Objective To explore a nomogram model based on clinical characteristics and immune indicators for predicting the efficacy of tyrosine kinase inhibitor(TKI)against chronic myeloid leukemia(CML).Methods Clinical data was retrospectively collected from 100 patients with CML treated with TKI between January 2021 and January 2023 in Tangshan Gongren Hospital.Patients were divided into the best response and warning/treatment failure groups according to therapeutic efficacy.Factors affecting therapeutic efficacy were analyzed using logistic regression analysis,and a nomogram model was constructed.Results The best response and warning/treatment failure groups showed significant differences in red blood cell distribution width(RDW),platelet count(PLT),ELTS score,Th 1/CD4+,Treg/CD4+ratio,white blood cell count,and absolute value of natural killer cells(P＜0.05).Logistic regression confirmed that the above indicators were influencing factors(P＜0.05),indicating that the model was meaningful,and had a high goodness of fit as well as high predictive value.Conclusion The nomogram model constructed based on RDW,PLT,and other factors can effectively predict the thera-peutic efficacy of AKI in treating CML.

Objective To explore a nomogram model based on clinical characteristics and immune indicators for predicting the efficacy of tyrosine kinase inhibitor(TKI)against chronic myeloid leukemia(CML).Methods Clinical data was retrospectively collected from 100 patients with CML treated with TKI between January 2021 and January 2023 in Tangshan Gongren Hospital.Patients were divided into the best response and warning/treatment failure groups according to therapeutic efficacy.Factors affecting therapeutic efficacy were analyzed using logistic regression analysis,and a nomogram model was constructed.Results The best response and warning/treatment failure groups showed significant differences in red blood cell distribution width(RDW),platelet count(PLT),ELTS score,Th 1/CD4+,Treg/CD4+ratio,white blood cell count,and absolute value of natural killer cells(P＜0.05).Logistic regression confirmed that the above indicators were influencing factors(P＜0.05),indicating that the model was meaningful,and had a high goodness of fit as well as high predictive value.Conclusion The nomogram model constructed based on RDW,PLT,and other factors can effectively predict the thera-peutic efficacy of AKI in treating CML.

Objective To investigate the dynamics of NK cells and Treg cells,as well as their potential prognostic significance in relation to TKI discontinuation among patients diagnosed with chronic myeloid leukemia(CML).Methods In this study,a total of 200 patients diagnosed with CML were randomly selected and divided into two groups:the discontinuation group(n=100)and the non-discontinuation group(n=100).Within the discontinuation group,patients were further categorized into a recurrence subgroup(n=41)and a non-recurrence subgroup(n=59).Clinical data and follow-up information of these patients were retrospectively analyzed.Logistic regression analysis was performed to investigate the impact of various variables on patient outcomes following drug discontinuation,as well as to explore independent factors influencing recurrence in these individuals.Receiver operating characteristic(ROC)curve analysis was employed to assess the predictive value of NK cells and Treg cells for TKI discontinuation outcomes.A significance level of P<0.05 was considered statistically significant.Results The proportion of patients treated with interferon in the discontinuation group was significantly higher than that in the non-discontinuation group(P<0.05).Moreover,the former group exhibited a significantly higher number of NK cells(P<0.05)and Treg cells(P<0.01)compared to the latter group.Compared to the recurrence group,there was a significant increase in the proportion of patients using interferon in the non-recurrence group(P<0.05),along with longer durations of TKI treatment and deep molecular response(DMR)duration(P<0.05).The number of NK cells and Treg cells in the non-recurrence group was significantly higher than that in the recurrence group(P<0.01).Logistic regression analysis found that the use of interferon(OR=1.25,95%CI:1.11～2.03,P<0.001),duration of DMR(OR=1.16,95%CI:1.08～1.92,P<0.05),NK cells(OR=1.64,95%CI:1.14～2.28,P<0.01),and Treg cells(OR=1.83,95%CI:1.15～2.42,P<0.01)were all influencing factors for the recurrence of patients after drug discontinuation.The results of ROC curve analysis showed that the AUC of NK cells combined with Treg cells for predicting the recurrence of TKI after discontinuation was 0.892(95%CI:0.857～0.927,P<0.001).Conclusion The frequencies of NK cells and Treg cells were significantly elevated in patients who remained recurrence-free following TKI discontinuation,highlighting the potential predictive value of combined NK cell and Treg cell analysis for drug cessation in CML patients.

Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

American ginseng (Panax quinquefolius L.) is a well-known Asian traditional herbal medicine with a large market demand. The plant is native to eastern North America, and its main producing areas worldwide are decreasing due to continuous cropping obstacles and environmental changes. Therefore, the identification of maximum similarities of new ecological distribution of P. quinquefolius, and prediction of its response to climate change in the future are necessary for plant introduction and cultivation. In this study, the areas with potential ecological suitability for P. quinquefolius were predicted using the geographic information system for global medicinal plants (GMPGIS) based on 476 occurrence points and 19 bioclimatic variables. The results indicate that the new ecologically suitable areas for P. quinquefolius are East Asia and the mid-eastern Europe, which are mainly distributed in China, Russia, Japan, Ukraine, Belarus, North Korean, South Korea, andRomania. Under global climate change scenarios, the suitable planting areas for P. quinquefolius would be increased by 9.16%-30.97%, and expandingnorth and west over the current ecologically suitable areas by 2070. The potential increased areas that are ecologically suitable include northern Canada, Eastern Europe, and the Lesser Khingan Mountains of China, and reduced regions are mainly in central China, the southern U.S., and southern Europe. Jackknife tests indicate that the precipitation of the warmest quarter was the important climatic factor controlling the distribution of P. quinquefolius. Our findings can be used as auseful guide for P. quinquefolius introduction and cultivation in ecologically suitable areas.

BACKGROUNDAt present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis.

METHODSA total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs.

RESULTSCompared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stem cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations of microRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result of microarray analysis.

CONCLUSIONSThere is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.

Adult ; Embryo Implantation ; genetics ; physiology ; Endometrium ; metabolism ; Female ; Humans ; Infertility, Female ; genetics ; MicroRNAs ; genetics ; Microarray Analysis ; Pregnancy ; Real-Time Polymerase Chain Reaction

Calcium Ionophores ; metabolism ; Female ; Fertilization in Vitro ; adverse effects ; Humans ; Infant, Newborn ; Karyotype ; Male ; Oocytes ; cytology ; metabolism ; Sperm Injections, Intracytoplasmic ; adverse effects

BACKGROUNDMono-(2-ethylhexyl) phthalate (MEHP), the metabolite of di-(2-ethylhexyl) phthalate (DEHP), was suspected to be toxic to human embryos. This study contributes to investigating its toxic effects by an embryonic stem cell test (EST) based on two human embryonic stem cell (hESCs) lines.

METHODSCH1 established in our own lab and H1, a federally registered cell line were two human embryonic stem cell lines used in this test. Four endpoint measurements were performed consisting of cell viability, proliferation ability, apoptosis as well as changes of gene expression patterns after spontaneous differentiation were determined. For measuring effects on the first three endpoints, the cells were treated with various concentrations of MEHP dissolved in dimethyl sulfoxide (DMSO) and only with DMSO which served as control and harvested after 5 days. For measuring effects during spontaneous differentiation, the RNA of embryoid bodies (EBs) formed after 8 days' MEHP exposure was collected and changes in differentiation specific gene expression patterns were analyzed by quantitative real time RT-PCR.

RESULTSAs a result the viability and proliferation ability of both cell lines decreased significantly at 1000 µmol/L MEHP, while there was no effect on apoptosis or cell morphology. In addition MEHP also changed the gene expression pattern in the EBs of both cell lines.

CONCLUSIONMEHP in a high dose was cytotoxic and affected the development of hESCs, which indicates its embryo toxicity in human embryos.

Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Diethylhexyl Phthalate ; analogs & derivatives ; toxicity ; Dose-Response Relationship, Drug ; Embryonic Stem Cells ; drug effects ; pathology ; Humans

OBJECTIVETo investigate the association between the single nucleotide polymorphisms (SNPs) of paraoxonase-2 (PON2) gene and the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels [>85 dB (A)].

METHODSA case-control study was conducted in Chinese Han population exposed to high noise levels. The subjects were divided into case group (n = 127) and control group (n = 136) according to the Diagnostic criteria of occupational noise-induced deafness (GBZ 49-2007). The case group was composed of 127 workers with a mean binaural high-frequency hearing threshold not less than 40 dB, as measured using an electro-audiometer, while the control group was composed of 136 workers with a mean binaural high-frequency hearing threshold less than 40 dB, as measured using the electro-audiometer, who were on shift in the same position as the cases and matched with them for age, sex, and years of noise exposure. Peripheral venous blood (2 ml) was collected from each subject during physical examination to extract genomic DNA, and genotypes were identified using a TaqMan probe.

RESULTSPON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT+TT were the risk factors for occupational noise-induced deafness, and the adjusted odds ratios (95%confidence intervals) were 5.87 (3.11∼11.07), 5.92 (3.10∼11.32), 5.53 (2.93∼10.45), and 5.93 (3.10∼11.34), respectively. In addition, the higher the noise exposure levels, the higher the risk of developing occupational noise-induced deafness among the individuals carrying mutant genotypes.

CONCLUSIONPON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT +TT may be associated with the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels, and the effects of mutant genotypes and noise exposure levels may be mutually enhanced.

Adult ; Aryldialkylphosphatase ; genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Hearing Loss, Noise-Induced ; etiology ; genetics ; Humans ; Male ; Middle Aged ; Noise, Occupational ; adverse effects ; Polymorphism, Single Nucleotide ; Risk Factors

Total or near-total fertilization failure after intracytoplasmic sperm injection (ICSI) is a rare event, but it occurs repeatedly because of sperm defects in activating oocyte. The case presents a successful pregnancy and live birth after calcium ionophore A23187 (A23187) activation on one-day-old unfertilized oocytes in a patient whose husband suffered oligoasthenoteratozoospermia, and who had experienced repeated near-total fertilization failure after ICSI. In the second ICSI cycle, only one oocyte was fertilized while nine were unfertilized. Oocyte activation with A23187 were performed on the one-day-old unfertilized oocytes after ICSI and resulted in fertilization and embryo transfer. A clinical pregnancy was achieved and a healthy baby was born. To our knowledge, this is the first reported case of a healthy birth after oocyte activation on the one-day-old unfertilized oocyte. This indicates that "rescue oocyte activation" on one-day-old unfertilized oocytes after ICSI may be helpful for preventing total or near-total fertilization failure after ICSI.
Adult ; Female ; Fertilization in Vitro ; methods ; Humans ; Live Birth ; Male ; Oocytes ; cytology ; Pregnancy ; Sperm Injections, Intracytoplasmic ; methods