Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

Objective To investigate the relationship between the threonine and tyrosine kinase(TTK)gene and eyelid basal cell carcinoma(BCC).Methods Bioinformatics methods were used to screen the core gene(namely,TTK)associated with the occurrence and development of BCC from the Gene Expression Omnibus(GEO)database.Surgically removed eyelid BCC tissue specimens(BCC cells were divided into BBC Grade Ⅰ,Ⅱ and Ⅲ groups by tumor grade)and be-nign tumor tissue specimens(Control group)were collected from Ziyang Central Hospital for subsequent experiments.Cel-lular immunofluorescence assay(CIA)was used to detect the expression of the TTK gene in benign and malignant eyelid tumor cells.After knocking down TTK in BCC cells through transfection with lentiviruses(the cells transfected with LV-TTK-shRNA were taken as the TTK-shRNA group,and those transfected with LV-BBC-shRNA were taken as the BBC nega-tive control group),CIA was used to detect the expression of key proteins Bcl-2 and Bax in the apoptotic signaling pathway of each group of cells.Results The bioinformatics analysis showed that the TTK gene was the core gene associated with the occurrence and development of eyelid BCC.CIA detection results revealed that the fluorescence signal intensities in the tumor cytoplasm of Control,BCC Grade Ⅰ,Ⅱ,and Ⅲ groups were 1.03±0.07,1.28±0.11,1.58±0.13 and 1.92±0.17,respectively.The fluorescence signal intensity gradually increased,and the difference in fluorescence signal intensity among the four groups was statistically significant(all P＜0.05).Compared with that in the Control group(1.02±0.05),the cell fluorescence intensity was increased in the BCC negative control group(1.74±0.12)and decreased in the TTK-shRNA group(1.31±0.09)(P＜0.05).The difference in cell fluorescence intensity was significant among the Control,BCC nega-tive control and TTK-shRNA groups(all P＜0.05).The fluorescence intensity of the anti-apoptotic protein Bcl-2 was 1.04±0.12 in the Control group,2.12±0.23 in the BCC negative control group,and 1.43±0.15 in the TTK-shRNA group.The fluorescence intensity of the pro-apoptotic protein Bax was 1.02±0.08 in the Control group,0.64±0.11 in the BCC negative control group,and 1.47±0.16 in the TTK-shRNA group.After TTK knockdown,the expression level of BcL-2 in BCC cells decreased,and that of Bax increased.The fluorescence intensities of BcL-2 and Bax were significantly different among the Control,BCC negative control and TTK-shRNA groups(all P＜0.05).Conclusion The TTK gene plays a role in the regulation of eyelid BCC cell proliferation,and this effect is closely related to the PI3K-AKT-Bcl-2/Bax signaling path-way.

Nursing practice is an important component of the healthcare service system and plays a crucial role in achieving the strategic goal of"Healthy China Initiative".Facing the growing health needs and increasingly complex health issues,the concept of Population Medicine,which aims to maximize the overall and long-term health benefits of the population,is expected to provide new theoretical foundations for the nursing practice in China.Integrating the concept of Population Medicine into nursing practice can give full play to the professional value of nursing workers,improve nursing quality,and promote the construction of Healthy China.This review summarized the development of the concept of Population Medicine,its specific connotation and its application in the field of nursing practice,and relevant suggestions are put forward,providing references for scholars to deepen the integration and application of Population Medicine in nursing practice and promote the development of nursing in China.

Objective To explore the value of a CT radiomics model in differentiating Xpert MTB/RIF-negative pulmonary tuber-culosis(PTB)from non-tuberculous mycobacteria pulmonary disease(NTM-PD).Methods A retrospective analysis was performed on 90 patients with Xpert MTB/RIF-negative PTB and 127 patients with NTM-PD.All patients were randomly divided into training set and testing set at the ratio of 7∶3.Radiomics features were extracted from chest CT images.Feature dimensionality reduction and selection were sequentially performed using the maximum relevance and minimum redundancy(mRMR)algorithm and the least absolute shrinkage and selection operator(LASSO)algorithm.Clinical,radiomics,and combined models were constructed by multi-variable logistic regression.The area under the curve(AUC)of receiver operating characteristic(ROC)curve was utilized to assess the model diagnostic performance.Calibration curves were used to evaluate model stability,and the decision curve analysis(DCA)was used to evaluate the clinical utility.Results The combined model had the highest diagnostic performance in both training and testing sets,with AUC of 0.90 and 0.86,respectively,which were higher than clinical and radiomics models.The calibration curve showed that the combined model had a good consistency between the predicted and the actual observations,and DCA revealed the highest clinical benefit.Conclusion The clinical-radiomics combined model has excellent predictive ability in differentiating Xpert MTB/RIF-negative PTB from NTM-PD,which can provide robust support for clinical diagnosis.

Objective To explore the value of a CT radiomics model in differentiating Xpert MTB/RIF-negative pulmonary tuber-culosis(PTB)from non-tuberculous mycobacteria pulmonary disease(NTM-PD).Methods A retrospective analysis was performed on 90 patients with Xpert MTB/RIF-negative PTB and 127 patients with NTM-PD.All patients were randomly divided into training set and testing set at the ratio of 7∶3.Radiomics features were extracted from chest CT images.Feature dimensionality reduction and selection were sequentially performed using the maximum relevance and minimum redundancy(mRMR)algorithm and the least absolute shrinkage and selection operator(LASSO)algorithm.Clinical,radiomics,and combined models were constructed by multi-variable logistic regression.The area under the curve(AUC)of receiver operating characteristic(ROC)curve was utilized to assess the model diagnostic performance.Calibration curves were used to evaluate model stability,and the decision curve analysis(DCA)was used to evaluate the clinical utility.Results The combined model had the highest diagnostic performance in both training and testing sets,with AUC of 0.90 and 0.86,respectively,which were higher than clinical and radiomics models.The calibration curve showed that the combined model had a good consistency between the predicted and the actual observations,and DCA revealed the highest clinical benefit.Conclusion The clinical-radiomics combined model has excellent predictive ability in differentiating Xpert MTB/RIF-negative PTB from NTM-PD,which can provide robust support for clinical diagnosis.

Objective:To investigate the impact of minocycline on myocardial injury in diabetes cardiomyopathy(DCM)rats by regulating 5'-AMP activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator activator receptor gamma coactiva-tor 1α(PGC-1α)signal pathway.Methods:SD rats were fed with high-fat diet for 4 weeks,and then a single intraperitoneal injection of 35 mg/kg streptozotocin was used to induce the DCM model.They were randomly grouped into model group,low-dose minocycline(20 mg/kg)group,high-dose minocycline(40 mg/kg)group,high-dose minocycline+Dorsomorphin(AMPK inhibitor,0.2 mg/kg)group,with 12 rats in each group,another 12 normal rats were fed with normal feed for 4 weeks,and then were given a single intraper-itoneal injection of the same dose of citric acid buffer,which was set as a sham operation group,after the intervention with minocy-cline and Dorsomorphin,and the fasting blood glucose(FBG),total cholesterol(TC)and triglyceride(TG)were measured;left ven-tricular ejection fraction(LVEF)and left ventricular short axis shortening(FS)were measured by ultrasound;HE staining and Mas-son staining were applied to detect the pathological morphology of myocardial tissue of rats in each group;the levels of serum and myo-cardial tissue inflammation IL-6,IL-18,and myocardial tissue oxidative stress indicators-superoxide dismutase(SOD)and malondial-dehyde(MDA)were measured with the kit;Western blot was applied to detect the expression of AMPK/SIRT1/PGC-1α pathway pro-tein in myocardial tissue of rats in each group.Results:Compared with the sham operation group,the myocardial tissue in the model group was seriously damaged,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocar-dial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myocardial tissue were obviously increased(P<0.05),the levels of LVEF,FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were obviously decreased(P<0.05);compared with the model group,the myocardial tissue damage of rats in the low-dose and high-dose minocycline groups were reduced,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myocardial tissue were decreased(P<0.05),the LVEF,the levels of FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were increased(P<0.05);compared with the low-dose minocycline group,the myocardial tissue damage in the high-dose minocycline group was further reduced,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myo-cardial tissue were further decreased(P<0.05),the levels of LVEF,FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were further increased(P<0.05);compared with the high-dose minocycline group,the myocar-dial tissue damage of rats in the high-dose minocycline+Dorsomorphin group increased,the levels of FBG,TC and TG,the cross-sec-tional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tis-sue,and the level of MDA in myocardial tissue were increased(P<0.05),the LVEF,the levels of FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were decreased(P<0.05).Conclusion:Minocycline can reduce oxidative stress and inflammation in DCM rats by activating AMPK/SIRT1/PGC-1α signal,and improve glycolipid metabolism,thereby reducing myocardial injury and repairing cardiac function in rats.

P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

Objective:To establish a day 4 embryo evaluation protocol by analyzing embryonic characteristics affecting blastocyst formation, and validate its clinical effectiveness.Methods:This retrospective cohort study included clinical data from 1 037 patients who underwent fresh in vitro fertilization and embryo transfer (IVF-ET) on day 4 in Center for Reproductive Medicine of Xingtai Meihe Reproductive and Genetic Hospital between January 2018 and April 2024. Morphological assessments were performed at (92±2) h post-fertilization. After excluding 1 326 embryos selected for fresh transfer, 2 723 embryos underwent blastocyst culture. To address selection bias in transferred embryos, the scoring system was primarily based on high-quality blastocyst formation rates. Multivariate binary regression analysis evaluated how day 4 developmental stage, fragmentation rate, stage-specific cleavage patterns, multinucleation/vacuolization affected transferable blastocyst formation rate and high-quality blastocyst rate. Regression coefficients determined parameter weights for high-quality blastocyst formation, establishing a day 4 embryo scoring protocol that compared outcomes across different grades. The scoring system was validated by comparing transferable blastocyst formation rate, high-quality blastocyst rate, and implantation rate among different day 4 embryo grades. All embryos were further rescored according to three previously reported evaluation schemes [Feil 2008, Gemma 2015, and European Society of Human Reproduction and Embryology (ESHRE) 2011]. The predictive values of these three day 4 scoring systems and the day 4 scoring system established in this study were compared using the area under the curve (AUC) receiver operating characteristic (ROC) curve in predicting the formation rate of transferable blastocyst, the formation rate of high-quality blastocyst, and implantation rate. Results:In the prediction of high-quality blastocyst formation, early blastocyst showed the highest influence weight compared to embryos with the ratio of blastomere numbers on day 4 to those on day 3 (BNR) <1.2 ( B=3.398, OR=29.915, P<0.001), followed by fragmentation <10% versus ≥50% ( B=1.263, OR=3.535, P<0.001), a stage-specific cleavage pattern ( B=0.903, OR=2.467, P=0.005), and absence of multinucleation or vacuoles ( B=0.797, OR=2.218, P=0.007). Using the newly developed day 4 scoring system, embryos were graded A, B, C, D, E. Transferable blastocyst formation rates were 88.57% (279/315), 76.99% (241/313), 56.11% (280/499), 40.27% (238/591) and 14.22% (143/1 005), respectively; high-quality blastocyst rates were 51.42% (162/315), 35.46% (111/313), 20.04% (100/499), 9.47% (56/591) and 3.98% (40/1 005). All inter-group differences were statistically significant (all P<0.005). Implantation rates for transferred embryos of grades A-E declined sequentially: 63.18% (381/603), 56.19% (322/573), 38.29% (54/141), 26.53% (13/49) and 9.67% (3/31). The day 4 embryo scoring system proposed in this study demonstrated significantly higher predictive efficacy for transferable blastocyst formation rate (AUC=0.812), high-quality blastocyst formation rate (AUC=0.804), and implantation rate (AUC=0.603) compared with Feil 2008 (AUC=0.797, P<0.001; AUC=0.781, P<0.001; AUC=0.585, P<0.001), Gemma 2015 (AUC=0.773, P<0.001; AUC=0.771, P<0.001; AUC=0.542, P=0.006), and ESHRE 2011 (AUC=0.710, P<0.001; AUC=0.745, P<0.001; AUC=0.592, P<0.001). We also observed the presence of pseudo-compacted embryo, whose transferable blastocyst formation rate [38.28% (49/128)] and high-quality blastocyst formation rate [7.03% (9/128)] were similar to those of cleavage-stage embryos with a BNR≥1.2. Conclusion:The established day 4 morphological assessment system reliably predicts the potential to transferable blastocyst and high-quality blastocyst, and effectively forecasts implantation rates.

AIM:This study aims to investigate the effects of Feixin decoction(FXD)on pyroptosis of pulmo-nary artery smooth muscle cells(PASMCs)by modulating nuclear factor κB(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway,and to explore how FXD attenuates hypoxic pulmonary hypertension(HPH)in mice.METHODS:A mouse model of HPH was established using the Sugen 5416 combined hypoxia(SuHx)method.Sixty C57BL/6 mice were randomly divided into 6 groups:control group,SuHx group,sildenafil group,and low-,medium-and high-dose FXD groups,with 10 mice in each group.Five weeks after treatment,echocardiographic pa-rameters,including pulmonary artery acceleration time(PAT),pulmonary artery ejection time(PET),right ventricular anterior wall thickness at diastole(RVAWd)and tricuspid annular plane systolic excursion(TAPSE),were measured.Right ventricular systolic pressure(RVSP)was assessed via right heart catheterization.Right ventricular hypertrophy in-dex(RVHI)was determined by weighing the hearts.Histological examination using HE staining was conducted to observe pathological changes in small pulmonary arteries and the right ventricle,while Masson staining was used to assess fibrosis in the right ventricular wall.Immunofluorescence staining was used to detect co-localized expression of α-smooth muscle actin(α-SMA)with NLRP3,N-terminal fragment of gasdermin D(N-GSDMD)and caspase-1 in the pulmonary arteries.Western blot analysis was conducted to measure the protein levels of NF-κB,p-NF-κB,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),N-GSDMD,interleukin(IL)-1β,IL-18 and cleaved caspase-1 in lung tissues.Transmission electron microscopy was employed to observe the ultrastructure of PASMCs.RE-SULTS:Compared with control group,the mice in SuHx group exhibited elevated RVSP and RVHI(P＜0.01),de-creased right heart function(P＜0.01),increased right ventricular wall fibrosis,and pulmonary vascular remodeling(P＜0.01).There was also increased co-localized expression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pul-monary arteries(P＜0.01),as well as elevated levels of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tissues(P＜0.01),indicating induced pyroptosis of PASMCs.Compared with SuHx group,FXD treat-ment significantly reduced RVSP and RVHI,improved right ventricular function,and attenuated right ventricular wall fi-brosis and pulmonary vascular remodeling(P＜0.05 or P＜0.01).Treatment with FXD also decreased the co-localized ex-pression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pulmonary arteries(P＜0.05 or P＜0.01),and down-regulated the protein expression of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tis-sues(P＜0.05 or P＜0.01),thereby attenuating the pyroptosis of PASMCs.CONCLUSION:FXD attenuates pulmonary vascular remodeling and right ventricular dysfunction in a mouse model of HPH.This effect may be attributed to its inhibi-tion of NF-κB/NLRP3 pathway,which subsequently reduces the pyroptosis of PASMCs.

Thermal ablation (TA) is a widely applied minimally invasive treatment for benign thyroid nodules and low-risk papillary thyroid microcarcinoma. Compared to conventional surgery, TA offers advantages such as minimal trauma, rapid recovery, and no scarring. However, this procedure may lead to various complications, including intraoperative pain, nerve injury, hemorrhage, tracheal injury, skin burns, vasovagal reactions, nodule rupture, and thyroid dysfunction. Although TA demonstrates excellent safety and efficacy, further standardization of procedural protocols is necessary to minimize the incidence of complications.