Objective:To compare the efficacy and safety of continuous venetoclax combined azacitidine (VA) chemotherapy and intermedium/high-dose cytarabine (I/HDAC) consolidation in patients with acute myeloid leukemia (AML) fit for standard chemotherapy (transform from UNFIT) .Methods:Clinical data of patients who were fit for standard chemotherapy were collected among those with AML who underwent VA induction in the Department of Hematology, the Second Hospital of Hebei Medical University. The overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), and incidence of adverse events were analyzed retrospectively.Results:This study enrolled 69 patients, consisting of 46 cases in the VA group and 23 cases in the I/HDAC group. We revealed the following. ① The median OS, RFS, EFS were 26.18, 24.69, 20.34 months in the VA group, and 34.14, 30.99, 28.42 months in the I/HDAC group, respectively, with no statistically significant difference (all P>0.05). Median OS of patients who underwent I/HDAC consolidation with European Leukemia Net (ELN) favorable-risk, positive measurable residual disease (MRD), wild type FLT3, or IDH1/2 mutation was significantly longer than those who received VA ( P<0.05). ②Adverse events rate of grade 3 - 4 neutropenia, grade 3 - 4 thrombocytopenia, and bacteremia were significantly lower in the VA group than in the I/HDAC group ( P<0.05) . Conclusions:I/HDAC consolidation was more likely to help get survival benefits for patients with ELN favorable-risk, positive MRD, wild type FLT3, or IDH1/2 mutation. Continuous VA chemotherapy exhibited superior safety than I/HDAC consolidation.

Objective:To compare the efficacy and safety of continuous venetoclax combined azacitidine (VA) chemotherapy and intermedium/high-dose cytarabine (I/HDAC) consolidation in patients with acute myeloid leukemia (AML) fit for standard chemotherapy (transform from UNFIT) .Methods:Clinical data of patients who were fit for standard chemotherapy were collected among those with AML who underwent VA induction in the Department of Hematology, the Second Hospital of Hebei Medical University. The overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), and incidence of adverse events were analyzed retrospectively.Results:This study enrolled 69 patients, consisting of 46 cases in the VA group and 23 cases in the I/HDAC group. We revealed the following. ① The median OS, RFS, EFS were 26.18, 24.69, 20.34 months in the VA group, and 34.14, 30.99, 28.42 months in the I/HDAC group, respectively, with no statistically significant difference (all P>0.05). Median OS of patients who underwent I/HDAC consolidation with European Leukemia Net (ELN) favorable-risk, positive measurable residual disease (MRD), wild type FLT3, or IDH1/2 mutation was significantly longer than those who received VA ( P<0.05). ②Adverse events rate of grade 3 - 4 neutropenia, grade 3 - 4 thrombocytopenia, and bacteremia were significantly lower in the VA group than in the I/HDAC group ( P<0.05) . Conclusions:I/HDAC consolidation was more likely to help get survival benefits for patients with ELN favorable-risk, positive MRD, wild type FLT3, or IDH1/2 mutation. Continuous VA chemotherapy exhibited superior safety than I/HDAC consolidation.

Objective:To evaluate the optimization effect of ultrasound-guided erector spinae plane block (ESPB)combined with general anesthesia on Nuss procedure in pediatric patients with pectus excavatum undergoing Nuss procedure.Methods:One hundred and eight pediatric patients of either sex, aged 7-18 yr, with body mass index within the normal range, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective Nuss procedure, were randomized into 3 groups ( n=36 each) using a random number table method: ultrasound-guided ESPB combined with general anesthesia group (group E), thoracic epidural anesthesia plus general analgesia group (group T), and general analgesia group (group G). Pediatric patients received ultrasound-guided bilateral ESPB (0.3% ropivacaine was injected, 0.5 ml/kg bilateral total volume [maximum 20 ml]) or thoracic epidural anesthesia (0.3% ropivacaine 0.5 ml/kg [maximum 20 ml/side]) after induction of anesthesia in group E and group T, respectively. All the three groups underwent general anesthesia, anesthesia was induced with propofol 2-3 mg/kg, sufentanil 0.3-0.5 μg/kg and cis-atracurium 0.1-0.2 mg/kg and maintained with propofol 6-10 mg·kg -1·h -1 and remifentanil 0.1-0.3 μg·kg -1·min -1. The patients were endotracheally intubated and mechanically ventilated after anesthesia induction. The parent-controlled intravenous analgesia (PCIA) was used for patients in all the three groups postoperatively. The consumption of intraoperative remifentanil and postoperative consumption of sufentanil for PCIA in each period after surgery were recorded. The time to the first rescue analgesia, consumption of ibuprofen and postoperative complications were also recorded. Results:Compared with group G, the intraoperative consumption of remifentanil and postoperative consumption of sufentanil for PCIA in each period were significantly decreased, the time to the first rescue analgesia was prolonged, and the consumption of ibuprofen was decreased in group E ( P<0.05). There was no significant difference among the three groups ( P>0.05). Conclusions:ESPB combined with general analgesia is helpful in reducing postoperative hyperalgesia in pediatric patients undergoing the Nuss procedure.

IgG4-associated disease (gG4-RD) is a systemic immune-mediated fibroinflammatory disease that can involve almost all organs and systems, and the main clinical manifestations are enlargement or mass of the affected organs. The typical pathological features of the disease are a large number of lymphocytoplasmic infiltration in the pathological tissue, accompanied by mat fibrosis and obliterated phlebitis, and most patients may have elevated serum IgG4 levels. At present, the specific pathogenesis of the disease is not clear. In recent years, the mechanism of intestinal microbiome dysregulation in the occurrence and development of autoimmune diseases has been gradually clarified. However, the association between the gut microbiome and IgG4-RD is still poorly understood. Therefore, this article will review the progress of intestinal microbiome research of IgG4-RD.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

AIM:From the perspective of regulating mitochondrial complex I activity by DJ-1 protein,this study aims to explore the mechanism of DJ-1-mediated resveratrol(RES)preconditioning in protecting against oxidative stress injury induced by myocardial ischemia-reperfusion(I/R)in rats.METHODS:After intramyocardial injection of lentivirus carrying DJ-1 shRNA(sh-DJ-1)or negative control(NC)shRNA,the myocardial I/R model was constructed by ligating the left anterior descending branch of the rat coronary artery.Sprague-Dawley(SD)rats were randomly divided in-to 6 groups:sham group,I/R group,RES+I/R group,NC+RES+I/R group,sh-DJ-1+RES+I/R group,and IACS-010759(mitochondrial complex I inhibitor)+RES+I/R group,with 10 rats in each group.The rats in RES treatment groups were given RES(20 mg/kg)via gavage for 7 d prior to the myocardial I/R modeling,once daily.Moreover,the rats in sham and I/R groups received an equivalent volume of normal saline via gavage.Myocardial infarction area and cardiac function were assessed by TTC staining and echocardiography,respectively.The MitoSOX fluorescent probe was used to detect levels of mitochondrial reactive oxygen species(ROS)in the myocardium.The levels of malondialdehyde(MDA),superoxide dis-mutase(SOD)and lactate dehydrogenase(LDH)in the serum were detected using kits.Western blot and co-immunopre-cipitation assays were used to observe the interaction between DJ-1 and the two subunits,ND-1 and NDUFA4,of the mito-chondrial complex I.RESULTS:Compared with I/R group,RES pretreatment significantly reduced the myocardial in-farction area,mitochondrial ROS levels,serum LDH activity,and serum MDA content(P＜0.01).It also elevated left ventricular ejection fraction,left ventricular fractional shortening and serum SOD activity(P＜0.01).Pretreatment with RES increased the expression and mitochondrial translocation of DJ-1(P＜0.01),promoted the interaction between DJ-1 and ND-1/NDUFA4,which in turn protected the activity of mitochondrial complex I(P＜0.01).However,when the ex-pression of DJ-1 was suppressed,the protective effects of RES against myocardial I/R injury were significantly inhibited compared with RES+I/R group(P＜0.05 or P＜0.01).CONCLUSION:Pretreatment with RES increases the expression and mitochondrial translocation of DJ-1,and facilitates the interaction of DJ-1 with ND1 and NDUFA4 subunits of mito-chondrial complex I,thus preserving the activity of mitochondrial complex I and attenuating myocardial I/R-induced oxida-tive stress damage.

AIM: To explore the role and mechanism of silent mating type information regulator 2 homolog 3 (SIRT3) in attenuation of intestinal ischemia-reperfusion (I/R) injury by dexmedetomidine in mice. METHODS: Twenty-four healthy male C57BL mice were divided into 4 groups randomly (n=6): sham operation group (Sham group), intestinal ischemia-reperfusion group (I/R group), dexmedetomidine group (Dex group), SIRT3 inhibitor 3-TYP group (3-TYP group). Superior mesenteric artery was clamped for 45 min followed by reperfusion for 2 h to establish intestinal I/R model in I/R group, Dex group, and 3-TYP group. Sham group received sole sham operation. 1 h prior to onset of ischemia, 3-TYP was injected into mice in 3-TYP group intraperitoneally (5 mg/kg, diluted to 0.3 mL), and 0.3 mL normal saline into mice in Dex group intraperitoneally. 30 min prior to onset of ischemia, dexmedetomidine was injected into mice in 3-TYP group and Dex group intraperitoneally (25 μg/kg, diluted to 0.3 mL). 1 h and 30 min prior to onset of ischemia, 0.3 mL normal saline was injected into mice in Sham group and I/R group intraperitoneally, respectively. 2 h of after reperfusion, the mice were sacrificed under anesthesia. Intestinal tissues were took and observed for pathological changes under light microscope after HE staining, and the injury was assessed via the Chiu's score method, and activities of SIRT3 and superoxide dismutase 2 (SOD2) were detected via spectrophotometry, and malondialdehyde (MDA) via spectrophotometry. RESULTS: The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in I/R group, Dex group and 3-TYP group compared to Sham group (P<0.05). The pathological injury was alleviated, and the Chiu's score declined remarkably in Dex group and 3-TYP group compared to I/R group (P<0.05); and the MDA level declined remarkably, while activity level of SIRT3 and SOD2 elevated remarkably in Dex group compared to I/R group (P<0.05); and there was no significant difference both in the activity level of SIRT3 and SOD2 and in the MDA level between 3-TYP group and I/R group. The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in 3-TYP group compared to Dex group (P<0.05). CONCLUSION: SIRT3 and its downstream SOD2 are involved in mediating the effect of attenuation of intestinal ischemia-reperfusion injury through inhibiting oxidative stress response by dexmedetomidine.

Objective:This study aims to reveal the special immune infiltrating environment and possible immune escape mechanism of giant cell tumor of bone through single-cell sequencing data.Methods:The fresh samples obtained from 4 patients with primary giant cell tumor of bone from January 2018 to December 2021 were collected, and single-cell transcriptome sequencing was performed on the 10X platform to explore the characteristics and immune environment of giant cell tumor of bone by using t-distributed stochastic neighbor embedding ( t-SNE). The main cell types and signal pathways of immune cell regulation and function in giant cell tumor of bone were observed by cell communication analysis. Results:Cell clustering, the definition of basic cell types, the classification of immune cells, and the mutual regulatory relationship between cell types were analyzed for 35 643 single-cell data from 4 giant cell tumor samples of bone. It was found that giant cell tumor of bone was composed of 9 basic cell types, in which the immune cells were mainly CD8 + T cells (51%) and the non-immune cells were mainly fibroblast like spindle stromal cells (74%). The immune infiltration of giant cell tumor of bone is dominated by cytotoxic CD8 + T cells and lacks exhausted CD8 + T cells. CD4 + T cells are characterized by high expression of immune checkpoint genes CTLA4 and TIGIT. In giant cell tumor of bone, immune cells mainly act on multinucleated osteoclast like giant cells through PARs and CCL signaling pathways, but not stromal cells. Conclusion:This study defined the main cell types of giant cell tumor of bone through single cell sequencing data, and further revealed the composition characteristics of its immune infiltration, and found that the target of its immune cells was mainly multinuclear osteoclast like giant cells, which provided effective information for further understanding the occurrence and development of giant cell tumor of bone.

microRNA (miRNA) is a class of 19-25 nucleotide highly conserved single-stranded non-coding RNA that is widely found in plants and animals. Their biological effect is to negatively regulate target gene expression at the post-transcriptional level through complementary pairing with mRNA. Intestinal I/R injury is more common in clinical practice, and ischemia-reperfusion will cause intestinal mucosal barrier damage, and it is related to the occurrence, development, and outcome of many clinical diseases. Many studies have shown that the miRNA subtype genes miR-34a-5p, miR-351-5p, miR-682, miR-21, etc. affect the intestinal I/R injury process to some extent by regulating a series of signal transduction. Therefore, revealing the role of miRNA in intestinal I/R injury and providing a new direction for the diagnosis and treatment of I/R.