Objective:To assess the safety and efficacy of Blinatumomab in treating children with acute B-lymphoblastic leukemia（B-ALL）.Methods:The clinical data of 10 B-ALL children who were admitted to the Department of Pediatrics，the First Affiliated Hospital of Xi’an Jiaotong University from May 2022 to April 2024 and treated with Blinatumomab were analyzed retrospectively.Results:All the 10 cases had a complete remission of bone marrow and all minimal residual disease（MRD）were negative. Serious adverse events were reported after chemotherapy，including intracranial venous sinus thrombosis with acute cerebral infarction，acute pancreatitis，paralytic ileus，syndrome of abnormal secretion of antidiuretic hormone，severe pneumonia，liver injury，sepsis（β-lactamase resistant Escherichia coli，Pseudomonas aeruginosa），oral mucositis，persistent agranulocytosis with bloodstream infection. All patients interrupted chemotherapy and received Blinatumomab injections for 14 days. During treatment，there was hematological toxicity，which resulted in grade 3-4 neutropenia in 5 cases within the first 7 days. Transient low-grade fever was observed in 4 cases of non-hematological toxicity during days 1-3 of treatment. One patient experienced a headache on the 7th day of treatment，which worsened on the 14th day，but it improved with mannitol treatment. Mild liver injury was present in 3 cases. Interleukin-6 reached a peak of 71.86 pg/mL on the second day of treatment in one case，whereas it was normal in others. All patients were found to be free of cytokine release syndrome. T lymphocyte count increased in 5 patients after 14 days of Blinatumomab treatment，but B lymphocyte count and serum immunoglobulin levels declined in 10 patients. Hypogammaglobulinemia was observed in 3 of these patients. The median follow-up time was 7.8（3.0-24.0）months. All patients achieved MRD-negative complete remission and 6-month overall survival rate and progression-free survival were both 100%.Conclusion:Children with B-ALL can benefit from using Blinatumomab，which is safer than conventional chemotherapy，as a new treatment strategy for those who cannot tolerate traditional chemotherapy.

Acute carbon monoxide poisoning (ACMP) is a common harmful gas poisoning. Underwent systematic treatment and a 2-3 week pseudo-healing period, some ACMP patients may still develop delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). DEACMP is the most severe complication that could happen to ACMP patients and comes with an exceeding high disability rate. Early identification and adequate intervention measures of DEACMP are particularly crucial for preventing its occurrence in clinical practice. At present, multiple studies have found that after ACMP occurred, a series of biomarkers showed predictive value for detecting the occurrence and development of DEACMP. This paper reviews these biomarkers and their predictive effects on DEACMP, aiming to provide theoretical guidance for the prevention and intervention of DEACMP.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Acute carbon monoxide poisoning (ACMP) is a common harmful gas poisoning. Underwent systematic treatment and a 2-3 week pseudo-healing period, some ACMP patients may still develop delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). DEACMP is the most severe complication that could happen to ACMP patients and comes with an exceeding high disability rate. Early identification and adequate intervention measures of DEACMP are particularly crucial for preventing its occurrence in clinical practice. At present, multiple studies have found that after ACMP occurred, a series of biomarkers showed predictive value for detecting the occurrence and development of DEACMP. This paper reviews these biomarkers and their predictive effects on DEACMP, aiming to provide theoretical guidance for the prevention and intervention of DEACMP.

Objective:To assess the safety and efficacy of Blinatumomab in treating children with acute B-lymphoblastic leukemia（B-ALL）.Methods:The clinical data of 10 B-ALL children who were admitted to the Department of Pediatrics，the First Affiliated Hospital of Xi’an Jiaotong University from May 2022 to April 2024 and treated with Blinatumomab were analyzed retrospectively.Results:All the 10 cases had a complete remission of bone marrow and all minimal residual disease（MRD）were negative. Serious adverse events were reported after chemotherapy，including intracranial venous sinus thrombosis with acute cerebral infarction，acute pancreatitis，paralytic ileus，syndrome of abnormal secretion of antidiuretic hormone，severe pneumonia，liver injury，sepsis（β-lactamase resistant Escherichia coli，Pseudomonas aeruginosa），oral mucositis，persistent agranulocytosis with bloodstream infection. All patients interrupted chemotherapy and received Blinatumomab injections for 14 days. During treatment，there was hematological toxicity，which resulted in grade 3-4 neutropenia in 5 cases within the first 7 days. Transient low-grade fever was observed in 4 cases of non-hematological toxicity during days 1-3 of treatment. One patient experienced a headache on the 7th day of treatment，which worsened on the 14th day，but it improved with mannitol treatment. Mild liver injury was present in 3 cases. Interleukin-6 reached a peak of 71.86 pg/mL on the second day of treatment in one case，whereas it was normal in others. All patients were found to be free of cytokine release syndrome. T lymphocyte count increased in 5 patients after 14 days of Blinatumomab treatment，but B lymphocyte count and serum immunoglobulin levels declined in 10 patients. Hypogammaglobulinemia was observed in 3 of these patients. The median follow-up time was 7.8（3.0-24.0）months. All patients achieved MRD-negative complete remission and 6-month overall survival rate and progression-free survival were both 100%.Conclusion:Children with B-ALL can benefit from using Blinatumomab，which is safer than conventional chemotherapy，as a new treatment strategy for those who cannot tolerate traditional chemotherapy.

Objective:To evaluate the clinical efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT）in children with severe aplastic anemia（SAA）.Methods:Twenty-seven cases with SAA who had been treated with allo-HSCT from January 2020 to December 2022 were retrospectively analyzed and reviewed.Results:（1）A total of 27 SAA patients were enrolled，including 18 males and 9 females，with a median age of 8 (2-15) years.There were 20 cases of SAA-Ⅰ type,7 cases of SAA-Ⅱ type.Based upon donor sources，three cases of matched sibling donors hematopoietic stem cell transplantation,and 24 cases of haploidentical hematopoietic stem cell transplantation were adopted.（2）Hematopoietic reconstruction was achieved in all 27 cases.The median implantation time of neutrophils and platelets was 10（9-20）days and 12（7-26）days respectively.The cumulative incidence of acute graft-versus-host disease（GVHD）was 66.67%（18/27）.The incidence of grade Ⅰ-Ⅱ was 55.56%（15/27）and that of grade Ⅲ-Ⅳ was 11.11%（3/27）.The incidence of chronic GVHD was 7.41%（2/27）.Transplant-associated thrombotic microangiopathy (TA-TMA) occurred in 7.41%（2/27）patients,cytomegalovirus viremia in 62.96%（17/27）patients,epstein-barr virus infection in 33.33%（9/27）patients,and 14.81%（4/27）patients progressed to post-transplant lymphoproliferative disorder (PTLD).（3）The median follow-up time was 12 (2-28) months.The overall survival rate was 96.29%.Twenty-six patients survived,and one patient died due to multiple complications of severe acute GVHD,TA-TMA,cytomegalovirus infection,PTLD and secondary epilepsy.Conclusion:Allo-HSCT is an effective therapy for SAA in children.The effective rate of this research is 96.29%.Acute GVHD is still the key to therapy.The incidence rate of acute GVHD is 66.67% in this study.The blood incompatibility of donor and recipient may affect the incidence of GVHD.The intensity of GVHD prevention should be reduced after HLA-matched sibling donor-hematopoietic stem cell transplantation so as to avoid the complications of virus recurrence and PTLD.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.

Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high efficiency.Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation.Therefore,optogenetic techniques can provide new insights into oral biological processes at different levels,ranging from the subcellular and cellular levels to neural circuits and behavioral models.Here,we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research,focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo(orofacial movement,licking,eating,and drinking),such as channelrhodopsin(ChR),archaerhodopsin(Arch),and halorhodopsin from Natronomonas pharaonis(NpHR).We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis.In addition,optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies.Although the scope of optogenetic tools is increasing,there are limited large animal experiments and clinical studies in dental research.Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019(COVID-19),studying oral bacterial biofilms,enhancing craniomaxillofacial and periodontal tissue regeneration,and elucidating the possible pathogenesis of dry sockets,xerostomia,and burning mouth syndrome.

Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.