Acute lymphoblastic leukemia (ALL) is a common hematological malignant tumor with high malignancy , great harm and high recurrence rate. In addition, the treatment process of ALL is complicated and the treatment cost is high , which not only brings great pain to patients , but also increases the economic burden of patients' families and even society . The pathogenesis of ALL is still inconclusive , but studies have found that environmental factor and genetic factor may play an important role in the pathogenesis of ALL . Therefore , this paper summarizes the reports on environmental chemical exposure factors and ALL epigenetics studies in recent years , and tries to review the relationship between environmental chemical exposure and pathogenesis of ALL , so as to provide reference ideas for clinical research.

Objective: To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Purpose: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes. Materials and Methods: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. Results: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Conclusion Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Objective:To investigate the correlation between the degree of hepatic fibrosis and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS) and its predictive value.Methods:Patients with AIS received intravenous thrombolysis at Nanjing Jiangbei Hospital from January 2018 to March 2023 were retrospectively included. Hepatic fibrosis-4 index (FIB-4) was used to evaluate the degree of hepatic fibrosis in patients. FIB-4 ≥ 2.67 was defined as severe hepatic fibrosis. END was defined as an increase of ≥4 from baseline on the National Institutes of Health Stroke Scale (NIHSS) score within 24 h after intravenous thrombolysis. The relevant factors of END were analyzed through univariate analysis and multivariate logistic regression model. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of FIB-4 for END. Results:A total of 313 patients were included, of which 184 (58.8%) were male, aged 64.8±11.8 years old. The median baseline NIHSS score was 6 (interquartile range, 4-9), and the median FIB-4 was 1.76 (interquartile range, 1.28-2.56). Forty-five patients (14.4%) experienced END. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, higher FIB-4 was significantly independently correlated with END (odds ratio 2.121, 95% confidence interval 1.422-3.162; P=0.001). ROC curve analysis shows that FIB-4 has a good predictive value for END (the area under the curve 0.689, 95% confidence interval 0.595-0.784; P=0.001). The optimal cutoff value of FIB-4 was 1.82, and its sensitivity and specificity in predicting END were 71.1% and 54.9%, respectively. Conclusion:FIB-4 has good predictive value for END in patients with AIS after intravenous thrombolysis.

The bone marrow microenvironment is a complex network structure composed of non-hematopoietic cells,hemato-poietic stem cells,extracellular matrix,and various cytokines,which is beneficial to maintain normal hematopoietic function in the body.Once bone marrow microenvironment changes,the types and functions of cells in the bone marrow will change,thereby causing the occurrence of leukemia.Leukemia is a malignant clonal disease that is not only related to abnormal proliferation and differentiation of tumor cells,but also closely related to immune dysfunction.Exosomes,immune cells,mesenchymal cells and bone marrow stromal cells(BMSCs)in the bone marrow microenvironment all have immunoregulation effects and can participate in the formation of immune suppression in leukemia,leading to disease progression.Therefore,this article aims to review the mechanism and effects of bone mar-row microenvironment on the pathogenesis of leukemia so as to provide new ideas for leukemia treatment.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays

Objective:To investigate the correlation between malnutrition and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Patients with ischemic stroke received intravenous thrombolysis in the Department of Neurology, Nanjing Jiangbei People's Hospital from January 2018 to December 2021 were retrospectively enrolled. Nutritional status was assessed by geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI). END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale score within 24 h after intravenous thrombolysis compared with the baseline value. The demographic and baseline clinical data of the patients in the END group and the non-END group were compared. Multivariate logistic regression analysis was used to determine the independent correlation between malnutrition and END. Results:A total of 256 patients were enrolled, including 156 males (60.9%), aged 65.6±12.0 years. According to GNRI and PNI, there were 122 (46.7%) and 62 (24.2%) patients with malnutrition respectively. END occurred in 37 patients (14.5%) during hospitalization. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, there was a significant independent correlation between malnutrition and END after intravenous thrombolysis in patients with acute ischemic stroke (severe malnutrition as assessed by GNRI compared to normal nutritional status: odds ratio 5.736, 95% confidence interval 1.033-31.866, P=0.046; severe malnutrition as assessed by PNI compared to normal nutritional status: odds ratio 4.928, 95% confidence interval 1.589-15.282, P=0.006). Conclusion:Malnutrition is very common in patients with acute ischemic stroke and has a significant correlation with END after intravenous thrombolysis.

Objective:To investigate the short-term efficacy and safety of albumin-bound paclitaxel combined with nedaplatin followed by concurrent radiotherapy in treatment of stage Ⅲ massive cervical cancer.Methods:The clinical data of 84 patients with massive cervical cancer admitted to Harbin Medical University Cancer Hospital from April 2019 to April 2020 were retrospectively analyzed. According to the different treatment regimens, patients were divided into the observation group and the control group, each with 42 cases. The observation group received albumin-bound paclitaxel combined with nedaplatin followed by concurrent radiotherapy, and the control group received solvent-based paclitaxel combined with nedaplatin followed by concurrent radiotherapy. The short-term efficacy and adverse reactions of the two groups were compared.Results:The partial remission (PR) rate of the observation group and the control group at 1 month of treatment was 92.9% (39/42) and 35.7% (15/42), respectively, and the difference was statistically significant ( χ2 = 29.867, P < 0.01). The complete remission (CR) rate of the observation group and the control group at 1 month after treatment was 59.5% (25/42) and 38.1% (16/42), respectively, and the difference was statistically significant ( χ2 = 3.859, P = 0.049). The incidence of diarrhea of the observation group was lower than that of the control group [33.33% (14/42) vs. 54.8% (23/42)], and the difference was statistically significant ( χ2 = 3.913, P = 0.048). There were no statistical differences in the incidence of hematological adverse reactions and abnormal liver and kidney functions between the two groups (all P > 0.05). Conclusion:The albumin-bound paclitaxel combined with nedaplatin followed by concurrent radiotherapy have a good short-term efficacy in treatment of stage Ⅲ massive cervical cancer, and the adverse reactions are tolerable.

Objective:To investigate the relationship between plasma Dickkopf-1 and early neurological deterioration (END) and outcome in patients with acute ischemic stroke.Methods:From January 2020 to December 2020, consecutive patients with first-ever ischemic stroke form the Department of Neurology, Nanjing Jiangbei Hospital were included. All patients were hospitalized within 24 h after onset. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d after admission increased by ≥2 or motor function score increased by ≥1 compared with the baseline. Poor outcome was defined as the modified Rankin Scale score >2 at 90 d after onset. Multivariate logistic regression analysis was used to determine the independent correlation between plasma Dickkopf-1 and END and outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of plasma Dickkopf-1 for END and poor outcome. Results:A total of 176 patients were enrolled, including 92 males (52.3%), aged 66.7±9.6 years. The median Dickkopf-1 was 4.30 μg/L, 52 patients (29.5%) developed END, and 81 (46.0%) had poor outcome. Multivariate logistic regression analysis showed that the higher Dickkopf-1 was an independent predictor of END (odds ratio [ OR] 1.696, 95% confidence interval [ CI] 1.223-2.351; P=0.002) and poor outcome ( OR 1.566, 95% CI 1.156-2.121; P=0.004). ROC curve analysis showed that plasma Dickkopf-1 had good predictive value for END, and its area under the curve was 0.717 (95% CI 0.634-0.801); the optimal cut-off value was 4.40 μg/L, and the corresponding predictive sensitivity and specificity were 71.2% and 60.5%, respectively. Dickkopf-1 also had good predictive value for poor outcome, and its area under the curve was 0.701 (95% CI 0.624-0.778); the optimal cut-off value was 4.25 μg/L, and the corresponding predictive sensitivity and specificity were 65.4% and 61.1%, respectively. Conclusion:Plasma Dickkopf-1 has good predictive value for END and poor outcome in patients with acute ischemic stroke.