Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

OBJECTIVE: To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP). METHODS: The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot. RESULTS: In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01). CONCLUSION Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.
Abietanes/therapeutic use* ; Osteosarcoma/enzymology* ; Cisplatin/therapeutic use* ; Humans ; Cell Line, Tumor ; Animals ; Apoptosis/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MAP Kinase Signaling System/drug effects* ; Bone Neoplasms/enzymology* ; Cell Cycle/drug effects* ; Xenograft Model Antitumor Assays ; Mice ; Drug Resistance, Neoplasm/drug effects* ; Neoplasm Invasiveness ; Mice, Inbred BALB C

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine/therapeutic use* ; Daunorubicin/therapeutic use* ; Female ; Homoharringtonine/therapeutic use* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Male ; Middle Aged ; Nuclear Proteins ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Cytarabine/therapeutic use* ; Hematopoietic Stem Cell Transplantation ; Humans ; Idarubicin/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy* ; Neutropenia ; Prospective Studies ; Recurrence ; Retrospective Studies

OBJECTIVE: To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients. METHODS: The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed. RESULTS: Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications. CONCLUSION For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

OBJECTIVE: To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1). METHODS: The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed. RESULTS: In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188)；RFS (62.5% vs 38.9%) (P=0.166). CONCLUSION Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.
Adult ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Homeodomain Proteins ; genetics ; Humans ; Immunophenotyping ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; therapy ; Recurrence ; Remission Induction

Child ; Chromosomes, Human, Y ; genetics ; Female ; Humans ; Lower Extremity ; pathology ; Lymphedema ; diagnosis ; genetics ; Noonan Syndrome ; diagnosis ; genetics

Objective: To compare the time of the recovery of neutrophils or leukocytes by pegylated recombinant human granulocyte stimulating factor (PEG-rhG-CSF) or common recombinant human granulocyte stimulating factor (rhG-CSF) in the myelosuppressive phase after induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients. At the same time, the incidences of infection and hospitalization were compared. Methods: A prospective randomized controlled trial was conducted in patients with newly diagnosed AML who met the enrollment criteria from August 2014 to December 2017. The patients were randomly divided into two groups according to a 1:1 ratio: PEG-rhG-CSF group and rhG-CSF group. The time of neutrophil or leukocyte recovery, infection rate and hospitalization interval were compared between the two groups. Results: 60 patients with newly diagnosed AML were enrolled: 30 patients in the PEG-rhG-CSF group and 30 patients in the rhG-CSF group. There were no significant differences in age, chemotherapy regimen, pre-chemotherapy ANC, WBC, and induction efficacy between the two groups (P>0.05) . The median time (range) of ANC or WBC recovery in patients with PEG-rhG-CSF and rhG-CSF were 19 (14-35) d and 19 (15-26) d, respectively, with no statistical difference (P=0.566) . The incidences of infection in the PEG-rhG-CSF group and the rhG-CSF group were 90.0%and 93.3%, respectively, and there was no statistical difference (P=1.000) . The median days of hospitalization (range) was 20.5 (17-49) days and 21 (19-43) days, respectively, with no statistical difference (P=0.530) . Conclusions: In AML patients after induction therapy, there was no significant difference between the application of PEG-rhG-CSF and daily rhG-CSF in ANC or WBC recovery time, infection incidence and hospitalization time.
Granulocyte Colony-Stimulating Factor/therapeutic use* ; Humans ; Induction Chemotherapy/adverse effects* ; Leukemia, Myeloid, Acute/drug therapy* ; Neutropenia ; Neutrophils ; Prospective Studies ; Recombinant Proteins

OBJECTIVETo evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML).

METHODSClinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent. The incidences of IPA and systemic antifungal treatment during induction chemotherapy were analyzed for both groups.

RESULTSAmong 102 enrolled cases, 42 cases received voriconazole and other 60 received posaconazole as primary prophylaxis. IPA occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred in 4 cases of posaconazose group, and all were possible cases. The incidence of IPA during remission-induction chemotherapy in variconazole group equaled to posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in voriconazole group and 4 cases in posaconazole group received intravenous anti aspergillosis drugs preemptive treatment, and no significant difference of prophylactic success rate was observed between two groups (88.1% vs. 86.7%) (P=0.831). Visual disturbance was the most common adverse event occurred in voriconazole group, but no significant differences of incidences of other adverse effects were observed when compared with posaconazole group.

CONCLUSIONAccording to similar prophylactic effect with posaconazole, voriconazole appears to be a good alternative for primary prophylaxis of IPA during remission-induction chemotherapy in AML patients.