05). Prior to treatment, the Karnofsky Performance Status scores in the experimental and control groups were (70.68 ± 3.75) points and (70.29 ± 5.11) points ( t = 0.34, P = 0.790), respectively. After treatment, the Karnofsky Performance Status scores in the experimental group were significantly higher than those in the control group [(67.02 ± 5.87) points vs. (62.37 ± 3.59) points, t = -5.29, P < 0.05]. The incidence of adverse reactions in the experimental group was significantly higher than that in the control group [40.00% (12/30) vs. 36.67% (11/30), χ2 = 0.07, P = 0.790). Additionally, the incidence of myelosuppression in the experimental group was significantly lower than that in the control group [56.67% (17/30) vs. 86.67% (26/30), χ2 = 6.90, P = 0.030]. Conclusion:Compared with chemotherapy alone, Kanglaite injection combined with chemotherapy can effectively relieve the clinical symptoms of patients with advanced non-small cell lung cancer, leading to improved prognosis.

Objective:To explore the effects of body mass index (BMI) on the incidence of nocturnal hypertension in patients with hypertension.Methods:Totally 341 hospitalized hypertensive patients treated at the Affiliated Hospital of Jining Medical University from February to May 2023 were selected by convenience sampling. Patients' general information, clinical data, and 24-hour ambulatory blood pressure results were collected. A binomial Logistic regression analysis was conducted to investigate the factors affecting the occurrence of nocturnal hypertension in these patients. The relationship between BMI and the incidence of nocturnal hypertension was examined using threshold effect tests and smooth curve fitting.Results:The binomial Logistic regression analysis indicated that blood phosphate level was a factor influencing the occurrence of nocturnal hypertension in hypertensive patients ( P<0.05). Smooth curve fitting and threshold effect test results showed that the relationship between BMI and the incidence of nocturnal hypertension was curve-correlated, with a turning point at 24.61 kg/m 2. To the left of the turning point, there was no correlation ( P=0.130) ; to the right, there was a correlation ( P=0.016) . Conclusions:When the BMI of hypertensive patients exceeds 24.61 kg/m 2, the likelihood of nocturnal hypertension increases with rising BMI, providing a precise intervention target for weight management-based patient care in hypertension.

Objective:To investigate the predictive value of YKL-40 at admission on stroke-associated pneumonia (SAP) and poor outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to Taixing People’s Hospital from February 2020 to March 2021 were enrolled prospectively. The poor outcome was defined as 3-6 points on the modified Rankin Scale at 90 d after onset. Multivariate logistic regression analysis was used to determine the independent predictors of SAP and poor outcome, and the predictive value of serum YKL-40 on SAP and poor outcome was evaluated by receiver operating characteristic (ROC) curve. Results:A total of 377 patients with AIS were enrolled. The median serum YKL-40 was 127.16 μg/L. One hundred and four patients (27.6%) had SAP, and 126 (33.4%) had poor outcomes at 90 d after onset. Multivariate logistic regression analysis showed that after adjusting for confounding factors, YKL-40 was the independent predictors of SAP (odds ratio [ OR] 1.005, 95% confidence interval [ CI] 1.003-1.008; P=0.001) and poor outcome at 90 d ( OR 1.009, 95% CI 1.006-1.011; P=0.001). The ROC curve analysis showed that the area under the curve of YKL-40 for predicting SAP was 0.769 (95% CI 0.713-0.824; P<0.001), the best cutoff value was 168.70 μg/L, and the sensitivity and specificity were 71.2% and 75.1% respectively; the area under the curve of YKL-40 for predicting poor outcome at 90 d was 0.787 (95% CI 0.735-0.840; P<0.001), the best cutoff value was 195.56 μg/L, and the sensitivity and specificity were 68.3% and 84.1% respectively. Conclusion:Higher serum YKL-40 at admission has a good predictive value for SAP and poor outcome at 90 d in patients with AIS.

Objective:To investigate the effect of individualized and generalized dual track continuous health education on patients with endometrial cancer after operation.Methods:From January 2019 to January 2020, 96 patients with endometrial cancer in the Second Affiliated Hospital of Henan University of traditional Chinese Medicine were enrolled. They were all treated with surgery. According to the random number table method, they were divided into the control group and the study group, with 48 cases in each group. However, during the whole study period, some patients were affected by various factors, and the final number of patients in the study group was 45 cases (dual track continuous health education combined with individualization and generalization) and 45 cases in the control group(routine continuous health education). Before the intervention and 3 months after the intervention, the obstetrics and Gynecology nurses who had received relevant training adopted self-made health knowledge awareness questionnaire, self-care ability assessment scale (ESCA), Medical Coping Style Questionnaire (MCMQ) and simple quality of life scale (SF-36).The patients' mastery of disease knowledge,self-care ability,coping style and quality of life were evaluated.Results::After the intervention,the awareness of health knowledge was 42.23±2.58 in the study group and 35.71±3.26 in the control group, and the difference was statistically significant ( t value was 4.508, P<0.01). After the intervention, the self-care skills, self responsibility, self-concept, health knowledge level and total score of the study group were 9.45±1.58, 11.82±1.63, 61.12±6.52, 10.56±1.33 and 31.83±2.21 respectively, while those of the control group were 5.34±0.75, 7.85±0.92, 68.23±6.45, 6.35±0.94 and 19.54±1.26 respectively, and the difference between the two groups was statistically significant ( t value was 11.025-16.444, P<0.05). After the intervention, the scores of facing,avoiding and yielding in the study group were 19.39±3.29, 10.58±2.40, 9.20±3.12 respectively, and those in the control group were 15.97±3.77, 14.56±3.00, 13.02±2.50 respectively, with significant difference between the two groups( t value was 4.459, 6.762, 6.220, P<0.01). After the intervention, the scores of physiological function,physical pain,social function,mental health,emotional function,vitality and general health in the study group were 80.23±8.12, 22.19±2.63, 44.98±4.25, 76.25±7.64, 69.58±6.23, 70.05±7.22 and 78.31±7.52 respectively, while those in the control group were 59.63±5.14, 52.37±5.38, 41.16±4.73, 57.28±5.36, 55.25±5.27, 46.89±4.52 and 48.96±4.37 respectively, the difference between the two groups was statistically significant( t value was 3.630-11.870, P<0.05). Conclusions:The implementation of individualized and generalized dual track continuous health education in patients with endometrial cancer after surgery has a significant effect, can significantly improve the patient's mastery of disease health knowledge, enhance their self-care ability and positive coping ability, so as to improve their quality of life, which is worthy of clinical promotion.

Objective To analyze the expression of interleukin 16 (IL-16) in atherosclerosis (AS) patients, and to study the roles of IL-16in the pathogenesis of AS.Methods Thirty AS patients in Affiliated Hospital of Jining Medical College from August 2015to August 2016were randomly selected as the case group and twenty-nine healthy subjects were selected as the healthy control group.Peripheral blood of the subjects were collected.IL-16levels were determined with enzyme-linked immunosorbent assay (ELISA).Reverse transcriptase-polymerase chain reaction was applied to analyze IL-16mRNA level.IL-16expression in the atherosclerotic plaque samples was detected with immunohistochemical analysis.IL-16expression in aortic atherosclerotic plaque of AS patients and atherosclerotic ApoE-/-mice were analyzed by immunohistochemical staining.The aortic plaque changes of AS mice injected intraperitoneally with recombinant IL-16were detected.Results Both IL-16protein levels and IL-16mRNA levels were higher in case group than those of healthy control group, the difference was statistically significant (P＜0.05).The IL-16mRNA was highly expressed in the atherosclerotic plaque.The aortic plaque area of the mice underwent IL-16intraperitoneal injection were decreased while the plaque stability increased.Conclusion IL-16levels elevated in both AS patients and AS mice, which suggested that IL-16might play aprotective role against AS.

Objective: To explore the clinical and laboratory characteristics and therapeutic effect of acute promyelocytic leukemia (APL) with t(2;17;15). Methods: The G-banding technique was used for karyotypic analysis in a female patient with APL who was admitted to the First Affiliated Hospital of Zhengzhou University in December 2018. PML-RARα fusion gene was quickly detected by fluorescence in situ hybridization (FISH). The real-time quantitative polymerase chain reaction (RT-PCR) was used to detection 43 kinds of fusion gene, and the gene mutations were detected by next generation sequencing (NGS). The induction therapy was given with oral retinoic acid+ intravenous infusion of arsenic trioxide, followed by 3 courses of retinoic acid+ arsenic trioxide consolidation therapy. Results: The G-banding karyotypic analysis demonstrated 46, XX, t(2;17;15) (q31;q21;q22)[8]/46, XX[2]. FISH results indicated that 62.0% of analyzed cells were positive for the PML-RARα fusion gene. RT-PCR further revealed the positive PML-RARα fusion gene transcript. NGS detection of gene mutations showed no obvious abnormalities. After 39 days of induction therapy with retinoic acid and arsenic trioxide, the patient achieved complete remission (CR). The karyotype was 46XX[20], and PML-RARα/ABL was 0/100. Then, the patient was treated with 3 courses of consolidation therapy, and the results remained in CR. Conclusions APL with complex t(2;17;15) (q31;q21;q22) is rare, and the morphological characteristics are not typical, but it is still associated with the formation of PML-RARα fusion gene. Retinoic acid+ arsenic trioxide has a good therapeutic effect, and the long-term efficacy still needs follow-up.

Objective To observe the effects of Huoxue Chubi Decoction on contents of PDGF-A and TGF-βin skin lesion of scleroderma mimicking mice models;To discuss its possible mechanism. Methods Thirty mice were randomly assigned into blank group, model group, TCM high-, medium-, low-dose group, with six mice in each group. Other than blank group, the rest of the 4 groups were given bleomycin-hydrocholoride 0.1 mL intradermal injection daily for 3 weeks to establish scleroderma mice models. From week 4 to 7, blank group and model group received gavage with equal amount of distilled water daily;TCM high-, medium-, low dosage group received gavage with Huoxue Chubi Decoction with different concentrations of 44.8, 22.4, 11.2 g/kg daily. The pathological changes in the skin tissue samples taken from each group were observed under microscope;the thickness of skin from each group was measured and the expression of PDGF-A, TGF-β, type-Ⅰ collagen (COL-Ⅰ) and type-Ⅲ collagen (COL-Ⅲ) were tested through immunohistochemical staining. Results Compare with blank group, the dermis tissue of model group was thicker, with the presence of thicker and greater number of collagen fibers, as well as infiltration of inflammatory cells. Compare with model group, thickness of skin and dermis collagen growth of TCM high-, medium-, low-dose group were milder varied by the concentration of the decoction. The result of immunohistochemical staining showed that the expressions of PDGF-A, TGF-β, COL-Ⅰ and COL-Ⅲ of modelgroup significantly increased than blank group (P<0.01); the expression of the mentioned indicators were statistically significant lower in the TCM high-, medium-, low-dose group than model group; The expressions of PDGF-A and TGF-β showed a positive correlation with the amount of COL-Ⅰ and COL-Ⅲpresented in each group. Conclusion Huoxue Chubi Decoction can suppress collagen expression and fibroblast formation in skin lesion of scleroderma mice models by down regulating the expressions of TGF-β and PDGF-A, thus demonstrate its potential in scleroderma treatment.

Erythrocyte Indices ; Erythrocytes ; Hepacivirus ; Humans ; Liver Diseases ; blood ; virology