Objective To investigate the relationship between serum microRNA-101-3p(miR-101-3p),pol-ypeptide N-acetylgalactosaminyltransferase 1(GALNT1)and the efficacy and prognosis of neoadjuvant chem-otherapy(NAC)in breast cancer.Methods A total of 203 breast cancer patients who underwent NAC in this hospital from January 2017 to August 2019 were selected as breast cancer group.They were divided into the ineffective group and the effective group according to the therapeutic effect of NAC,and divided into the death group and the survival group according to the 5-year survival situation.Additionally,203 healthy women who underwent routine physical examination during the same period were selected as the control group.The clini-cal data and the levels of serum miR-101-3p and GALNT1 were detected and compared.The binding sites of miR-101-3p and GALNT1 were predicted through the online database.Pearson correlation analysis was per-formed to assess the correlation between serum miR-101-3p and GALNT1 expression in breast cancer pa-tients.The relationship between serum miR-101-3p,GALNT1 and the efficacy and prognosis of NAC in breast cancer patients were analyzed by multivariate unconditional Logistic regression and Cox regression.The pre-dictive value of serum miR-101-3p and GALNT1 for the ineffectiveness and mortalit of NAC treatment in breast cancer patients were analyzed by receiver operating characteristic(ROC)curve.Results Compared with the control group,the expression level of serum miR-101-3p in the breast cancer group decreased,and the level of GALNT1 increased,and the differences were statistically significant(P＜0.05).Serum miR-101-3p in patients with breast cancer was negatively correlated with GALNT1(P＜0.05).High expression of Ki-67,≥4 axillary lymph node metastases after surgery and high expression of GALNT1 were independent risk factors for ineffective NAC treatment in breast cancer patients(P＜0.05),and high expression of miR-101-3p was an independent protective factor(P＜0.05).TNM stage Ⅲ,postoperative axillary lymph node metastasis ≥10,and high expression of GALNT1 were independent risk factors for ineffective NAC treatment in breast cancer patients(P＜0.05),while high expression of miR-101-3p was an independent protective fac-tor(P＜0.05).The predictive efficacy of combined detection of serum miR-101-3p and GALNT1 for ineffec-tive NAC treatment and death in breast cancer patients was higher than that predicted by either of them alone(both P＜0.05).Conclusion Low serum miR-101-3p and high GALNT1 expression in breast cancer patients are closely related to NAC efficacy and prognosis.The combination of the two has a high predictive value for both the efficacy and prognosis of NAC.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Chimeric antigen receptor (CAR) T-cell therapy has achieved breakthroughs in treating relapsed/refractory B-cell malignancies. However, it still faces challenges, including complex manufacturing processes, limited indications, T-cell exhaustion, and insufficient durability of therapeutic efficacy. CRISPR/Cas9, a highly efficient and relatively simple gene-editing technology, offers new avenues for overcoming these limitations. This review briefly outlines the working mechanism of CRISPR/Cas9 and focuses on its recent applications and clinical practices in developing universal CAR T-cells, enhancing T-cell function, and extending CAR T-cell therapy to T-cell and myeloid leukemias. Furthermore, this review highlights optimization strategies developed over the past two years to enhance the editing precision, delivery efficiency, and safety of the CRISPR/Cas9 system, aiming to provide insights for the optimal design and clinical application of CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy has achieved breakthroughs in treating relapsed/refractory B-cell malignancies. However, it still faces challenges, including complex manufacturing processes, limited indications, T-cell exhaustion, and insufficient durability of therapeutic efficacy. CRISPR/Cas9, a highly efficient and relatively simple gene-editing technology, offers new avenues for overcoming these limitations. This review briefly outlines the working mechanism of CRISPR/Cas9 and focuses on its recent applications and clinical practices in developing universal CAR T-cells, enhancing T-cell function, and extending CAR T-cell therapy to T-cell and myeloid leukemias. Furthermore, this review highlights optimization strategies developed over the past two years to enhance the editing precision, delivery efficiency, and safety of the CRISPR/Cas9 system, aiming to provide insights for the optimal design and clinical application of CAR T-cell therapy.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

As an important method to detect intracranial arterial stenosis or occlusive disease,transcranial Doppler(TCD)has been widely used in clinical practice because of its low price and easy operation.The scope of application of TCD includes,but is not limited to,the diagnosis and collateral evaluation of intracranial artery stenosis or occlusive disease,intraoperative monitoring of carotid endarterectomy,assessment of brain death,etc.,but the characteristics of TCD blood flow changes of some special structures of intracranial arteries need to be improved.This paper presented 3 cases with special intracranial artery structures,and comprehensively analyzes the blood flow spectrum on TCD based on medical images,in order to improve clinicians'exploration experience on similar cases and the level of cerebrovascular ultrasound.

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Objective:To investigate the effect of backfilling on the deformity of lacrimal sulcus and blepharobuccal sulcus after special treatment of the fat from orbital septum of the pouch in the lower intra-palpebral approach.Methods:From November 2019 to September 2022, a total of 42 patients (13 males and 29 females) aged 16-47(23.8±6.9) years with orbital septal fat swelling were treated by the surgical department of Beijing Huangsi Medical Cosmetic Clinic after the removal of orbital fat mass by the intraocular pouch approach. With mild, moderate, and severe lacrimal sulci and blepharobuccal depression deformity, the lower eyelid skin was not relaxed. The naturally herniated orbital septal adipose mass was cut off through the lower eyelid conjunctival incision approach, and then granulated into a 1 ml syringe, which was accurately filled into the depressed area of lacrimal sulci and blepharobuccal sulci according to the depressions marked before surgery.Results:The incisions of all 42 patients healed in the first stage without hematoma and infection, and the subcutaneous ecchymosis of 2 cases was observed by local hot compress 48 h later and the ecchymosis subsided 1 week. Follow-up was performed at 1 month, 2 months and 3 months, respectively. Among them, 35 patients underwent the operation of removing the lower eyelid bag and orbital septum cellulite and backfilling to correct the malformation of lacrimal sulci, and the postoperative effect was satisfactory. The symptoms of puffed eye bags, blepharobuccal sulci and lacrimal sulci depression disappeared, and the wound healed in one stage. 7 patients with eye bags accompanied by lacrimal sulci and blepharobuccal sulci were told before surgery that they might need two fat fillings due to insufficient fat content in the orbital septa and slight indentations. One month later, granular fat was taken from the legs to fill the lacrimal sulci and blepharobuccal sulci with satisfactory results.Conclusions:The treatment after the removal of orbital septum cellulite and the correction of lacrimal sulcus and blepharobuccal sulcus deformity are simple and satisfactory, and worthy of clinical application.

Objective:To investigate the correlation between serum vascular endothelial growth factor (VEGF), von Willebrand factor (vWF) and coagulation index and prognosis of differentiated thyroid cancer (TC) .Methods:136 TC patients admitted in Department of Head and Neck Surgery Shanxi Cancer Hospital from Jan. 2021 to Dec. 2022 were selected as TC group, and 80 patients with confirmed thyroid benign nodule during the same period were selected as control group. VEGF, vWF and coagulation indexes were compared between the two groups. The tumor free survival was calculated by Kaplan-Meier method.Results:Compared with the control group, the levels of VEGF, vWF, TT, Fbg in TC group were higher, and the levels of PT, APTT were lower ( P < 0.001). Compared with patients < 55 years old, the levels of VEGF, vWF, TT and Fbg were higher in patients ≥55 years old, and the levels of PT and APTT were lower ( P < 0.001). Compared with papillary carcinoma, the levels of VEGF, vWF, TT and Fbg were higher in follicular carcinoma patients, and the levels of PT and APTT were lower ( P < 0.001). The levels of VEGF, vWF, TT and Fbg were higher and the levels of PT and APTT were lower in patients with TNM stage III to IV than in patients with TNM stage I to II ( P < 0.001). Compared with patients without lymph node metastasis, VEGF, vWF, TT, Fbg levels were higher in patients with lymph node metastasis, and PT, APTT levels were lower ( P < 0.001). Compared with patients with tumor size < 2 cm, VEGF and vWF levels were higher in patients with tumor size ≥ 2 cm ( P < 0.001). Survival curve analysis showed that the tumor free survival of high VEGF, high vWF, high TT and high Fbg groups was shorter than that of low VEGF, low vWF, low TT and low Fbg groups (Log-rank=9.149, 8.856, 4.683, 5.867, P < 0.001) . Conclusion:VEGF, vWF and coagulation indexes in TC patients were correlated with clinicopathological features, and were helpful to predict postoperative tumor-free survival.

Objective:To investigate the correlation between serum vascular endothelial growth factor (VEGF), von Willebrand factor (vWF) and coagulation index and prognosis of differentiated thyroid cancer (TC) .Methods:136 TC patients admitted in Department of Head and Neck Surgery Shanxi Cancer Hospital from Jan. 2021 to Dec. 2022 were selected as TC group, and 80 patients with confirmed thyroid benign nodule during the same period were selected as control group. VEGF, vWF and coagulation indexes were compared between the two groups. The tumor free survival was calculated by Kaplan-Meier method.Results:Compared with the control group, the levels of VEGF, vWF, TT, Fbg in TC group were higher, and the levels of PT, APTT were lower ( P < 0.001). Compared with patients < 55 years old, the levels of VEGF, vWF, TT and Fbg were higher in patients ≥55 years old, and the levels of PT and APTT were lower ( P < 0.001). Compared with papillary carcinoma, the levels of VEGF, vWF, TT and Fbg were higher in follicular carcinoma patients, and the levels of PT and APTT were lower ( P < 0.001). The levels of VEGF, vWF, TT and Fbg were higher and the levels of PT and APTT were lower in patients with TNM stage III to IV than in patients with TNM stage I to II ( P < 0.001). Compared with patients without lymph node metastasis, VEGF, vWF, TT, Fbg levels were higher in patients with lymph node metastasis, and PT, APTT levels were lower ( P < 0.001). Compared with patients with tumor size < 2 cm, VEGF and vWF levels were higher in patients with tumor size ≥ 2 cm ( P < 0.001). Survival curve analysis showed that the tumor free survival of high VEGF, high vWF, high TT and high Fbg groups was shorter than that of low VEGF, low vWF, low TT and low Fbg groups (Log-rank=9.149, 8.856, 4.683, 5.867, P < 0.001) . Conclusion:VEGF, vWF and coagulation indexes in TC patients were correlated with clinicopathological features, and were helpful to predict postoperative tumor-free survival.