[Best evidence summary for awake prone positioning in treating hypoxemic due to COVID-19 infection].

Objective: To retrieve, evaluate, and summarize the best evidence for the treatment of hypoxemia in patients with COVID-19 infection using the awake prone positioning, with the aim of guiding healthcare professionals in the standardized implementation of this therapy. Methods: A systematic search was conducted in databases including UpToDate, BMJ Best Practice, JBI Evidence-Based Healthcare Center, American Association of Critical-Care Nurses, Intensive Care Society, European Respiratory Society, World Health Organization website, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang. The retrieved literature was subjected to quality assessment and evidence extraction. Results: A total of ten publications were included, consisting of one thematic evidence summary, one guideline, two systematic reviews, three randomized controlled trials, and three expert consensus statements. This summary synthesizes thirty key pieces of evidence in five categories: organizational management and training, risk assessment, preparatory operations, implementation key points, and risk control. Conclusions: Awake prone positioning is beneficial for improving hypoxemia in patients with COVID-19 and is easy to implement. Medical institutions should develop nursing management systems, operational standards, and best practices for awake prone positioning based on evidence-based evidence in order to improve the quality of care management for such patients.

[Research progress of direct-acting antiviral drugs in the treatment of chronic hepatitis C-related cirrhosis].

Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.

The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis.

OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.

[Analysis of advanced fibrosis in metabolic dysfunction-associated fatty liver disease patients with chronic hepatitis B].

Objective: To investigate the clinical and pathological characteristics of chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD), as well as associations with advanced fibrosis. Methods: CHB patients who underwent liver biopsy at Tianjin Second People's Hospital from June 2016 to September 2019 were included in the study. The patients were divided into two groups based on whether they had concomitant MAFLD; a CHB group and a MAFLD-CHB group. t-tests and Chi-square tests were used to compare pathological characteristics and basic features in the two groups. Logistic regression analysis was used to analyze factors associated with advanced fibrosis. Results: The CHB group included 110 patients, and the MAFLD-CHB group included 272 patients. There were significant differences in smoking, alcohol consumption, hypertension incidence, body metabolic index, alanine aminotransferase, gamma-glutamyl transferase (GGT), high-density lipoprotein, low-density lipoprotein, fasting plasma glucose, and platelets (PLT) between the two groups (all P<0.05). The MAFLD-CHB group had a higher incidence of advanced fibrosis than the CHB group (P<0.05). In logistic regression analysis MAFLD [odds ratio (OR)=2.204, 95% confidence interval (CI) 1.018-4.774, P=0.045], GGT (OR=1.008, 95%CI 1.002-1.013, P=0.005), and PLT (OR=0.995, 95%CI 0.991-0.999, P=0.019) were associated with advanced fibrosis (all P<0.05). In the MAFLD-CHB group type 2 diabetes (OR=3.281, 95%CI 1.375-7.832, P=0.007), GGT (OR=1.011, 95%CI 1.003-1.018, P=0.005), and PLT (OR=0.993, 95%CI 0.988-0.998, P=0.004) were associated with advanced fibrosis (P<0.05). Conclusion: Patients with MAFLD-CHB are more likely to develop advanced fibrosis than patients with CHB alone. In the MAFLD-CHB group type 2 diabetes mellitus was associated with advanced fibrosis. It is important to strictly control relevant risk factors in MAFLD-CHB patients, especially in patients with type 2 diabetes.

Bioactivity and genome analysis of Bacillus amyloliquefaciens GL18 isolated from the rhizosphere of Kobresia myosuroides in an alpine meadow.

The unique eco-environment of the Qinghai-Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 107 cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and ß-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress.

The economic burden of coronary heart disease in mainland China.

OBJECTIVES: The aim of this study was to systematically evaluate the current economic burden of coronary heart disease (CHD) in mainland China and provide a reference for the formulation of policies to reduce the economic burden of CHD. STUDY DESIGN: A systematic literature review was conducted of empirical studies on the economic burden of CHD over the past 20 years. METHODS: PubMed, Web of Science, Embase, China Knowledge Resource Integrated Database and the WANFANG database were comprehensively searched for relevant articles published between 1 January 2000 and 22 December 2021. Content analysis was used to extract the data, and Stata 17.0 software was used for analysis. The median values were used to describe trends. RESULTS: A total of 35 studies were included in this review. The annual median per-capita hospitalisation expense and the average expense per hospitalisation were $3544.40 ($891.64-$18,371.46) and $5407.34 ($1139.93-$8277.55), respectively. The median ratio on medical consumables expenses, drug expenses, medical examination expenses and treatment expenses were 41.59% (12.40%-63.73%), 26.90% (7.30%-60.00%), 9.45% (1.65%-33.40%) and 10.10% (2.36%-66.00%), respectively. The median per-capita hospitalisation expense in the eastern, central and western regions were $9374.45 ($2056.13-$18,371.46), $4751.5 ($2951.95-$8768.93) and $3251.25 ($891.64-$13,986.38), respectively. The median average expense per hospitalisation in the eastern and central regions were $6177.15 ($1679.15-$8277.55) and $1285.49 ($1239.93-$2197.36), respectively. The median average length of stay in the eastern, central and western regions were 9.3 days, 15.2 days and 16.1 days, respectively. CONCLUSIONS: The economic burden of CHD is more severe in mainland China than in developed countries, especially in terms of the direct economic burden. In terms of the types of direct medical expenses, a proportion of medical examination expenses, treatment expenses and drug expenses were lowest in the eastern region, but medical consumables expenses were the highest in this region. This study provides guidance for the formulation of policies to reduce the economic burden of CHD in mainland China.

[Summary of best evidence for pulse contour cardiac output monitoring in severe burn patients].

Objective: To summarize the best evidence for pulse contour cardiac output (PiCCO) monitoring in severe burn patients. Methods: A bibliometric approach was used. Foreign language databases including UpToDate, BMJ Best Practice, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, PubMed, Web of Science, Embase, Medline, and Guideline International Network, as well as Chinese databases such as China National Knowledge Infrastructure, Wanfang Database, and VIP Database were systematically retrieved to obtain all the publicly published evidence on PiCCO monitoring in severe burn patients in each database from the establishment of each database to May 2022, including guidelines, expert consensus, evidence summary, systematic review, and original research. The literature was screened and evaluated for the quality, from which the evidences were extracted, evaluated, and classified to summarize the best evidences. Results: Three guidelines, two expert consensuses, one evidence summary (with two systematic reviews being traced), two systematic reviews, three randomized controlled trials, one cohort study, and one case-control study were retrieved and included, with good quality of literature. Totally 37 pieces of best evidences about PiCCO monitoring in severe burn patients were summarized from the aspects of pre-operation evaluation, pipe placement and operation, monitoring system establishment, pipeline maintenance, and supervision and education. Conclusions: Totally 37 pieces of best evidences about PiCCO monitoring in severe burn patients are summarized from 5 aspects, providing a basis for the clinical implementation of scientific and standardized PiCCO monitoring and nursing management.

[Liver fibrosis screening, evaluation pathway, and management in patients with fatty liver].

Non-alcoholic fatty liver disease (NAFLD) is not a benign condition, especially in patients with non-alcoholic steatohepatitis (NASH) combined with liver fibrosis grades F2-4, who have a higher risk of liver-related events and mortality. Thus, this population is considered "at-risk" for developing NASH. China has a large NAFLD patient population, so how to screen for those with liver fibrosis is an important socio-economic concern. At the moment, serological models, liver stiffness detection based on vibration-controlled transient elastography, and magnetic resonance elastography (MRE) are the only non-invasive tests (NITs) for liver fibrosis. The prevention and treatment guidelines for NAFLD at home and abroad are reviewed here, based on the research progress of NITs in recent years, so as to suggest screening, evaluation pathways, and management for liver fibrosis in patients with NAFLD.

MRI manifestations of central nervous system leukaemia and cytological analysis of the cerebrospinal fluid.

AIM: To investigate the magnetic resonance imaging (MRI) features and explore the value of MRI in the diagnosis of central nervous system leukaemia (CNSL). MATERIALS AND METHODS: A retrospective study was performed in 68 patients with leukaemia who underwent cranial MRI between January 2020 and June 2022 at Institute of Hematology and Blood Diseases Hospital. RESULTS: A total of 33 patients fulfilled the requirements for inclusion. The findings showed that 87.9% patients exhibited neurological symptoms, and 23 patients showed abnormal MRI findings. No differences were observed between the MRI+ and MRI- groups in terms of age, sex, neurological symptoms, glucose in the cerebrospinal fluid (CSF), chloride in the CSF, abnormal cells detected using conventional cytology (CC), bone marrow status at the diagnosis of CNSL, signal intensity ratio, and mortality, except for protein concentration and the number of leukaemic cells detected using flow cytometry (FCM) in the CSF. Kaplan-Meier survival analysis in patients with leukaemia revealed no statistical differences in the median survival times between the MRI+ group and MRI- group. Cox regression analysis and multivariate analysis showed no significant difference in survival rate between the MRI+ and MRI- groups. Kappa consistency test shows weak diagnostic consistency between MRI and CC, and weak diagnostic inconsistency between MRI and FCM. CONCLUSION: MRI could serve as an important complementary tool to CC and FCM in the diagnosis of CNSL, especially in patients without leptomeningeal involvement.

[Different rapid maxillary expansion methods in the treatment of adult patients with obstructive sleep apnea hypopnea syndrome].

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common sleep respiratory disorder characterized by upper respiratory collapse during sleep, with a high prevalence and potentially fatal complications. Currently, maxillary transverse deficiency are considered to be an important pathogenic factor of OSAHS. For patients with poor compliance with positive airway pressure therapy, rapid maxillary expansion can increase the volume and ventilation of the upper respiratory tract, which is an alternative treatment. This paper reviewed the current research on surgically assisted rapid palatal expansion, miniscrew assisted rapid palatal expansion, and distraction osteogenesis maxillary expansion in the treatment of adult OSAHS. By comparing the indications, contraindications, complications, efficacy and long-term stability of the three treatment methods, it provided reference for treatment of patients with OSAHS.

[Mutational features of immunoglobulin heavy chain variable region gene in patients with chronic lymphocytic leukemia].

Objective: To investigate the mutational features of the immunoglobulin heavy chain variable region (IgHV) gene in patients with chronic lymphocytic leukemia (CLL) using immunophenotypic and molecular genetic methods. Methods: The laboratory results of 266 CLL patients who underwent IgHV gene examination at Sino-US diagnostics laboratory from February 2020 to February 2021 were analyzed for the IgVH mutational status and presence of specific IgVH fragments. In addition, their immunophenotypic, molecular, chromosomal karyotypic, and FISH profiles were investigated and correlated with the IgVH mutational status. Results: Among 266 patients, 172 were male and 94 were female, with a media age of 67 years (20-82 years).There were more patients with mutated IgHV (m-IgHV) than unmutated IgHV (un-IgHV) (69.2%∶30.8%). There was association of VH family and the presence of gene fragments: the overall incidence of VH families including VH3 family (142/266, 53.4%), VH4 family (75/266, 28.2%), and VH1 family (34/266, 12.8%) was about 95%, among which the proportion of VH4-34 (26/266, 9.8%), VH3-23 (25/266, 9.4%), VH3-7 (24/266, 9.0%), and VH4-39 (16/266, 6.0%) was about 35%. VH3-20 and VH3-49 only occurred in un-IgHV (P<0.05). In addition, the expression rates of CD38 (26.3% vs. 3.0%), CD79b (71.1%∶45.5%) and 11q deletion (25.5%∶5.3%) were higher in un-IgHV, and single trisomy 12 (37.9%∶5.6%) were more commonly found in m-IgHV (P<0.05). MYD88 was one of the major mutation genes in m-IgHV, while ATM had the highest mutation rate in un-IgHV. Conclusion: CLL patients have differential expression in terms of IgHV gene mutations, correlating to their immunophenotype and genetics characteristics.

[Clinical features of immune checkpoint inhibitor-related myositis in patients with urological cancer].

OBJECTIVE: Immune checkpoint inhibitors (ICI) have significantly improved the treatment efficacy of a variety of malignant tumors. However, patients may experience a series of special side effects during treatments with ICI. Immune-related myositis after ICI treatment is characterized by autoimmune rheumatic and musculoskeletal damage, which is relatively rare. To analyze the clinical characteristics and outcomes of ICI-associated myositis in urological tumors, we summarized the clinical manifestations, electrophysiological and pathological characteristics, treatments and outcomes in 8 patients. METHODS: The clinical data of the 8 patients with immune-related myositis after ICI treatment for urological tumors treated in the Department of Urology, Peking University First Hospital from March 2018 to March 2022 were retrospectively analyzed for demographic characteristics, drug regimen, clinical symptoms, laboratory indices, electromyography examination, pathological manifestations and outcomes. RESULTS: The eight patients included 2 females and 6 males with a median age of 68 years, all treated with ICI for urological neoplasms, including 2 upper tract urothelial carcinoma (UTUC), 3 renal cell carcinoma (RCC), and 3 bladder cancer (BCa). The median time between the first ICI treatment and the detection of immune-related myositis was 39.5 days, and the median duration of treatment was 2 sessions. The main symptoms were muscle pain and weakness, 5 cases with ptosis, 3 cases with secondary rhabdomyolysis, 5 cases with myocarditis, 1 case with myasthenia gravis, and 1 case with enterocolitis. Among them, patients with immune-related myocarditis had a shorter interval from the first anti-programmed cell death protein-1 (PD-1) therapy to the onset of immune-related myositis (P=0.042) compared with patients without myocarditis. The 8 patients had significant elevation of transaminases and muscle enzyme profile indexes, and 5 patients showed positive auto-antibodies. 3 patients had perfected muscle biopsies and showed typical skeletal muscle inflammatory myopathy-like pathological changes with CD3+, CD4+, CD8+, CD20+ lymphocytes and CD68+ macrophage infiltration. After the diagnosis of immune-related myositis, all the 8 patients immediately discontinued ICI therapy and improved after intravenous administration of methylprednisolone alone or in combination with gamma-globulin. CONCLUSION: Immune-related myositis after ICI treatment is an immune-related adverse reactions (irAEs) with unique clinical and pathological features, commonly combined with cardiovascular adverse reactions. Immediate discontinuation of ICI and initiation of glucocorticoid therapy may improve the patient's condition in a timely manner.

[Inflammatory factors in periodontitis patients and their effects toward the occurrence of gestational diabetes mellitus: a case-control study].

Objective: To explore the effects of periodontitis and inflammatory factors toward the occurrence of gestational diabetes mellitus (GDM). Methods: Pregnant women who came to the Department of Obstetrics, Northwest Women's and Children's Hospital for prenatal examinations during March to November of 2021 were invited to participate in this study. Participants with GDM who met the inclusion criteria (n=100) were assigned into the case group; while healthy participants (n=100) were assigned into the control group. Information of participants from the two groups were collected by questionnaires and periodontal statuses were clinically recorded in the meantime. Gingival crevicular fluid (GCF) and venous blood were also collected from participants of two groups to analyze the expression levels of inflammatory factors like C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-33. Factors different between the two groups were included in the multivariate regression analysis model to determine the risk factors of GDM. Results: The age of participants was (33.4±5.1) years in case group and (30.5±4.5) years in control group respectively, which had statistical differences (t=4.33,P<0.001). Besides, the body mass index of participants from case group was also significantly higher than control group [(28.11±3.85) kg/m2 vs. (23.31±3.15) kg/m2, t=9.65, P<0.001]. Participants with GDM had more adverse periodontal clinical parameters. Prevalence of periodontitis in GDM group was 47.0% (47/100) compared with 29.0% (29/100) in control group (χ²=6.88, P=0.009). Multivariate regression analysis results indicated that periodontitis was a critical risk factor for the occurrence of GDM (OR=1.882, P<0.001). Besides, GCF IL-8, serum TNF-α, IL-8 and IL-10 were also risk factors of GDM due to their higher expressions. Among them, TNF-α in serum (OR=2.077) and IL-8 in serum (OR=2.060) had more significant impacts (P<0.001). Conclusions: This study demonstrated that periodontitis was associated with the occurrence of GDM. Up-regulation of serum pro-inflammatory mediators leaded by local periodontal inflammatory microenvironment might play a critical role in this pathological process.

[Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study].

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.

[Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study].

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.

[Clinical and genetic characteristics of patients with newly diagnosed acute promyelocytic leukemia: a single-center retrospective of 790 cases].

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.

Antibiotic use from formal and informal healthcare providers in the Democratic Republic of Congo: a population-based study in two health zones.

OBJECTIVE: In the Democratic Republic of Congo and other low-resource countries, community-acquired pathogens are increasingly resistant to most locally available antibiotics. To guide efforts to optimize antibiotic use to limit antibiotic resistance, we quantified healthcare provider-specific and community-wide antibiotic use. METHODS: From household surveys, we estimated monthly healthcare visit rates by provider. From healthcare visit exit surveys, we estimated prevalence, defined daily doses, and access/watch/reserve distribution of antibiotic use by provider. Combining both, we estimated community-wide antibiotic use rates. RESULTS: Of 88.7 (95% CI 81.9-95.4) healthcare visits per 1000 person-months (n = 31221), visits to private clinics (31.0, 95% CI 30.0-32.0) and primary health centres (25.5, 95% CI 24.6-26.4) were most frequent. Antibiotics were used during 64.3% (95% CI 55.2-73.5%, 162/224) of visits to private clinics, 51.1% (95% CI 45.1-57.2%, 245/469) to health centres, and 48.8% (95% CI 44.4-53.2%, 344/454) to medicine stores. Antibiotic defined daily doses per 1000 inhabitants per day varied between 1.75 (95% CI 1.02-2.39) in rural Kimpese and 10.2 (95% CI 6.00-15.4) in (peri) urban Kisantu, mostly explained by differences in healthcare utilisation (respectively 27.8 versus 105 visits per 1000 person-months), in particular of private clinics (1.23 versus 38.6 visits) where antibiotic use is more frequent. The fraction of Watch antibiotics was 30.3% (95% CI 24.6-35.9%) in private clinics, 25.6% (95% CI 20.2-31.1%) in medicine stores, and 25.1% (95% CI 19.0-31.2%) in health centres. Treatment durations <3 days were more frequent at private clinics (5.3%, 9/169) and medicine stores (4.1%, 14/338) than at primary health centres (1.8%, 5/277). DISCUSSION: Private healthcare providers, ubiquitous in peri-urban settings, contributed most to community-wide antibiotic use and more frequently dispensed Watch antibiotics and shortened antibiotic courses. Efforts to optimize antibiotic use should include private providers at community level.

[Characteristics of fusion gene expression in acute lymphoblastic leukemia].

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.

COPB2: a transport protein with multifaceted roles in cancer development and progression

The Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex and is responsible for the transport of vesicles between the Golgi apparatus and the endoplasmic reticulum. It plays an important role in maintaining the integrity of these cellular organelles, as well as in maintaining cell homeostasis. More importantly, COPB2 plays key roles in embryonic development and tumor progression. COPB2 is regarded as a vital oncogene in several cancer types and has been implicated in tumor cell proliferation, survival, invasion, and metastasis. Here, we summarize the current knowledge on the roles of COPB2 in cancer development and progression in the context of the hallmarks of cancer (AU)